Objective This study sought to establish a non-alcoholic fatty liver disease(NAFLD)model in Wistar-SD hypercholesterolemia(WSHc)rats induced by a high-fat diet and to reveal the pathogenesis of NAFLD in these rats through the Srebp-1 gene.Methods After 2 weeks of dietary treatment,thirty 6-week-old WSHc rats were divided into High-fat control group,HFD+AAV no load group,and HFD+AAV group,with 10 rats in each group.The HFD+AAV no load group and HFD+AAV group were intravenously injected with a vector virus and an shRNA-containing virus,respectively.WSHc rats were fed with a normal fat diet as a normal control group.Serum levels of ALT,AST,TBIL,ALP,TBA,GLU,CHOL,and TG were measured every 2 weeks.After a further 8 weeks of feeding,the rats were euthanized and livers were excised for HE staining,Oil Red O staining,Masson staining,and Sirius red staining to observe the morphology,lipid deposition,and fibrosis of the liver tissues.RT-qPCR was performed to detect the expression of lipid metabolism-related genes namely Srebp-1,Aacs,FASN and LDLR in the livers.Furthermore,hepatocytes were isolated,cultured,and divided into a normal control group and a high-fat control group.Next,expression of the Srebp-1 gene was detected by RT-qPCR.Srebp-1 knockout(KO)hepatocytes were constructed,then TG content was detected and the lipid accumulation was observed by Oil Red O staining.Results After 10 weeks of high-fat diet treatment,serum ALT(P＜0.001),ALP(P＜0.001),TBA(P＜0.05),GLU(P＜0.001),and CHOL(P＜0.001)significantly increased in WSHc rats.Abnormal lipid deposition with formation of large vacuolar lipid droplets and fibrotic lesions in livers were observed.The mRNA expression of Srebp-1 noticeably increased in WSHc rats(P＜0.001).Moreover,compared with the high-fat control group,the ALT(P＜0.05)and GLU(P＜0.01)in the HFD+AAV group decreased,and liver lipid deposition and the formation of large vacuolar lipid droplets were alleviated.Expressions of genes such as FASN(P＜0.05)and LDLR(P＜0.01)were significantly upregulated.Additionally,there was a significant increase in the expression of Srebp-1 in hepatocytes of the high-fat control group(P＜0.001),while after Srebp-1 gene knockout,cellular TG levels decreased and the degree of lipid droplet aggregation was reduced.Conclusions The Srebp-1 gene plays a regulatory role in hepatic lipid metabolism and deposition,modulating the expression of lipid metabolism-related genes in WSHc rats with NAFLD.In vitro experiments demonstrated that downregulation of Srebp-1 alleviates lipotoxic injury in hepatocytes,suggesting that the development of NAFLD in WSHc rats is closely associated with abnormally high expressions of the Srebp-1 gene.

Objective This study sought to establish a non-alcoholic fatty liver disease(NAFLD)model in Wistar-SD hypercholesterolemia(WSHc)rats induced by a high-fat diet and to reveal the pathogenesis of NAFLD in these rats through the Srebp-1 gene.Methods After 2 weeks of dietary treatment,thirty 6-week-old WSHc rats were divided into High-fat control group,HFD+AAV no load group,and HFD+AAV group,with 10 rats in each group.The HFD+AAV no load group and HFD+AAV group were intravenously injected with a vector virus and an shRNA-containing virus,respectively.WSHc rats were fed with a normal fat diet as a normal control group.Serum levels of ALT,AST,TBIL,ALP,TBA,GLU,CHOL,and TG were measured every 2 weeks.After a further 8 weeks of feeding,the rats were euthanized and livers were excised for HE staining,Oil Red O staining,Masson staining,and Sirius red staining to observe the morphology,lipid deposition,and fibrosis of the liver tissues.RT-qPCR was performed to detect the expression of lipid metabolism-related genes namely Srebp-1,Aacs,FASN and LDLR in the livers.Furthermore,hepatocytes were isolated,cultured,and divided into a normal control group and a high-fat control group.Next,expression of the Srebp-1 gene was detected by RT-qPCR.Srebp-1 knockout(KO)hepatocytes were constructed,then TG content was detected and the lipid accumulation was observed by Oil Red O staining.Results After 10 weeks of