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2025, Volume 46, Issue 12
2025,
46(12):
1-8.
doi: 10.12259/j.issn.2095-610X.S20251201
Abstract:
The overuse of antibiotics has led to a rapid increase of antibiotic-resistant bacteria, making bacterial infections difficult to control effectively and posing a serious threat to human health. As antibiotic resistance problems become increasingly severe and the development of new antibiotics lags, finding more effective treatment strategies has become an urgent need in global public health. Bacteriophages, as a potential therapeutic option, have attracted increasing attention in recent years; however, bacteriophages have limitations such as a narrow host range and lysogeny. Synergistic effects between bacteriophages and antibiotics enhance bacteriophage lytic activity, reduce antibiotic dosage, significantly lower the risk of resistance development, and demonstrate superior antimicrobial efficacy. This review summarizes the mechanisms and research progress of bacteriophage-antibiotic synergy, aiming to further advance research and clinical application of combined bacteriophage-antibiotic therapy and provide new solutions to address the problem of antibiotic resistance.
The overuse of antibiotics has led to a rapid increase of antibiotic-resistant bacteria, making bacterial infections difficult to control effectively and posing a serious threat to human health. As antibiotic resistance problems become increasingly severe and the development of new antibiotics lags, finding more effective treatment strategies has become an urgent need in global public health. Bacteriophages, as a potential therapeutic option, have attracted increasing attention in recent years; however, bacteriophages have limitations such as a narrow host range and lysogeny. Synergistic effects between bacteriophages and antibiotics enhance bacteriophage lytic activity, reduce antibiotic dosage, significantly lower the risk of resistance development, and demonstrate superior antimicrobial efficacy. This review summarizes the mechanisms and research progress of bacteriophage-antibiotic synergy, aiming to further advance research and clinical application of combined bacteriophage-antibiotic therapy and provide new solutions to address the problem of antibiotic resistance.
2025,
46(12):
9-20.
doi: 10.12259/j.issn.2095-610X.S20251202
Abstract:
Objective To investigate the roles of lipid metabolism-related genes ASP and PPARα in atherosclerosis （AS）. Methods Datasets GSE9874, GSE28829, and GSE21545 were retrieved from the GEO database and intersected to identify common differentially expressed genes （DEGs）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the DEGs. Protein-protein interaction （PPI） networks were constructed using the String database, and critical genes were screened using Cytoscape software. Additionally, interacting genes of critical genes were identified using the GeneMANIA database, and molecular docking predictions were performed using HDOCK software, with further in vivo experimental validation, Atherosclerosis model was established in C57BL/6J mice. Oil Red O staining was used to observe plaque deposition areas in the whole aorta and aortic sinuses of each group. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in aortic sinus tissues. ELISA was used to detect serum lipid levels and expression levels of PCSK9, ASP, and PPARα. Reverse transcription quantitative PCR （RT-qPCR） and Western blotting （WB） were used to detect mRNA and protein expression levels of ASP and PPARα in aortic tissues. Co-immunoprecipitation （CO-IP） analysis was performed to investigate the interaction between ASP and PPARα proteins. Results A total of 35 differentially expressed genes in AS were identified, primarily enriched in cholesterol transfer activity, phosphatidylcholine transport activity, ABC transporters, and autophagy pathways. PPI and Cytoscape analyses identified ASP as a critical gene. Through the GeneMANIA database, PPARα was identified as an interacting gene of ASP. Molecular docking predictions revealed a strong interaction between the two proteins forming a stable structure. In vivo experiments showed that compared with the normal diet group, the high-fat diet and atherosclerosis groups exhibited varying degrees of damage to aortic morphology with increased plaque area; serum lipid levels were significantly elevated and ASP mRNA and protein levels in aortic tissues were significantly increased (P < 0.05), while PPARα levels showed the opposite pattern. Compared with the high-fat diet group, these indicators in the atherosclerosis group showed statistically significant differences （P < 0.05）. CO-IP analysis confirmed the interaction between ASP and PPARα. In ASP-knockdown mice, atherosclerotic plaques and serum lipid levels decreased while PPARα expression levels increased (P < 0.05). Conclusion ASP and PPARα participate in the development of atherosclerosis and may be closely related to lipid metabolism.
2025,
46(12):
21-29.
doi: 10.12259/j.issn.2095-610X.S20251203
Abstract:
Objective To explore the effects of long non-coding RNA （lncRNA） H19 on neuroinflammation and cognitive function in a vascular dementia （VD） model. Methods A VD mouse model was established by bilateral common carotid artery occlusion. Forty-eight mice were randomly and equally divided into four groups: sham surgery group, model group, NC group, and shRNA-H19 group. The sham surgery group underwent no ligation. Following successful model establishment, AAV2/1-shRNA-vehicle and AAV2/1-shRNA-H19 were injected into the brain of mice in the NC group and shRNA-H19 group, respectively. Cognitive levels was assessed useing Morris water maze test. Pathological changes in the hippocampal CA1 region and neuronal injury were observed by HE and Nissl staining. Neuronal apoptosis was detected by TUNEL staining. Levels of tumor necrosis factor-α （TNF-α）, interleukin （IL）-1β, and IL-6 in hippocampal tissue were measured by enzyme-linked immunosorbent assay （ELISA）. Expression of ionized calcium-binding adapter molecule-1 （Iba-1） protein in the hippocampal CA1 region was detected by immunofluorescence staining. Expression of H19, B-cell lymphoma-2 （Bcl-2）, cleaved caspase-3, toll-like receptor 4 （TLR4）, and nuclear factor-kappa B （NF-κB） protein and/or mRNA in hippocampal tissue were detected by quantitative real-time polymerase chain reaction （qRT-PCR） and/or Western blot. Results Compared with the model group, shRNA-H19 mice exhibited improved cognitive function （P < 0.05）, reduced pathological changes and neuronal injury in the hippocampal CA1 region, elevated Bcl-2 levels in hippocampal tissue, and decreased neuronal apoptosis rate, H19, TNF-α, IL-1β, IL-6, Iba-1, cleaved caspase-3, TLR4, and NF-κB p-p65/NF-κB p65 levels （P < 0.05）. The NC group showed no significant differences in the above indicators （P > 0.05）. Conclusion Inhibition of H19 expression in hippocampal tissue ameliorates neuroinflammation and improve cognitive function in VD mice, inhibits neuronal apoptosis and microglial infiltration in the hippocampal CA1 region. The underlying mechanism may be related to downregulation of the TLR4/NF-κB p65 signaling pathway.
