Background and Aims:Preventive temporary stoma has been widely used in surgeries for rectal cancer as a simple and effective method to reduce the severity of postoperative anastomotic leakage.However,some patients with preventive temporary stomas cannot undergo reversal due to various factors,resulting in a permanent stoma.Permanent stomas remain a common adverse outcome in clinical practice,and the reasons behind this are not entirely clear.This study analyzes a continuous surgical sample from a single center to explore the risk factors for forming permanent stoma. Methods:The clinical data of patients who underwent anal-preserving rectal cancer surgery with preventive temporary stoma in Gastrointestinal Cancer Center Ⅲ of Peking University Cancer Hospital from January 2020 to March 2023,with over 12 months of follow-up,were retrospectively collected.The occurrence of permanent stoma was analyzed,and the clinical variables of patients with permanent stoma were compared to those who underwent stoma reversal,along with an analysis of the risk factors for permanent stoma formation.Permanent stoma was defined as ostomy reversal failure for more than 12 months. Results:A total of 299 patients were included,among which 268(89.63％)underwent stoma reversal(stoma closure group),and 31(10.37％)did not(permanent stoma group).Compared to the stoma closure group,the permanent stoma group had a higher incidence of distant organ metastasis at diagnosis(7.5％vs.25.85％,P=0.003)and also had higher proportions of T3 and T4 stages,N2 stage,and clinical stage Ⅳ(all P＜0.05)with an elevated overall postoperative complication rate(19.0％vs.41.9％,P=0.003)as well as a higher rate of severe complications(1.1％vs.9.7％,P=0.016)and an increased incidence of anastomotic leakage(4.9％vs.19.4％,P=0.006).Logistic regression analysis revealed that the presence of distant organ metastasis at diagnosis(OR=5.41,95％CI=1.80-16.27,P=0.003),and occurrence of anastomotic leakage(OR=4.44,95％CI=1.15-17.09,P=0.030)were independent risk factors for the formation of permanent stomas. Conclusion:At present,some patients still cannot undergo reversal of their preventive temporary stoma,resulting in permanent stoma.The formation of permanent stomas is closely related to a low tumor location,distant organ metastasis at diagnosis,and the occurrence of anastomotic leakage.

Objective:To investigate the computed tomography (CT)-based integrated deep learning model for qualitative and quantitative classification of hepatic portal vein.Methods:The retrospective study was conducted. The CT imaging data of 291 patients undergoing upper-abdomen enhanced CT examination in the Beijing Tsinghua Changgung Hospital of Tsinghua University from October 2017 to January 2019 were collected. There were 195 males and 96 females, aged (51±12)years. The hepatic portal vein was reconstructed using the three-dimensional reconstruction system. Three-dimensional point cloud was input to the encoder model to obtain the three-dimen-sional reconstructed vectorized representation, which was used for qualitative classification and quantitative representation classification. Measurement data with normal distribution were repre-sented as Mean± SD, and comparison between groups was conducted using the paired t test. Count data were repre-sented as percentages or absolute numbers, and comparison between groups was analyzed using the paired chi-square test. Results:(1) Three-dimensional reconstruction of portal vein and anatomical classification. Three-dimensional structure was reconstructed in the 291 patients. Classification of main hepatic portal vein showed 211 cases of Akgul type A, 29 cases of Akgul type B, 16 cases of Akgul type C, 10 cases of Akgul type D, and 25 cases of unclassifiable. (2) Prediction of qualitative classification of main hepatic portal vein. Of the 291 patient samples, 25 unclassifiable or poor quality samples were excluded, 266 samples were used for automated qualitative classification of the main portal vein by machine model. There were 211 cases of Akgul type A, 29 cases of Akgul type B, 26 cases of Akgul type C&D. The Macro-F1 of 266 patients was 61.93%±40.50% and the accuracy was 84.99%, versus 32.38%±19.81% and 61.65% of Random classifier, showing significant differ-ences between them ( t=7.85, χ2=62.89, P<0.05). (3) Quantitative representation of portal vein classification. The probabilities of quantitative classification for Akgul qualitative classification of similar samples included P@1 as 73%±45%, P@3 as 70%±37%, P@5 as 69%±35%, P@10 as 67%± 32%, mean reciprocal rank(MRR) as 80%±34%, versus 57%±50%, 58%±35%, 58%±32%, 58%± 30%, 70%±37% of the baseline model, showing significant differences between the two analytical methods ( t=5.22, 5.11, 5.00, 4.99, 3.47, P<0.05). Conclusion:The automated classification model for the hepatic portal vein structure was constructed using CT-based three-dimensional reconstruc-tion and deep learning technology, which can achieve automatic qualitative classification and quanti-tatively describe the hepatic portal vein structure.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was ^“LANCET INFECT DIS^”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak，Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.

