Zhizichi Tang （栀子豉汤）， first recorded in Treatise on Febrile and Miscellaneous Diseases （《伤寒杂病论》） by ZHANG Zhongjing， a medical sage during the Han dynasty， is one of the classical prescriptions in traditional Chinese medicine （TCM）. It plays an important role in the clinical practice of TCM because of its dispersing and transparent characteristics. It is one of the representative parts of “dispersing fire stagnation” and is used mainly for the treatment of various symptoms caused by heat depression in the chest and diaphragm. Pharmacological research has found that it has multiple effects， such as sedative hypnosis and anti-depression， inhibiting oxidative stress and inflammatory responses， regulating the intestinal flora， improving insulin resistance and endocrine metabolism disorders， reducing liver toxicity， and protecting the nerve and heart. Clinical studies have confirmed that its treatment of anxiety， depression， insomnia， and other diseases has few side effects and high safety. Combined with the analysis of TCM syndrome and pharmacological effects， Zhizichi Tang also shows potential in treating other diseases such as heart， lung system， spleen and stomach， liver system， endocrine， and metabolic system diseases. Therefore， the authors， by searching Chinese and foreign literature， especially in recent five years， systematically reviewed and summarized the research progress on Zhizichi Tang in six aspects of TCM syndrome， dosage and administration， chemical composition， pharmacological effects， clinical application， and adverse reactions， aiming to provide a reference for further research and clinical application of Zhizichi Tang.

Alternative splicing (AS) serves as a fundamental regulatory mechanism in gene expression, contributing to proteomic diversity by generating an array of mRNA isoforms from precursor mRNA via distinct splice site combinations. In light of the limited therapeutic options currently available, the exploration of AS as a target for drug development is of paramount importance. This review offers an exhaustive analysis of the biological functions and underlying molecular mechanisms associated with various AS-induced splice variants, RNA-binding proteins, and cis-elements, highlighting their significance as clinical biomarkers. We place particular emphasis on the current therapeutic applications of AS in an array of lung diseases, including but not limited to lung cancer, cystic fibrosis, silicosis, acute respiratory distress syndrome, pneumonia, asthma, chronic obstructive pulmonary diseases, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis. The review delves into the role of AS events in the diagnosis and treatment of lung diseases, focusing on the regulatory influence of splicing factors and RNA-binding proteins, while also enumerating the mutated components implicated in AS misregulation. Consequently, a comprehensive understanding of the intricate mechanisms governing these splicing events could potentially offer novel avenues for the development of splicing-targeted therapeutics and diagnostic tools for the prevention and treatment of lung diseases.

As green, sustainable, and environmentally friendly material processing processes using biological cells or enzymes to achieve substance conversion, bioprocesses play an increasingly important role in biomanufacturing. It is difficult to optimize bioprocesses because of the complex relationship at multiple levels and multiple scales. The knowledge of mesoscale behaviors is the key to understanding the dynamics of bioprocesses and to sort out the complex relationships of parameter variations in the spatial-temporal domain. Mesoscale numerical simulation paves a way for understanding these phenomena, and the integration of artificial intelligence (AI) and mesoscale simulation offers new vitality into the optimization of bioprocesses. This article reviews the progress in mesoscale simulation and AI optimization of bioprocesses and discusses the possible development directions, aiming to promote the development of this field.
Artificial Intelligence ; Biotechnology/trends* ; Computer Simulation

Objective: To translate the Maternal Blue Scale (MBS) into Chinese, and evaluate the reliability and validity. Methods: The MBS was translated back-translated, culturally adapted and pre-tested according to the Brislin translation model to develop the Chinese version of MBS. Postpartum women from obstetrics centers in three tertiary general hospitals in Shandong Province were selected using convenience sampling method to assess the reliability and validity of the Chinese version of MBS. Content validity was evaluated based on expert ratings. Criterion-related validity was evaluated using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS) as the criterion. Structural validity was evaluated using exploratory and confirmatory factor analyses. Reliability was assessed by calculating Cronbach's α and split-half reliability. Receiver operating characteristic (ROC) curve was plotted to evaluate predictive validity. Results: Totally 500 questionnaires were allocated, and 479 valid ones were recovered, with an effective recovery rate of 95.80%. The Chinese version of MBS consisted of 32 items across 6 dimensions: mother-infant communication, infant feeding, role adaptation, maternal responsibilities, family acceptance and social support. The item-level content validity index ranged from 0.900 to 1.000, and the scale-level content validity index/average was 0.990. The correlation coefficient between the Chinese version of MBS scores and the Chinese version of EPDS scores was 0.675 (P<0.05). Exploratory factor analysis extracted 6 common factors, with a cumulative variance contribution rate of 74.581%. Confirmatory factor analysis indicated good model fit, with a root mean square error of approximation of 0.014, a goodness of fit index of 0.896, a comparative fit index of 0.996, an incremental fit index of 0.996, a normed fit index of 0.913, and a Tucker-Lewis index of 0.995. The overall Cronbach's α was 0.924, and the split-half reliability was 0.765. The Cronbach's α of each dimension ranged from 0.809 to 0.956, and the split-half reliability ranged from 0.807 to 0.966. The area under the ROC curve was 0.909 (95%CI: 0.880-0.937). At the optimal cutoff score of 75.5, the Youden index reached its maximum of 0.698, with a sensitivity of 0.874 and a specificity of 0.824. Conclusion The Chinese version of MBS has good reliability and validity, and it is suitable to evaluate maternal blue among Chinese postpartum women.

