The biotin synthesis pathway in Mycobacteria tuberculosis is a new target for the development of anti-tuberculosis drugs / 药学学报

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Development of membrane anatomy theory in gastric cancer surgery / 中华胃肠外科杂志

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).

Membrane anatomy-based splenic hilar lymph node dissection for gastric cancer / 中华胃肠外科杂志

There is a consensus that selectively perform splenic lymph node dissection is necessary for high-risk patients with proximal gastric cancer to achieve radical treatment. However, there are still some outstanding issues that need to be solved during the practice of splenic lymph node dissection. These include poorly defined boundaries, technical difficulties, and blurred boundaries in No. 10 and No. 11 lymph nodes, etc. Membrane anatomy has achieved successful applications in the field of gastric and colorectal surgery in recent years. The study of membrane anatomy in the splenic hilum region is controversial due to the special location of the splenic hilum, which involves multiple organs and affiliated mesentery undergoing complex rotation, folding, and fusion during embryonic development. In this manuscript, we summarize the following points based on existing research and personal experience regarding membrane anatomy. 1. There is a membrane anatomical structure that can be used for lymph node dissection in the splenic hilum region. 2. The membrane structure in the splenic hilum region can be divided into two layers: the superficial layer is composed of the dorsal mesogastrium, and the deep layer is composed of Gerota fascia, the tail of the pancreas, and the mesentery of the transverse colon (from head to tail). 3. There is a loose space between the two layers that can be used for separation during surgery. The resection of the dorsal mesogastrium belongs to D2 dissection. The No. 10 lymph node in the deeper layer belongs to the duodenal mesentery, and the resection of the No.10 lymph node exceeds D2 dissection. The complete excision of the gastric dorsal mesentery is consistent with the D2+CME surgical mode proposed by Gong Jianping's group.

A decade's review for membrane anatomy: the setting,events in it, order formed by primary fascia and serous membrane / 中华胃肠外科杂志

The successful report of total mesorectal excision (TME)/complete mesocolic excision (CME) has encouraged people to apply this concept beyond colorectal surgery. However, the negative results of the JCOG1001 trial denied the effect of complete resection of the "mesogastrium" including the greater omentum on the oncological survival of gastric cancer patients. People even believe that the mesentery is unique in the intestine, because they have a vague understanding of the structure of the mesentery. The discovery of proximal segment of the dorsal mesogastrium (PSDM) proved that the greater omentum is not the mesogastrium, and further revised the structure (definition) of the mesentery and revealed its container characteristics, i.e. the mesentery is an envelope-like structure, which is formed by the primary fascia (and serosa) that enclose the tissue/organ/system and its feeding structures, leading to and suspended on the posterior wall of the body. Breakdown of this structure leads to the simultaneous reduction of surgical and oncological effects of surgery. People quickly realized the universality of this structure and causality which cannot be matched by the existing theories of organ anatomy and vascular anatomy, so a new theory and surgical map- membrane anatomy began to form, which led to radical surgery upgraded from histological en bloc resection to anatomic en bloc resection.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Related factors of endogenous erythropoietin and its association with 10-year risks of cardiovascular disease in a community-based Chinese study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the associated factors of endogenous erythropoietin (EPO) and its association with 10-year risks of atherosclerotic cardiovascular disease in a Chinese community-based general population.@*METHODS@#The participants of this study were from an atherosclerosis cohort survey which was established by the Department of Cardiology, Peking University First Hospital in 2011. The cohort survey was performed in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China. The inclusion criteria of this study were: (1) endogenous EPO was measured; (2) health questionnaire data and other clinical data were complete; (3) participatants who had cardiovascular or cerebrovascular diseases (defined as self-reported coronary heart disease, stroke or transient ischemic attack) or anemia or estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) at baseline were excluded. Multivariate linear regression model was used to examine the associated factors of endogenous EPO. The participants were grouped into low (< 5%), moderate (5%-10%) and high risk (≥10%) groups, based on predicted 10-year cardiovascular disease risk using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) equations.@*RESULTS@#A total of 4 013 participants were included. Mean age of them was (55.9±8.2) years, 62.2% (n=2 496) of them were female, and 46.3% (n=1 859), 70.9% (n=2 845), 21.9% (n=879) had hypertension, dyslipidemia and diabetes, individually. The average body mass index was (26.1±3.3) kg/m2. The median of EPO level was 12.8 (9.3-17.4) IU/L and 25.1% (n=998) were at high 10-years risk of cardiovascular disease. Hemoglobin (β=-0.05, 95%CI: -0.07 to -0.04) and eGFR ≥90 mL/(min·1.73 m2) (β=-0.05, 95%CI: -0.07 to -0.04) were associated with lower in transformed EPO levels while hypertension (β=0.08, 95%CI: 0.05 to 0.12) and obesity (β=0.14, 95%CI: 0.09 to 0.18) were associated with higher in transformed EPO levels in multivariate linear regression analyses. Ten-year cardiovascular disease risks were positively associated with in transformed EPO levels (β=0.07, 95%CI: 0.05 to 0.09). The participants at moderate and high cardiovascular disease risks had significant higher EPO levels than the low risk group (all P < 0.05).@*CONCLUSION@#In community-based Beijing populations, endogenous EPO was associated with hemoglobin, renal function, obesity and hypertension. Individuals at high 10-years cardiovascular disease risks have higher endogenous EPO levels. Endogenous EPO may be a potential risk marker of cardiovascular disease.

