Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective    To analyze a new classification of the left apicoposterior segmental bronchus and summarize its clinical significance. Methods     We accessed the computed tomography imaging data of the inpatients treated in the Department of Thoracic Surgery, Henan Provincial People's Hospital between January and November 2021. We observed and classified the branching pattern of the left apicoposterior segmental bronchus (B1+2) using three-dimensional computed tomography bronchography and angiography (3D-CTBA) technique. And we filtered out the patients who underwent thoracoscopic left apicoposterior segmentectomy and analyzed their clinical data retrospectively to summarize the instructing significance of different bronchial classification in the accurate and safe operation of left apicoposterior segmentectomy. Results     Finally 240 patients were collected, including 131 males and 109 females with a median age of 51.0 (19.0-77.0) years. The anatomical pattern of the left apicoposterior segmental bronchus was divided into four main types based on the branching pattern of the outer subsegmental bronchi (B1+2c): type Ⅰ 10% (24 patients), type Ⅱ 54% (130 patients) , type Ⅲ 17% (40 patients) , type Ⅳ 18% (43 patients) and other variations 1% (3 patients). Thirty-two patients smoothly underwent thoracoscopic left apicoposterior segmentectomy, including 23 patients of type Ⅰ and type Ⅱ receiving LS1+2 resection, the other 9 patients of type Ⅲ and type Ⅳ receiving LS1+2 resection (3 patients), LS1+2c resection (4 patients) and LS1+2(a+b) resection (2 patients). Conclusion     This new classification systematically and concisely elucidates the branching characteristics of the left apicoposterior bronchus. Different branching types are instructive to the left apicoposterior segmentectomy.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

BACKGROUND:Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density(BMD).However,it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD. OBJECTIVE:To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach,provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease. METHODS:We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables(P＜5×10-8).The main outcomes of the study included osteoporosis and BMD at five different sites,including total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects.Weighted median,simple median,weighted mode and MR-Egger regression were used as supplementary analyses.Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios(OR)and 95%confidence intervals(CI).Heterogeneity was assessed using Cochran's Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests. RESULTS AND CONCLUSION:The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis(OR=1.123,95%CI:1.077-1.171;P=4.02×10-8).Heterogeneity test(P=0.388)indicated no significant heterogeneity among the single nucleotide polymorphisms.MR-Egger intercept(P=0.571)tests did not detect horizontal pleiotropy,and sensitivity analysis showed no evidence of bias in the study results.There was no causal relationship between rheumatoid arthritis and BMD at the five different sites.The total body BMD(OR=1.000,95%CI:0.988-1.012;P=0.925),lumbar spine BMD(OR=0.999,95%CI:0.982-1.016;P=0.937),femoral neck BMD(OR=1.001,95%CI:0.986-1.016;P=0.866),heel BMD(OR=0.996,95%CI:0.989-1.004;P=0.419),and forearm BMD(OR=1.063,95%CI:0.970-1.031;P=0.996)indicated no significant association.MR-Egger intercept analysis did not detect potential horizontal pleiotropy(total body BMD:P=0.253;lumbar spine BMD:P=0.638;femoral neck BMD:P=0.553;heel BMD:P=0.444;forearm BMD:P=0.079).Rheumatoid arthritis may contribute to the development of osteoporosis through the interaction between chronic inflammation and bone formation,resorption,and absorption.Additionally,the use of glucocorticoids and the presence of autoantibodies(such as anti-citrullinated protein antibody)in patients with rheumatoid arthritis showed associations with osteoporosis.Future research should focus on monitoring systemic inflammatory markers,standardized use of glucocorticoids,and regular screening for osteoporosis risk in patients with rheumatoid arthritis.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To explore the effects of aerobic exercise on learning and memory functions, hippocampal synaptic plasticity and the ADPN signaling pathway in diabetic rats.Methods:6-week-old male SD rats were randomly divided into a blank control group(NC group)and a high-fat diet group, and a rat model for diabetes was induced by feeding rats in the high-fat diet group with a high-fat diet combined with intraperitoneal instillation of low-dose streptozotocin(STZ)for 5 weeks.Rats in the high-fat diet group were further divided into a diabetic group(DC group)and a diabetic aerobic exercise group(DM group)after successful establishment of the model.Rats in the DM group were subjected to aerobic exercise for eight weeks and then the Morris water maze test was conducted to assess learning and memory functions, relevant serum markers were measured, Golgi staining was used to examine synaptic changes in the hippocampus, and Western blot was carried out to detect hippocampal protein expression levels of adiponectin(ADPN), AMP-activated protein kinase(AMPK), glucose transporter 4(GLUT4), synaptic plasticity-related protein synaptophysin(SYN)and postsynaptic density protein 95(PSD-95)for rats in each group.Results:Serum FBG and HBA1c in diabetic rats were markedly significantly decreased after 8 weeks of aerobic exercise( P<0.01), and serum ADPN and insulin were significantly increased after 8 weeks of aerobic exercise( P<0.05).When test results from the three groups of rats compared, the F value was 69.248 for FBG, 6.740 for INS, 7.017 for HBA1C and 14.315 for serum ADPN.The results of the water maze test and hippocampal Golgi staining showed that the escape latency of diabetic rats was highly significantly decreased after 8 weeks of aerobic exercise( P<0.01).The platform crossing times, the number of dendritic branches and the dendritic spine density in the hippocampal CA3 region of diabetic rats were significantly increased after 8 weeks of aerobic exercise( P<0.05).When results from the three groups of rats were compared, the F value was 13.934 for escape latency, 5.864 for platform crossing times, 9.307 and 6.734 for the number of dendritic branches and the density of dendritic spine in hippocampal CA3 region.Hippocampal PSD-95, SYN, ADPN, p-AMPK, and GLUT4 protein expression levels of diabetic rats were significantly increased( P<0.05)after 8 weeks of aerobic exercise.When results from the three groups of rats were compared, the F value was 15.137 for SYN, 5.415 for PSD-95, 9.687 for ADPN, 27.761 for GLUT4, and 9.298 for p-AMPK. Conclusions:Eight weeks of aerobic exercise can improve the learning and memory functions of diabetic rats, and the mechanisms may be related to exercise-induced hippocampal ADPN/AMPK/GLUT4 signaling activation in rats, leading to enhanced synaptic plasticity in the hippocampus.