2025,
46(12):
30-39.
doi: 10.12259/j.issn.2095-610X.S20251204
Abstract:
Objective To investigate the mechanism of the HDAC3/GATA-2 molecular axis in osteogenic differentiation of human dental pulp stem cells （hDPSCs）. Methods The hDPSCs cell line was cultured in osteogenic induction medium （OM）. Plasmids of oe-NC, oe-HDAC3 and oe-GATA-2 were constructed and transfected into the cells. Transfection efficiency was assessed by RT-qPCR and Western blot. Alkaline phosphatase （ALP） staining and alizarin red S （ARS） staining were used to evaluate ALP activity and mineralization nodules in cells. RT-qPCR and Western Blot were used to detect the expression levels of osteogenic key indicators COL1A1, ALP, BMP2, and RUNX2. GST-pull down and Co-Immunoprecipitation （CO-IP） were used to validate the interaction of HDAC3 and GATA-2 interaction, and immunofluorescence （IF） staining was performed to detect cellular expression. Results HDAC3 expression was significantly reduced during osteogenic differentiation of hDPSCs （P < 0.0001 ）. Overexpression of HDAC3 significantly attenuated ALP staining and activity （P = 0.0001 ）, as well as reduced the production of mineralized nodules in hDPSCs cells. The expression levels of COL1A1 （P = 0.0029 ）, ALP （P = 0.0001 ）, BMP2 （P = 0.0001 ） and RUNX2 （P = 0.0007 ） were inhibited after overexpression of HDAC3. HDAC3 interacted with GATA-2, and overexpression of HDAC3 decreased the expression of GATA-2 in cells （P = 0.0028 ）. Co-transfection of oe-GATA-2 reversed the inhibitory effects of HDAC3 overexpression, increasing ALP staining and activity （P = 0.0043 ） and mineralization nodules in cells. In the oe-HDAC3 + oe-GATA-2 group, the expression levels of COL1A1 （P = 0.0001 ）, ALP （P = 0.0423 ）, BMP2 （P < 0.0001 ）, and RUNX2 （P = 0.0005 ） were further elevated. Conclusion HDAC3 inhibited the osteogenic differentiation of hDPSCs by targeting and negatively regulating the expression of GATA-2.
2025,
46(12):
40-48.
doi: 10.12259/j.issn.2095-610X.S20251205
Abstract:
Objective To investigate the mechanism by which Glu/GABA regulation of neurotransmitter balance improves behavioral abnormalities in a rat model of Tourette syndrome （TS）. Methods Forty-eight SPF-grade SD rats were randomly divided into four groups: normal control group, model group, Glu/GABA 1 group （10 mg/kg） and Glu/GABA 2 group （20 mg/kg）, with 12 rats in each group. Except for the normal control group, the remaining rats received intraperitoneal injections of 250 mg/（kg·d） IDPN for 7 consecutive days to establish TS model. After successful model establishment, each group received gavage intervention for 6 weeks. Stereotyped behavior scores were assessed using blinded methods before intervention, at week 3, and week 6. Total spontaneous activity distance was detected using a video activity monitoring system. After intervention, brain tissue was harvested for HE staining to count neurons in the cortex, striatum, and thalamus, and transmission electron microscopy was used to observe myelin morphology. HPLC was used to detect Glu and GABA levels in brain tissues; immunofluorescence was used to determine their fluorescence intensity, so as to explore the effect of Glu/GABA on TS model rats. Results Stereotyped behavior scores and total spontaneous activity distance in the model group and Glu/GABA intervention groups were significantly higher than in the normal control group （P < 0.05）. After 6 weeks of intervention, stereotyped behavior scores and total spontaneous activity distance in Glu/GABA groups 1 and 2 were significantly reduced compared to the model group （P < 0.001）, with no statistical difference between the two intervention groups （P > 0.05）. Neuron counts in the cortex, striatum, and thalamus of the model group decreased, with myelin lamellae loosening and axonal damage. After Glu/GABA intervention, neuron counts recovered （P < 0.01） and myelin structure improved. Compared with normal group, the model group showed significantly elevated brain Glu levels and fluorescence intensity, and significantly decreased GABA（P < 0.01）. Glu/GABA intervention reversed these changes （P < 0.01）. Conclusion Glu/GABA effectively reduces stereotyped behavior scores and spontaneous activity distance in TS model rats, repairs neuronal damage and myelin abnormalities in the cortex, striatum, and thalamus, and regulates brain Glu and GABA levels to normal balanced states, thereby exerting therapeutic effects on TS.