Clinical Characteristics and Survival Analysis of Carbapenem-Resistant Pseudomonas Aeruginosa Colonized or Infected Patients with Hematological Disorders / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.@*METHODS@#The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.@*RESULTS@#A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).@*CONCLUSIONS@#Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Risk Prediction Model for Pulmonary Fungal Infections in Patients with Lung Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Mechanism of Modified Danggui Shaoyao San in treatment of chronic atrophic gastritis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification / 中国药理学通报

Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.

Survey on the application of external cardiopulmonary resuscitation in Chinese children with sudden cardiac arrest / 中华儿科杂志

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.

Primary synovial sarcoma of lung: a clinicopathological analysis of 12 cases / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, molecular features and differential diagnosis of primary synovial sarcoma of the lung (PSSL). Methods: Twelve cases of PSSL were collected at Henan Provincial People's Hospital, during May 2010 and April 2021, and their clinicopathological parameters were summarized. SS18-SSX, H3K27Me3, and SOX2 were added to the original immunomarkers to evaluate their diagnostic value for PSSL. Results: The age of 12 patients when diagnosed ranged from 32 to 75 years (mean of 50 years). There were 7 males and 5 females, 2 left lung cases and 10 right lung cases. Of the 6 patients who underwent surgical resection, five cases were confined to lung tissue (T1), one case had mediastinal invasion (T3), two cases had regional lymph node metastasis (N1), and none had distal metastasis. Microscopically, 11 cases showed monophasic spindle cell type and one case showed biphasic type composed of mainly epithelial cells consisting of cuboidal to columnar cells with glandular and cribriform structures. It was difficult to make the diagnosis by using the biopsy specimens. Immunohistochemistry (IHC) showed CKpan expression in 8 of 12 cases; EMA expression in 11 of 12 case; TLE1 expression in 8 of 12 cases; S-100 protein expression in two of 12 cases; various expression of bcl-2 and vimentin in 12 cases, but no expression of SOX10 and CD34 in all the cases. The Ki-67 index was 15%-30%. The expression of SS18-SSX fusion antibody was diffusely and strongly positive in all 12 cases. SOX2 was partially or diffusely expressed in 8 of 12 cases, with strong expression in the epithelial component. H3K27Me3 was absent in 3 of 12 cases. SS18 gene translocation was confirmed by fluorescence in situ hybridization (FISH) test in all 12 samples. Six cases underwent surgery and postoperative chemotherapy, while the other six cases had chemotherapy alone. Ten patients were followed up after 9-114 months, with an average of 41 months and a median of 26 months. Five patients survived and five died of the disease within two years. Conclusions: PSSL is rare and has a broad morphological spectrum. IHC and molecular tests are needed for definitive diagnosis. Compared with current commonly used IHC markers, SS18-SSX fusion antibody has better sensitivity to PSSL, which could be used as an alternative for FISH, reverse transcription-polymerase chain reaction or next generation sequencing in the diagnosis of PSSL.

Effect of Sparganii Rhizoma-Curcumae Rhizoma-medicated serum on proliferation, apoptosis, and migration of human ectopic endometrial stromal cells: based on JAK2/STAT3 signaling pathway / 中国中药杂志