high-fat diet treatment,serum ALT(P＜0.001),ALP(P＜0.001),TBA(P＜0.05),GLU(P＜0.001),and CHOL(P＜0.001)significantly increased in WSHc rats.Abnormal lipid deposition with formation of large vacuolar lipid droplets and fibrotic lesions in livers were observed.The mRNA expression of Srebp-1 noticeably increased in WSHc rats(P＜0.001).Moreover,compared with the high-fat control group,the ALT(P＜0.05)and GLU(P＜0.01)in the HFD+AAV group decreased,and liver lipid deposition and the formation of large vacuolar lipid droplets were alleviated.Expressions of genes such as FASN(P＜0.05)and LDLR(P＜0.01)were significantly upregulated.Additionally,there was a significant increase in the expression of Srebp-1 in hepatocytes of the high-fat control group(P＜0.001),while after Srebp-1 gene knockout,cellular TG levels decreased and the degree of lipid droplet aggregation was reduced.Conclusions The Srebp-1 gene plays a regulatory role in hepatic lipid metabolism and deposition,modulating the expression of lipid metabolism-related genes in WSHc rats with NAFLD.In vitro experiments demonstrated that downregulation of Srebp-1 alleviates lipotoxic injury in hepatocytes,suggesting that the development of NAFLD in WSHc rats is closely associated with abnormally high expressions of the Srebp-1 gene.

Objective To establish a rat model of hyperuricemic nephropathy(HN)using a multifactorial induction method of potassium oxazinate combined with adenine and yeast feed to observe the intervention effect of Qiling granules(QLG).Methods Fifty-eight SPF-grade male SD rats were selected,and 10 rats were randomly allocated to the normal control(NC)group.The remaining rats were induced by multiple factors to establish HN rat models.After 2 weeks of modeling,submandibular blood samples were taken to detect serum UA,CREA,BUN,TG,and TC.Forty HN rats with bleeding clearance UA and body weight close to the mean were selected.They were randomly divided into a model(M)group,QLG low dose(QLG-L)groups,QLG high dose(QLG-H)group,and a positive control(PC)group,with 10 rats in each group,using a stratified randomization method.Each group was given corresponding drugs by gavage daily,and after continuous administration for 4 weeks,submandibular blood samples were taken to detect serum UA,CREA,BUN,TG,and TC.After euthanasia of the rats,liver tissue was taken to detect XOD and ADA activity.Renal tissue was taken for HE and Gomori hexamine silver staining,and the protein expression of GLUT9,OAT1,VCAM-1,and TGF-β in the kidneys was observed using immunohistochemistry and Western blot method.Results Compared with the NC group,the M group's serum levels of UA,CREA,BUN,TC,and TG,as well as liver XOD and ADA activities,were significantly increased(P＜0.01).The renal tissue of the model rats showed significant pathological changes.The area of renal tubules positive for urate and the expression of GLUT9,VCAM-1,and TGF-β proteins in the kidneys were significantly increased(P＜0.01,P＜0.05),while the expression of OAT1 was significantly reduced(P＜0.01).Compared with the M group,each treatment group showed significantly reduced serum UA levels,liver XOD,ADA activity,and renal VCAM-1 protein expression(P＜0.01,P＜0.05).The serum CREA and BUN levels and renal TGF-β protein expression of rats in the QLG-L group were significantly reduced(P＜0.05,P＜0.01).The serum CREA and BUN levels and renal GLUT9 protein expression of rats in the QLG-H group were also significantly reduced(P＜0.01,P＜0.05).The urate deposition and renal injury caused by each treatment were reduced to varying degrees,but there were no significant differences among groups(P＞0.05).Conclusions A stable HN rat model can be induced by gavage of potassium oxyzinate and adenine in combination with yeast feed.QLG can effectively treat HN by improving UA metabolic disorders,reducing the renal inflammation and urate deposition that cause renal damage in HN model rats.Its mechanism of action is related to a reduction in serum UA,CREA,BUN,and TG levels;liver XOD and ADA activities;and the expression of GLUT9,OAT1,VCAM-1,and TGF-β proteins in the kidneys.