2025,
46(12):
49-57.
doi: 10.12259/j.issn.2095-610X.S20251206
Abstract:
Objective To investigate the protective role and potential mechanisms of γ-aminobutyric acid type A receptor （GABA_AR） against oxygen-glucose deprivation/reoxygenation （OGD/R）-induced astrocyte injury. Methods C8-D1A astrocytes were used to establish an OGD/R injury model, which was randomly divided into four groups: the normal control group （NC）, the OGD/R model group, the GABA_AR agonist CL218872 intervention group （OGD/R+CL218872）, and the inhibitor MRK-016 intervention group （OGD/R+MRK-016）. Cell proliferation was assessed by EdU staining, apoptosis was analyzed by flow cytometry, GABA_AR and glial fibrillary acidic protein （GFAP） expression were examined by immunofluorescence staining, and brain-derived neurotrophic factor （BDNF） expression was determined by Western blotting. Results Compared with the OGD/R group, the OGD/R+CL218872 group showed significantly increased cell proliferation rate （P < 0.05） , markedly decreased apoptosis rate（P < 0.01）, upregulated expression of both GABA_AR and GFAP（P < 0.05） significantly elevated BDNF protein expression level（P < 0.05）, and significantly reduced levels of inflammatory factors IL-6 （P < 0.01） and TNF-α （P < 0.05）. The OGD/R+MRK-016 group showed opposite changes in all parameters. Conclusion GABA_AR activation can attenuate OGD/R-induced astrocyte injury by promoting astrocyte proliferation, inhibiting apoptosis and inflammatory response, and upregulating the expression of BDNF and GFAP.
2025,
46(12):
58-68.
doi: 10.12259/j.issn.2095-610X.S20251207
Abstract:
Objective To investigate the role of bone marrow-derived mesenchymal stem cell （BMSCs）-derived exosomes （Exo） in transferring signal transduction and transcriptional activator 3 （STAT3） protein in myocardial infarction （MI）. Methods A rat MI model was established by ligation of the left anterior descending coronary artery. The animals were randomly divided into Sham, MI, and BMSCs-Exo groups. Additionally, Exo-pcDNA, Exo-pcDNA-STAT3, Exo-si-NC, and Exo-si-STAT3 groups were established to investigate the effects of upregulating or inhibiting STAT3 expression in Exo on cardiac function. At 2 and 4 weeks after surgery, rat electrocardiograms （ECG） and hemodynamic parameters were measured, including left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP）, maximum rate of pressure rise in left ventricle （+dp/dtmax）, and maximum rate of pressure decline in left ventricle （−dp/dtmax）. Western blot （WB） analysis was used to detect the expression levels of related proteins in myocardial tissue, including phosphorylated signal transducer and activator of transcription 3 （p-STAT3）, B-cell lymphoma-2 （Bcl-2）, Bcl-2-associated X protein （Bax）, and cleaved caspase-3 （Cleaved-caspase-3）. Results Compared with the MI group, the BMSCs-Exo group showed significant recovery of ST segment, QRS wave, and QT interval （F = 23.462, P < 0.001）, and decreased arrhythmia incidence （χ2 = 7.248, P = 0.009）. Simultaneously, LVEDP decreased, and LVSP and ±dp/dtmax improved （F = 19.601, P < 0.001）. In the transfection groups, compared with the Exo-pcDNA group, the Exo-pcDNA-STAT3 group showed elevated S wave amplitude （P < 0.05） and reduced arrhythmia incidence to 37.5%. Compared with the Exo-si-NC group, the Exo-si-STAT3 group showed prolonged QT interval, widened T wave, and decreased S wave amplitude （F = 30.592, P < 0.001）, with arrhythmia rate increased to 87.5%. Cardiac function assessment showed that the Exo-pcDNA-STAT3 group had decreased LVEDP （F = 14.937, P < 0.001）, while the Exo-si-STAT3 group showed elevated ASBP, LVSP, and +dp/dtmax （F = 16.213, P < 0.001）, suggesting increased cardiac workload. WB results showed that the Exo-pcDNA-STAT3 group had upregulated p-STAT3 and Bcl-2 expression, while Bax and Cleaved-caspase-3 were downregulated （F = 331.518, 901.008, 545.635, and 516.670, P < 0.001）; conversely, the Exo-si-STAT3 group showed opposite trends. Conclusion BMSCs-derived exosomes improve cardiac function, reduce arrhythmias, and attenuate myocardial apoptosis after MI by delivering STAT3. Upregulation of STAT3 enhances the cardioprotective effects of exosomes, whereas STAT3 inhibition weakens these benefits.
2025,
46(12):
69-74.
doi: 10.12259/j.issn.2095-610X.S20251208
Abstract:
Objectives To investigate the correlation between coagulation function indicators and International Staging System （ISS） staging in newly diagnosed multiple myeloma （NDMM） patients, and to establish a predictive model for ISS high-risk staging based on coagulation indicators. Methods A total of 114 NDMM patients from May 2021 to December 2024 were collected as the model development cohort and randomly divided into training set （80 cases） and internal validation set （34 cases） at a ratio of 7∶3; 52 patients from January to June 2025 were collected as external validation cohort. Patients were stratified into stage I/II group and stage III group according to ISS staging, and differences in coagulation function indicators between the two groups were compared. Spearman correlation analysis was used to evaluate the correlations between coagulation indicators and β2-microglobulin （β2-MG） and albumin （ALB）. Binary logistic regression was employed to identify independent risk factors for ISS high-risk staging, and a nomogram prediction model was constructed to assess its predictive performance. Results In ISS stage III patients, levels of prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （FIB）, thrombin time （TT）, and thrombomodulin （TM） were all significantly higher than those in ISS stage I/II patients （all P < 0.05）. Correlation analysis showed that all five coagulation function indicators were positively correlated with β2-microglobulin, while PT, APTT, and TT were negatively correlated with albumin. Multivariate logistic regression analysis revealed that PT, TT, and TM were independent risk factors for ISS high-risk staging. The nomogram prediction model based on PT, TT, and TM showed an AUC of 0.849, with sensitivity of 90.6% and specificity of 67.6%. Conclusions PT, TT, and TM are closely associated with ISS staging and can serve as independent risk factors for high-risk staging.
