Objective To explore the types of symptom clusters in patients with bladder instillation and identify the core symptoms through symptom network analysis,and to provide evidence for symptom management of the patients.Methods Convenience sampling was used to select 226 patients with bladder instillation for bladder cancer at a Tier-IIIA hospital in Guiyang from March 2023 to July 2024.Data were collected through review of medical record,general information questionnaires and symptom assessment questionnaires specific to the patients with bladder instillation.Exploratory factor analysis was used to extract symptom clusters,and symptom relationships were analysed using R language for network layout and centrality calculations.Results A total of 223 patients with bladder cancer completed the survey.Four symptom clusters were identified,namely the urinary system symptom cluster,digestive system symptom cluster,somatic symptom cluster and psychological symptom cluster,with a cumulative variance contribution rate of 66.038%.The symptom network analysis showed strong associations between dysuria and urethral pain during catheterisation,incomplete emptying and dysuria,as well as distress and poor sleep quality.In terms of centrality indicators,the top three symptoms by strength were dysuria(rS=2.26),incomplete emptying(rS=0.99)and poor sleep quality(rS=0.90).Of the expected impacts,the top three were dysuria(rE=2.09),poor sleep quality(rE=1.34)and frequency of urinary(rE=0.55).Regarding the closeness centrality,the top three were dysuria(rC=2.23),incomplete emptying(rC=0.64)and poor sleep quality(rC=0.54).Dysuria had the highest strength,expected impact and closeness centrality,indicating the dysuria was the core symptom in the patients with bladder cancer.Conclusion For the patients with bladder instillation experience,multiple and interconnected symptoms appear at the same time and together they form a symptom clusters,of which the pain in urination is the core symptom.Medical staff should consider symptom prevalence and core symptoms and to develop the targeted and precise management strategies for targeted nursing.

Objective:To explore the effects and possible mechanism of intestinal microbiota on lung injury in mice with acute necrotizing pancreatitis (ANP).Methods:The experimental mice were randomly assigned to normal control group (CON group), ANP model group (ANP group) and intestinal germ-free group (ABX group), with 6 mice in each group. The ANP mouse model was constructed by intraperitoneal injection of caerulein (100 μg/kg, for 10 times) at an interval of 1 hour each time, followed by 10 mg/kg lipopolysaccharide injection. Mice in ABX group were treated by Abx solution (0.5 g/L vancomycin, 1 g/L neomycin, 1 g/L metronidazole, and 1 g/L ampicillin), 1 ml/100 g gavage for 28 days before preparation of the ANP model. The CON group was injected intraperitoneally with an equal volume of PBS. Histopathologic examination of the pancreas, lungs, and terminal ileum was routinely performed. Serum amylase levels were measured using enzymatic kinetic chemistry, and serum diamine oxidase (DAO) and lung tissue myeloperoxidase (MPO) activities were measured using ELISA assay. Expression of inflammatory factors, pyroptosis-related molecules in lung tissue and intestinal epithelial tight junction proteins was detected by fluorescence quantitative PCR. Western blotting was used to detect the expression of the