ObjectiveTo study the effect of Bazi Bushen capsules on delaying the aging process of naturally aging mice and its mechanism. MethodThe mice were randomly divided into four groups according to their body weight， namely， aging group， low-dose Bazi Bushen capsules group （1 g·kg^-1）， high-dose Bazi Bushen capsules group （2 g·kg^-1）， and rapamycin group （0.002 g·kg^-1）. The debilitating signs were detected by behavioral tests and the weakness index was measured. The percentages of spleen T and B lymphocytes， effector T cells （TE）， memory T cells （TM）， naive T cells （TN）， helper T cells （Th）， cytotoxic T cells （Tc） ，Th1 cells， Th2 cells， and regulatory T cells （Treg） were determined by flow cytometry. Cell proliferation and the cell counting kit-8 （CCK-8） assay was used to detect the proliferation of lymphocytes in mice. The hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the mouse spleen. The expression of cyclin-dependent kinase inhibitor 2A （p16） and cyclin-dependent kinase inhibitor 1A （p21） was detected by immunohistochemistry （IHC）. The mRNA expression of senescence-related proteins p16 and p21 was determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the inflammatory cytokines， including tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin （IL）-1β， IL-2， IL-4， IL-10， and IL-12 p70， in peripheral blood of mice were detected by Luminex. ResultAs compared with the aging group， mice in the Bazi Bushen capsules and rapamycin groups showed significantly improved debilitating signs and reduced weakness index scores （P<0.05， P<0.01）， increased proportions of T cells， TN cells， Tc cells， Th2 cells， and Treg cells in the spleen， decreased proportions of TE cells， TM cells， Th cells， Th1 cells （P<0.05， P<0.01）， and increased proliferation of splenic lymphocytes （P<0.05， P<0.01）. In the Bazi Bushen capsules and rapamycin groups， clear structure of the red and white marrow marginal zone was observed in the spleen of mice， the area of the white marrow was increased， and the area of the red marrow was correspondingly decreased. The protein and mRNA expression of aging-related proteins p16 and p21 in the spleen was decreased （P<0.01）， the levels of serum pro-inflammatory cytokines IL-1β， IL-2， IL-12 p70， IFN-γ， and TNF-α levels were decreased， and the levels of IL-4 and IL-10 were increased （P<0.05， P<0.01） in the Bazi Bushen capsules and rapamycin groups as compared with the aging group. ConclusionBazi Bushen capsules have the effect of regulating the debilitating signs of natural aging mice， regulating the immune homeostasis and inflammation level of the body， and reducing cell aging.

OBJECTIVE To clarify whether the thera-peutic effect of escitalopram on depression patients is cor-related with traditional Chinese medicine syndrome types,and to provide a basis for more accurate drug applica-tion.METHODS A total of 235 depression patients were recruited and classified according to traditional Chinese medicine syndrome differentiation into 5 types:liver and qi stagnation(45),liver stagnation and fire transformation(43),liver qi stagnation and spleen deficiency(79),heart and spleen deficiency(20),and liver and kidney deficiency(38).All patients were treated with escitalopram(10 mg·d-1)for eight weeks.The Montgomery Depression Rating Scale(MADRS)and the 17 Hamilton Depression Rating Scale(HAMD-17)were used to score before treatment and 2,4,and 8 weeks after treatment,respectively.RESULTS Compared with before treatment,the MADRS and HAMD-17 scores and remission rates of each syn-drome type significantly improved with increasing medica-tion duration.The MADRS score relief rate of liver and kidney deficiency type was the most significant(69.3%),significantly higher than the other four syndrome types(47.5%-52.6%,P<0.05);The remission rate of HAMD-17 score was significantly higher than that of heart and spleen deficiency(50.7%vs.28.5%,P＜0.05).The remis-sion rate of HAMD-17 score in liver and qi stagnation type(52.2%)was significantly higher than that in liver stagnation and spleen deficiency type(37.0%,P＜0.01)and heart spleen deficiency type(28.5%,P＜0.05).CON-CLUSION Escitalopram may have a more significant therapeutic effect on patients with liver and kidney defi-ciency and liver stagnation depression.This study pro-vides a new approach for the more effective and accu-rate application of traditional Chinese medicine syndrome differentiation in the selection of clinical antidepressants.