2025,
46(12):
75-83.
doi: 10.12259/j.issn.2095-610X.S20251209
Abstract:
Objective To verify the expression pattern of p16 at the clinical and cellular levels, and further explore the effects of p16 on the cell cycle and fatty acid metabolism of human gallbladder cancer （GBC） cells. Methods The gallbladder specimens were collected from 60 patients who underwent cholecystectomy at the Second Affiliated Hospital of Kunming Medical University from January 2021 to December 2022. Among them, 30 specimens were from cases of gallstones with cholecystitis, and 30 specimens were from gallbladder cancer （GBC）. Real-time fluorescent quantitative reverse transcription PCR （RT-qPCR） was used to detect p16 mRNA levels in GBC samples and cholecystitis samples. Immunohistochemical staining was performed to detect p16 protein expression levels in GBC samples and cholecystitis samples. CCK-8 assay was used to detect the proliferative capacity of stably transfected cell lines. Flow cytometry was employed to detect apoptosis and cell cycle progression in tumor cells. RT-qPCR was used to detect the expression of peroxisome-related genes, mitochondrial oxidation-related genes, and fatty acid synthesis-related genes in cancer cells with low p16 expression. Results The expression of p16 mRNA and p16 protein in GBC was significantly higher than that in chronic cholecystitis （P < 0.05）. After p16 downregulation, the apoptosis rate of tumor cells decreased, the proportion of cells in G0/G1 phase decreased, the S phase proportion increased, and cell division accelerated, with statistically significant differences （P < 0.0001 ）. After p16 downregulation, most related genes in GBC were significantly upregulated, with statistically significant differences （P < 0.05）. Conclusions p16 is significantly highly expressed in GBC. p16 can inhibit the progression of GBC cell cycle. p16 may affect the occurrence and development of GBC cells through regulating the pathway of fatty acid metabolism.
2025,
46(12):
84-91.
doi: 10.12259/j.issn.2095-610X.S20251210
Abstract:
Objective To investigate and analyze the correlation between serum soluble CD276 （sCD276） and human epididymis protein 4 （HE4） levels in ovarian cancer patients and postoperative recurrence. Methods A retrospective study enrolled 52 ovarian cancer patients treated at the Affiliated Hospital of Shandong Second Medical University from February 2022 to April 2023 as the study group. Additionally, 50 normal healthy subjects examined during the same period were selected as the control group. Serum levels of sCD276 and HE4 were compared, and the correlation between serum sCD276 and HE4 levels and pathological characteristics of ovarian cancer patients was determined. Patients underwent one-year postoperative follow-up and were stratified into a recurrence group （n = 12） and non-recurrence group （n = 40） based on recurrence status during follow-up. Serum sCD276 and HE4 levels were compared between the two groups. Cox regression analysis was employed to identify high-risk factors for postoperative recurrence. Receiver operating characteristic （ROC） curves were constructed to analyze the predictive value of sCD276 and HE4 for postoperative recurrence. Kaplan-Meier survival analysis was performed. Results Compared with the control group, serum sCD276 and HE4 levels were elevated in the study group. Compared with the non-recurrence group, the recurrence group showed elevated serum sCD276 and HE4 levels, as well as significant differences in tissue differentiation degree, lymph node metastasis, postoperative residual tumor diameter, carcinoembryonic antigen （CEA）, regulatory T lymphocyte （Treg） ratio, folate receptor 1 （FOLR1）, and carbohydrate antigen 125 （CA125）（P < 0.05）. Cox regression analysis identified tissue differentiation degree, lymph node metastasis, postoperative residual tumor diameter, CEA, Treg ratio, FOLR1, sCD276, and HE4 were all risk factors for postoperative recurrence in ovarian cancer. ROC curve analysis revealed that combined detection of sCD276 and HE4 had superior diagnostic efficacy compared with single-marker detection, with statistically significant differences （P < 0.05）. Kaplan-Meier survival analysis showed that patients with high levels of sCD276 and HE4 had higher mortality rates than those with low levels （P < 0.05）. Conclusion Serum sCD276 and HE4 levels are elevated in ovarian cancer patients and are associated with postoperative recurrence.
2025,
46(12):
92-100.
