ObjectiveTo investigate the effects of artemisinin （ART） on histopathological damage and salivary secretion in the submandibular gland （SMG） of mice with Sjögren's syndrome （SS） model，and on the expression of aquaporin 5 （AQP5） in SMG cells. MethodsThe NOD/Ltj mice were used as a model of SS and randomly divided into the SS model group，the ART group，and the hydroxychloroquine sulfate （HCQ） group，with six mice per group. Another 6 female BALB/c mice at the same week were selected as the control group. Mice in the ART group was fed with the ART solution daily in the dosage of 50 mg·kg^-1，and mice in the HCQ group was given with the HCQ solution （1 300 mg·kg^-1）. Mice in the SS model and control groups were given saline daily. The treatment lasted for 8 weeks. The 24-hour average water intake，salivary flow rate，SMG pathology scores of mice in each group were measured，as well as the expression levels of AQP5 protein and gene in the SMG tissues. ResultsCompared with the control group，the 24-hour average water intake of mice in the model group was significantly increased （P<0.01），and the saliva flow rate was significantly decreased （P<0.01）. Compared to the SS model group，the 24-hour average water intake of mice in the ART and HCQ groups was significantly reduced （P<0.01），and the salivary flow rate was significantly increased in the ART group（P<0.01），comparisons between groups showed that the ART was superior to the HCQ in reducing water intake and improving saliva flow rate in SS model mice （P<0.05）. The HE staining results showed that，compared with the normal group，the number of lymphocyte infiltration foci in SMG tissue in the model group increased，and the pathological score increased （P<0.01）. Compared to the SS model group，after the intervention of the ART and HCQ，the number of lymphocytic infiltration foci in the SMG tissue decreased，the area of the lymphocytic infiltration foci was reduced，and the pathology score of the SMG tissues was lowered in the ART group（P<0.01）. However，there was no difference in pathological scores between the ART and HCQ groups . The results of IHC，Western blot，and Real-time PCR showed that，compared with the normal group，the expression levels of AQP5 protein and gene in SMG tissue in the model group significantly decreased （P<0.05）. Comparing with the SS model group，the ART and HCQ groups could significantly up-regulated the expression levels of AQP5 protein and mRNA in the SMG tissue，and the treatment effect was better than that of HCQ. ConclusionART was able to ameliorate SMG structural damage and salivary secretion function in SS model mice，and its mechanism of action may be related to the up-regulation of AQP5 protein and gene expression levels in SMG cells.

AIM:To evaluate the application effec-tiveness of a Bayesian mixture model based on the principal stratum strategy for estimating the com-plier average causal effect(CACE)in clinical trials with non-compliance.METHODS:Using a non-infe-riority randomized controlled trial investigating a novel drug for primary type 2 diabetes mellitus(non-inferiority margin:-0.4)as a case study,the primary analysis applied a Bayesian mixture model under the monotonicity assumption to estimate CACE of between-group differences in glycated he-moglobin(HbA1c)changes within the compliant stratum,followed by non-inferiority testing.Sensi-tivity analyses included a Bayesian mixture model relaxing the monotonicity assumption and compar-ing results with per-protocol set(PPS)analysis.RE-SULTS:In the primary analysis,the posterior mean of CACE for HbA1c change in the compliant stratum was 0.081％,with a one-sided 97.5％credible inter-val lower bound of-0.124,exceeding the non-infe-riority margin(-0.4％),supporting the non-inferiori-ty efficacy of the novel drug in the compliant stra-tum(P(H1|Data)=1).Consistent findings were ob-served in PPS analyses(estimated effect:0.136％;one-sided 97.5％credible interval lower bound:-0.069％),further validating methodological robust-ness.CONCLUSION:In clinical trials with noncom-pliance as an intercurrent event,the Bayesian mix-ture model under the principal stratum strategy ef-fectively adjusts for compliance-related bias and yields conservative,robust estimates of causal ef-fects,supporting its value in efficacy evaluation un-der complex compliance scenarios.

PURPOSE: Early mortality in major trauma has decreased, but MODS remains a leading cause of poor outcomes, driven by trauma-induced cytokine storms that exacerbate injuries and organ damage. METHODS: This prospective cohort study included 79 major trauma patients (ISS >15) treated in the National Center for Trauma Medicine, Peking University People's Hospital, from September 1, 2021, to July 31, 2023. Patients (1) with ISS >15 (according to AIS 2015), (2) aged 15-80 years, (3) admitted within 6 h of injury, (4) having no prior treatment before admission, were included. Exclusion criteria were (1) GCS score <9 or AIS score ≥3 for TBI, (2) confirmed infection, infectious disease, or high infection risk, (3) pregnancy, (4) severe primary diseases affecting survival, (5) recent use of immunosuppressive or cytotoxic drugs within the past 6 months, (6) psychiatric patients, (7) participation in other clinical trials within the past 30 days, (8) patients with incomplete data or missing blood samples. Admission serum inflammatory cytokines and pathophysiological data were analyzed to develop machine learning models predicting MODS within 7 days. LR, DR, RF, SVM, NB, and XGBoost were evaluated based on the area under the AUROC. The SHAP method was used to interpret results. RESULTS: This study enrolled 79 patients with major trauma, and the median (Q₁, Q₃) age was 51 (35, 59) years (52 males, 65.8%). The inflammatory cytokine data were collected for all participants. Among these patients, 35 (44.3%) developed MODS, and 44 (55.7%) did not. Additionally, 2 patients (2.5%) from the MODS group succumbed. The logistic regression model showed strong performance in predicting MODS. Ten key cytokines, IL-18, Eotaxin, MCP-4, IP-10, CXCL12, MIP-3α, MCP-1, IL-1RA, Cystatin C, and MRP8/14 were identified as critical to the trauma-induced cytokine storm and MODS development. Early elevation of these cytokines achieved high predictive accuracy, with an AUROC of 0.887 (95% CI 0.813-0.976). CONCLUSION Trauma-induced cytokine storms are strongly associated with MODS. Early identification of inflammatory cytokine changes enables better prediction and timely interventions to improve outcomes.
Humans ; Prospective Studies ; Middle Aged ; Male ; Female ; Adult ; Aged ; Cytokine Release Syndrome/etiology* ; Adolescent ; Young Adult ; Aged, 80 and over ; Wounds and Injuries/complications* ; Cytokines/blood* ; Multiple Organ Failure/diagnosis* ; Machine Learning

