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Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Proteins are fundamental carriers as the structural elements and biochemically active entities responsible for catalysis, transport, and regulation. These functions are depending on the protein folding into precise three-dimensional structures, interacting with ligands, and conformational changes. This article reviews the recent progress of nanopores in single-molecule protein sensing, involving the identification of polypeptides and proteins, the conformation changes of protein folding, the molecular structure responsible to the pH of solutions, the molecular interactions, and protein sequencing. These studies provide clues to understand life activities and facilitate the early diagnosis of diseases and design of drugs for precise treatment.
Nanopores ; Proteins/chemistry* ; Biosensing Techniques/methods* ; Protein Folding ; Humans

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 brain metastasis (BM) prediction model for limited-stage small cell lung cancer (LS-SCLC) patients who achieved complete response (CR) or partial response (PR) after thoracic chemoradiotherapy, and to explore the value of prophylactic cranial irradiation (PCI) in different risk groups.Methods:Clinical data of 274 patients with LS-SCLC who achieved CR/PR after thoracic chemoradiotherapy in Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2021 were retrospectively analyzed, including 144 cases in the PCI group and 130 in the non-PCI group. The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. The bootstrap method, receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA) were employed to evaluate the predictive power and clinical benefits of the model. Patients were stratified into high- and low-risk groups based on risk scores. The brain metastases-free survival (BMFS), progression-free survival (PFS), extracranial progression-free survival (ePFS) and overall survival (OS) were compared between patients with and without PCI in different risk-stratified populations using the log-rank test.Results:The nomogram included five variables: systemic immune inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), pro-gastrin-releasing peptide precursor (ProGRP), neuron-specific enolase (NSE), and blood calcium. The area under the ROC curve (AUC) of the nomogram in predicting 1- and 2-year BMFS was 0.761 and 0.822. In the low-risk group, there was no significant difference in the BMFS ( P=0.374), PFS ( P=0.551), ePFS ( P=0.508) and OS ( P=0.767) between the PCI and non-PCI groups. In the high-risk group, PCI could significantly increase the BMFS ( P<0.001) and PFS ( P=0.022), while there was no significant difference in the ePFS ( P=0.963) and OS ( P=0.632). And propensity score-matching (PSM) analysis showed similar results. Conclusions:PCI does not improve OS in LS-SCLC patients regardless of high or low risk of BM. However, PCI significantly prolong the BMFS and PFS in patients at a high risk of BM.

Objective To investigate the effect of interleukin-9(IL-9)on the growth of lung adenocarcinoma in mice and its possible mechanism of action.Methods Mouse lung adenocarcinoma CMT167 cells were inoculated subcutaneously in BALB/C mice to construct a subcutaneous transplantation tumor model of mouse lung adenocarcinoma and to observe the effect of IL-9 on the growth of mouse tumors.Flow cytometry(FCM)and Western blot(WB)were used to detect the expression of IL-9 recep-tor(IL-9R)in mouse lung adenocarcinoma CMT167 cells.CMT167 cells were treated with different concentrations of IL-9 in vitro,and changes in cell viability and apoptosis were observed at different time points.Changes in the percentages of myeloid-derived immunosuppressive cells(MDSCs),CD4+T cells,and CD8+T cells in the tumor tissues of mice were analyzed by using FCM.Results Compared with mice in control group,the growth of mouse lung subcutaneous graft tumors was significantly in-hibited,and the weight of graft tumor was reduced after IL-9 treatment(both P＜0.01).Compared with the control group,the expression of IL-9R in mouse lung adenocarcinoma CMT167 cells was significantly increased(P＜0.01).After treatment with different concentrations of IL-9 in vitro,there were no significant changes in the viability and apoptosis of mouse lung adenocar-cinoma CMT167 cells compared to the control group.The number of MDSCs in mouse tumor tissues was decreased after IL-9 treatment(P＜0.05),while proportions of CD4+T cells and CD8+T cells in tumor tissues were increased(P＜0.01).Conclu-sion IL-9Reduces the number of MDSCs and increases the proportions of CD4+T cells and CD8+T cells in mouse tumor tis-sues,therefore inhibits the growth of lung adenocarcinoma tumors in mice.