doi: 10.12259/j.issn.2095-610X.S20251211
Abstract:
Objective To investigate the significance of serum tumor necrosis factor superfamily member 14 （TNFSF14）, toll-like receptor 7 （TLR7）, and soluble cluster of differentiation 14 subtype （sCD14-ST） levels in evaluating disease severity and prognosis in children with pneumonia associated with respiratory syncytial virus （RSV） infection. Methods A total of 154 children with RSV infection-related pneumonia admitted between July 2024 and July 2025 were enrolled as the disease group, classified into mild group （n = 52） and severe group （n = 102） based on disease severity. Simultaneously, 154 healthy children who underwent routine physical examinations at our hospital served as the control group. Serum levels of TNFSF14, TLR7, and sCD14-ST were measured using ELISA. According to prognosis, patients were divided into poor prognosis group （n = 35） and good prognosis group （n = 119）. ROC curve analysis was performed to evaluate the value of serum TNFSF14, TLR7, and sCD14-ST levels in assessing disease severity and prognosis in children with RSV infection-related pneumonia. Multivariate Logistic regression analysis was used to identify independent factors affecting poor prognosis. Results Serum levels of TNFSF14, TLR7, and sCD14-ST in the disease group were significantly higher than in the control group （P < 0.05）. Compared with the mild group, children in the severe group showed significantly elevated serum levels of TNFSF14, TLR7, and sCD14-ST （P < 0.05）. Spearman rank correlation analysis demonstrated that serum levels of TNFSF14, TLR7, and sCD14-ST showed significant positive correlations with chest X-ray （CXR） lesion extent grade at admission （all P <0.001）, with TNFSF14 showing the strongest correlation （rs = 0.484） followed by TLR7 （rs = 0.421） and sCD14-ST （rs = 0.349）. Stratified analysis showed that in the severe group, the correlations between all three markers and lesion extent grade （TNFSF14: rs = 0.525, TLR7: rs = 0.493, sCD14-ST: rs = 0.424; All P <0.001） were significantly stronger than in the mild group （TNFSF14: rs = 0.31, TLR7: rs = 0.27, sCD14-ST: rs = 0.24; all P <0.05）. Compared with single marker detection, combined measurement of serum TNFSF14 （Z = 4.884, P < 0.001）, TLR7 （Z = 2.792, P = 0.003）, and sCD14-ST （Z = 4.803, P < 0.001） levels had a higher evaluation value for disease severity in children with RSV infection-related pneumonia. Significant differences were observed between the poor and good prognosis groups in lesion extent grade, lesion type, and presence of complications （P < 0.05）. Compared with the good prognosis group, the poor prognosis group showed significantly elevated serum levels of TNFSF14, TLR7, and sCD14-ST （P < 0.05）. Compared with individual detection, the combined detection of serum TNFSF14 （Z = 3.902, P < 0.001）, TLR7 （Z = 3.434, P < 0.001）, and sCD14-ST （Z = 2.394, P = 0.017） levels had a higher prognostic value for children with RSV pneumonia. Multivariate logistic regression analysis revealed that serum levels of TNFSF14 （OR = 4.351）, TLR7 （OR = 2.635）, sCD14-ST （OR = 1.695）, diffuse infiltration （OR = 4.121）, and presence of complications （OR = 3.570） were independent factors affecting poor prognosis in children with RSV infection-related pneumonia （P < 0.05）. Conclusion Serum levels of TNFSF14, TLR7, and sCD14-ST are significantly elevated in children with RSV infection-related pneumonia. Combined detection of these three markers enhances the evaluation value for assessing disease severity and prognosis.
2025,
46(12):
101-111.
doi: 10.12259/j.issn.2095-610X.S20251212
Abstract:
Objective To investigate the concordance between mismatch repair （MMR） protein and microsatellite instability （MSI） detection in colorectal cancer （CRC） in Yunnan Province, the similarity of their biological characteristics, and to preliminarily screen independent factors that may lead to discordance between the two detection methods. Methods A retrospective collection of medical records from 412 native Yunnan CRC patients who visited the First Affiliated Hospital of Kunming Medical University between January 2021 and December 2024 was conducted. Kappa analysis was employed to assess the concordance between MMR and MSI testing, with percentags representing the matching degree between MMR and MSI status. Chi-square test was used for univariate analysis, Bonferroni correction for multiple comparisons, and logistic regression models for multivariate analysis to further screen independent factors associated with discordance between these two detection methods. Results （1） Consistency: Among 412 colorectal cancer patients in Yunnan Province, the incidence of deficient MMR （dMMR） and microsatellite instability-high （MSI-H） were 12.1% and 8.5%, respectively. Using MSI testing as the gold standard, the sensitivity and specificity of MMR testing were 82.9% and 94.4%, respectively, with positive and negative predictive values of 58.0% and 98.3%, respectively. The overall concordance rate between the two tests was 93.5%. Kappa analysis demonstrated high concordance between the two assays across the general population, Han Chinese patients, and ethnic minority patients （general population: Kappa=0.647 > 0.6, P < 0.001; Han Chinese patients: Kappa=0.621 > 0.6, P < 0.001; ethnic minority patients: Kappa=0.808 > 0.8, P < 0.001）. （2） MMR protein deficiency patterns: Among 50 dMMR patients, the most prevalent deficiency type was combined MLH1-PMS2 deletion （42.0%）, and MSI-H accounted for 58.0% in dMMR patients, of which MSH2-MSH6 combined deficiency showed the highest proportion of MSI-H （85.7%）. （3） Biological characteristic similarities: History of polyposis, tumour location, differentiation degree, and M stage were all independently associated with MSI and MMR status. Additionally, MSI status was independently associated with age, family history of cancer, and tumour size （P < 0.05）. （4） Independent factors associated with MMR-MSI test concordance: History of polyposis and tumour location were independently associated with concordance between the two tests; while tumour location and differentiation degree were independently associated with concordance of MSI detection in dMMR （P < 0.05）. Conclusion In Yunnan Province, MMR and MSI testing for CRC demonstrate high concordance and similar biological characteristics. Inconsistencies between the two tests are more likely to occur in CRC with a history of polyposis and non-rectal locations. dMMR-type CRC, such inconsistencies are more likely to be found in patients with moderately to highly differentiated tumours and those with tumors in the left-sided colon. Meanwhile, there is also a close correlation between the MSI classification of CRC and its clinicopathological features.