Aim To predict and validate the mechanism of wenshen xuanbi tang(WSXBT) in treatment of osteoporosis (OP) based on network pharmacology, molecular docking techniques and in vivo experimental techniques. Methods Network pharmacology was used to screen the key ingredients and core targets of WSXBT for the treatment of osteoporosis. Metascape database was used for gene ontology (GO) biological process enrichment analysis and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis of core targets. AutoDockTools 1. 5. 7 software was applied in molecular docking to simulate the binding activity of key active ingredients to core targets. To study the efficacy of WSXBT on rats with osteoporosis and to verify the related targets and pathways, rat models of osteoporosis were established by excising the bilateral ovaries of rats. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum OPG, PINP and RANKL content. Biomechanical tester was applied to test the biomechanics of rat femurs. Micro-CT was applied to detect the femoral bone density. Then, Western blot was employed to measure the protein expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt). Results A total of 156 active ingredients of WSXBT were screened, involving 229 potential targets, 23 core targets and 145 signaling pathways. The molecular docking results showed that five key ingredients, including quercetin, kaempferol, naringenin, isobavachin and licochalcone a, possessed good binding ability to the core targets of PIK3R1 and AKT1. The results of in vivo experiments showed that WSXBT could significantly increase bone density, improve bone tissue microstructure, enhance femur biomechanics and increase PINP expression and OPG/RANKL ratio in rats with osteoporosis. Results of WB showed that WSXBT significantly increased p-PI3K/PI3K and p-Akt/Akt ratios. Conclusions WSXBT could improve bone mineral density in postmenopausal osteoporotic rats through PI3K/ Akt signaling pathway and increasing OPG/RANKL ratio.

Objective To observe the expression changes of microRNA-375(miR-375)and microRNA-665(miR-665)in the serum of gastric cancer patients,and to explore the relationship between the expression changes of the two and clinical pathological characteristics and prognosis.Methods A total of 85 gastric canc-er patients diagnosed in the hospital from January 2018 to January 2020 were selected as gastric cancer group,85 patients with chronic gastritis were selected as the gastritis group.Gastric cancer patients were divided into survival group(48 cases)and death group(37 cases)based on their mortality within 3 years.Fluorescence quantitative PCR(qRT-PCR)method was applied to detect the relative expression levels of miR-375 and miR-665 in serum,the relationship between their expression and the clinical pathological characteristics of patients was analyzed.Kaplan-Meier method was applied to analyze the relationship between the expression of miR-375 and miR-665 and the 3-year survival rate of gastric cancer patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of the relative expression levels of miR-375 and miR-665 in serum for the death of the patients patients.Results The relative expression levels of miR-375 and miR-665 in the serum in gastric cancer group were lower than those in the gastritis group(t=28.183,22.361,P<0.001).The relative expression levels of miR-375 and miR-665 in the serum in the survival group were higher than those in the death group(t=8.094,8.330,P<0.001).The relative expression levels of miR-375 and miR-665 in serum of gastric cancer patients with tumor infiltration depth of T3+T4,TNM stage Ⅲ-Ⅳ,tis-sue grade Ⅲ,and lymph node metastasis were lower than those of gastric cancer patients with tumor infiltra-tion depth of T1+T2,TNM stage Ⅰ-Ⅱ,tissue grade Ⅰ and Ⅱ,and no lymph node metastasis(P<0.05).The 3-year cumulative survival rate of patients with high expression of miR-375 was 84.44%,which was high-er than 25.00%of patients with low expression of miR-375(χ2=30.442,P<0.05).The 3-year cumulative survival rate of patients with high expression of miR-665 was 74.47%,which was higher than 34.21%of pa-tients with low expression of miR-375(χ2=13.853,P<0.05).The area under the curve of serum miR-375,miR-665 and combined prediction for the death in gastric cancer patients was 0.913,0.902 and 0.971,respec-tively,with sensitivity of 86.49%,67.57%and 94.59%,and specificity of 83.33%,97.92%and 91.67%,re-spectively.Conclusion The low expression of miR-375 and miR-665 in serum may be closely related to the oc-currence,development,and poor prognosis of gastric cancer.

Purpose::To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome.Methods::In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO 2:FiO 2, and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q 1, Q 3), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves. Results::Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively ( p < 0.001), with the area under curve of 0.804 (sensitivity of 88.2%, specificity of 64.7%) and 0.770 (sensitivity of 88.2%, specificity of 64.7%), respectively. There was a significant difference in mechanical ventilation duration between the successful weaning group and the failure weaning group (8 (6, 13) vs. 12 (7.5, 17.3), p = 0.043). The incidence of ventilator-associated pneumonia in the successful weaning group was significantly lower than in the failed weaning group (0.2‰ vs. 2.3‰, p = 0.001). There was a significant difference noted between these 2 groups in the 28-day mortality (11.8% vs. 66.7%, p = 0.003). Conclusion::The median ΔP% in the first 4 days of mechanical ventilation showed good predictive performance in predicting the outcome of weaning from mechanical ventilation within 14 days. Further study is needed to confirm this finding.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.