Based on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway, this study investigated the effect of medicated serum of Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) on the proliferation, apoptosis, migration, and secretion of inflammatory factors of ectopic endometrial stromal cells(ESCs). Specifically, human ESCs were primary-cultured. The effect of different concentration(5%, 10%, 20%) of SR-, CR-, and SR-CR combination-medicated serum, and AG490 solution(50 μmol·L~(-1)) on the proliferation of ESCs was detected by methyl thiazolyl tetrazolium(MTT) assay, and the optimal dose was selected accordingly for further experiment. The cells were classified into normal serum(NS) group, SR group(10%), CR group(10%), combination(CM) group(10%), and AG490 group. The apoptosis level of ESCs was detected by flow cytometry, and the migration ability was examined by wound healing assay. The secretion of interleukin(IL)-1β, IL-6, and tumor necrosis factor(TNF)-α was determined by enzyme-linked immunosorbent assay(ELISA). The protein levels of cysteinyl aspartate specific protei-nase-3(caspase-3), B-cell lymphoma(Bcl-2), and Bcl-2-associated X protein(Bax) and the levels of phosphorylated(p)-JAK2 and p-STAT3 were detected by Western blot. The results showed that the viability of ESCs cells was lowered in the administration groups compared with the blank serum group(P<0.01), especially the 10% drug-medicated serum, which was selected for further experiment. The 10% SR-medicated serum, 10% CR-medicated serum, and 10% CM-medicated serum could increase the apoptosis rate(P<0.01), up-regulate the protein expression of caspase-3 and Bax in cells(P<0.05 or P<0.01), down-regulate the expression of Bcl-2(P<0.01), decrease the cell migration rate(P<0.05 or P<0.01), and reduce the secretion levels of IL-1β, IL-6, and TNF-α(P<0.05 or P<0.01), and levels of p-JAK2 and p-STAT3(P<0.05 or P<0.01). Compared with the SR and CR groups, CM group showed low cell viability(P<0.01), high protein expression of caspase-3 and Bax(P<0.05 or P<0.01), and low protein expression of Bcl-2 and p-JAK2(P<0.05). After incubation with CM, the apoptosis rate was higher(P<0.05) and the migration rate was lower(P<0.01) than that of the CR group. The p-STAT3 protein level of CM group was lower than that of the RS group(P<0.05). The mechanism of SR, CR, and the combination underlying the improvement of endometriosis may be that they blocked JAK2/STAT3 signaling pathway, inhibited ESC proliferation, promoted apoptosis, weakened cell migration, and reduced the secretion of inflammatory factors. The effect of the combination was better than that of RS alone and CR alone.

Study on untargeted metabolomics of Codonopsis pilosula from different producing areas based on ultra-performance liquid chromatography tandem high resolution mass spectrometry / 药学学报

Lu Dangshen, a traditional authentic medicinal material of Codonopsis Radix is mainly produced in Shangdang (Changzhi) area of Shanxi Province. Baitiao Dangshen is mainly produced in Gansu Province. Codonopsis Radix contains many kinds of components such as phenylpropanoids, polyalkynes, alkaloids, terpenes, fatty acids, flavonoids, and so on. At present, the effect of producing areas on its chemical compositions has not been systematically studied. This study analyzed the differences of metabolites among Codonopsis pilosula from different producing areas by UPLC-HRMS. PCA, OPLS-DA coupled with Thermo mzcloud online and local databases were used to compare the overall differences of metabolites among Codonopsis pilosula from different producing areas, and the chemical constituents were identified to further screen and find out the different metabolites and analyze the metabolic pathways by information retrieval in HMDB, PubChem, Chemspider and KEGG databases. The results showed that 72 differential metabolites were identified in this study. There were 15 kinds of up-regulated and 57 kinds of down-regulated metabolites of Lu Dangshen compared with Baitiao Dangshen. The top 30 metabolic pathways were analyzed by KEGG enrichment, and the most important metabolic pathways were phenylpropanoid biosynthesis, which was demonstrated that phenylpropanoid biosynthesis pathway and related intermediate metabolites could be used as the characteristics of distinguishing Lu Dangshen from different habitats of Codonopsis pilosula. The present study provided a basis for analyzing the influence of producing areas on the chemical components of Codonopsis pilosula and reasonably evaluating the quality of Codonopsis Radix, and also provided a new idea for expounding the authenticity of Lu Dangshen.

Analysis of the progress of clinical trials for ophthalmic drug in China, 2022 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the progress of clinical trials for ophthalmic drugs in China in 2022 and discuss its changes with 2014 to 2021, thus providing the latest data reference for the development of new drug and the implementation of clinical trials, and a basis for decision-making.METHODS: In this cross-sectional study, we retrieved the drug clinical trials registration and information disclosure platform of National Medical Products Administration database. Drug clinical trials for eye diseases registered from January 1 to December 31, 2022 were included. Number(proportion)was used to describe the characteristics of clinical trials for ophthalmic drug, the indication, the trial phase, the efficacy and the geographical distribution.RESULTS:A total of 55 clinical trials for ophthalmic drug were included, which accounted for 1.66% of all clinical trials, showing a steady growth trend. Main drug type was chemical drugs with the highest proportion of 58.18%. The top three indications with the most clinical trials were age-related macular degeneration, myopia and dry eye. Two gene drugs emerged in 2022, and 7 drugs carried out ≥2 trials, of which atropine sulfate and recombinant anti-vascular endothelial growth factor(VEGF)humanized monoclonal antibody were the most(7 and 5 respectively). Most trials were in phase I and phase III stages, accounting for 36.36% and 27.27% respectively. The median start-up time of phase I trials in 2022 was 2.72(0.77, 3.47)mo, which was significantly shorter than 3.87(3.00, 6.30)mo of 2014～2021(Z=-2.630, P=0.009), and there were no significant differences between BE, phase II, III, IV comparing with 2014～2021(P&#x003E;0.05).CONCLUSIONS: In 2022, the number and implementation efficiency of clinical trials for ophthalmic drugs in China increased steadily. The indications are mainly fundus disease, myopia and dry eye. Most new drugs are in the early stage of research and development or close to market. Gene therapy drugs began to emerge.