ObjectiveTo investigate the feasibility of applying electronic nose technology to rapidly identify Bletillae Rhizoma and its approximate decoction pieces. MethodA total of 134 batches of Bletillae Rhizoma and its approximate decoction pieces， including 45 batches of Bletillae Rhizoma， 30 batches of Gastrodiae Rhizoma， 30 batches of Polygonati Odorati Rhizoma and 29 batches of Bletillae Ochraceae Rhizoma， were collected as test samples. The olfactory sensory data of the samples were collected by PEN3 electronic nose as the independent variable（X）. Based on the identification results of the 2020 edition of Chinese Pharmacopoeia and local standards， as well as the high performance liquid chromatography（HPLC） fingerprint and original purchase information of 134 batches of the decoction pieces， the benchmark data Y of the identification model were obtained， and four chemometric methods of principal component analysis-discriminant analysis（PCA-DA）， partial least squares-discriminant analysis（PLS-DA）， least square-support vector machine（LS-SVM） and K-nearest neighbor（KNN） were used to establish the binary identification model for 45 batches of Bletillae Rhizoma and 89 batches of non-Bletillae Rhizoma and the quadratic identification model of the four kinds of decoction pieces， that is， Y=F（X）. ResultAfter leave-one-out cross validation， the positive discrimination rates of the above four models were 97.01%， 97.01%， 98.51% and 97.01% in the binary identification， and 97.76%， 89.55%， 98.51% and 97.01% in the quadratic identification， respectively. The highest positive discrimination rate could reach 98.51% for the binary and quadratic identification models， and LS-SVM algorithm is both the optimal one， the most suitable kernel functions were chosen as radial basis function and linear kernel function， respectively. The optimal models discriminated well with no unclassified samples. ConclusionElectronic nose technology can accurately and rapidly identify Bletillae Rhizoma and its approximate decoction pieces， which can provide new ideas and methods for rapid quality evaluation of other decoction pieces.

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

【Objective】 To study the level of occult hepatitis B virus methylation and replication related genes, and to explore the effect of the former on the latter. 【Methods】 The cases in control group (healthy control, n=3), occult hepatitis B group (occult HBV group, n=3) and hepatitis B group (HBV group, n=3) were detected by Illumina methylation 850k chip. The difference analysis, GO analysis and KEGG analysis were carried out. The methylation and virus replication related genes DNMT1, DNMT2, Dnmt3a and ZHX2 were screened for RT-PCR. 【Results】 The methylation level of occult HBV group and HBV group was significantly higher than that of the control group. Difference analysis showed that there were 1 050 differential methylation sites in occult HBV group with the methylation level greater than non-methylation level, and 1 340 differential methylation sites as the opposite compared with the control group. In HBV group, there were 1 008 differential methylation sites with methylation level greater than non-methylation level, and 1 242 differential methylation sites as the opposite. Go analysis showed that compared with the control group, the differential gene expression in occult HBV group and HBV group was significantly related to many anabolic processes in biological process (BP), cell composition (CC) and molecular function (MF). The enrichment analysis of KEGG pathway between the control group and the occult HBV group showed that the differential genes were mainly involved in adhesion junction, basal cell carcinoma, endometrial carcinoma, EB virus infection, hepatocellular carcinoma and other signal pathways. The enrichment analysis of KEGG pathway in occult HBV group and HBV group showed that the differential genes were mainly involved in AMPK signal pathway, cell cycle, endometrial cancer, hepatitis C, hepatocellular carcinoma and other signal pathways. DNMT1 and DNMT3a in occult HBV group and HBV group were significantly higher while ZHX2 was significantly lower than those in control group. 【Conclusion】 The methylation level of occult HBV group and HBV group increased significantly while ZHX2 decreased significantly. Hypermethylation inhibited the expression of ZHX2 and changed the replication of hepatitis B virus. Hepatitis B virus DNA methylation provides a theoretical basis for the replication mechanism of hepatitis B virus and a new method for the treatment of hepatitis B virus.