Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Following the core outcome set standards for development(COS-STAD), this study aims to construct core outcome set(COS) for clinical research on traditional Chinese medicine(TCM) treatment of simple obesity. Firstly, a comprehensive review was conducted on the randomized controlled trial(RCT) and systematic review(SR) about TCM treatment of simple obesity that were published in Chinese and English databases to collect reported outcomes. Additional outcomes were obtained through semi-structured interviews with patients and open-ended questionnaire surveys for clinicians. All the collected outcomes were then merged and organized as an initial outcome pool, and then a preliminary list of outcomes was formed after discussion by the working group. Subsequently, two rounds of Delphi surveys were conducted with clinicians, methodology experts, and patients to score the importance of outcomes in the list. Finally, a consensus meeting was held to establish the COS for clinical research on TCM treatment of simple obesity. A total of 221 RCTs and 12 SRs were included, and after integration of supplementary outcomes, an initial outcome pool of 141 outcomes were formed. Following discussions in the steering advisory group meeting, a preliminary list of 33 outcomes was finalized, encompassing 9 domains. Through two rounds of Delphi surveys and a consensus meeting, the final COS for clinical research on TCM treatment of simple obesity was determined to include 8 outcomes: TCM symptom scores, body mass index(BMI), waist-hip ratio, waist circumference, visceral fat index, body fat rate, quality of life, and safety, which were classified into 4 domains: TCM-related outcomes, anthropometric measurements, quality of life, and safety. This study has preliminarily established a COS for clinical research on TCM treatment of simple obesity. It helps reduce the heterogeneity in the selection and reporting of outcomes in similar clinical studies, thereby improving the comparability of research results and the feasibility of meta-analysis and providing higher-level evidence support for clinical practice.
Humans ; Obesity/therapy* ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Drugs, Chinese Herbal/therapeutic use*

Objective To investigate the regulatory mechanism of the central nervous system in patients with refractory overactive bladder (rOAB) using diffusion tensor imaging (DTI) and graph theory analysis. Methods A total of 43 rOAB patients (rOAB group) and 46 matched healthy controls (HC group) were recruited during May and Nov.2024. All participants were scanned with DTI, and surveyed with the overactive bladder symptom score (OABSS), and overactive bladder questionnaire (OAB-q). Their age, gender, height, weight, and educational years were collected.DTI plus graph theory analysis was employed to explore the alterations in global and local topological properties of the brain structural network in rOAB patients. Brain regions showing significant group differences in structural metrics [specifically, the right paracentral lobule (PCL.R) ]were further used as seed points for functional connectivity (FC) analysis. Correlations between the nodal clustering coefficient (NCp) of the identified region, FC strength, OABSS, and OAB-q score were investigated. Results The OABSS [8 (6,10) vs.0 (0,1) ]and OAB-q [71 (53,80) vs.20 (19,24) ]were higher in the rOAB group than the HC group (P<0.001). Graph theory analysis revealed no statistically significant differences in global network metrics between the two groups (P>0.05). However, the NCp was significantly higher in the PCL.R of rOAB group compared to HC group (P<0.05, FDR-corrected).FC analysis using the PCL.R as a seed region demonstrated significantly reduced FC value in the left cerebellar crus Ⅱ (Cerebelum_Crus2_L) of the rOAB group (P<0.05, FDR-corrected). Partial correlation analysis showed that the NCp of PCL.R was positively correlated with both OABSS (r=0.255, P=0.018) and OAB-q score (r=0.257, P=0.017). Conversely, the FC of Cerebelum_Crus2_L was significantly negatively correlated with OABSS (r=-0.545, P<0.001) and OAB-q score (r=-0.535, P<0.001). Conclusion Patients with rOAB exhibit distinct brain structural network alterations compared to healthy individuals, primarily manifestation in the NCp value of PCL.R increased, and the FC intensity of Cerebelum_Crus2_L is significantly weakened. These alterations in the topological properties of the structural network may be implicated in the pathogenesis of rOAB.

Objective To investigate the expression significance and prognostic value of long non-coding RNA tumor susceptibility candidate gene 9(lncRNA CASC9)and YKT6 in oral squamous cell carcinoma(OSCC).Methods A total of 110 patients with OSCC treated in the Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine from January 2016 to January 2018 were selected as the study objects.The mRNA expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue and adjacent tissues was detected by real-time fluorescence quantitative PCR.Immunohistochemistry was used to detect YKT6 protein expression in OSCC cancer tissue and adjacent tissues.Kaplan-Meier curves were used to analyze the influence of different lncRNA CASC9 and YKT6 mRNA expression on the prognosis of OSCC patients.Cox regression model was used to analyze the prognostic factors of OSCC.Results The lncRNA CASC9 and YKT6 mRNA expression in OSCC cancer tissues were 3.12±0.57 and 2.69±0.42,respectively,which were significantly higher than those in adjacent tissues(1.02±0.25,1.13±0.21),and the differences were statistically significant(t=35.386,34.843,P＜0.05).The positive rate of YKT6 protein in OSCC cancer tissues was 81.82％(90/110),which was higher than that in adjacent tissues[9.09％(10/110)],and the difference was statistically signifi-cant(x2=117.333,P＜0.05).There was a positive correlation between lncRNA CASC9 mRNA expression and YKT6 mRNA expression in OSCC cancer tissues(r=0.788,P＜0.001).The lncRNA CASC9 and YKT6 mRNA expressions in cancer tissues of OSCC with TNM stages m to Ⅳ,low differentiation and lymph node metastasis were higher than those in cancer tissues of OSCC with TNM stages Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,the difference was statistically significant(all P＜0.05).The 5-year cu-mulative survival rate of lncRNA CASC9 high expression group and YKT6 mRNA high expression group was lower than that of lncRNA CASC9 low expression group and YKT6 mRNA low expression group,and the difference was statistically significant(Log-rank X2=7.080,8.741,P=0.008,0.003).High expression of ln-cRNA CASC9,high expression of YKT6 mRNA,TNM stage m to Ⅳ,low differentiation and lymph node me-tastasis were prognostic risk factors in OSCC patients.Conclusion The expression of lncRNA CASC9 and YKT6 in OSCC cancer tissue is elevated,which can be used as tumor markers to evaluate the prognosis of OS-CC patients.

