Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Objective To investigate the relationship between triple motif protein(TRIM)3,TRIM44 and clinicopathological parameters and prognosis in human papillomavirus(HPV)positive cervical cancer tissues.Methods The cancer tissues and adjacent normal cervical tissues(≥2 cm from the resection margin of the cancer)of 158 patients with HPV positive cervical cancer admitted to the hospital from February 2019 to Feb-ruary 2021 were selected,and the cancer tissues of 100 patients with HPV negative cervical cancer admitted to the hospital during the same period were selected.The positive expression rates of TRIM3 and TRIM44 in cancer tissues of HPV positive cervical cancer patients and their adjacent normal cervical tissues,and cancer tissues of HPV negative cervical cancer patients were detected and compared by immunohistochemistry.The relationship between the positive expression rate of TRIM3 and TRIM44 and the clinicopathological parame-ters of HPV positive cervical cancer patients was analyzed.The 3-year cumulative survival rate of patients with negative/positive TRIM3 expression and negative/positive TRIM44 expression were analyzed by Kaplan-Meier survival curve.The influencing factors of the prognosis of HPV positive cervical cancer patients were analyzed by COX regression model.Results Compared with adjacent normal cervical tissues and HPV nega-tive cervical cancer tissues,the positive expression rate of TRIM3 in HPV positive cervical cancer tissues was significantly decreased(P＜0.05),and the patients expression rate of TRIM44 was significantly increased(P＜0.05).Compared with the patients with FIGO stage Ⅰ A-Ⅰ B and no lymph node metastasis,the pa-tients with FIGO stage Ⅱ A and lymph node metastasis,the positive rate of TRIM3 expression decreased sig-nificantly(P＜0.05),while the positive rate of TRIM44 expression increased significantly(P＜0.05).A total of 3 patients were lost during the 3-year follow-up among 158 HPV positive cervical cancer patients,and 155 patients were finally followed up.Kplan-Meier survival curve showed that,the 3-year cumulative survival rate in TRIM3 negative expression group was significantly lower than that in TRIM3 positive expression group(P＜0.05).The 3-year cumulative survival rate in TRIM44 positive expression group was significantly lower than that in TRIM44 negative expression group(P＜0.05).COX regression analysis showed that lymph node metastasis,FIGO stage,negative expression of TRIM3 and positive expression of TRIM44 were risk factors for the prognosis of HPV positive cervical cancer patients(P＜0.05).Conclusion The expression of TRIM3 is low and the expression of TRIM44 is high in HPV positive cervical cancer tissues,which is relate to lymph node metastasis,FIGO stage and decrease 3-year cumulative survival rate.

Objective:To explore the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia using network pharmacology; To verify the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia through animal experiments.Methods:The active components and potential targets of Shiwei Chaihu Shugan Powder were searched in TCMSP and Uniprot databases. Breast hyperplasia genes were searched in GeneCards and OMIM databases. The intersection targets were obtained by online tool Venny, and the "drug-component-target" network was constructed by Cytoscape 3.8.2 software. The protein interaction (PPI) network was constructed using the String platform, and GO function and KEGG pathway enrichment analysis were performed using the DAVID annotation database. Molecular docking was performed using PDB, PubChem database, PyMOL 2.1 and AutoDockvina 1.2.5 software to predict the biological mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia. Rats were divided into blank group, model group, tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups according to the random number table method, with 6 rats in each group. Except for the blank group, the other groups were prepared with the modified estrogen-progesterone-induced rat mammary hyperplasia model. Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups were intragastrically administered with Shiwei Chaihu Shugan Powder solution at 7.425 g/kg, 14.850 g/kg, and 29.700 g/kg respectively, while the tamoxifen group was intragastrically administered with 2.1 mg/kg tamoxifen. The blank group and the model group were intragastrically administered with the same volume of drinking water, once a day, for consecutive 28 d. The thickness of the mammary gland was measured by small animal ultrasound. The height and width of the nipples were measured by vernier calipers. The levels of serum E2 and P were detected by ELISA. The morphology of mammary tissue was observed by HE staining. The expressions of ERα, ERβ, SRC-1 and CBP/p300 proteins were detected by Western blot.Results:A total of 92 active components and 274 disease-drug intersection targets were screened out. GO functional enrichment analysis showed that Shiwei Chaihu Shugan Powder was closely related to positive regulation of gene expression, positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, negative regulation of apoptosis process, response to heterogeneous stimulation, and regulation of hormone levels. KEGG enrichment analysis showed that the core targets might be related to NF-κB signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, PI3K/Akt signaling pathway, and regulating hormone levels. Molecular docking results showed that the core components had a good binding energy with the core target and a stable conformation. Compared with the model group, the thickness of the mammary gland in the tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups decreased ( P<0.01), the serum P level increased ( P<0.05), the expressions of ERα, SRC-1, and CBP/p300 proteins decreased ( P<0.01), and the expression of ERβ protein increased ( P<0.01); the height of the nipples in the Shiwei Chaihu Shugan Powder medium- and high-dosage groups and the tamoxifen group decreased ( P<0.01), and the serum E2 level increased ( P<0.05). Conclusion:Shiwei Chaihu Shugan Powder may play a role in the treatment of breast hyperplasia by regulating the levels of estrogen and related proteins.