2025,
46(12):
112-122.
doi: 10.12259/j.issn.2095-610X.S20251213
Abstract:
Objective To explore the clinical efficacy and impact on sleep quality of short-term spinal cord stimulation （stSCS） and short-term dorsal root ganglion stimulation （stDRG） in treating zoster associated neuralgia （ZAN）. Methods A total of 124 patients with ZAN diagnosed and treated at the Second Hospital of Hebei Medical University between September 2022 and May 2024 were selected and divided into Group A （stSCS） and Group B （stDRG） according to different treatment modalities, with 62 cases in each group. After propensity score matching （PSM） to balance covariates between groups, clinical efficacy was compared. Changes in visual analogue scale （VAS）, pain-DETECT questionnaire （PD-Q）, Hamilton anxiety scale （HAMA）, Hamilton depression scale （HAMD） scores, inflammatory indicators, phosphatidylinositol-3-kinase （PI3K）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway indicators and polysomnography parameters before and after treatment were analyzed, and the correlation between each indicator and PSOI score was explored. Results There was no statistically significant difference in clinical efficacy, long-term recurrence rate and adverse reactions between the two groups （P > 0.05）. Difference-in-differences （DID） analysis showed no significant baseline differences in VAS, PD-Q, HAMA, and HAMD scores between groups （P > 0.05）; all scores significantly improved over time, and the net effects of different treatment methods on each score were evident （P < 0.05）. Repeated-measures ANOVA showed that the inflammatory indicators, PI3K/AKT/mTOR signaling pathway indicators, and polysomnography parameters in both groups changed significantly over time, with evident between-group and interaction effects （P < 0.05）. Pearson correlation analysis demonstrated stable correlations between PSQI, VAS, PD-Q, HAMA, and HAMD scores and inflammatory markers, PI3K/AKT/mTOR signaling pathway indicators, and polysomnography parameters （P < 0.05）. Conclusion Both stSCS and stDRG can effectively improve quality of life of ZAN patients, with stSCS demonstrating greater advantages in sustained analgesic efficacy and stable sleep-improving effects.
2025,
46(12):
123-130.
doi: 10.12259/j.issn.2095-610X.S20251214
Abstract:
Objective To investigate the correlation between serum interleukin-10 （IL-10）, cytotoxic T lymphocytes （CTL） and Epstein Barr virus （EBV）-associated infectious mononucleosis （IM） complicated with liver damage in children. Methods A prospective study was conducted on 215 children with EBV-associated IM admitted to Hainan Hospital of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Children's Hospital of Wujiang District, Suzhou and Handan First Hospital from September 2021 to May 2025. Participants were divided into complicated group （with hepatic impairment） and non-complicated group （without hepatic impairment） based on the presence or absence of concurrent hepatic impairment. Additionally, 215 healthy children during the same period were selected as the control group. Clinical data, serum IL-10 and CTL levels were compared among groups. Restricted cubic spline （RCS） analysis was used to assess the correlation between serum IL-10, CTL, and hepatic impairment in children with EBV-associated IM. Logistic regression analysis was performed to identify relevant factors affecting hepatic impairment in children with EBV-associated IM. Receiver operating characteristic （ROC） curves were used to evaluate the predictive value of serum IL-10, CTL, and their combination for hepatic impairment in children with EBV-associated IM. Results Pre-treatment serum IL-10 and CTL levels in children with EBV-associated IM were higher than those in the control group （P < 0.05）. EBV DNA in the complicated group was higher than in the non-complicated group （P < 0.05）. Pre-treatment and 3-day post-treatment IL-10 and CTL levels in the complicated group were significantly higher than in the non-complicated group, with statistical significance （P < 0.05）. RCS model analysis revealed optimal fitting when the number of knots was 3, with significant likelihood ratio test （P < 0.05）. Serum IL-10 demonstrated a "U"-shaped dose-response relationship with hepatic impairment in children with EBV-associated IM （P < 0.05）, with a high-risk threshold of 14.90 pg/mL. CTL showed a non-linear relationship with hepatic impairment, characterized by gradual stability followed by elevation （P < 0.05）, with a high-risk threshold of 46.10%. Logistic regression analysis showed that after adjusting for EBV DNA, IL-10>14.90 pg/mL and CTL>46.10% remained independent risk factors for hepatic impairment in children with EBV-associated IM （P < 0.05）. ROC curve analysis showed that the AUC value of IL-10+CTL （0.850, 95%CI: 0.795-0.895） was significantly higher than the individual AUC values of either marker （P < 0.05）. Pre-treatment and 3-day post-treatment IL-10 and CTL levels in children with moderate hepatic impairment were significantly higher than in those with mild impairment, with statistical significance （P < 0.05）. Conclusion Serum IL-10 and CTL are correlated with hepatic impairment in children with EBV-associated IM, with high-risk thresholds of 14.90 pg/mL and 46.10%, respectively. Combined detection of both markers enhances the predictive value for concurrent hepatic impairment and provides clinical guidance.
2025,
46(12):
131-137.
doi: 10.12259/j.issn.2095-610X.S20251215
Abstract:
Objective To explore the predictive assessment and risk factor analysis of the FRAIL Scale （Frailty）, Clinical Frailty Scale （CFS）, and Reported Edmonton Frail Scale （REFS） for delirium in elderly frail patients. Methods A total of 187 elderly frail hospitalized patients admitted to the Department of Geriatric Medicine at Chengdu Sixth People's Hospital from January to December 2023 were selected as research subjects. The FRAIL, CFS, and REFS scales were used to assess the frailty index. Patient data were collected and a delirium-related risk cohort was constructed. The incidence of delirium, duration of occurrence, and prognostic outcomes were recorded. The FRAIL, CFS, and REFS scale scores between patients with and without delirium were analyzed. Clinical characteristics were compared between the two groups. Logistic regression analysis was used to identify risk factors for delirium in elderly frail patients, and ROC curve analysis was performed to evaluate the predictive efficacy of FRAIL, CFS, and REFS for delirium occurrence in elderly frail patients. Results Among the 187 elderly frail hospitalized patients, 34 cases （18.18%） developed delirium, and 153 cases （81.82%） did not develop delirium. The FRAIL, CFS, and REFS scale scores in the delirium group were significantly higher than in the non-delirium group （P < 0.05）. There were significant differences between the two groups in age, stroke history, malnutrition, cognitive impairment, activity limitation, and severe pain （P < 0.05）. Logistic regression results showed that age ≥75 years, stroke, malnutrition, cognitive impairment, activity limitation, severe pain, FRAIL, CFS, and REFS were all risk factors for delirium in elderly frail patients （P < 0.05）. ROC curve analysis demonstrated that REFS had a higher area under the ROC curve （AUC = 0.813, 95%CI: 0.739-0.843） for predicting delirium in elderly frail patients compared to FRAIL and CFS. Conclusions The main factors affecting delirium occurrence in elderly frail patients are related to age ≥75 years, stroke, malnutrition, cognitive impairment, activity limitation, severe pain, and degree of frailty. The REFS scale demonstrates superior predictive efficacy for delirium compared to the FRAIL and CFS scales.
