Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

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.

OBJECTIVE: To evaluate the feasibility and safety of Liuzijue exercise (LE) for the clinical effect in patients after cardiac surgery. METHODS: Totally 120 patients who underwent cardiac surgery and were admitted to the Cardiothoracic Intensive Care Unit of Nanjing Drum Tower Hospital between July and Oclober, 2022 were allocated to the LE group, the conventional respiratory training (CRT) group, and the control group by a random number table at a ratio of 1:1:1; 40 patients in each group. All patients received routine treatment and cardiac rehabilitation. LE group and CRT group respectively performed LE and CRT once a day for 30 min for 7 days. Control group did not receive specialized respiratory training. The forced vital capacity, forced expiratory volume in 1 s, peak inspiratory flow rate, peak expiratory flow rate, maximum inspiratory pressure, maximum expiratory pressure, modified Barthel index (MBI), and Hamilton Rating Scale for Anxiety (HAM-A) were evaluated before, after 3 and 7 days of intervention. In addition, the postoperative length of hospital stay (LOS) and the adverse events that occurred during the intervention period were compared. RESULTS: A total of 107 patients completed the study, 120 patients were included in the analysis. After 3 days of intervention, the pulmonary function, respiratory muscle strength, MBI and HAM-A of all 3 groups improved compared with that before the intervention (P<0.05 or P<0.01). Compared with the control group, pulmonary function and respiratory muscle strength were significantly improved in the CRT and LE groups (P<0.05 or P<0.01). MBI and HAM-A were significantly improved in the LE group compared with the control and CRT groups (P<0.05 or P<0.01). On the 7th day after intervention, the difference was still statistically significant (P<0.01), and was significantly different from that on the 3rd day (P<0.05 or P<0.01). In addition, on the 7th day of intervention, the pulmonary function and respiratory muscle strength in the LE group were significantly improved compared with those in the CRT group (P<0.01). MBI and HAM-A were significantly improved in the CRT group compared with the control group (P<0.01). There were no significant differences in postoperative LOS among the 3 groups (P>0.05). No training-related adverse events occurred during the intervention period. CONCLUSIONS LE is safe and feasible for improving pulmonary function, respiratory muscle strength, the ability to complete activities of daily living and for relieving anxiety of patients after cardiac surgery (Registration No. ChiCTR2200062964).
Humans ; Activities of Daily Living ; Breathing Exercises ; Cardiac Surgical Procedures/adverse effects* ; Respiratory Muscles ; Muscle Strength/physiology*

Aim To prepare prostate cancer exosomes containing melittin and observe their uptake by prostate cancer cells. Methods Cells treated with starvation for different time were screened for exosome extraction. Exosomes from PC-3 cells were extracted by ultracentrifugation, and the extracted particles were examined by transmission electron microscopy, nanoparticle tracking analyzer(NTA), and Western blot. Melittin exosome system was prepared by repeated freeze-thaw method, incubation at room temperature as well as electroporation, and the size of encapsulation efficiency was measured by centrifugation. A high-performance liquid chromatography(HPLC)method was applied to assay the content of melittin exosomes(exo-mel). Fluorescence inverted microscopy was employed to evaluate the uptake of melittin exosomes by PC-3 cells, DU145 cells as well as LNCaP cells. Results The results of starvation treatment showed that 24 h starvation treatment was the optimal time point. TEM results showed that the exosomes were round or oval in shape with a distinct membranous structure, and the diameter was around 100 nm. The reagent protein concentration for NTA analysis of exosomes was 0.222 g·L-1. The results of Western blot for the marker proteins of exosomes showed that Alix and CD63 were positively expressed, which indicated that the exosomes could be obtained by starvation culture of PC-3 cells and ultracentrifugation. The results of entrapment efficiency showed that the entrapment efficiency of electroporation method was 17.51% ± 2.39%, that of repeated freeze-thaw method was 11.46% ± 1.02%, and that of room temperature incubation method was 3.93% ± 2.44%. The encapsulation efficiency of electroporation was the highest with significant difference(P<0.05). The uptake assay showed that PC-3 cells could efficiently take up exo-mel in a time-dependent manner, and DU145 cells and LNCaP cells also could take up exo-mel over time. Conclusions Exosomes can be accessed by starvation treatment and high-speed centrifugation, and the prostate cancer melittin exosome system prepared by electroporation method could be taken up by prostate cancer cells.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