Objective To investigate the effect of visceral fat area (VFA) on perioperative related indi-cators and short-term prognosis of patients with colorectal cancer (CRC).Methods Clinical data of 102 pa-tients who underwent laparoscopic radical surgery for CRC in the First Affiliated Hospital of Baotou Medical College from September 2020 to August 2023 were retrospectively analyzed.All patients underwent preopera-tive abdominal CT examination,and the transverse CT images at the level of the third lumbar vertebra (L3) were selected.VFA was measured using Slice-O-Matic software,and patients were divided into the high VFA group (VFA≥100 cm2) and the low VFA group (VFA<100 cm2) based on the measurement results.Clinical data,patho-logical data,surgical data,postoperative complications,and perioperative coagulation and inflammation indicators were collected.Results Compared with the low VFA group,the high VFA group had higher BMI,longer hospital stay,greater intraoperative blood loss,and fewer lymph node dissections (P<0.05).The WBC and PCT lev-els before and after surgery in the high VFA group were higher than those in the low VFA group (P<0.05). Compared with preoperative levels,WBC,C-reactive protein (CRP),PCT,plasma prothrombin time (PT), plasma fibrinogen (FIB),and international standardized ratio (INR) increased and PLT decreased in both groups after surgery,the differences were statistically significance (P<0.05);Compared with preoperative conditions,the activated partial prothrombin time (APTT) in the high VFA group and the thrombin time (TT) decreased in the low VFA group decreased after surgery,the differences were statistically significant (P<0.05).The total incidence of postoperative complications (21.2％) and the incidence of incision compli-cations (15.4％) in the high VFA group were higher than that in the low VFA group (4.0％,2.0％),the differences were statistically significant (P<0.05).Conclusion Colorectal cancer patients with high VFA during the perioperative period exhibit higher levels of inflammation indicators and poorer prognosis.

Persistent pulmonary hypertension of the newborn (PPHN) is a common and critical disease in the neonatus characterized by persistent pulmonary hypertension and hypoxemia, with a high mortality.Except for intubation and ventilator support, recognized treatments often require the application of pulmonary vasodilators drugs, such as inhaled nitric oxide, Sildenafil, etc, each with its own advantages.In recent years, L-citrulline, as a potential therapeutic option, has shown huge potential in PPHN treatment.The purpose of this review is to explore the possible potential of L-citrulline in the treatment of PPHN in terms of therapeutic mechanism, pharmacokinetics, current status of research and future perspectives.

Objective:To predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer based on preoperative inflammatory and immune nutritional indicators,and to construct a nomo-gram prediction model,providing a basis and tool for preoperative diagnosis of lymph node metastasis in cervical cancer.Methods:A retrospective analysis was conducted on the clinical data of 307 patients preoperatively diag-nosed with early-stage cervical cancer who underwent surgical treatment at the Obstetrics and Gynecology De-partment of the Second Affiliated Hospital of Zhengzhou University from January 2018 to July 2023.R software was used to randomize the groups into a training set(n=231)and a validation set(n=76)in a 3∶1 ratio.Uni-variate and multivariate logistic regression analyses were employed to identify factors influencing lymph node me-tastasis in patients preoperatively diagnosed with early-stage cervical cancer.R software was used to establish a nomogram prediction model and draw receiver operating characteristic(ROC)curves and calibration curves for validation.Results:① The results of univariate logistic regression analysis showed that positive lymphovascular invasion,platelet-to-lymphocyte ratio(PLR)≥151.70,neutrophil-to-white blood cell ratio(NWR)≥0.65,plate-let-to-albumin ratio(PAR)≥ 4.94,preoperative systemic immune-inflammation index(SII)≥604.03,and sys-temic inflammatory response index(SIRI)≥ 1.05 were associated with lymph node metastasis(P＜0.05).②Multivariate logistic regression analysis found that positive lymphovascular invasion,NWR≥0.65,and PAR≥4.94 were independent risk factors for lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer(OR＞1,P＜0.05).③ A nomogram was constructed to predict lymph node metastasis in patients preoperatively diagnosed with early-stage cervical cancer.The ROC curve shows an area under the train-ing set curve(AUC)of 0.821 and a validation set AUC of 0.858.The calibration curve shows an average abso-lute error of 0.024 for the training set and 0.059 for the validation set.Conclusions:The prediction model for lymph node metastasis in cervical cancer constructed using preoperative inflammatory and immune nutritional indi-cators such as NWR,PAR is helpful for gynecological oncologists to predict lymph node metastasis in cervical cancer patients before surgery.

Objective:To clarify the effect of the reform of Sichuan medical association on the coordinated development of medical re-sources supply and regional economy,and provide a basis for continuing to promote the coordinated development.Methods:Based on the panel data of 18 prefecture-level cities and 3 autonomous prefectures in Sichuan Province from 2009 to 2021,the medical resources invest-ment and economic development level of each city(state)in Sichuan Province were calculated by entropy weight method.Through the cou-pled coordination model,the degree of coordinated development was measured.The discontinuous time series model is used to measure the impact of the implementation of the medical association policy on the degree of coordinated development.Results:From 2009 to 2021,the supply of medical resources in Sichuan Province showed an overall upward trend,but the characteristics of the first concentration were ob-vious.In 2021,the coupling degree between medical resources investment and economic development in Sichuan Province is high(0.808),but the coupling coordination degree was still in a barely coordinated stage(0.540).The implementation of the reform of medical associa-tion effectively promoted the coordinated development of medical resource supply and regional economy.Conclusion:Local governments need to further strengthen the building of medical associations.By making long-term medical resources planning and exploring the role of digital technology in the medical field,it will further promote the expansion and balanced distribution of high-quality medical resources.