ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

Objective To analyze survival outcomes and influencing factors among patients with colorectal cancer in Yunnan Province. Methods Clinical data were retrospectively collected from 4 892 patients with colorectal cancer. Survival data were obtained through follow-up. Overall survival (OS) was calculated by using the Kaplan-Meier method. Univariate analysis was performed by applying the log-rank test. Meanwhile, multivariate analysis employed the Cox proportional hazards regression model. Results The 1-, 3-, 5-, and 10-year OS rates for the entire cohort were 91.90%, 74.40%, 64.40%, and 28.70%, respectively. Univariate analysis revealed that age, ethnicity, region, differentiation grade, TNM stage, clinical stage, metastatic status, histological type, and treatment modality (chemotherapy, radiotherapy, and surgery) were associated with patient prognosis (all P<0.05). Multivariate analysis identified age (HR=1.250), region (HR=1.262), differentiation grade (HR=0.761), clinical stage (HR=3.128), and treatment modality (chemotherapy, HR=0.644; radiotherapy, HR=1.605; surgery, HR=0.384) as independent factors affecting survival prognosis in patients with colorectal cancer (all P<0.001). Conclusion Age, region, clinical stage, and treatment modality are independent factors influencing survival among patients with colorectal cancer in Yunnan Province. In clinical practice, these factors should be integrated to develop individualized prevention and treatment strategies, thereby improving patient outcomes.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

Objective:To evaluate the efficacy of dexzopiclone combined with repetitive transcranial magnetic stimulation (rTMS) for post-stroke sleep disorders (PSSD) and its effects on sleep electroencephalography and neuroelectrophysiological parameters.Methods:180 PSSD patients admitted to Yulin First Hospital (December 2019-December 2020) were randomized into medication group ( n=90, dexzopiclone) and rTMS group ( n=90, dexzopiclone+rTMS). Outcomes included clinical efficacy, sleep quality [Pittsburgh Sleep Quality Index (PSQI), Self-Rating Scale for Sleep (SRSS)], electroencephalogram parameters [sleep latency (SL), total sleep time (TST), sleep efficiency], neuroelectrophysiological indices [bilateral motor thresholds], biochemical markers [S100β protein, brain-derived neurotrophic factor (BDNF)], adverse reactions, and 1-year recurrence rate. Results:After treatment, the rTMS group had a significantly higher efficacy (92.22%, 83/90) compared to the medication group (81.11%, 73/90) ( χ2=4.81, P=0.028). Compared to post-treatment, PSQI decreased to [7.47 (6.63,8.69) points vs. 13.56 (3.15,19.51) points] in the rTMS group and [9.56 (8.59,11.11) points vs. 14.01 (2.58,20.55) points] in the medication group ( U=8.82, 8.38; both P<0.001). SRSS scores decreased to [(15.23±2.88) points vs. (28.81±4.99) points) ( t=32.74, P<0.001) and (19.54±3.59) points vs. (28.15±4.71) points) ( t=19.68, P<0.001)], respectively. Compared to before treatment, the rTMS group had lower scores than the medication group ( U=7.80, t=8.88; P<0.01). SL reduced to (27.65±5.12) min vs. (44.92±8.21) min ( t=24.58, P<0.001) in rTMS group and (38.78±6.34) min vs. (45.23±8.56) min ( t=8.24, P<0.001) in medication groups. TST increased to (348.50±56.27) min vs. (299.21±52.14) min ( t=8.63, P<0.001) and (311.42±55.39) min vs. (275.65±52.23) min ( t=6.31, P<0.001), sleep efficiency improved to (70.96±12.33%) vs. (57.43±10.98%) ( t=11.01, P<0.001) and (62.37±11.28%) vs. (56.78±10.72%) ( t=4.82, P<0.001), while the rTMS group showed greater improvement ( t=4.46, 4.88; P<0.001). Compared to before treatment, left motor thresholds decreased to (55.65±2.48)% vs. (64.37±3.12)% and (61.76±3.17)% vs. (65.12±3.45)% post-treatment ( t=29.54, 9.63; P<0.001), with significant intergroup differences ( t=14.40, P<0.001). Right motor thresholds decreased to (56.28±3.45)% vs. (67.42±3.61)% and (60.89±3.39)% vs. (66.62±3.54)% ( t=29.94, 15.69; P<0.001), with intergroup differences ( t=9.04, P<0.01). Compared to before treatment, serum S100β levels decreased in both group post-treatment (23.65±3.23) ng/L vs. (65.37±7.89) ng/L and (29.76±3.61) ng/L vs. (63.48±7.34) ng/L ( t=71.19, 58.43; P<0.001), with lower levels in the rTMS group ( t=11.97, P<0.001). Compared to before treatment, BDNF increased to (554.48±69.78) ng/L vs. (502.82±64.11) ng/L and (524.90±67.66) ng/L vs. (505.12±64.45) ng/L post-treatment ( t=7.32, 2.84; P=0.001, 0.030), with higher levels in the rTMS group ( t=2.89, P=0.004). Adverse reaction rates were 4.44% (4/90) and 3.33% (3/90), respectively ( χ2=0.15, P=0.700). Recurrence rates were 1.18% (1/85) in the rTMS group and 3.90% (3/77) in the medication group ( χ2=0.37, P=0.544). Conclusion:The combination of dexzopiclone and repetitive transcranial magnetic stimulation (rTMS) demonstrates significant advantages and efficacy in treating post-stroke sleep disorders (PSSD). This approach comprehensively improves patients' sleep quality, EEG parameters and neuroelectrophysiological indicators while enhancing the regulatory effects of brain-derived neurotrophic factor (BDNF). Additionally, the therapy exhibits a favorable safety profile and prognosis.