The potential quality markers(Q-markers) of Polygoni Perfoliati Herba were studied based on analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology, and spectrum-effect relationship analysis. The AHP-EWM was used for quantitative identification of the Q-markers. To be specific, AHP was applied for the weight analysis of the validity, testability, and specificity of the first-level indexes, and EWM for the analysis of the second-level indexes supported by literature and experimental data. Based on literature and network pharmacology, the validity analysis was to study the component-target-disease-efficacy network, and select the components with the strongest correlation with the efficacy of clearing heat and removing toxin, diuresis and alleviating edema, and relieving cough. For the testability analysis, the high performance liquid chromatography(HPLC) and literature research were used to determine the 10 components in Polygoni Perfoliati Herba, and the fingerprints of Polygoni Perfoliati Herba were established at the same time. The specificity analysis was based on the statistics of the number of plants in which the components existed. Thereby, the 11 compounds: quercetin, oleanolic acid, ellagic acid, gallic acid, kaempferol, rutin, esculetin, quercetin-3-O-glucuronide, ursolic acid, protocatechuic acid, and ferulic acid, were identified as potential Q-markers. The 11 compounds were identified to have high anti-inflammatory activity, indicating that the 11 Q-markers may be the functional material basis. The result in this study is expected to serve as a reference for the quality control of Polygoni Perfoliati Herba.
Analytic Hierarchy Process ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Entropy ; Quercetin

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.
Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Hyperbilirubinemia, Neonatal/therapy* ; Infant, Newborn ; Obstetrics ; Patient Discharge ; Pregnancy ; Retrospective Studies

TCM formulae are the important guidances for clinical application of traditional Chinese medicines, which follow the principles of diagnosis and treatment in TCM. Elucidating the bio-active components of TCM formulae is the key to the modernization and internationalization of traditional Chinese medicines. With the rapid development of modern instruments and technology, many new theories, methods and strategies are emerging, which upgrade the research of TCM formulae into a higher level. Only when the medicinal efficacy, bio-active components, function mechanism of TCM formulae are understood, we can guarantee TCM safety and quality control. In this paper, we summarized the latest modern research thoughts and methods on bio-active components of TCM formulae including formula decomposition study, serum pharmacology and serum pharmacochemistry, association analysis, biochromatography, network pharmacology, metabolomics and proteomics, so as to provide reference for the research and development of TCM in the future.
Biological Products ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Metabolomics ; Proteomics

Herb pair， a common form of compounding in Chinese medicinal prescriptions， reflects the experience of pharmacists in clinical medication in the past. It is characterized by simple composition while has the basic characteristics of Chinese medicine compounding. The combination of two medicinal herbs can enhance effect or reduce toxicity. Coptidis Rhizoma （CR） has the effects of clearing heat， drying dampness， purging fire， and removing toxin. Euodiae Fructus （EF） is acrid， bitter， and hot-natured， which can not only warm the Yang Qi in spleen and stomach to dissipate cold and relieve pain， but also descend stomach Qi and prevent vomiting. Furthermore， it can warm the liver and kidney. CR and EF form a typical cold-heat herb pair， which oppose and yet also complement each other. Specifically， their cold and heat natures interact with each other to clear liver fire， harmonize stomach for descending adverse Qi， relieve depression， and dissipate mass. CR clears the intestine and stops dysentery， while EF warms the middle and promotes the circulation of Qi. The combination of them can thus clear heat， dry dampness， and relieve pain. Modern pharmacological studies have demonstrated that CR-EF has not only significant efficacy against digestive system diseases but also good anti-cancer， anti-inflammatory， anti-ulcer， and lipid-lowering activities. Therefore， the article summarized the effect enhancement and toxicity reduction of the herb pair at the levels of cellular molecule， isolated organ， and whole animal， and clarified the mechanism of its pharmacological action. It will provide a theoretical basis for further development and clinical use of the herb pair.