The risk of post-transfusion hepatitis(PTH)primarily stems from blood transfusion containing HBV-infected blood that is HBsAg-negative,specifically during the serological window period(WP)and occult HBV infection(OBI).OBI is a low viral replication form of HBV,making it a challenge in hepatitis B virus infection prevention and control,and a significant transmission source of post-transfusion hepatitis.Although nucleic acid testing(NAT)can reduce the occurrence of post-transfusion hepatitis to some extent,some OBI-infected individuals exist among blood donors,representing a potential risk of HBV transmission through blood.This article primarily summarizes an overview of OBI's concept,serological characteristics,genomic features,pathogenesis mechanisms,epidemiological characteristics,and advances in detection strategies,to provide theoretical basis for the collection,quality control and safe use of blood products for the OBI population.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Heart failure is a fatal stage of end-stage cardiovascular disease,which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates.Intestinal microecology is the largest and most com-plex microecosystem of human body.It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract.In recent years,with the deepening of the study of intestinal flora,more and more studies have found that the im-balance of intestinal microecology can cause changes of metabolites in heart failure patients,which is one of the key triggers for the development of heart failure,therefore,using the intestinal microbial homeostasis as a new entry point for the treat-ment of heart failure will be a hotspot in medical research.However,the theory of Chinese medicine,"the spleen is the guardian",covers the physiological functions of the spleen,such as the spleen's main function of transporting,spleen's main function of ascending and clearing,and its main function of hiding camping,etc.,and the functions of intestinal flora and the"spleen is the guardian"are similar to a certain extent.Therefore,this paper starts from a holistic viewpoint and takes the theory of"spleen as the guardian"in Chinese medicine as an entry point to elaborate on the pathogenesis of intes-tinal microecological imbalance and heart failure,so as to provide a reference for Chinese medicine treatment or drug re-search.

Objective Meta-analysis was performed to evaluate the clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst.Methods Randomized controlled trials comparing fenestration decompression and curettage in treatment of jaw cysts were retrieved from PubMed,Cochrane Library,CNKI,SinoMed,VIP and Wanfang data from built databases to June 2024.A Meta-analysis was performed using RevMan 5.4 software to compare the rate of capsule volume reduction,bone hyperplasia thickness and bone density at 3,6 and 12 months after treatment with two methods.Results A total of 14 literatures were included.At 3,6 and 12 months after operation,rate of capsule volume reduction and bone density after fenestration decompression were significantly better than that after curettage.At 6 and 12 months after operation,bone hyperplasia thickness after fenestration decompression were significantly greater than that after curettage.Conclusion Fenestration decompression is superior to curettage in the treatment of jaw cyst in terms of rate of capsule volume reduction,bone hyperplasia thickness and bone density.