Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To test the practical effect of the research projects outpatient strategy for application of the National Natural Science Foundation (NSFC) in a hospital of Chinese medicine.Methods:We compared the number and success rate of the National Natural Science Foundation of China grant awards before and after the implementation of the research projects outpatient strategy, and further analyzed the promotional effect of the research projects outpatient strategy on general programs and youth scientists funds through univariate analysis and multivariate Logistic regression.Results:Since the implementation of the research projects outpatient strategy, both the number of NSFC grant awards and the success rate continuously increased, indicating that the strategy played a positive role in improving the overall success rate of the hospital. However, this effect was primarily reflected in the assistance provided to applications for youth scientists funds. The main favorable factor for winning general programs was the applicant′s preliminary foundation. Applicants who have previously received NSFC funding had a higher success rate.Conclusions:The strategy of research projects outpatient can promote the winning of NSFC youth scientists funds.

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis (SAP) and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group (SHAM),SAP model group (SAP),and Chaihuang Qingyi Huoxue Granule (CH)group,with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5％ sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage,while the CH group received 1.2 g·kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation,eight rats from each group were sacrificed to collect abdominal aortic blood,pancreatic and ileal tissues for analysis. Ascites,pancreatic and ileal tissues were observed. Serum amylase(AMY) and lipase (LPS) levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points,the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels,pancreatic and ileal histopathological scores increased,and Claudin-1 protein expression in ileal tissue markedly decreased (all P<0.05). The differences in abundance of microbial community increased,while the evenness of community composition reduced. The microbial richness showed no significant change (P>0.05),but the microbial diversity decreased(P<0.05). Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 decreased,whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced,and the evenness of community composition increased. The microbial richness showed no significant change(P>0.05),but the microbial diversity increased (P<0.05). Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira,Ruminococcus,Bifidobacterium,and Bacteroides S24-7 increased,whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH,pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group(P<0.05). The differences in abundance of microbial community reduced,and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP,which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

Objective:To establish a polymerase chain reaction(PCR)method to accurately discriminate the crude materials and aqueous extract of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorff and Ptyas korros.Methods:Specific primers were designed using mitochondrial Cytb gene(CO1)as a target gene,and annealing temperature,number of cycles and the type of DNA polymerases were optimized.The mixed samples were detected by this method.Results:By this multiplex allele-specific PCR identification method,135,182,246 and 197 bp of specific fragments were amplified from DNA templates of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros,respectively,following the conditions:cycle number of 35,annealing temperature of 62 ℃.The adulterants and the blank control showed no bands.The method could simultaneously and accurately identify the snake-derived components in the mixed samples.Conclusion:The method can be used to identify the samples of Zaocys dhumnades,Elaphe carinata,Elaphe meollendorffi and Ptyas korros simultaneously,accurately and rapidly,and is suitable for the identification of standard decoctiond and formula granules samples.

OBJECTIVE To explore the detoxification mechanism of Terminalia chebula Retz(TCR)soup-processed Euphorbia fischeriana Steud.(EFS)based on LC-MS and simulation processing.METHODS The changes of chemical composition of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup were analyzed by LC-MS.Mice were orally administered with alcoholic extracts of crude EFS,alcoholic extracts of water-processed EFS,alcoholic extracts of TCR soup,alcoholic extracts of TCR soup-processed EFS,dichloromethane extracts of crude EFS,dichloromethane extracts of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup,respectively.Toxicity changes in TCR soup-processed EFS and dichloromethane extracts of crude EFS after simulation processing with TCR soup were evalu-ated by fecal water contents,release levels of TNF-α and IL-1β,and intestinal pathology.RESULTS A total of 115 and 53 com-pounds were identified in EFS and TCR soup,respectively.The contents of 58 and 12 compounds significantly decreased and signifi-cantly increased respectively in EFS after processing with TCR soup.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the crude and water-processed EFS groups(P<0.01),and no-table intestinal injury was observed.Compared to the crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in both the TCR soup group and the TCR soup-processed EFS group(P<0.01),and repaired intestinal injury was observed.After simulation processing for the dichloromethane extracts of crude EFS with TCR soup,the ion intensity change rates for diterpenoids and tannin phenolic acid compounds ranged from-6.75%to 8.09%and 66.06%to 100.00%,respectively.The ion intensity change rates of diterpenoids in the dichloromethane extracts of TCR soup-processed EFS ranged from-9.92%to 54.72%with almost no tannin phenolic acid compounds.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the dichloromethane extracts of crude and TCR soup-processed EFS groups(P<0.01),and severe intestinal injury was observed.Compared to the dichloromethane extracts of crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in the group of the dichloromethane extracts of crude EFS after simulation processing with TCR soup(P<0.01),with no apparent intestinal injury.CONCLUSION TCR soup pro-cessing can alleviate the intestinal toxicity of EFS.The detoxification mechanism may involve the introduction of a large number of tan-nin phenolic acid compounds in TCR soup during the processing of EFS,which plays a pharmacological antagonistic role in the animal body.

Purpose To study the expression of of mono-clonal and polyclonal TRPS1 antibodies in synovial sarcoma,and to explore the value of TRPS1 in the diagnosis and differen-tial diagnosis of synovial sarcoma and the sensitivity and speci-ficity of polyclonal TRPS1 for the diagnosis of synovial sarcoma.Methods Immunohistochemical EnVision method was used to detect the expression of monoclonal and polyclonal TRPS1 anti-bodies in the synovial sarcomas and its mimickers.Results A-mong 31 cases of synovial sarcoma,the positive rates of poly-clonal and monoclonal TRPS1 antibodies were 54.8％and 93.5％,respectively.Of 30 synovial sarcoma mimicking le-sions,2 were positive for TRPS1(polyclonal antibody),which was 6.67％,and TRPS1 was more frequently expressed in syno-vial sarcoma than in non-synovial sarcoma(P＜0.05).The sensitivity of polyclonal TRPS1 antibody for the diagnosis of syn-ovial sarcoma was 93.5％,and the specificity was 93.3％.Conclusion Polyclonal TRPS1 antibody has a higher sensitivity and specificity for the diagnosis of synovial sarcoma and it there-fore is recommended in routine pathologic diagnosis.