Objective To investigate the prevalence of zika virus(ZIKV),dengue virus(DENV)and chikungunya virus(CHIKV)infections in blood donors in Kunming,China.Methods A total of 10 662 samples from blood donors in Kunming from August 2022 to October 2023 were randomly collected,and ZIKV RNA,DENV RNA and CHIKV RNA were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR).Results Effec-tive test results were obtained from 10 554 samples,and no positive case of ZIKV RNA,DENV RNA and CHIKV RNA was found in this investigation.Conclusion The risk of ZIKV,DENV and CHIKV infections among blood donors in Kunming is low,and there is no immediate need for routine screening for these viruses among blood donors in this region.

Objective To investigate the therapeutic effect of cholesterol sulfate(CS)on the Hashimoto's thyroiditis mouse model.Methods Female NOD.H-2h4 mice were fed with 0.05％NaI in different periods and treated with CS by intraperitoneal injection for two consecutive weeks.HE staining was used to visualize and score the degree of lymphocyte infiltration in the thyroid;serum levels of thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),thyroxine(T4),and thyroid stimulating hormone(TSH)were detected by ELISA.The proportions of B cells and Treg,Th17,Th1,and Th2 cells were analyzed by immunofluorescence staining flow cytometry.Results HE staining showed that the inflammatory score of thyroid tissue in mice after intraperitoneal injection of CS in the 8-week group and the 16-week group decreased significantly(P＜0.05).In the 64-week group,there was no significant difference between the treatment group and the induction group(P=0.31).Serological analysis showed that after CS intervention,the levels of TgAb and TPOAb in mice induced by 0.05％NaI significantly lowered(P＜0.05)in the 8-week group and the 16-week group,while thyroid function(TSH and T4 levels)of the mice changed significantly only in the 16-week group.Flow cytometry analysis showed that in the 8-week group,after CS intervention the proportions of B lymphocytes and Th1,Th2,Th17 and Treg cells in mice were significantly changed(P＜0.05).Conclusion CS has significant therapeutic and remission effects on the early and middle stages of Hashimoto's thyroiditis.

Purpose To investigate the value of MYB and Notch1 immunohistochemical staining in the differential diagno-sis of classic adenoid cystic carcinoma of the breast(C-AdCC)and solid-basaloid adenoid cystic carcinoma of the breast(SB-AdCC).Methods MYB and Notch1 immunohistochemical staining were performed in 20 cases of C-AdCC,6 cases of SB-AdCC and 65 cases of other breast lesions in the archives of pa-thology department.26 cases of AdCC were detected by FISH,and 6 cases of SB-AdCC were detected by NGS.Results MYB immunohistochemical staining showed that C-AdCC(20/20)was moderately or strongly positive,while SB-AdCC(4/6)was mod-erately or strongly positive.Collagenous spherulosis(5/5)showed focal or diffuse weak positivity;Malignant adenomyoepi-thelioma(3/3)was focally moderately or strongly positive;8 matrix-producing carcinomas and 9 secretory carcinomas and 40 non-specific triple-negative breast cancers were negative.Immu-nohistochemistry of Notch1 showed diffuse moderate positive for SB-AdCC(3/6)and negative for C-AdCC(20/20).3 cases of malignant adenomyoepithelioma,5 cases of collagenous spherulo-sis,8 cases of matrix-producing carcinoma,9 cases of secretory carcinoma and 40 cases of non-specific triple-negative breast cancer were negative.FISH showed MYB gene disruption in C-AdCC(12/19)and NGS showed SB-AdCC(3/6)Notch1 muta-tion.Conclusion Moderately or strongly diffuse expression of MYB and Notch1 by immunohistochemistry can assist in the dif-ferentiation of C-AdCC from SB-AdCC,and it can be further clarified by molecular detection when it is difficult to distinguish malignant adenomyoepithelioma.

Diabetes mellitus(DM)is an endocrine metabolic disease mainly characterized by chronic hyperglycemia,which seriously threatens the health and quality of life of human beings,and with the improvement of living standard and unhealthy lifestyle in China,the incidence of DM continues to rise and tends to be younger,so it is urgent to carry out in-depth research on hypoglycemic treatment.DM is pathologically based on absolute or relative insulin deficiency,and there is no radical cure for it,and Western medicine mostly adopts insulin injection or oral hypoglycemic drugs for symptomatic treatment,which is effective but prone to toxic side effects in long-term use.Chinese medicine has the advantages of multi-path and multi-target in treating DM,and plays a role in lowering blood sugar by promoting insulin secretion,improving insulin resistance,regulating glucolipid metabolism and anti-oxidative stress,etc.Its efficacy is remarkable and the rate of toxic side effects is low.In recent years,there have been more studies on the mechanism of action of traditional Chinese medicine and compound prescriptions on animal models of DM.By reviewing the relevant literature in recent years,the author has systematically sorted out the mechanism of hypoglycemic action of single Chinese medicine,traditional Chinese medicine compound prescriptions,effective components of traditional Chinese medicine and their related experimental designs,from promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glycosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal stress.The study and experimental design of the hypoglycemic mechanism of Chinese medicine were summarized in terms of promoting insulin secretion,inhibiting gluconeogenesis,promoting glycogen synthesis,improving insulin resistance,inhibiting glucosidase activity,alleviating oxidative stress damage,inhibiting inflammatory response and regulating intestinal flora,etc.,with a view to providing reference for the wider clinical application of Chinese medicine in hypoglycemia and its in-depth pharmacodynamic study.

Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.