This paper discussed how to set the limit of impurities in the quality standard when the impurities in small-molecular innovative drugs were metabolites.Firstly,through the analysis and interpretation of each relevant guideline,in combination with the review cases of FDA and EMA,found out the conditions for qualification of im-purity,and then establ ish the acceptable limit of impurities based on the test results of multiple batches,the incre-ments of production process and storage process.

Objective:To explore the posttraumatic growth of first stroke patients and analyze its dynamic development trajectory.Methods:From January to December 2022, 180 stroke patients admitted to Xinxiang Central Hospital were selected as research subjects by convenience sampling. The Posttraumatic Growth Inventory (PTGI) score was dynamically evaluated at the end of the first month (M 1), second month (M 2), third month (M 3), fourth month (M 4), fifth month (M 5), and sixth month (M 6) of onset. The latent class growth model (LCGM) was used to analyze the developmental trajectory categories, and multiple Logistic regression was used to analyze the influencing factors of posttraumatic growth trajectory categories. Results:A total of 180 questionnaires were distributed, and 177 valid questionnaires were collected, with a valid response rate of 98.33% (177/180). Within six months, the patient's PTGI score gradually increased, with the lowest PTGI score (29.11±5.65) at M 1 and the highest proportion of low-level growth, accounting for 85.31% (151/177). At M 6, the PTGI score was (42.14±13.04), and the proportion of low-level growth was 40.68% (72/177). Two latent categories of posttraumatic growth, namely sustained low growth type and growth improvement type, were identified, with 72 cases of sustained low growth type and 105 cases of growth improvement type. Gender ( OR=2.648, P=0.008), age ( OR=1.055, P=0.002), education level ( OR=6.403, P<0.001), and stroke type ( OR=2.863, P=0.014) were the influencing factors for posttraumatic growth trajectories among stroke patients. Conclusions:Post traumatic growth in stroke patients is a dynamic state of change, with low overall levels and a common type of sustained low growth. There may be differences in the sociodemographic and disease characteristics of patients with different types of posttraumatic growth trajectories, providing reference for the development of clinical nursing strategies, but further research is still needed.