Background:Gastric adenocarcinoma of the fundic gland type(GA-FG)and oxyntic gland adenoma(OGA)are rare variants of the gastric neoplasms exhibiting fundic differentiation.However,their endoscopic recognition and diagnosis is difficult in clinical practice.Aims:To explore the endoscopic and clinicopathological features of GA-FG and OGA,and to discuss the surgical methods and clinical outcomes.Methods:A retrospective analysis was conducted on 19 cases with a total of 22 lesions diagnosed as GA-FG or OGA through histopathology at the Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University School of Medicine from January 2020 to May 2023.Data on the diagnosis,treatment and follow-up among these patients were collected and analyzed.Results:Females were slightly more than males(12:7),with an average age of 54 years.Eighteen patients had single lesions,while one had 4 synchronous multifocal lesions.All the lesions located in the non-atrophic gastric fundic area of the upper and middle third of the stomach.Nine lesions were misdiagnosed as gastric fundic gland polyps initially.The tumors were small,with the average diameter of 7.4 mm.Most of the lesions(77.3%)showed fading or whitening changes under white light endoscopy.While under magnifying endoscopy with narrow-band imaging,obscure demarcation line,and dilated intervening part and crypt-opening could be observed in over half of the lesions,but irregular microvascular pattern was absent.Six lesions exhibited submucosal infiltration(GA-FG)without lymphovascular invasions.Eighteen lesions were diagnosed as chief cell predominant type,one was parietal cell predominant type,and three were mixed type.Endoscopic submucosal dissection and endoscopic mucosal resection were performed in 17 cases.No severe perioperative complications occurred,and no local recurrence and metastasis were detected during follow-up period.Conclusions:GA-FG and OGA mainly occur in the non-atrophic gastric fundic area,with small lesions exhibiting fading changes under endoscopy.The pathological type is primarily chief cell predominant type.This kind of lesion can be easily misdiagnosed as gastric fundic gland polyps.Endoscopic therapy appears to be effective and safe for them with a favorable prognosis.

Background:Gastric adenocarcinoma of the fundic gland type(GA-FG)and oxyntic gland adenoma(OGA)are rare variants of the gastric neoplasms exhibiting fundic differentiation.However,their endoscopic recognition and diagnosis is difficult in clinical practice.Aims:To explore the endoscopic and clinicopathological features of GA-FG and OGA,and to discuss the surgical methods and clinical outcomes.Methods:A retrospective analysis was conducted on 19 cases with a total of 22 lesions diagnosed as GA-FG or OGA through histopathology at the Shanghai Sixth People′s Hospital,Shanghai Jiao Tong University School of Medicine from January 2020 to May 2023.Data on the diagnosis,treatment and follow-up among these patients were collected and analyzed.Results:Females were slightly more than males(12:7),with an average age of 54 years.Eighteen patients had single lesions,while one had 4 synchronous multifocal lesions.All the lesions located in the non-atrophic gastric fundic area of the upper and middle third of the stomach.Nine lesions were misdiagnosed as gastric fundic gland polyps initially.The tumors were small,with the average diameter of 7.4 mm.Most of the lesions(77.3%)showed fading or whitening changes under white light endoscopy.While under magnifying endoscopy with narrow-band imaging,obscure demarcation line,and dilated intervening part and crypt-opening could be observed in over half of the lesions,but irregular microvascular pattern was absent.Six lesions exhibited submucosal infiltration(GA-FG)without lymphovascular invasions.Eighteen lesions were diagnosed as chief cell predominant type,one was parietal cell predominant type,and three were mixed type.Endoscopic submucosal dissection and endoscopic mucosal resection were performed in 17 cases.No severe perioperative complications occurred,and no local recurrence and metastasis were detected during follow-up period.Conclusions:GA-FG and OGA mainly occur in the non-atrophic gastric fundic area,with small lesions exhibiting fading changes under endoscopy.The pathological type is primarily chief cell predominant type.This kind of lesion can be easily misdiagnosed as gastric fundic gland polyps.Endoscopic therapy appears to be effective and safe for them with a favorable prognosis.