pyroptosis molecules caspase-1 and GSDMD in lung tissue, and intestinal epithelial tight junction proteins. Changes of bacterial distribution in lung tissue were measured by fluorescence in situ hybridization. Results:The pathological scores of pancreatic tissue of CON, ANP, and ABX group were (0.67±0.26), (7.33±0.82), and (5.67±0.81); the pathological scores of lung tissue were (1.67±0.41), (5.67±0.41), and (3.58±0.58); the pathological scores of ileal tissue were (0.58±0.52), (3.83±0.75), and (4.33±0.82); the serum amylase levels were (403.95±93.11), (1037.24±126.77), and (647.32±145.90)U/L; the MPO levels in lung tissue were (0.23±0.03), (0.63±0.09), and (0.48±0.05)U/g. ABX group had significantly lower scores in pancreatic and lung tissues, serum amylase levels, and MPO levels in lung tissue compared to ANP group, and all the differences were statistically significant (all P value <0.05). The expression level in pancreatis tissue from CON, ANP and ABX group of IL-1β mRNA was 1.84±0.90, 36.26±5.56 and 16.65±6.43, IL-6 mRNA was 1.07±0.15, 2.90±0.42 and 1.34±0.62, TNF-α mRNA was 0.47±0.11, 0.76±0.11 and 0.46±0.07, HMGB1 mRNA was 0.38±0.02, 0.72±0.22 and 0.44±0.08, caspase-1 mRNA was 1.07±0.18, 2.04±0.31 and 0.85±0.54, ASC mRNA was 1.24±0.19, 5.68±0.41 and 3.89±1.47, GSDMD mRNA was 0.79±0.17, 0.94±0.14 and 0.61±0.08, IL-18 mRNA was 0.83±0.27, 4.17±0.79 and 3.57±0.03, respectively. The expression of IL-1β, IL-6, TNF-α, HMGB1, caspase-1, ASC, and IL-18 mRNA in lung tissue was significantly increased in ANP group compared to the CON group; conversely, ABX group showed a significant decrease in the expression of these markers compared to ANP group; and all the differences were statistically significant (all P values <0.05). The protein level of caspase-1 in lung tissue of CON, ANP and ABX group was 1.59±0.51, 2.28±0.13, 1.38±0.47, and that of GSDMD was 1.90±0.09, 2.20±0.07 and 1.76±0.27, respectively, which in ANP group were significantly higher than in CON group, but in ABX group was significantly lower than in ANP group, and all the differences were statistically significant (all P values <0.05). The serum DAO levels of CON, ANP, and ABX group were (0.06±0.15), (0.52±0.11) and (0.58±0.11) ng/ml; the expression level of ileum tissue of claudin1 mRNA and protein was 0.98±0.26, 0.42±0.18, 0.32±0.24 and 1.05±0.08, 0.82±0.09, 0.19±0.04; occludin mRNA and protein was 0.91±0.07, 0.31±0.05, 0.32±0.14 and 1.03±0.07, 0.61±0.04, 0.64±0.11; ZO-1 mRNA and protein was 1.01±0.08, 0.80±0.28, 0.60±0.28, and 0.86±0.10, 0.99±0.30, 0.62±0.30. The serum DAO level was significantly elevated in both ANP and ABX groups compared to the CON group. The mRNA and protein expression of claudin-1 and occludin in both ANP and ABX groups were significantly lower than those in CON group; the expression of claudin-1 in ABX group was significantly downregulated compared to ANP group; and all the differences were statistically significant (all P values <0.05). The relative fluorescence intensities of lung tissue in CON, ANP, and ABX groups were 0.03±0.01, 0.06±0.01, and 0.04±0.01, respectively, which in ANP group was significantly higher compared to CON group, but in ABX group was significantly lower than ANP group; all the differences were statistically significant (all P values <0.05). Conclusions:Intestinal microbiota may attenuate acute pancreatitis-associated acute lung injury by inhibiting the pyroptosis pathway in lung tissue.