2025,
46(12):
138-146.
doi: 10.12259/j.issn.2095-610X.S20251216
Abstract:
Objective To investigate the expression of LIM-only protein 2 （LMO2） and cell cycle-associated protein 1 （CAPRIN1） in pancreatic cancer tissues, and their correlation with clinicopathological features and prognosis, and to validate their effects on pancreatic cancer cell function through in vitro knockdown experiments. Methods Ninety pancreatic cancer patients admitted to Xingtai Central Hospital between August 2015 and March 2018 and pathologically confirmed were enrolled. Cancer tissue specimens were collected as the case group, while adjacent non-tumor tissue （>2 cm from the cancer margin, pathologically confirmed without cancer infiltration or abnormal lesions） served as the control group. Immunohistochemistry （IHC） was used to detect the expression levels of LMO2 and CAPRIN1, and their relationships with clinicopathological features including differentiation degree, lymph node metastasis, and TNM staging were analyzed in conjunction with clinical data. A two-year follow-up was conducted, and survival was analyzed using the Kaplan-Meier method, while independent prognostic factors were assessed with the Cox proportional hazards regression model.In vitro experiments, PANC-1 and BxPC-3 cell lines were selected, and specific siRNA targeting LMO2, CAPRIN1, or combined knockdown was performed using Lipofectamine 3000. Knockdown efficiency was verified by qPCR and Western blot, and cell proliferation and migration were assessed using CCK-8, EdU, wound healing, and Transwell assays. Results IHC results showed that the positive expression rates of LMO2 and CAPRIN1 were significantly higher in pancreatic cancer tissues than in adjacent tissues （P = 0.009; P = 0.012）. High LMO2 expression was associated with differentiation degree （P = 0.026） and lymph node metastasis （P = 0.007）, while high CAPRIN1 expression was significantly correlated with TNM staging （P = 0.019）, differentiation degree （P = 0.018）, and lymph node metastasis （P = 0.004）. Correlation analysis revealed a positive correlation between LMO2 and CAPRIN1 expression （P = 0.013）. Follow-up results showed that survival rates in patients with high LMO2 and high CAPRIN1 expression were significantly lower than in those with low expression （P = 0.015; P = 0.021）. Multivariate Cox regression analysis indicated that high LMO2 expression （P = 0.031）, high CAPRIN1 expression（P = 0.019）, TNM stage III+IV （P = 0.005）, poor/moderate differentiation （P = 0.047）, and lymph node metastasis （P = 0.027） were all independent risk factors for prognosis in pancreatic cancer patients. In vitro experimental results showed that knockdown of LMO2 or CAPRIN1 significantly inhibited PANC-1 and BxPC-3 cell proliferation and migration ability, with combined knockdown showing more pronounced effects （P < 0.001）. Conclusion High expression of LMO2 and CAPRIN1 in pancreatic cancer tissue is associated with adverse clinicopathological features and poor survival outcomes. In vitro functional experiments further verified their critical roles in pancreatic cancer cell proliferation and migration, suggesting that LMO2 and CAPRIN1 may serve as potential prognostic biomarkers and therapeutic targets for pancreatic cancer.
2025,
46(12):
147-153.
doi: 10.12259/j.issn.2095-610X.S20251217
Abstract:
Objective To explore the diagnostic value of ultrasound combined with serum interleukin-1β （IL-1β） and cytokeratin 19 fragment antigen 21-1 （CYFRA21-1） in ovarian cancer. Methods From July 2020 to July 2023, 250 patients with ovarian tumors admitted to Cangzhou Integrated Chinese and Western Medicine Hospital were enrolled. Among them, 114 patients confirmed as having ovarian cancer by pathological examination comprised the ovarian cancer group. Additionally, 114 patients were randomly selected from the remaining 136 patients with benign tumors to form the control group. All study subjects underwent diagnosis using color ultrasound diagnostic equipment. Serum levels of IL-1β and CYFRA21-1 were detected using the enzyme linked immunosorbent assay （ELISA） method. Kappa test was used to analyze the consistency between diagnostic methods and surgical pathological results. Multivariate logistic regression analysis was performed to identify risk factors for ovarian cancer occurrence. Receiver operating characteristic （ROC） curve analysis was used to evaluate the diagnostic value of ultrasound combined with serum IL-1β and CYFRA21-1 for ovarian cancer. Results Serum levels of IL-1β and CYFRA21-1 in the ovarian cancer group were significantly elevated compared to the control group （P < 0.05）. Compared with clear cell carcinoma, serum levels of IL-1β and CYFRA21-1 in patients with mucinous adenocarcinoma and serous adenocarcinoma were significantly elevated （P < 0.05）. Serum levels of IL-1β and CYFRA21-1 in ovarian cancer patients showed a progressive increase across stages I<stage II<stage III<stage IV （P < 0.05）. Elevated serum levels of IL-1 β and CYFRA21-1 were risk factors for ovarian cancer （P < 0.05）. The area under the curve （AUC） for the combined ultrasound with serum IL-1β and CYFRA21-1 in diagnosing ovarian cancer was significantly higher than the AUC values of single-indicator diagnosis （Zultrasound～ultrasound+IL-1β+CYFRA21-1=3.782, P < 0.001; ZIL-1β～ultrasound+IL-1β+CYFRA21-1=4.046, P < 0.001; ZCYFRA21-1～ultrasound+IL-1β+CYFRA21-1=7.279, P < 0.001）. Based on pathological examination results, the consistency of combined diagnosis （Kappa value=0.789） was higher than ultrasound alone （Kappa value=0.658）. Conclusion The combined diagnostic approach of ultrasound with serum IL-1β and CYFRA21-1 demonstrates high diagnostic efficacy for ovarian cancer.