ObjectiveThis study aims to explore risk factors for the development of major adverse cardiovascular and cerebrovascular events （MACCEs） in middle-aged and elderly patients with type 2 diabetes mellitus complicated with stable angina pectoris （T2DM-SAP） based on real-world clinical data in traditional Chinese medicine （TCM）， so as to develop a COX proportional risk prediction model and visualize the predicted results using a nomogram. MethodBased on the clinical scientific research information sharing system， the medical records of 586 T2DM-SAP patients （45-94 years old） were collected from January 2012 to December 2019， including age， gender， course of disease， major medical history， laboratory examination， tongue image， pulse image， TCM syndrome， and major treatment drugs. MACCE outcome indicators of patients were obtained by telephone follow-up and re-hospitalization records. The data was divided into a training set and a validation set according to 7∶3. In the training set， COX univariate analysis was used to determine the risk factors for MACCE in T2DM-SAP patients， and then variables were screened by forward-backward stepwise regression method， so as to establish a MACCE risk prediction model and construct a nomogram. The predictive efficacy of the model was reflected by the C-index， receiver operating characteristic （ROC） curve， calibration map， and clinical decision curve. ResultThe history of cerebrovascular disease ［Hazard ratio （HR）=1.983， 95% confidence interval （CI，1.314-2.993）］， low-density lipoprotein （LDL-C/mmol·L^-1）≥4.1［HR=2.683， 95%CI（1.461-4.925）］， dull red tongue ［HR=1.955， 95%CI（1.273-3.002）］， dull purple tongue ［HR=4.214， 95%CI（2.017-8.803）］， white thick coating ［HR=3.030， 95%CI（1.634-9.293）］， thin and weak pulse ［HR=2.233， 95%CI（1.283-3.888）］， and syndrome of wind-phlegm blocking collaterals ［HR=2.007， 95%CI（1.179-3.418）］ were found to be risk factors in middle-aged and elderly T2DM-SAP patients. Insulin ［HR=0.604， 95%CI（0.399-0.914）］， glycosidase inhibitor ［HR=0.627， 95%CI（0.409-0.962）］， and TCM treatment ［HR=0.328， 95%CI（0.214-0.503）］ were protective factors in middle-aged and elderly T2DM-SAP patients. The prediction model was constructed based on the above risk factors. The C-index of the model was 0.818 （95% CI 0.777 -0.859） in the training set and 0.814 （95% CI 0.773-0.855） in the validation set， and the change of C-index over time was plotted. The AUC of patients for 5， 10， 15 years in the training set was 0.71， 0.67， and 0.61. The AUC of patients for 5， 10， and 15 years in the validation set was 0.60， 0.68， and 0.63， respectively. The calibration map and clinical decision curves of 5， 10， 15 years were drawn in the training set and the validation set， respectively. The model was well calibrated and clinically effective. ConclusionThe history of cerebrovascular disease， LDL， dull red tongue， dull purple tongue， white thick coating， thin and weak pulse， and syndrome of wind-phlegm blocking collaterals are risk factors for MACCE in middle-aged and elderly T2DM-SAP patients， and insulin， glycosidase inhibitors， TCM treatment are protective factors for MACCE in middle-aged and elderly T2DM-SAP patients. A clinical prediction model is established accordingly. This model has good discrimination， calibration degree， and clinical effectiveness and provides a scientific basis for the prevention and treatment of MACCE in middle-aged and elderly T2DM-SAP patients.

Objective:To provide a basis for improving the design and implementation of policies for ensuring the supply of pediatric drugs in China.Method:Based on the perspective of pharmaceutical enterprises,reviewed literature and conducts questionnaire surveys to identify the constraints in the development of pediatrict drugs throughout the entire drug lifecycle,and analyzes the constraints'concentration and urgency.Result:The main constraints include:difficulty in conducting clinical trials for children;the current registration and approval rules lack consideration for the specificity of pediatric drugs and specific requirements for application materials;lack of implementation rules and measures in the implementation process of incentive policies for pediatric drug production;The market interest mechanism of pediatric drugs is not yet perfect.Among them,research and development and payment for use are currently relatively concentrated issues.Discussion and suggestions:It is recommended that China fully utilize existing clinical trial data of pediatric and broaden sources,take multiple measures to increase investment in pediatric drug R&D;Develop special guidelines for pediatric drug application and encourage adult drug registration to submit pediatric research plans;Explore the optimization path of pediatrict drug production and supply based on typical cases;Provide more space for pediatric drugs in the rules of drug use and payment.

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Multisystem inflammatory syndrome in children(MIS-C)is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak.The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms,and severe cases can involve toxic shock and cardiac dysfunction.Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies.The pathogenesis and pathophysiology of MIS-C remain unclear,though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor.Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care.This review article provides a comprehensive overview of the definition,epidemiology,pathogenesis,clinical presentation,diagnosis,treatment,and prognosis of MIS-C.