Objective To explore the types of symptom clusters in patients with bladder instillation and identify the core symptoms through symptom network analysis,and to provide evidence for symptom management of the patients.Methods Convenience sampling was used to select 226 patients with bladder instillation for bladder cancer at a Tier-IIIA hospital in Guiyang from March 2023 to July 2024.Data were collected through review of medical record,general information questionnaires and symptom assessment questionnaires specific to the patients with bladder instillation.Exploratory factor analysis was used to extract symptom clusters,and symptom relationships were analysed using R language for network layout and centrality calculations.Results A total of 223 patients with bladder cancer completed the survey.Four symptom clusters were identified,namely the urinary system symptom cluster,digestive system symptom cluster,somatic symptom cluster and psychological symptom cluster,with a cumulative variance contribution rate of 66.038%.The symptom network analysis showed strong associations between dysuria and urethral pain during catheterisation,incomplete emptying and dysuria,as well as distress and poor sleep quality.In terms of centrality indicators,the top three symptoms by strength were dysuria(rS=2.26),incomplete emptying(rS=0.99)and poor sleep quality(rS=0.90).Of the expected impacts,the top three were dysuria(rE=2.09),poor sleep quality(rE=1.34)and frequency of urinary(rE=0.55).Regarding the closeness centrality,the top three were dysuria(rC=2.23),incomplete emptying(rC=0.64)and poor sleep quality(rC=0.54).Dysuria had the highest strength,expected impact and closeness centrality,indicating the dysuria was the core symptom in the patients with bladder cancer.Conclusion For the patients with bladder instillation experience,multiple and interconnected symptoms appear at the same time and together they form a symptom clusters,of which the pain in urination is the core symptom.Medical staff should consider symptom prevalence and core symptoms and to develop the targeted and precise management strategies for targeted nursing.

Objective:To explore the effects and possible mechanism of intestinal microbiota on lung injury in mice with acute necrotizing pancreatitis (ANP).Methods:The experimental mice were randomly assigned to normal control group (CON group), ANP model group (ANP group) and intestinal germ-free group (ABX group), with 6 mice in each group. The ANP mouse model was constructed by intraperitoneal injection of caerulein (100 μg/kg, for 10 times) at an interval of 1 hour each time, followed by 10 mg/kg lipopolysaccharide injection. Mice in ABX group were treated by Abx solution (0.5 g/L vancomycin, 1 g/L neomycin, 1 g/L metronidazole, and 1 g/L ampicillin), 1 ml/100 g gavage for 28 days before preparation of the ANP model. The CON group was injected intraperitoneally with an equal volume of PBS. Histopathologic examination of the pancreas, lungs, and terminal ileum was routinely performed. Serum amylase levels were measured using enzymatic kinetic chemistry, and serum diamine oxidase (DAO) and lung tissue myeloperoxidase (MPO) activities were measured using ELISA assay. Expression of inflammatory factors, pyroptosis-related molecules in lung tissue and intestinal epithelial tight junction proteins was detected by fluorescence quantitative PCR. Western blotting was used to detect the expression of the pyroptosis molecules caspase-1 and GSDMD in lung tissue, and intestinal epithelial tight junction proteins. Changes of bacterial distribution in lung tissue were measured by fluorescence in situ hybridization. Results:The pathological scores of pancreatic tissue of CON, ANP, and ABX group were (0.67±0.26), (7.33±0.82), and (5.67±0.81); the pathological scores of lung tissue were (1.67±0.41), (5.67±0.41), and (3.58±0.58); the pathological scores of ileal tissue were (0.58±0.52), (3.83±0.75), and (4.33±0.82); the serum amylase levels were (403.95±93.11), (1037.24±126.77), and (647.32±145.90)U/L; the MPO levels in lung tissue were (0.23±0.03), (0.63±0.09), and (0.48±0.05)U/g. ABX group had significantly lower scores in pancreatic and lung tissues, serum amylase levels, and MPO levels in lung tissue compared to ANP group, and all the differences were statistically significant (all P value <0.05). The expression level in pancreatis tissue from CON, ANP and ABX group of IL-1β mRNA was 1.84±0.90, 36.26±5.56 and 16.65±6.43, IL-6 mRNA was 1.07±0.15, 2.90±0.42 and 1.34±0.62, TNF-α mRNA was 0.47±0.11, 0.76±0.11 and 0.46±0.07, HMGB1 mRNA was 0.38±0.02, 0.72±0.22 and 0.44±0.08, caspase-1 mRNA was 1.07±0.18, 2.04±0.31 and 0.85±0.54, ASC mRNA was 1.24±0.19, 5.68±0.41 and 3.89±1.47, GSDMD mRNA was 0.79±0.17, 0.94±0.14 and 0.61±0.08, IL-18 mRNA was 0.83±0.27, 4.17±0.79 and 3.57±0.03, respectively. The expression of IL-1β, IL-6, TNF-α, HMGB1, caspase-1, ASC, and IL-18 mRNA in lung tissue was significantly increased in ANP group compared to the CON group; conversely, ABX group showed a significant decrease in the expression of these markers compared to ANP group; and all the differences were statistically significant (all P values <0.05). The protein level of caspase-1 in lung tissue of CON, ANP and ABX group was 1.59±0.51, 2.28±0.13, 1.38±0.47, and that of GSDMD was 1.90±0.09, 2.20±0.07 and 1.76±0.27, respectively, which in ANP group were significantly higher than in CON group, but in ABX group was significantly lower than in ANP group, and all the differences were statistically significant (all P values <0.05). The serum DAO levels of CON, ANP, and ABX group were (0.06±0.15), (0.52±0.11) and (0.58±0.11) ng/ml; the expression level of ileum tissue of claudin1 mRNA and protein was 0.98±0.26, 0.42±0.18, 0.32±0.24 and 1.05±0.08, 0.82±0.09, 0.19±0.04; occludin mRNA and protein was 0.91±0.07, 0.31±0.05, 0.32±0.14 and 1.03±0.07, 0.61±0.04, 0.64±0.11; ZO-1 mRNA and protein was 1.01±0.08, 0.80±0.28, 0.60±0.28, and 0.86±0.10, 0.99±0.30, 0.62±0.30. The serum DAO level was significantly elevated in both ANP and ABX groups compared to the CON group. The mRNA and protein expression of claudin-1 and occludin in both ANP and ABX groups were significantly lower than those in CON group; the expression of claudin-1 in ABX group was significantly downregulated compared to ANP group; and all the differences were statistically significant (all P values <0.05). The relative fluorescence intensities of lung tissue in CON, ANP, and ABX groups were 0.03±0.01, 0.06±0.01, and 0.04±0.01, respectively, which in ANP group was significantly higher compared to CON group, but in ABX group was significantly lower than ANP group; all the differences were statistically significant (all P values <0.05). Conclusions:Intestinal microbiota may attenuate acute pancreatitis-associated acute lung injury by inhibiting the pyroptosis pathway in lung tissue.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Chondroitin sulfate sodium is a sulphated glycosaminoglycan composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine,prepared from the cartilage tissue of land or marine animal by a specific extraction and purification process.Chondroitin sulfate sodium is considered to have anti-osteoarthritis effect and many other potential physiological activities.It has broad application prospects and development space in the fields of health food,cosmetics,and drugs.This paper reviews the preparation process of chondroitin sulfate sodium,development and problems of microbial synthesis technology and the research status of anti-osteoarthritis activity based on cells models,animal models and clinical randomized controlled trials(RCT).The limitations of current research are analyzed and corresponding strategies are proposed to provide reference for further standardization and development of chondroitin sulfate sodium.

