ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus （T2DM）， and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were randomly assigned to the model group， metformin group， and low-， medium-， and high-dose Jiangtang No. 3 prescription groups， and a normal group was also set. Daily gavage was administered for 8 weeks as follows： metformin at 0.1 g·kg^-1·d^-1， Jiangtang No. 3 prescription granules at 1.62， 3.24， 6.48 g·kg^-1·d^-1 for the respective dose groups， and sterile water for the normal and model groups. Rat body weight， fasting blood glucose （FBG）， oral glucose tolerance test （OGTT）， and insulin tolerance test （ITT） were measured. After drug intervention， enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL）， high-density lipoprotein cholesterol （HDL）， non-esterified fatty acids （NEFA）， interleukin （IL）-1β， IL-18， and insulin （INS）. Hematoxylin-eosin （HE） staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， NOD-like receptor protein 3 （NLRP3）， Caspase-1， IL-1β， IL-18， and gasdermin D （GSDMD） in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group， Jiangtang No. 3 prescription groups exhibited significantly increased body weight （P<0.05， P<0.01）， significantly reduced FBG （P<0.05， P<0.01）， significant reductions in TC， TG， NEFA， and LDL （P<0.05， P<0.01）， and a significant increase in HDL （P<0.01）. Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased （P<0.01）， the homeostatic model assessment of insulin resistance （HOMA-IR） index was significantly reduced （P<0.05， P<0.01）， and adipose tissue pathology was improved. The protein expression levels of TLR4， NF-κB， NLRP3， Caspase-1， IL-1β， IL-18， and GSDMD were markedly decreased （P<0.05， P<0.01）， and the mRNA expression levels of these indicators were also significantly downregulated （P<0.05， P<0.01）. Some effects were superior to those of the positive control drug metformin， and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses， disordered glucose and lipid metabolism， and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators， improves glucose and lipid metabolism and insulin resistance， and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue， thereby influencing downstream inflammatory mediators.

Objective To investigate the therapeutic effects of varying treatment durations of recombinant human brain natriuretic peptide(rhBNP)on heart failure following percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 196 STEMI patients with heart failure(HF)following emergency percutaneous coronary intervention(PCI)were enrolled and randomly assigned to one of four groups:control group(n=53),short-course rhBNP group(n=47),medium-course rhBNP group(n=50),and long-course rhBNP group(n=46).The rates of cardiovascular mortality and HF-related rehospitalization were evaluated at 30 days and 6 months post-treatment.Serum levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP),matrix metalloproteinase-9(MMP-9),tissue inhibitor of matrix metalloproteinase-1(TIMP-1),left ventricular end-diastolic diameter(LVEDD),and left ventricular ejection fraction(LVEF)were measured at 24 hours,3 days,1 week,30 days,and 6 months after HF treatment initiation.Results Compared with the control group,both the short-and medium-term rhBNP groups showed a significant reduction in cardiovascular mortality and HF-related rehospitalization rates in the long-term rhBNP group at 30 days and 6 months(P<0.05).Additionally,the medium-term rhBNP group exhibited lower HF-related rehospitalization rates than both the control and short-term rhBNP groups(P<0.05).Serum levels of NT-proBNP,MMP-9,and LVEDD significantly decreased in the short-term rhBNP group within 24 hours compared to the control group(P<0.05),while TIMP and LVEF levels increased(P<0.05).In comparison with the short-term rhBNP group,the medium-term rhBNP group demonstrated sustained reductions in NT-proBNP,MMP-9,and LVEDD levels at 72 hours,1 week,30 days,and 6 months(P<0.05),accompanied by increases in TIMP and LVEF(P<0.05).Furthermore,the long-term rhBNP group showed greater improvements than the medium-term group,with significantly lower NT-proBNP,MMP-9,and LVEDD levels and higher TIMP and LVEF values at 1 week,30 days,and 6 months(P<0.05).In terms of the adverse reactions,the incidence of hypotension in the control group,short course rhBNP group,medium course rhBNP group and long course rhBNP group increased successively(P<0.05).Conclusion The clinical efficacy of rhBNP in STEMI patients with HF following PCI gradually improved as the treatment duration increased,but the incidence of hypotension also rose accordingly.

Multiple sclerosis(MS)is a complex autoimmune disorder characterized by inflammatory demyelination in the central nervous system.Prominent symptoms include damage to myelin sheaths in the brain,optic nerve,and spinal cord,as well as axonal dysfunction;however,the exact causes and mechanisms of MS remain unclear.Genetic and environmental factors are thought to interact via autoimmune mechanisms,potentially triggering the disease.Recent studies suggest that abnormal activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play a critical role in the pathogenesis of MS.In this context,this review summarizes the molecular mechanisms underlying NLRP3 activation and its connection to MS,considering relevant literature from the past decade.The findings aim to provide insights into the progression of MS and to identify potential therapeutic strategies by elucidating the underlying mechanisms.