2025,
46(12):
154-161.
doi: 10.12259/j.issn.2095-610X.S20251218
Abstract:
Stress urinary incontinence is one of the most common pelvic floor dysfunctions affecting millions of women worldwide. Currently, conservative treatment methods widely adopted in clinical practice have relatively limited efficacy, necessitating the exploration of innovative treatment approaches beyond traditional methods. In recent years, new treatment methods such as physical therapy techniques （e.g., high-intensity focused electromagnetic stimulation）, regenerative medicine and biomaterials, and telerehabilitation models have gradually become prominent as potential interventions for SUI. These therapies may effectively alleviate urinary incontinence symptoms and improve the quality of life for patients. This review discusses the mechanisms of action and clinical translation progress of several aforementioned therapies in SUI, aiming to provide innovative and practical reference solutions for clinical practice in SUI management.
Stress urinary incontinence is one of the most common pelvic floor dysfunctions affecting millions of women worldwide. Currently, conservative treatment methods widely adopted in clinical practice have relatively limited efficacy, necessitating the exploration of innovative treatment approaches beyond traditional methods. In recent years, new treatment methods such as physical therapy techniques （e.g., high-intensity focused electromagnetic stimulation）, regenerative medicine and biomaterials, and telerehabilitation models have gradually become prominent as potential interventions for SUI. These therapies may effectively alleviate urinary incontinence symptoms and improve the quality of life for patients. This review discusses the mechanisms of action and clinical translation progress of several aforementioned therapies in SUI, aiming to provide innovative and practical reference solutions for clinical practice in SUI management.
2025,
46(12):
162-170.
doi: 10.12259/j.issn.2095-610X.S20251219
Abstract:
Objective To clarify the internal structure and population characteristics of clinical reasoning ability among clinical medical interns, construct targeted training tools, and provide evidence for clinical reasoning education reform. Methods A multi-center stratified sampling method was adopted to select 321 clinical medicine interns who underwent clinical internships in 6 hospitals from July 2023 to April 2024. A self-designed "Clinical Thinking Ability Assessment Questionnaire" was used for the survey. Correlation analysis and factor analysis were conducted to explore the ability structure, while K-means clustering was applied to identify group characteristics. Based on these findings, a Python case library was designed and its effectiveness was verified through a randomized controlled trial. Results Clinical thinking ability demonstrated a three-dimensional structure comprising "diagnostic association, decision-making for treatment planning, and knowledge application, " with a cumulative variance explanation rate of 84.21%. Multi-population validation showed good model fit （χ2/df = 2.31～2.45, RMSEA = 0.065～0.069）. Clustering analysis identified three ability groups: high （33.33%）, moderate （42.68%）, and low （23.99%）, with statistically significant differences across all dimensions （P < 0.01）. After intervention with the case library, the improvement of core shortcoming dimensions in the intervention group was significantly higher than that in the control group （diagnostic relevance of high-ability group: F = 32.67; scheme decision-making ability of medium-ability group: F = 48.32; knowledge application ability of low-ability group: F = 41.56, all P < 0.01）. Conclusion The three-dimensional structure and population characteristics of clinical thinking ability provide targeted guidance for precision training. The Python case library facilitates the transition of clinical thinking cultivation toward "data-driven" approaches.
2025,
46(12):
171-180.
doi: 10.12259/j.issn.2095-610X.S20251220
Abstract:
Objective To analyze potential latent class of frailty and influencing factors in lung cancer radiotherapy patients, and to explore the relationship between different frailty categories and symptom distress. Methods A convenience sampling method was used to recruit 241 lung cancer radiotherapy patients admitted to the Radiotherapy Department of a tertiary Grade-A oncology hospital in Yunnan Province from April to December 2023. Data were collected using questionnaires including: general demographic survey of lung cancer radiotherapy patients, frailty phenotype scale, Anderson Symptom Assessment Scale, and Nutritional Risk Screening 2002. Latent class analysis was employed to identify heterogeneity of frailty among different populations of lung cancer radiotherapy patients. Multinomial logistic regression analysis was used to explore factors influencing the internal heterogeneity of frailty. Generalized linear modeling was applied to analyze the impact of different frailty classes on patients' symptom burden. Results Results: Frailty in lung cancer radiotherapy patients presented three latent classes: pre-frailty group （30.29%）, frailty with unintentional weight loss group （35.68%）, and severe frailty with decreased physical activity group （34.02%）. Radiotherapy frequency （P < 0.05）, age （P < 0.05）, and nutritional risk score （P < 0.05） were identified as influencing factors for latent classes of frailty. Latent frailty classes were significant predictors of symptom burden scores （P < 0.001）. Conclusion Frailty in lung cancer radiotherapy patients demonstrates population heterogeneity, with varying influencing factors across different classes. Latent frailty classes significantly impact symptom burden scores.
