OBJECTIVE To establish the project approval evaluation system for traditional Chinese medicine （TCM） preparations in medical institutions guided by new drug conversion， to improve the success rate of approval for TCM preparations in medical institutions and lay the foundation for the later drug conversion. METHODS Research and development team used the literature research method and brainstorming method to list and organize relevant elements of project evaluation and determine the initial indicator system. Experts were consulted using the Delphi method to confirm the evaluation index. The weights were calculated based on the proportion of importance scores for each indicator and assigned specific scores to each item. The indicator system was used to evaluate 31 TCM preparations applied for filing by various departments of our hospital from April to July 2023. RESULTS After two rounds of 17 experts’ consultation， the final TCM preparation system included five primary indicators， i.e. theoretical basis， clinical research foundation， pharmaceutical foundation， prescription， and clinical value， as well as 17 secondary indicators including prescription source， traditional Chinese medicine theory， clinical positioning and so on. Human experience was considered as the item which would be rejected as one vote. Based on the above indicator system， our hospital further improved the filing and project approval process for TCM preparations in medical institutions. Among the 31 TCM preparations applied for filing by various departments from April to July 2023， 8 TCM preparations with a score ≥65 were selected for development. CONCLUSIONS The evaluation system is objective， comprehensive， and highly operable. It is suitable for the selection of TCM preparations in medical institutions before research and development.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To investigate the effect of transcranial alternating current stimulation(tACS)on cerebral blood flow(CBF)in patients with Alzheimer's disease(AD).Methods A ret-rospective study was conducted on 21 mild AD patients admitted in our hospital from September 2019 to April 2022.All of them received tACS treatment for 3 weeks.Mini-mental state examina-tion(MMSE),auditory verbal learning test(AVLT)and MRI were applied to obtain the data at baseline(T0),the end of the treatment(T1)and in three months after treatment(T2).Z-trans-form CBF(zCBF)was performed to reduce individual variability.The changes in MMSE and AVLT scores,as well as brain zCBF and CBF values before and after tACS treatment were ana-lyzed.Spearman correlation analysis was used to examine the relationship of zCBF and CBF with cognitive scores.Results In the AD patients,their MMSE score was significantly increased at T1 than at T0[22.00(20.00,25.00)vs 20.00(18.00,21.50),P＜0.01].Based on voxel analysis,the AD patients exhibited significantly increased zCBF in the bilateral frontal and temporal cortex at T1,and in the right frontal and temporal cortex at T2 when compared with the levels at T0(P＜0.05).The most pronounced increase in zCBF was observed in the right insular.Based on region of inter-est analysis,increased zCBF and CBF in the right frontal and temporal cortex at T1 were observed(P＜0.05).There was a positive correlation between the change of CBF in the right frontal cortex and AVLT-recognition recall at T1(r=0.617,P=0.005)and between the change of CBF in the left frontal cortex and MMSE at T2(r=0.596,P=0.012).Conclusion MRI 3D-ASL can objec-tively evaluate the changes of CBF in AD patients after tACS treatment,and it provides a reliable imaging marker for evaluating the efficacy of tACS.

Objective To investigate the endoscopic ultrasonography(EUS)features of benign esophageal stenosis in children.Methods A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022.The clinical manifestations,EUS findings,and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children.Results A total of 42 children with benign esophageal stenosis were included.Among these children,19(45% )had anastomotic stenosis after surgery for esophageal atresia,with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS,and had 0-12 sessions of endoscopic treatment(average 2.1 sessions);5 children(12% )had corrosive esophageal stenosis and 1 child(2% )had physical esophageal stenosis,with unclear stratification of the esophageal walls on EUS,and they had 2-9 sessions of endoscopic treatment(average 5.3 sessions);1 child(2% )had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology;16 children(38% )had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS,among whom 6 received endoscopic treatment.During follow-up,95% (40/42)of the children had significant alleviation of the symptoms such as vomiting and dysphagia.Conclusions For benign esophageal stenosis in children,EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions,possible etiologies,and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications,thereby helping to optimize the treatment regimen.[Chinese Journal of Contemporary Pediatrics,2024,26(2):169-173]

Objective To explore the role pathway and pattern of the sex determining region box transcription factor 2 (SOX2) and its mRNA interaction with microRNA(miRNAs, miR) and circular RNA(circRNA) at 0 hour and 2 hours in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy, PH) model was prepared as described by Higgins, the hepatocytes were isolated according to the method of Smedsrod et al, the expression changes of mRNA, miRNA and circRNA [together named as competing endogenous RNAs(ceRNA)] were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at the 0 hour and 2 hours after PH, the ratio value of SOX2 mRNA shows 1.00±0.09 and 2.15±0.48, miR-3558-3p displays 4.53± 0.10 and 0.81±0.16, circRNA_18404 shows 1.24±0.04 and 11.10±0.57, circRNA_18045 displays 1.97±0.47 and 4.44± 0.23. At the same time, the eight kinds of cell dedifferentiation-related genes AT-rich interaction domain 5A (ARID5A), activating transcription factor 3 (ATF3), BTG anti-proliferation factor 2 (BTG2), etc, which are prometed in expression by SOX2, were down-regulated at 0 h after PH, but the cell differentiation-related genes interferon regulatory factor 6 (IRF6) and somatostatin (SST), which are inhibited in expression by SOX2, were up-regulated at 0 hour after PH. On the other hand, the eight kinds of cell dedifferentiation-related genes ARID5A, ATF3, BTG2, etc, which are promoted in expression by SOX2, were up-regulated at 2 hours after PH, but the cell differentiation-related gene SST, which is inhibited in expression by SOX2, was down-regulated, and IRF6 had no meaningful changes in expression at 2 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNA, SOX2, its mRNA is inhibited by miRNA, and the cell stem-related genes, which are regulated by SOX2, are helpful for the hepatocyte to be in differentiation state at 0 hour after PH and to be in stem state at 2 hours after PH.

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.
Artificial Intelligence ; Medicine, Chinese Traditional ; Reproducibility of Results ; Quality Control ; Intelligence ; Pharmaceutical Preparations

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden