Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

Ulcerative colitis （UC） is a chronic nonspecific inflammatory intestinal disease with a complex pathogenesis. Its recurrent attacks easily lead to persistent intestinal mucosal damage， resulting in a year-by-year increase in incidence and imposing a heavy burden on patients. Currently， the treatment of UC mainly relies on corticosteroids， immunosuppressants， and aminosalicylate preparations. However， these therapies are limited by significant side effects， strong drug resistance， and poor long-term prognosis. As one of the important inflammatory pathways， the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway can regulate the occurrence and development of UC through multiple pathways by modulating multiple downstream targets. Therefore， the JAK2/STAT3 signaling pathway offers a new research direction for the treatment of UC. Numerous studies have shown that the JAK2/STAT3 signaling pathway plays an important role in intestinal inflammatory responses， intestinal mucosal barrier damage， T helper cell 17 （Th17）/regulatory T cell （Treg） immune imbalance， intestinal epithelial cell apoptosis， and oxidative stress. Chinese medicine has attracted increasing attention because of its unique advantages， including fewer side effects， individualized diagnosis and treatment， and enhancement of efficacy with reduction of toxicity. In addition to traditional Chinese herbal formulas， more Chinese medicine monomers and extracts have played key roles because of their more precise therapeutic targets. In recent years， many studies have confirmed that Chinese medicine can exert therapeutic effects on UC by interfering with the JAK2/STAT3 signaling pathway， thereby alleviating intestinal inflammatory responses， repairing the intestinal mucosal barrier， regulating the balance of Th17/Treg immune cells， inhibiting intestinal epithelial cell apoptosis， and suppressing oxidative stress. This article summarizes and reviews recent research progress in this field from three aspects， including an overview of the JAK2/STAT3 signaling pathway， the relationship between the JAK2/STAT3 signaling pathway and UC， and the regulatory mechanisms of traditional Chinese medicine， with the aim of providing a theoretical basis for the future clinical treatment of UC and drug development.

AIM:To investigate the role and underlying mechanisms of NADPH oxidase 4(NOX4)/transient receptor potential channel subfamily C member 6(TRPC6)in the context of podocyte damage in diabetic nephropathya comprehensive investigative study was warranted.METHODS:(1)Male Sprague-Dawley rats were randomly divided in-to four distinct groups:a control group,a diabetic nephropathy group,a NOX4 inhibitor GKT137831-treated group,and a combined diabetic nephropathy with NOX4 inhibitor GKT137831-treated group,each consisting of 8～10 rats.The type 1 diabetes mellitus model was constructed via a single intraperitoneal injection of streptozotocin(STZ)(70 mg/kg),subse-quent to the successful induction of the model,GKT137831(at the dose of 5 mg/kg)was administered intraperitoneally.Regular monitoring of blood glucose levels was conducted,and urinary albumin excretion was quantified after 24 hours.Moreover,blood and kidney tissues were harvested for further analysis.(2)Mouse glomerular podocytes were divided into four distinct groups:a normal control group,a high glucose group,a GKT137831-treated group and a high glucose GKT137831-treated group.These podocytes were subsequently cultivated in vitro under high glucose conditions for 2 weeks.Thereafter,transfection of podocytes was carried out using NOX4 inhibitors and short interfering RNA targeting(siRNA)TRPC6.To detect the expression levels of NOX4 and TRPC6,a battery of techniques including Western blot,Immunohistochemistry,and reverse transcription polymerase chain reaction(RT-qPCR)were employed.(3)The morpho-logical changes of podocyte mitochondria under the condition of high glucose were observed by fluorescence confocal mi-croscopy,and the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α),mito-chondrial transcription factor A(TFAM),cytochromec oxidase subunit Ⅰ(COX Ⅰ)and cytochromec oxidase subunit Ⅳ(COX Ⅳ)in podocytes were assessed utilizing the Western blot technique.RESULTS:(1)Compared with normal con-trol group,mice with diabetic nephropathy manifested pronounced glomerular hypertrophy,thickening of basement mem-brane,expansion of the mesangial region,and an increased rate of urinary albumin excretion was observed.Analytical techniques such as Western blot and Immunohistochemistry showed a significant upsurge in the expression level of the NOX4 protein in kidney tissue,a diminished expression of glomerular podocyte protein(nephrin),an increased expression of interstitial cell markers(desmin),and an enhanced level of TRPC6 expression(P＜0.05).GKT137831 was assoiated with a reduction in desmin expression in renal tissue,preservation of glomerular nephrin expression,and a decrease in uri-nary albumin excretion(P＜0.05).(2)In vitro podocyte experiment,the expression of NOX4 and TRPC6 in podocyte was significantly increased in the context of high glucose(P＜0.05).Findings from Immunofluorescence and Western blot showed that GKT137831 effectively diminished the expression levels of TRPC6 and desmin while partially rescuing neph-rin expression in podocellular cells(P＜0.05).Western blot results showed that transfection of TRPC6 small interfering RNA could further promote the protective effect of GKT137831 on podiocytes.(3)Under high-glucose conditions,fluores-cence confocal microscopy revealed mitochondrial morphological damage in podocytes.However,therapeutic intervention with GKT137831 and transfection of TRPC6 siRNA partially rescued the mitochondrial structural integrity.Under high glucose conditions,immunoblot analysis demonstrated a marked decrement in the protein expression levels of PGC1α,TFAM,COX Ⅰ,and COX Ⅳ in podocytes.Importantly,GKT137831 and the transfection of TRPC6 siRNA significantly upregulated the levels of PGC1α,TFAM,COX Ⅰ,and COX Ⅳ(P＜0.05).CONCLUSION:In the context of the patho-genesis of diabetic nephropathy,the increased expression of NOX4 in the kidneys contributes to podocyte damage,with the effect being partially mediated via the TRPC6 channel.Inhibiting the NOX4-TRPC6 signaling pathway has the potential to ameliorate mitochondrial dysfunction in podocytes.This finding offers novel perspectives and strategies for the clinical di-agnosis and treatment of diabetic nephropathy.

AIM:To investigate the role and underlying mechanisms of NADPH oxidase 4(NOX4)/transient receptor potential channel subfamily C member 6(TRPC6)in the context of podocyte damage in diabetic nephropathya comprehensive investigative study was warranted.METHODS:(1)Male Sprague-Dawley rats were randomly divided in-to four distinct groups:a control group,a diabetic nephropathy group,a NOX4 inhibitor GKT137831-treated group,and a combined diabetic nephropathy with NOX4 inhibitor GKT137831-treated group,each consisting of 8～10 rats.The type 1 diabetes mellitus model was constructed via a single intraperitoneal injection of streptozotocin(STZ)(70 mg/kg),subse-quent to the successful induction of the model,GKT137831(at the dose of 5 mg/kg)was administered intraperitoneally.Regular monitoring of blood glucose levels was conducted,and urinary albumin excretion was quantified after 24 hours.Moreover,blood and kidney tissues were harvested for further analysis.(2)Mouse glomerular podocytes were divided into four distinct groups:a normal control group,a high glucose group,a GKT137831-treated group and a high glucose GKT137831-treated group.These podocytes were subsequently cultivated in vitro under high glucose conditions for 2 weeks.Thereafter,transfection of podocytes was carried out using NOX4 inhibitors and short interfering RNA targeting(siRNA)TRPC6.To detect the expression levels of NOX4 and TRPC6,a battery of techniques including Western blot,Immunohistochemistry,and reverse transcription polymerase chain reaction(RT-qPCR)were employed.(3)The morpho-logical changes of podocyte mitochondria under the condition of high glucose were observed by fluorescence confocal mi-croscopy,and the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α),mito-chondrial transcription factor A(TFAM),cytochromec oxidase subunit Ⅰ(COX Ⅰ)and cytochromec oxidase subunit Ⅳ(COX Ⅳ)in podocytes were assessed utilizing the Western blot technique.RESULTS:(1)Compared with normal con-trol group,mice with diabetic nephropathy manifested pronounced glomerular hypertrophy,thickening of basement mem-brane,expansion of the mesangial region,and an increased rate of urinary albumin excretion was observed.Analytical techniques such as Western blot and Immunohistochemistry showed a significant upsurge in the expression level of the NOX4 protein in kidney tissue,a diminished expression of glomerular podocyte protein(nephrin),an increased expression of interstitial cell markers(desmin),and an enhanced level of TRPC6 expression(P＜0.05).GKT137831 was assoiated with a reduction in desmin expression in renal tissue,preservation of glomerular nephrin expression,and a decrease in uri-nary albumin excretion(P＜0.05).(2)In vitro podocyte experiment,the expression of NOX4 and TRPC6 in podocyte was significantly increased in the context of high glucose(P＜0.05).Findings from Immunofluorescence and Western blot showed that GKT137831 effectively diminished the expression levels of TRPC6 and desmin while partially rescuing neph-rin expression in podocellular cells(P＜0.05).Western blot results showed that transfection of TRPC6 small interfering RNA could further promote the protective effect of GKT137831 on podiocytes.(3)Under high-glucose conditions,fluores-cence confocal microscopy revealed mitochondrial morphological damage in podocytes.However,therapeutic intervention with GKT137831 and transfection of TRPC6 siRNA partially rescued the mitochondrial structural integrity.Under high glucose conditions,immunoblot analysis demonstrated a marked decrement in the protein expression levels of PGC1α,TFAM,COX Ⅰ,and COX Ⅳ in podocytes.Importantly,GKT137831 and the transfection of TRPC6 siRNA significantly upregulated the levels of PGC1α,TFAM,COX Ⅰ,and COX Ⅳ(P＜0.05).CONCLUSION:In the context of the patho-genesis of diabetic nephropathy,the increased expression of NOX4 in the kidneys contributes to podocyte damage,with the effect being partially mediated via the TRPC6 channel.Inhibiting the NOX4-TRPC6 signaling pathway has the potential to ameliorate mitochondrial dysfunction in podocytes.This finding offers novel perspectives and strategies for the clinical di-agnosis and treatment of diabetic nephropathy.

