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.

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.

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.

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.

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.

Objective:To observe the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of radiation induced thrombocytopenia (RIT) .Methods:From January 2019 to March 2021, 204 cases (including 101 cases of radiotherapy alone and 103 cases of concurrent chemoradiotherapy) were collected retrospectively after radiotherapy and with decreased in blood platelet count <75×10 9/L in Jilin Cancer Hospital. These patients received rhTPO 15 000 U, once a day, subcutaneous, for at least 4 consecutive days, or met the withdrawal criteria blood platelet count ≥100×10 9/L, or the absolute value of blood platelet increase ≥50×10 9/L. The characteristics of blood platelet decline, treatment efficacy, and safety were analyzed. Results:The numbers of radiotherapy treatments with platelets lower than 75×10 9/L in the radiotherapy alone group and the concurrent chemoradiotherapy group were 19 (13, 22) and 13 (10, 17) times, respectively, indicating that patients in the concurrent chemoradiotherapy group experienced platelet decline earlier ( Z=-5.27, P<0.001), the lowest values of platelet decline in the two groups were 68 (45, 74) ×10 9/L and 62 (44, 74) ×10 9/L, respectively, with no statistically significant difference ( Z=-1.15, P=0.252). After received rhTPO treatment, the numbers of days that the two groups of patients had platelets <50×10 9/L were 7 (3, 13) d and 7 (5, 11) d, respectively, with no statistically significant difference ( Z=-1.13, P=0.281). After the patients received radiotherapy, rhTPO was started when the platelet count dropped to <75×10 9/L. The number of days required to recover to 75×10 9/L was 4 (2, 10) d in the radiotherapy alone group and 4 (2, 8) d in the concurrent chemoradiotherapy group, with no statistically significant difference ( Z=-1.07, P=0.285) ; the number of days required for platelets to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L was 8 (6, 14) d in the radiotherapy alone group and 11 (8, 16) d in the concurrent chemoradiotherapy group. The recovery time of the concurrent chemoradiotherapy group was longer than that of the radiotherapy alone group ( Z=-3.64, P<0.001). Regardless of the baseline level, there was no statistically significant difference in the number of days for platelets to recover to 75×10 9/L after rhTPO treatment between the radiotherapy alone group and the concurrent chemoradiotherapy group ( Z=-1.42, P=0.155; Z=-0.97, P=0.332). The number of days required for the two groups of patients to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (6, 14) d and 11 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.64, P<0.001). The numbers of days required for the two groups of patients with baseline platelets ≥50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L were 8 (4, 12) d and 10 (8, 16) d, respectively, with a statistically significant difference ( Z=-3.12, P=0.002). However, there was no statistically significant difference in the number of days required for the two groups of patients with baseline platelets <50×10 9/L to recover to 100×10 9/L or for the absolute value to increase by 50×10 9/L ( Z=-1.88, P=0.061). The total platelet elevation rate of rhTPO within 20 days of radiotherapy treatment for both groups of patients was 93.63% (191/204), of which 95.05% (96/101) was for radiotherapy alone and 92.23% (95/103) for concurrent chemoradiotherapy, with no statistically significant difference ( χ2=0.68, P=0.410). In addition, there was no statistically significant difference in gender ( χ2=3.47, P=0.063), age ( χ2=2.79, P=0.095), TNM staging ( χ2=5.07, P=0.167), and baseline platelet count ( χ2=0.62, P=0.822) between the two groups.During the radiotherapy cycle, 27 patients (13.23%) received blood platelet infusion, and 158 patients (77.45%) completed the radiotherapy plan without interruption. No rhTPO-related adverse reactions were found. Conclusion:rhTPO in the treatment for RIT can effectively promote the recovery of blood platelet without any adverse reactions, and has good safety.

Objective:To systematically evaluate the effect of bariatric and metabolic surgery on bone metabolism in obese patients.Methods:Search terms for the present meta-analysis included "bariatric surgery, metabolic surgery, sleeve gastrectomy, gastric bypass, bone metabolic indicators, bone mineral density", both in English and corresponding Chinese. PubMed, WOS, Cochrane, CNKI, and VIP databases were searched for longitudinal studies from the establishment of the database to September 20, 2022. The data on bone mineral density and bone metabolic markers in obese patients before and after bariatric surgery were extracted. RevMan5.4 and Stata17.0 software were used for Meta-analysis.Results:A total of 8 clinical studies with 420 patients were included. The results of the meta-analysis showed that compared with the preoperative baseline, lumbar spine bone mineral density ( WMD=0.05, 95% CI: -0.00~0.1), femoral neck bone mineral density( WMD=0.10, 95% CI: 0.05-0.15), hip bone mineral density( WMD=0.14, 95% CI: 0.10-0.17), and serum vitamin D 3 ( WMD=-4.87, 95% CI: -6.34--3.40)were decreased, while parathyroid hormone ( WMD=10.04, 95% CI: 5.32-14.76) was elevated after surgery. Conclusions:Current evidence demonstrates that metabolic and bariatric surgery can lead to decreased bone mineral density and impairs in bone metabolic markers early after surgery. Roux-en-Y gastric bypass surgery cause more adverse effects on bone metabolism than sleeve gastrectomy. The results imply that all patients undergoing metabolic and bariatric surgery should be monitored for bone metabolism and routinely take vitamin D and calcium supplements.

Objective:To analyze the incidence of gallstone formation after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) by meta-analysis.Methods:English terms for this meta-analysis included "bariatric surgery, gastric bypass, Roux-n-Y gastric bypass, RYGB, sleeve gastrectomy, SG, cholelithiasis, cholecystectomy, gallstone". Researched articles in Pubmed, Medline and Embase databases were searched up to February 2023 and retrieved for further analysis. The quality of each article was evaluated with Newcastle-Ottawa Scale (NOS). Generated data were analyzed with Revman 5.4.Results:Nine relevant cohort studies were retrieved for this meta-analysis, including a total of 24 255 RYGB patients and 4 500 SG patients. All articles met the requirements after the quality evaluation of NOS. The meta-analysis results showed that the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P<0.001). In subgroup analysis, by administering ursodeoxycholic acid (UDCA) for gallstone prevention, the incidence had no difference between the two groups ( P=0.090), while in the study without UDCA, the incidence of gallstones after RYGB was higher than SG ( P=0.005). In the studies with follow-up time no more than 24 months, the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P=0.050), but there was no statistical difference when following-up beyond 24 months ( P=0.240). Conclusions:Within 2 years after surgery, RYGB patients have more chances to develop gallstones than SG patients. However, beyond 2-year follow-up, there is no difference between the two procedures. Prophylactical utilization of UDCA after RYGB can effectively reduce the incidence of gallstone formation.