Inhibitory effect of astragalus membranaceus injection on apoptosis and autophagy induced by enterovirus 71 / 中国生物制品学杂志

@#Objective To investigate the effect of astragalus membranaceus（AM）injection on apoptosis and autophagy of human gastric epithelial cell line（GES⁃1）induced by enterovirus 71（EV71）. Methods GES⁃1 cells were cultured in vitro and divided into infected group（EV71 infected at a MOI of 3 and control group（no virus infected）. The morpho⁃logical changes of EV71 infected cells were observed by inverted microscope. The level of VP1 in GES⁃1 cells infected with EV71 was detected by Western blot；CCK⁃8 assay was used to detect the viability of GES⁃1 cells infected with EV71；Nuclear staining with DAPI was used to observe the morphological changes of nuclear apoptosis infected with EV71. GES⁃1 cells were divided into control group（without virus infection），infection group and AM intervention group with final concentration of 1，2. 5，5 and 10 μg／mL，respectively. Western blot was used to detect the effect of AM intervention on the expression of apoptosis⁃related proteins Caspase⁃3，PARP and autophagy⁃related proteins LC3 and P62 in GES⁃1 cells infected withEV71. CCK⁃8 method was used to detect the effect of AM intervention on the viability of GES⁃1 cells infected with EV71. Results GES⁃1 cells were round，shrunken with nuclear pyknosis and uneven size；VP1 level increased（t = 41. 56，P < 0. 01），cell viability decreased（t = 19. 07，P < 0. 01），Caspase⁃3 and PARP proteins were cut off（t = 35. 29 and 3. 648， P < 0. 01 and 0. 021 8，respectively），LC3Ⅱ／LC3Ⅰ ratio increased（t = 10. 16，P = 0. 000 5）and P62 protein was degraded（t = 68. 68，P < 0. 01）；AM inhibited the degradation of Caspase⁃3，PARP and P62 proteins induced by EV71 （t = 52. 66，59. 60 and 40. 22，respectively，each P < 0. 01）and increased the ratio of LC3Ⅱ／LC3Ⅰ（t = 5. 521，P = 0. 005 3），andreducedtheinhibitoryeffectofEV71ontheviabilityofGES⁃1cells（t =4. 420，P =0. 0115）. Conclusion EV71 infection induced apoptosis of GES⁃ 1 cells and AM intervention inhibited EV71 induced apoptosis by inhibiting EV71 induced autophagy.

Diagnostic Value of Structural MRI in Spinocerebellar Ataxia Type 3 / 中山大学学报(医学科学版)

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Association between early-life factors and pubertal timing in girls / 中国当代儿科杂志

OBJECTIVES@#To study the association between early-life factors (including birth weight, method of birth, gestational age, and history of gestational metabolic disorders) and pubertal timing in girls.@*METHODS@#The stratified cluster sampling method was used to select the girls in grades 2-3 and 7-8 from three primary schools and three middle schools in Guangzhou, China from March to December, 2019, and breast development was examined for all girls. A questionnaire survey was performed to collect the information on early-life factors. The multivariate logistic regression model was used to evaluate the association of gestational metabolic disorders, birth weight, method of birth, and gestational age with pubertal timing in girls. The Bootstrap method was used to assess the mediation effect of body mass index (BMI) (Z score) between high birth weight (≥4 000 g) and pubertal timing.@*RESULTS@#A total of 1 665 girls were enrolled, among whom 280 (16.82%) were judged to have early pubertal timing. The multivariate logistic regression analysis showed that high birth weight was associated with the increased risk of early pubertal timing (OR=2.12, 95%CI: 1.19-3.66, P=0.008). Nevertheless, no significant association was observed between other early-life factors and pubertal timing (P>0.05). The OR for the mediation effect of BMI (Z score) between high birth weight and early pubertal timing was 1.25 (95%CI: 1.09-1.47), accounting for 29.33% of the total effect of high birth weight on early pubertal timing.@*CONCLUSIONS@#High birth weight is associated with the increased risk of early pubertal timing in girls, and overweight/obesity may play a partial mediating role in the association between high birth weight and early pubertal timing in girls.