Objective To evaluate the feasibility and advantage of using withdrawable Sigma stent for the treatment of tracheo-esophageal fistular. Methods The stents were placed into trachea or/and esophagus by interventional or/and endoscopic technique. Results Esophageal cancerin 17 and benign disease in 2. Totally 38 stents were placed in 19 cases of patients (trachea 19, main bronchus 1, esophagus 18). Only one tracheal stent was placed in 2 cases. Two stents(one in trachea, another in esophagus) were placed in 15 cases ( 11 cases with 2 tubular type stent, 4 cases with one tubular and one bifurcated type stent). Three stents were placed in 2 cases. One stage placement of the stent in 35, withdrawed the stent and reinserted again in 3. All the patients have normal meal 2～4 days postoperatively. Only one patient had a little contrast in the trachea during X-ray exam but without symptoms, the fistulae completely sealed in 18 cases. Follow-up was fron 3 months to 3 year. 10 patients were still alive; the longest survival is 18 months. There were 9 deaths. The causes of death were pulmonary infection in 1, hemorrhage in 1, and systemic metastasis in 7 cases. Conclusion Sigma stent is can effectively treat tracheal or/and esophageal stenosis or fistular.

Objective To explore the effect of osthole on mast cells and expression of STAT5 gene and protein in them. Methods Passive cutaneous anaphylaxis was made in mice to copy eczema model, then the allergic mast cells were separated, and the ovalbumin was used to induce allergy of mast cells. Different concentrations of osthole were used to intervene the sensitized mast cells.Then the sensitized mast cells were divided into blank control group, osthole high-dose group and low-dose group.At the end of the experiment, morphology of the mast cells was detected by immunofluorescence technology.MTT assay was used to detect the influence of drugs on mast cells proliferation. RT-PCR and Western blotting were used to detect the expression of STAT5 gene and protein. Results As compared with blank control group, the number of mast cells in the osthole groups was significantly reduced, cells and nuclei obviously shrank, even apoptosis of some cells could be observed; the inhibition rate of mast cells in osthole groups was significantly increased in concentration-dependent manner ( P<0. 01 ) . As compared with blank control group (2.16±0.57), gene expression of STAT5 was significantly decreased in osthole high-dose group (0.59±0.12) and low-dose group (0.82±0.13) (P<0.01).The protein expression of STAT5 was also significantly decreased in osthole high-dose group and low-dose group as compared with blank control group (P<0.01). Conclusion Osthole can inhibit the proliferation of sensitized mast cells, and reduce the expression of STAT5 gene and protein.

Objective To investigate the effect of remimazolam on anesthetic effect and postoperative cognitive function during painless bronchoscopy in elderly patients.Methods A total of 90 patients with painless bronchoscopy admitted to Wenzhou People's Hospital were selected.And randomly dividing into 45 patients in control group,45 patients in observation group.The control group was given propofol,and the observation group was given remimazolam.Mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO2)were monitored.Effective time after induction,recovery time after withdrawal and discharge time were compared.Patient's cognitive function was assessed using the mini-mental state examination(MMSE),auditory word learning test(AVLT),shape connection test(STT),and animal language fluency test(AFT).Enzyme linked immunosorbent assay(ELISA)was used to determine substance P(SP),C-reactive protein(CRP),noradrenaline(NE),tumor necrosis factor-α(TNF-α)in serum,interleukin(IL)-6 and prostaglandin E2(PGE2)concentrations.Results Compared with the control group,the MAP of the observation group patients at time points T2 and T3 showed statistically significant differences(P<0.05);HR was especially significant at T2,T3 and T6 periods(P<0.05).SpO2 at T2 and T3(P<0.05).The awakening time,discharge time of the observation were shorter than control(P<0.05).At 1 day after surgery,the MMSE score,STT score,AFT score were significantly higher(P<0.05);The serum levels of SP,PGE2 and NE and IL-6,TNF-α and CRP were decreased in the control(P<0.05).The incidence of adverse reactions was 17.78％in control group and 8.89％in observation group(χ2=7.654,P=0.031).Conclusion Remazolam is used in painless bronchoscopy in elderly patients,intraoperative hemodynamics is stable,having little impact on postoperative cognitive function,and inhibits the release of inflammatory factors and the secretion of pain mediators,which is worthy of clinical use.

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.
Computational Biology ; Drugs, Chinese Herbal ; Humans ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Urinary Bladder Neoplasms/genetics*

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS There is a causal association and pleiotropic variants between GM and ICH.
Humans ; Genome-Wide Association Study ; Gastrointestinal Microbiome/genetics* ; Genetic Predisposition to Disease ; Cerebral Hemorrhage/genetics* ; Stroke

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.