Objective: To explore the clinical efficacy of Xiaoshuan enteric-coated capsule (XSECC) in treating cerebral infarction and its potential mechanism of action. Methods: Patients with acute ischemic stroke (AIS) of the qi deficiency and blood stasis type were randomly assigned to the control and observation groups. They were evaluated using the National Institutes of Health Stroke Scale (NIHSS), Activities of Daily Living (ADL), Hachinskilnchemic Scale (HIS), Barthel Index (BI), clinical efficacy scores, and TCM syndrome scores on days 0, 14, 30, and 90. Furthermore, VEGF and BDNF levels were measured on days 30 and 90. Finally, we analyzed the changes in each scale score and vascular neurological factor in both groups. Results: After 14 days of treatment, the difference values in NIHSS, ADL, and BI were higher, and TCM syndrome and clinical efficacy scores were increased in the observation group compared with those of the control group (all P < .05). After 30 days, the NIHSS, ADL, HIS, and TCM syndrome scores were decreased compared with those of the control group, while BI and clinical efficacy scores were increased (all P < .05). After 90 days, the difference value in ADL was higher, and TCM syndrome score was increased in the observation group compared with that of the control group (P = .047, P = .005, respectively). The levels of VEGF and BDNF were higher in the observation group than in the control group on days 14, 30, and 90 (all P < .05). VEGF and BDNF levels on day 0 were associated with prognosis of patients with AIS; therefore, they have a predictive value for the prognosis of acute cerebral infarction. Conclusions XSECC therapy can improve clinical outcomes in patients with acute and recurrent cerebral infarctions. Its mechanism of action may be associated with the secretion of VEGF and BDNF.

OBJECTIVE To establis h and validate a population pharmacokinetic model of docetaxel in malignant tumor patients. METHODS The clinical data of malignant tumor patients treated with chemotherapy regimen containing docetaxel in our hospital from June 2019 to December 2021 were retrospectively collected . According to the results of blood concentration detection ， based on the three -compartment model the nonlinear mixed effect model （NONMEM）was used ；covariates（age，weight，height， body surface area ，Karnofsky performance scale ，total protein ，albumin，total bilirubin ，aspartate aminotransferase ，alanine aminotransferase and serum creatinine ）affecting clearance （CL）were screened by “forward inclusion and backward exclusion ”； the population pharmacokinetic model of docetaxel was established . The model was tested for goodness -of-fit diagnosis and internal validation by Bootstrap . RESULTS A total of 264 measured blood concentrations of 132 patients with malignant tumors during chemotherapy were included . The covariates that had significant effect on CL of docetaxel were serum creatinine and total bilirubin （P＜0.01）. The results of Bootstrap analysis （parameter median values and 95% confidence intervals ）were close to predict results of the established model ；the final model estimated that the population typical value of docetaxel CL was 37.82 L/h. CONCLUSIONS The population pharmacokinetic model of docetaxel in malignant tumor patients is established successfully ， which can be used for the formulation and optimization of clinical individualized regimen .