Objective To investigate the therapeutic effects of varying treatment durations of recombinant human brain natriuretic peptide(rhBNP)on heart failure following percutaneous coronary intervention(PCI)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 196 STEMI patients with heart failure(HF)following emergency percutaneous coronary intervention(PCI)were enrolled and randomly assigned to one of four groups:control group(n=53),short-course rhBNP group(n=47),medium-course rhBNP group(n=50),and long-course rhBNP group(n=46).The rates of cardiovascular mortality and HF-related rehospitalization were evaluated at 30 days and 6 months post-treatment.Serum levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP),matrix metalloproteinase-9(MMP-9),tissue inhibitor of matrix metalloproteinase-1(TIMP-1),left ventricular end-diastolic diameter(LVEDD),and left ventricular ejection fraction(LVEF)were measured at 24 hours,3 days,1 week,30 days,and 6 months after HF treatment initiation.Results Compared with the control group,both the short-and medium-term rhBNP groups showed a significant reduction in cardiovascular mortality and HF-related rehospitalization rates in the long-term rhBNP group at 30 days and 6 months(P<0.05).Additionally,the medium-term rhBNP group exhibited lower HF-related rehospitalization rates than both the control and short-term rhBNP groups(P<0.05).Serum levels of NT-proBNP,MMP-9,and LVEDD significantly decreased in the short-term rhBNP group within 24 hours compared to the control group(P<0.05),while TIMP and LVEF levels increased(P<0.05).In comparison with the short-term rhBNP group,the medium-term rhBNP group demonstrated sustained reductions in NT-proBNP,MMP-9,and LVEDD levels at 72 hours,1 week,30 days,and 6 months(P<0.05),accompanied by increases in TIMP and LVEF(P<0.05).Furthermore,the long-term rhBNP group showed greater improvements than the medium-term group,with significantly lower NT-proBNP,MMP-9,and LVEDD levels and higher TIMP and LVEF values at 1 week,30 days,and 6 months(P<0.05).In terms of the adverse reactions,the incidence of hypotension in the control group,short course rhBNP group,medium course rhBNP group and long course rhBNP group increased successively(P<0.05).Conclusion The clinical efficacy of rhBNP in STEMI patients with HF following PCI gradually improved as the treatment duration increased,but the incidence of hypotension also rose accordingly.

Multiple sclerosis(MS)is a complex autoimmune disorder characterized by inflammatory demyelination in the central nervous system.Prominent symptoms include damage to myelin sheaths in the brain,optic nerve,and spinal cord,as well as axonal dysfunction;however,the exact causes and mechanisms of MS remain unclear.Genetic and environmental factors are thought to interact via autoimmune mechanisms,potentially triggering the disease.Recent studies suggest that abnormal activation of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome may play a critical role in the pathogenesis of MS.In this context,this review summarizes the molecular mechanisms underlying NLRP3 activation and its connection to MS,considering relevant literature from the past decade.The findings aim to provide insights into the progression of MS and to identify potential therapeutic strategies by elucidating the underlying mechanisms.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of semaglutide in the treatment of type 2 diabetes mellitus （T2DM）， and to provide reference for clinical drug use. METHODS Rapid health technology assessment was adopted. Retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， Wanfang database， CBM， domestic and foreign HTA official websites， HTA reports， systematic evaluation/meta-analysis and pharmacoeconomic studies about semaglutide in the treatment of T2DM were collected during the inception to May 1st， 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of included studies. RESULTS A total of 22 pieces of literature were included， involving 7 meta-analyses and 15 pharmacoeconomic studies. In terms of efficacy and safety， semaglutide showed significant advantages in controlling glycated hemoglobin （HbA1c）， fasting blood glucose， postprandial mean glucose， body mass index and achieving a target of glycosylated hemoglobin level ＜7%； also， there was no increased risk of hypoglycaemia or the incidence of serious adverse effects， but the risk of gastrointestinal adverse effects was significantly higher than other interventions. In terms of cost-effectiveness， results of foreign studies showed that semaglutide was more cost-effective， compared with other glucagon-like peptide-1 receptor agonists， sodium-glucose transporter protein 2 inhibitors， dipeptidyl peptidase-4 inhibitors. Research based on the perspective of China’s health system showed that semaglutide had a clear cost-effectiveness advantage over dulaglutide when using GDP per capita in 2020 （72477 yuan） as the payment threshold. CONCLUSIONS The semaglutide has excellent efficacy and good safety for the treatment of T2DM， with cost-effectiveness advantages over a number of drugs， but attention should be paid to the occurrence of gastrointestinal adverse effects.

