In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.

Objective:To analyze the clinicopathological features of giant ovarian masses(mean diameter≥10 cm)and analyze the clinical characteristics of patients in different age groups.Methods:The clinicopathological characteristics of 311 patients diagnosed with giant ovarian masses by surgery at Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2014 to December 2022 were retrospectively analyzed.Patients were further stratified by age and mass size to compare the differences of clinical and patho-logical features among different age groups and different mass diameter groups.Results:①The median age of thepatients were 44(24,60)years old.The first symptoms were as follows:ovarian mass discovered during physi-cal examination,abdominal pain,bloating,conscious abdominal distension,and symptoms of compression.②The surgical methods were as follows:unilateral oophorectomy(30.5％,95/311),ovarian cystectomy(28.9％,90/311),tumor staging or cytoreductive surgery(28.0％,87/311),total hysterectomy with bilateral adnexectomy(12.5％,39/311).③The pathological types were benign(49.5％,154/311),malignant(31.8％,99/311)and borderline(18.7％,58/311).④ Patients complained abdominal distension in＜20 years old group were signifi-cantly higher than the other two groups(P＜0.05).The ovarian resection rate in the＞50-year-old group was higher than that of the other two groups(P＜0.05),and the rate of unilateral ovarian resection in the＜20-year-old group was still as high as 30.1％(15/49).⑤ The size of the mass correlated with the duration of the disease.When the disease course was between 1 to 6 months,the mass diameter line＞30 cm was the most common(P＜0.05).The incidence of borderline tumors in the＞30 cm group was significantly higher than that in the other two groups,and the difference was statistically significant(P＜0.05).Conclusions:Ovarian mucinous and mucinous borderline tumors are the most common types of giant adnexal masses.The size of the mass tends to increase with the prolongation of the disease course.The incidence of borderline tumors increases with the in-crease of mass.Health education for young people should be strengthened.When abdominal pain,abdominal bloating,especially lower abdominal distension occurs,they should seek medical treatment in time to avoid adnex-ectomy due to borderline tumors.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

ObjectiveTo observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats （SHRs）. MethodA total of 75 male SHRs aged nine weeks were randomly divided into SHR group， Benazepril group （1.00 mg·kg^-1·d^-1）， high-dose Zhengan Xifengtang group （34.5 g·kg^-1·d^-1）， medium-dose Zhengan Xifengtang group （17.25 g·kg^-1·d^-1）， and low-dose Zhengan Xifengtang group （8.625 g·kg^-1·d^-1）. A total of 15 male Wistar-Kyoto （WKY） rats aged nine weeks were selected as the normal group. The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks. During the administration， the blood pressure of the rats was measured regularly. After the intervention， fresh feces were collected with a sterile frozen storage tube， and 16S amplicon information was collected and analyzed. Plasma， hippocampus， and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS） detection. ResultZhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs. Compared with the SHR group， Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs. At the phylum level， Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes， Tenericutes， and Candidatus Saccharibacteria. Compared with the SHR group， Zhengan Xifengtang increased the relative abundance of Blautia wexlerae， Fusicatenibacter saccharivorans， and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense， Intestinimonas butyriciproducens， Acetatifactor muris， Alloprevotella rava， and Oscillibacter valericigenes. Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens， Aerococcus， Butyrivibrio， Olsenella， Bifidobacterium， Clostridium XIVb， Allobaculum， and Fusicatenibacter and positively correlated with the relative abundance of Alloprevotella. Zhengan Xifengtang increased the contents of plasma， hippocampal 5-hydroxy tryptamine（5-HT）， and 5-hydroxyindole acetic acid（5-HIAA） in SHRs and decreased the contents of 5-HT and 5-HIAA in the ileum， and the content of 5-HT in the hippocampus was negatively correlated with that in the ileum. ConclusionZhengan Xifengtang can reduce the blood pressure of SHRs， which may be related to reducing the diversity of SHR microflora， regulating the structure of the microflora， increasing the relative abundance of 5-HT and short-chain fatty acids bacteria， and lowering the relative abundance of pathogenic bacteria related to intestinal inflammation.

There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.

Objective To mine and analyze the adverse event data of polatuzumab vedotin(Pola)and fam-trastuzumab deruxtecan-nxki(T-Dxd),so as to provide reference for clinical medication safety.Methods The adverse events reported from January 1,2004 to June 7,2023 were extracted based on openFDA database.The suspicious risk signals were screened by the Open Vigil 2.1 data platform and ranked by signal strength and frequency of occurrence;then ADEs were classified by reference to the MedDRA 26.0.Results A total of 7 164 and 22 870 ADE reports related to Pola and T-Dxd were obtained,and 104 and 95 suspicious ADE signals were detected,respectively.According to the signal intensity,cytomegalovirus enterocolitis(ROR=416.94)for Pola and interstitial lung disease[reporting odds ratio(ROR)=82.55]for T-Dxd ranked first,both of which were recorded in the drug instructions.According to the frequency of occurrence,the two drugs were most frequently associated with death(n=111)and nausea(n=285),respectively.The risk of Pola was associated with 12 systems/organs,of which 26 risk signals were not documented in the drug instruction,and the risk of T-Dxd was associated with 13 systems/organs,of which 18 risk signals were not documented in the drug instruction.Conclusion By tapping the ADE after real-world administration of Pola and T-Dxd,physicians are prompted to pay attention to the risk of adverse reactions in clinical use and actively take preventive and therapeutic measures to ensure the safety of patients'medication.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.