Hyperoxia is very common in critical patients, which causes varying degrees of pathophysiological damage. Hyperoxia is one of the main reasons for increasing mortality, prolonged hospital stay and poor prognosis of critical patients. Therefore, it is critical to carry out the standardized oxygen therapy. In this paper, we discussed the harmful effects of hyperoxemia to critically ill patients by reviewing the effect of hyperoxemia on cardiovascular and cerebrovascular, hyperoxia-induced lung injury, and the association of hyperoxemia with ventilator-associated pneumonia (VAP) and acute renal kidney injury (AKI). Meanwhile, we provided some management suggestions about standardized clinical oxygen therapy, oxygen therapy related research and clinical management of oxygen therapy, aimed at providing reference and research direction for standardizing clinical oxygenation process, reducing the occurrence of hyperoxemia, and making reasonable method for hyperoxemia prevention.

Objective:To investigate the risk factors of non-obstructive gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliopancreatic disease.Methods:The matched case-control study included 109 patients with non-obstructive gastric retention before ERCP as the case group, and 218 patients without gastric retention as the control group. The patients′ medical records including comorbidities, preoperative medication and laboratory indicators were compared between the two groups. Multivariate conditional logistic regression models were subsequently used to determine the risk factors for non-obstructive gastric retention before ERCP.Results:Logistic regression revealed that the jaundice ( OR=12.359, P<0.001), opiates use ( OR=3.009, P=0.001), somatostatin use ( OR=2.445, P=0.033), fasting hyperglycemia ( OR=1.513, P=0.045), hypokalemia ( OR=4.634, P=0.001) and hyponatremia ( OR=1.805, P=0.023) were independent risk factors for non-obstructive gastric retention before ERCP in patients with biliopancreatic disease. Conclusion:Except for gastrointestinal obstruction, jaundice, opiates use, somatostatin use, fasting hyperglycemia, hypokalemia and hyponatremia are all risk factors for gastric retention in patients with biliopancreatic disease. Comprehensive evaluation and early intervention for patients showing these risk factors are needed.

This paper summarized nursing points for caring 12 cases undergoing endoscopic ultrasonography guided biliary drainage(EUS-BD) in the treatment of malignant obstructive jaundice.All patients received EUS-BD after unsuccessful endoscopic retrograde cholangiopancreatography,including 5 patients undergoing EUS guided hepaticogastrostomy(EUS-HGS) and 7 patients undergoing EUS guided choledochoduodenostomy(EUS-CDS).Nursing points included:preoperative assessment,psychological care,preoperative gastrointestinal preparation,intraoperative cardiopulmonary function monitoring,collaboration in operation,postoperative monitoring,observation and nursing care for complications such as bleeding,bile leakage and the others.The average hospital stay was 10～16 d.Two patients developed complications(16.67％).A patient undergoing EUS-HGS developed bile leakage,biliary peritonitis,and pneumoperitoneum after the procedure,but was successfully recovered by placement of a second fully covered self-expendable metal stent in the primary metal stent,percutaneous abdominal drainage and antibiotic treatment.A patient undergoing EUS-CDS developed gastrointestinal bleeding,and was successfully treated with radiological intervention.

Objective To analyze the efficacy of endoscopic ultrasonography-guided biliary drainage ( EUS-BD) for malignant obstructive jaundice and the management of adverse events. Methods Clinical data of 12 patients with malignant obstructive jaundice, who underwent EUS-BD between April 2016 and January 2017, were retrospectively analyzed. All patients received EUS-BD after unsuccessful ERCP, including EUS-guided hepaticogastrostomy ( EUS-HGS ) , EUS-guided antegrade stenting ( EUS-AS ) , and EUS-guided choledochoduodenostomy(EUS-CDS). Procedure outcomes, serum bilirubin and liver enzyme levels before the procedure and 1 week after, complications, treatment results, hospitalization time and follow-up were recorded. Results Two patients underwent EUS-HGS, 3 underwent EUS-AS, and 7 underwent EUS-CDS. Total bilirubin ( t=3. 462, P=0. 005 ) , direct bilirubin ( t=3. 351, P=0. 006 ) , alanine transaminase (t=2. 399, P=0. 037), γ-glutamate transpeptidase (t=3. 256, P=0. 031) reduced significantly after the procedure. Two patients ( 16. 67％) developed complications. A patient undergoing EUS-HGS developed bile leakage, biliary peritonitis, and pneumoperitoneum. A patient undergoing EUS-CDS developed upper gastrointestinal bleeding. Both patients were successfully treated. There were no other adverse events, such as acute pancreatitis, subcutaneous emphysema, pneumothorax and emphysema. No procedure-related death occurred. The mean hospital stay was 13. 75 ± 6. 92 days ( range 5-26 days ) . Conclusion EUS-BD is a safe substitute after unsuccessful ERCP when performed by experienced biliary endoscopists. However, intensive care is necessary after the procedure for early detection and management of complications.