Nanchang University and Queen Mary University of London have integrated their educational and teaching advantageous resources to establish a Sino-foreign cooperative clinical medicine program in China. The program awards the degrees of Bachelor of Science in Biomedical Sciences and Bachelor of Clinical Medicine, aiming to cultivate well-rounded medical talents with both clinical and scientific research capabilities and an international perspective. By introducing biomedical courses and integrating them with basic medical courses, the program emphasizes basic knowledge, practical training, active learning, and the cultivation of scientific research skills and critical thinking ability. The evaluation parameters include academic output, innovation competitions, and the number of students pursuing graduate education. The results showed substantial increases in the number of SCI academic articles published by students in this program, the number of awards in innovation competitions, and the number of students pursuing graduate education. This program is a new attempt in the reform of medical education in China.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

Objective Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

To explore the application of sequential analysis in post-market safety dynamic surveillance of vaccines. Under the dynamic monitoring data of vaccines post-market approval, this research introduces the fundamental principles of maximizing sequential probability ratio test (MaxSPRT) and Bayesian sequential analysis, employing R software. Through an example of dynamic safety monitoring data of vaccines post-market approval, we analyze using the MaxSPRT and Bayesian sequential analysis. The MaxSPRT identified a safety signal in week 4 ( P<0.05), while Bayesian sequential analysis indicated that the 95% highest density interval for the RR value at week 4 is 1.13-3.27, suggesting the first appearance of a safety signal at week 4. The MaxSPRT and Bayesian sequential analysis effectively leverage continuously accumulating dynamic monitoring data, thereby serving as a valuable method for post-market safety surveillance of vaccines.

In recent years, with the exploration and development of machine learning algorithms in the medical scenario, their potential for application in clinical diagnosis and treatment has been gradually explored. Image-based machine learning algorithms have made a lot of progress in urological cancer-related research, and have been proven to have a positive effect on the diagnosis, treatment and prognosis of urological cancer. Despite the great impact of machine learning algorithms clinically, they are still in the exploratory stage, with many deficiencies and limitations.

Objective Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine （DIC） in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry， thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank （normal saline）， DIC （10 mg·kg^-1）， and DIC withdrawal （recovery period） groups （n=8）. The rats were continuously treated for 7 days， once a day， and the body weight and organ weight were recorded. The levels of interleukin-1 （IL-1）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum and immunoglobulin A （IgA）， immunoglobulin G （IgG）， and immunoglobulin M （IgM） in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was employed to screen the potential biomarkers of immune inflammation caused by DIC， and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β， TNF-α， lysophosphatidylcholine acyltransferase 2 （LPCAT2）， and farnesoid X receptor （FXR） in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the DIC group showed elevated levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）， and the DIC withdrawal group showcased lowered levels of IL-1β， IL-6， and TNF-α in the serum （P<0.01）. The levels of IgA， IgG， and IgM in the spleen of rats in the DIC group were decreased （P<0.01）， while those in the DIC withdrawal group were recovered （P<0.05， P<0.01）. Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC （32∶0）， LysoPC （20∶4/0∶0）， LysoPC （P-18∶0/0∶0）， taurochenodeoxycholic acid， taurocholic acid， LysoPC ［20∶5（5Z，8Z，11Z，14Z，17Z）/0∶0］， chenodeoxycholic acid， arachidonic acid， LysoPC （18∶0/0∶0）， LysoPC （15∶0/0∶0）， LysoPC （16∶0/0∶0）， and LysoPC （17∶0/0∶0） as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC， lipid metabolism disorders such as glycerophospholipid metabolism， primary bile acid metabolism， and arachidonic acid metabolism were enriched， which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group， the DIC group exhibited up-regulated mRNA levels of IL-1β， TNF-α， LPCAT2， and FXR （P<0.01）， and the up-regulation was decreased in the withdrawal group （P<0.01）. ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites， regulate the inflammatory metabolic pathway， reduce the inflammation level， and alleviate the metabolic disorders， thus attenuating the potential toxicity induced by DIC.