Objective:To predict the possible targets and signaling pathways of Jiangtang Xiaoke Granules in the treatment of diabetes mellitus (DM) using computer network pharmacology and molecular docking technology.Methods:The active components and targets of Jiangtang Xiaoke Granules were collected by ETCM; the targets of DM were searched from the databases of DisGeNET and GeneCards, and the intersections of the two were taken to draw a Venny diagram; String database was used for gene transformation and network interaction analysis; the network diagram was constructed with Cytoscape3.6.0; the predicted results were supported by molecular docking technology; GO and KEGG analysis was performed through Metascape database.Results:A total of 128 active components of Jiangtang Xiaoke Granules were screened, with 607 corresponding targets, 1 240 DM related targets, and 53 core targets. Molecular docking showed that the active components had good binding energy with the core targets. GO analysis yielded 46 functional items and KEGG analysis yielded 15 pathways.Conclusion:Jiangtang Xiaoke Granules regulate glucose homeostasis by participating in a variety of biological processes through multiple components, and multiple targets, including affecting lipids and atherosclerosis, Alzheimer disease, AMPK signaling pathway, Apelin signaling pathway, and glucagon signaling pathway.

We reported a patient intubated for more than 30 d following brain injury, transferred to our department with tracheocutaneous fistula and a 2 cm fistula between the trachea and the esophagus. We performed tracheal resection and esophageal closure with a latissimus dorsi myocutaneous flap interposed between suture lines. The patient continued mechanical ventilation after surgery and the tracheotomy was achieved 14 d after the beginning of surgical treatment. The patient was started oral feeding and discharged on the 10 d after tracheotomy and referred to a neuromotor recovery clinic for treatment of post-traumatic sequelae.

Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia (CML). Chemical degradation of Bcr-Abl

[摘 要] 目的：观察miR-26b-3p在食管鳞状细胞癌（ESCC）组织中的表达水平及其对ESCC细胞增殖、侵袭和迁移能力的影响，并探讨其分子调控机制。方法: 选取河北医科大学第四医院2018年4月1日至2018年12月25日手术切除的ESCC组织及相应癌旁组织各60例，利用qPCR法检测ESCC组织、癌旁组织和ESCC细胞中miR-26b-3p的表达。选取miR-26b-3p表达水平较低的ESCC细胞TE1和KYSE150，转染miR-26b-3p mimic，并设立阴性对照。利用细胞增殖实验、划痕愈合实验和Transwell实验检测过表达miR-26b-3p对TE1和KYSE150细胞增殖、迁移和侵袭能力的影响。荧光素酶报告基因实验检测miR-26b-3p与STAT3的3'UTR靶点部位的结合情况。随后同时转染miR-26b-3p mimic和pcDNA3.0-STAT3，利用细胞增殖实验、划痕愈合实验和Transwell实验检测STAT3是否可逆转过表达miR-26b-3p对细胞增殖、迁移和侵袭能力的影响。qPCR和WB法检测甲基化酶抑制剂5-Aza-DC对ESCC细胞甲基化的影响和miR-26b-3p与STAT3表达的影响。结果: miR-26b-3p在ESCC组织中的表达低于癌旁组织（P<0.01），其在ESCC细胞TE1、KYSE150和LYSE170中表达水平显著低于人正常食管上皮细胞HEEC（均P<0.01）。与miR-26b-3p NC组相比，miR-26b-3p mimic转染可明显上调TE1和KYSE150细胞中miR-26b-3p的表达（均P<0.01），但可明显抑制两种细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01）。荧光素酶报告基因实验结果表明，在TE1和KYSE150细胞中，miR-26b-3p明显抑制了野生型STAT3载体的荧光素酶活性（P<0.05或P<0.01），而突变型的荧光素酶活性不受影响。同时转染miR-26b-3p mimic和pcDNA3.0-STAT3可部分逆转miR-26b-3p mimic对TE1和KYSE150细胞增殖、迁移和侵袭能力的抑制作用（P<0.05或P<0.01）。5-Aza-DC处理后，TE1和KYSE150细胞中miR-26b-3p表达上调（均P<0.01）、STAT3 mRNA和蛋白水平降低（P<0.05），miR-26b-3p呈现去甲基化状态。结论: miR-26b-3p的启动子高甲基化导致其在ESCC组织和细胞中的表达下调，其作为抑癌因子可通过靶向STAT3而抑制ESCC细胞的增殖、侵袭和迁移能力。