OBJECTIVE To investigate the changes of isolation rates of multidrug-resistant organisms(MDROs)in Shaanxi Province from 2014 to 2023 so as to provide theoretical bases for prevention,control and surveillance of drug-resistant organisms.METHODS The data of MDROs that were detected by the networked units of Shaanxi Antimicrobial Resistance Surveillance System in 10 years from 2014 to 2023 were analyzed by WHONET 5.6 soft-ware and were compared with the national average levels.RESULTS The isolation rates of MDROs generally showed downward trends from 2014 to 2023(all P＜0.05).The isolation rate of methicillin-resistant Staphylo-coccus aureus(MRSA)dropped from 45.7％to 35.8％,and that of methicillin-resistant coagulase-negative Staph-ylococcus(MRCNS)decreased from 81.8％to 75.8％,higher than the national average levels.The isolation rate of vancomycin-resistant Enterococcus faecium(VREfm)dropped from 3.1％to 0.5％,and that of vancomycin-re-sistant Enterococcus faecalis(VRE fa)declined from 1.7％to 0,equal to or slightly lower than the national aver-age levels.Among the Streptococcus pneumoniae strains,the isolation rate of erythromycin-resistant S.pneumon-iae(ERSP)was higher than that of the penicillin-resistant S.pneumoniae(PRSP),the isolation rate of PRSP showed a downward trend(from 8.0％to 0.8％),while the isolation rate of ERSP rose slightly(from 96.2％to 98％),slightly higher than the national average levels.The isolation rate of carbapenem-resistant Escherichia coli(CR-ECO)showed a downward trend(from 2.3％to 1.0％),the isolation rate of carbapenem-resistant Klebsiella pneumoniae(CR-KPN)fluctuated and showed slightly rising trend(from 6.1％to 8.2％),slightly lower than the national average levels.The isolation rates of carbapenem-resistant Acinetobacter baumannii(CR-ABA)and carbapenem-resistant Pseudomonas aeruginosa(CR-PAE)strains showed downward trends(with CR-ABA de-creasing from 66.2％to 60.3％,CR-PAE declining from 32.6％to 19.7％),slightly higher than the national aver-age levels.CONCLUSIONS The isolation rates of the MDROs showed downward trends in Shaanxi Province from 2014 to 2023 except for ERSP and CRKP.The isolation rates of VRE and CRE are lower than the national average levels,while the isolation rates of other MDROs are slightly higher than the national average levels.

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