Objective To search and evaluate the relevant evidence of blood purification and anticoagulant management of perioperative liver transplantation patients,and to summarize the best evidence,so as to provide evidence-based evidence for clinical blood purification and anticoagulant management practice.Methods Evidence-based questions were determined.Systematic search was conducted on relevant domestic and foreign databases and websites for clinical decisions,guidelines,evidence summaries,system evaluations,and expert consensuses related to blood purification anticoagulation management.The retrieval period is from the establishment to May 2,2023.Literature screening,quality evaluation and evidence summary were conducted by 2 researchers.Results A total of 17 articles were included,including 2 clinical decisions,3 guidelines,2 evidence summaries,4 systematic evaluations and 6 expert consensuses.24 pieces of best evidence were summarized from 6 dimensions,including coagulation function evaluation,anticoagulant strategy,mode selection,vascular access,standardized operation implementation points and personnel organization management.Conclusion The best evidence was summarized in the study on perioperative blood purification and anticoagulant management of liver transplantation,which can provide evidence-based basis for clinical medical staff to implement anticoagulant management.However,it is necessary to further carry out evidence-based practice of perioperative blood purification and anticoagulant management of liver transplantation to verify its anticoagulation effect and nursing safety in clinical practice.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Purpose/Significance To compare and analyze the 2023 edition and 2011 edition of the health information data element standards,and to discuss the differences and improvements,so as to provide useful references and guidance for the update and imple-mentation of the standards.Method/Process The updated contents of the 2023 and 2011 editions of the health information data element standards are sorted out and compared,and the effects of the revision on the degree of standardization,the level of standardization,and the completeness and accuracy of data are analyzed and summarized.Result/Conclusion It is found that the 2023 edition has achieved significant improvements in data completeness and standardization.Additionally,targeted suggestions and strategies are proposed for the challenges and issues that might be faced during the implementation of the 2023 edition standards.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND:The researchers noted that upon embedding clinical-grade catgut and polyglycolide-co-lactide threads in the normal human"Zusanli"(ST 36)acupoint,the local area displayed temporal and inflammatory stimulatory effects,resulting in thread differentiation.However,the underlying mechanism behind thread involvement remains to be studied. OBJECTIVE:To investigate the expression levels of calcitonin gene-related peptide,5-hydroxytryptamine,leukotriene B4,and bradykinin at point"Zusanli"(ST 36)in rats after embedding catgut and polyglycolide-co-lactide respectively at different time points. METHODS:110 male SD rats were divided into a blank group(10 rats),a catgut embedding group(50 rats),and a polyglycolide-co-lactide embedding group(50 rats)according to the random number table method.In the blank group,no thread was embedded.In catgut embedding group and the polyglycolide-co-lactide embedding group,the thread was embedded in the left side of the ST36 acupoint once.Tissue was collected from the left side of the ST36 acupoint area 8 hours,3,7,14,and 21 days after embedding.The expression levels of calcitonin gene-related peptide and 5-hydroxytryptamine were detected by immunohistochemistry,and the contents of leukotriene B4 and bradykinin were detected by ELISA. RESULTS AND CONCLUSION:(1)Compared with the blank group,the expression of calcitonin gene-related peptide,5-hydroxytryptamine,bradykinin,and leukotriene B4 was significantly increased in the 8 hours,3,7,14,and 21 days of the catgut embedding group(P<0.05);calcitonin gene-related peptide expression was significantly increased in 8 hours,3,7,and 14 days in the polyglycolide-co-lactide embedding group(P<0.05);the expression of bradykinin was significantly increased in 8 hours,3,and 7 days(P<0.05);the expression of leukotriene B4 was significantly increased at 8 hours,3,7,14,and 21 days(P<0.05).(2)Compared with the polyglycolide-co-lactide embedding group,the expression of calcitonin gene-related peptide was increased at 7,14,21 days after thread embedding(P<0.05),and the expression of 5-hydroxytryptamine was increased at 8 hours,3,7,14 and 21 days after thread embedding(P<0.05);contents of leukotriene B4 and bradykinin in tissues were increased at 8 hours,3,14 and 21 days after embedding(P<0.05)in the catgut embedding group.(3)The results show that calcitonin gene-related peptide,5-hydroxytryptamine,leukotriene B4,and bradykinin in the acupoint region alter after catgut embedding in the ST36 of rats,as well as the alteration of calcitonin gene-related peptide,leukotriene B4,and bradykinin is found in the acupoint region after polyglycolide-co-lactide embedding in rats,which may be one of the mechanisms involved in the local time sensitive stimulus effects caused by embedding threads at acupoints.Moreover,there is a discernible difference between the two thread types.

OBJECTIVE To investigate the effects of ligustilide on chemotherapy resistance of cervical cancer cells based on Hippo-Yes-associated protein （YAP） signaling pathway. METHODS Human cervical cancer cisplatin-resistant cells HeLa/DDP were divided into control group， cisplatin group （10 μmol/L cisplatin）， cisplatin+ligustilide low-， medium- and high-concentration groups （10 μmol/L cisplatin+25， 50， 100 μmol/L ligustilide）. The proliferation， apoptosis， migration and invasion of HeLa/DDP cells were all detected in each group. The mRNA expressions of YAP and transcriptional coactivator with PDZ binding motif （TAZ） as well as the protein expressions of YAP， TAZ， matrix metalloproteinase 2 （MMP2）， Ki67， cleaved-caspase-3 and caspase-3 were determined in HeLa/DDP cells. RESULTS Compared with control group， the inhibitory rate， apoptotic rate and cleaved- caspase-3/caspase-3 of cisplatin group were increased significantly； scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were decreased significantly in cisplatin group （P＜0.05）. Compared with cisplatin group， the inhibitory rate of cell proliferation， apoptotic rate and cleaved-caspase-3/ caspase-3 were further increased in cisplatin+ligustilide low-， medium- and high-concentration groups， while scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were further decreased， in a dose-dependent manner （P＜0.05）. CONCLUSIONS Ligustilide can increase the sensitivity of drug-resistant cervical cancer cells to cisplatin by inhibiting Hippo-YAP signaling pathway.

Clinical trial is the gold standard for evaluating the efficacy and safety of interventions; however, it is limited by high costs and long time. Real-world data (RWD) can provide a robust data basis for comparative research, but the quality is uneven. This review introduces the target trial emulation, in which researchers, using RWD and following the design of clinical trials, define exposure and outcome in advance, set eligibility criteria, determine the time zero, estimate sample size, and plan statistical analysis, to enhance the quality of evidence for observational studies. This review preliminarily discusses the standard of evidence quality evaluation in target trial emulation. Then, the target trial emulation is shown through case interpretation.

Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.