Background:Recurrence after stone removal is common in patients with choledocholithiasis.Recent studies have indicated that dysbiosis in gut microbiota plays an important role in the formation of cholesterol gallstones.Aims:To explore the effect of probiotics supplementation on serum lipopolysaccharide(LPS)and the indicators of bile acid metabolism in patients with a high risk of cholesterol gallstone formation.Methods:Sixty choledocholithiasis patients undergoing ERCP lithotomy were recruited at the First Affiliated Hospital of Shihezi University from June 2021 to June 2023.Bile and stool samples were collected for bacterial culture.Then the patients were randomly allocated into two groups:patients in control group received conventional supportive therapy after calculus removal,while those in probiotics intervention group were given oral bifid triple viable enteric capsule 420 mg,twice a day for 6 months based on conventional therapy.Changes in serum levels of LPS,the cell wall component of Gram-negative bacteria,fibroblast growth factor 19(FGF19),the key molecule in bile acid metabolism,and cholesterol 7α-hydroxylase(CYP7A1),the rate-limiting enzyme of bile acid synthesis,were determined and compared between the two groups.Results:Escherichia coli and Klebsiella pneumoniae were the main pathogens in bile and stool of patients with choledocholithiasis.Six months after ERCP lithotomy,the serum levels of LPS and FGF19 were decreased,and the serum level of CYP7A1 was increased in both groups(all P<0.05),especially in probiotics intervention group(all P<0.05).Conclusions:Oral probiotics supplementation can reduce the serum LPS level and modulate the canonical pathway of enterohepatic circulation of bile acids--farnesoid X receptor(FXR)-FGF19 pathway in high-risk patients of cholesterol gallstone formation.These alterations reduce the cholesterol supersaturation in bile and inhibit the probability of cholesterol gallstone formation.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

Hypertension is one of the main factors leading to cardiovascular death.The number of cardiovascular patients were about 330 million in China,and 245 million among them were suffering from hypertensive in 2021.The rates of treatment and control of hypertension were less than 45.8%from 1991 to 2018.Therefore,it is of great clinical significance and social value to carry out hypertension related research.Animal models of hypertension are important tools to explore the pathogenesis of hypertension and evaluate the development of antihypertensive agents.At present,there are many ways to establish animal models of hypertension,by consulting and sorting out the relevant papers of animal models of hypertension at home and abroad,the author summarized and discussed the replication methods,principles,features and applications of commonly used animal models from four aspects,such as genetics,surgical induction,environmental induction and pharmaceuticals induction,in order to provide a reference for the selection and establishment of more scientific animal models of hypertension and lay the foundation for the combined treatment of hypertension with Chinese and Western medicine.

Background:Acute lung injury(ALI)is the most common organ dysfunction in severe acute pancreatitis(SAP).Somatostatin analogue octreotide is a common used drug in acute pancreatitis.Aims:To explore the protective mechanism of octreotide on lung injury in SAP mice.Methods:In the first part,the experimental mice were randomly assigned into four groups.SAP model was induced by caerulin and lipopolysaccharide,and the mice were sacrificed 24 hours,48 hours and 72 hours after establishment.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue myeloperoxidase(MPO)activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,Gasdermin D(GSDMD),interleukin(IL)-1β,IL-18 and inflammatory factors IL-6,tumor necrosis factor(TNF)-α,high mobility group protein B1(HMGB1)in lung tissue.Western blotting was used to detect protein expressions of NOD-like receptor thermal protein domain associated protein 3(NLRP3),caspase-1,GSDMD and IL-1β in lung tissue.In the second part,mice were randomly divided into control group,SAP group,and octreotide group.HE staining was used to observe the pathological score of pancreas and lung.Serum amylase and lung tissue MPO activity were detected.Real-time quantitative PCR was used to detect mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1.Immunofluorescence was used to detect protein expressions of NLRP3,caspase-1,GSDMD,ASC,IL-1β in lung tissue.Results:In the first part,compared with control group,pathological score of pancreas and lung tissue,serum amylase and MPO activity were significantly increased in SAP group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,GSDMD,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly increased(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD and IL-1β in lung tissue were significantly increased(all P<0.05),especially in 24 hours after establishment group.In the second part,compared with SAP group,pathological score of pancreas and lung tissue,serum amylase were significantly decreased in octreotide group(all P<0.05),mRNA expressions of pyroptosis-related molecules caspase-1,ASC,IL-1β,IL-18 and inflammatory factors IL-6,TNF-α,HMGB1 were significantly decreased in lung tissue in octreotide group(all P<0.05),protein expressions of NLRP3,caspase-1,GSDMD,ASC and IL-1β in lung tissue were significantly decreased(all P<0.05).Conclusions:Cell pyroptosis is involved in the occurrence and development of lung injury in SAP mice,and octreotide may attenuate lung injury in SAP mice by inhibiting pyroptosis.