Objective:To compare the effect and biotoxicity of tert-butyl acetate (TBA) and ethyl butyrate (EB) on stone dissolution in vitro.Methods:Ten gallstone samples from patients with multiple gallbladder stones were selected and the cholesterol content was analyzed by HPLC. Stone dissolution tests of TBA and EB were performed on cholesterol gallstone in vitro, and the weight of stone at each time point was recorded, meanwhile, methyl tert-butyl ether (MTBE) was used as the control. The inhibitory effects of MTBE, TBA and EB on proliferation of human normal liver cell line LO2 were analyzed by cell proliferation inhibition assay. Flow cytometry was used to analyze the effects of MTBE, TBA and EB on the early and late apoptosis of LO2 cells, and the changes of reactive oxygen species level in LO2 cells were also analyzed.Results:Of the 10 gallbladder gallstones, 6 were cholesterol gallstones and 4 were non-cholesterol gallstones. Stone dissolution experiment showed that the remaining stones of MTBE, TBA and EB groups were (47.83±3.84)%, (58.12±4.53)% and (75.75±4.61)% 30 minutes later. The remaining stones were (18.38±6.47)%, (33.82±6.22)% and (56.38±3.91)% 90 minutes later. MTBE had the best stone dissolution effect in vitro, the stone dissolution effect of TBA was slightly weaker than MTBE, and the stone dissolution effect of EB was relatively weak in all ( P<0.05). The cell proliferation inhibition experiment showed that the cell viability of the control group, MTBE group and TBA group were (100.00±4.46)%, (96.79±4.32)% and (93.72±3.51)%, respectively, and there were no significant differences among the three groups ( P>0.05). However, the cell viability of EB group (87.57±5.29)% was lower than the above three groups, and the differences were statistically significant ( P<0.001). The early apoptosis and late apoptosis of the control group were (1.67±0.15)% and (1.27±0.06)%, respectively. EB induced early apoptosis (15.90±0.53)% ( P<0.001) and late apoptosis (5.13±0.76)% ( P<0.05). However, MTBE and TBA had no significant effect on cell apoptosis ( P>0.05). Compared with control group, MTBE, TBA and EB all significantly inhibited the level of reactive oxygen species ( P<0.05), and the inhibitory effect of EB was the most obvious. Conclusions:TBA has good stone dissolution effect and biosafety for gallbladder cholesterol stones in vitro, while EB has relatively poor performance. TBA is a potential drug for gallstone dissolution.

Objective:To analyze the endoscopic characteristics of early gastric cancer and precancerous lesions after Helicobacter pylori ( H. pylori) eradication. Methods:From May 2019 to June 2022, at Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine, the medical data of patients diagnosed with differentiated early gastric cancer and precancerous lesions were collected. A total of 93 patients with early gastric cancer and precancerous lesions who had previous history of H. pylori infection and had undergone standardized eradication treatment were selected, and their endoscopic characteristics were retrospectively analyzed. Independent sample t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among 93 patients with early gastric cancer and precancerous lesions after H. pylori eradication, there were 56 males and 37 females, with an average age of (66.9±8.2) years old. The time after H. pylori eradication was 3.4 years (range 1.0 to 7.0 years). A total of 109 early gastric cancer and precancerous lesions were found, including 79 patients with single lesion and 14 patients with multiple lesions (30 lesions). There were 60 cases with 73 lesions in the early gastric cancer group and 33 cases with 36 lesions in the precancerous group. Among 93 patients, 89 cases (95.7%) were diagnosed with atrophy level above C-2 according to Kimura-Takemoto classification under endoscopy. The long diameter of 109 lesions was (1.38±0.70) cm and the short diameter was (1.04±0.53) cm. A total of 80 lesions (73.4%) were located in the lower 1/3 part of the stomach, and 53 lesions (48.6%) were located in the lesser curvature. A total of 106 lesions (97.2%) were superficial type (0-Ⅱ) under the endoscopy. The long diameter and short diameter in the early gastric cancer group after H. pylori eradication were both greater than those in the precancerous lesion group ((1.54±0.78) cm vs. (1.06±0.35) cm, (1.16±0.58) cm vs. (0.78±0.33) cm), and the differences were statistically significant ( t=3.53 and 3.73, both P<0.001). There was statistically significant difference in the morphological types between early gastric cancer group after H. pylori eradication and precancerous lesion group ( χ2=11.01, P=0.012). The main morphological type of early gastric cancer after H. pylori eradication was superficial depression type (0-Ⅱc), accounting for 45.2% (33/73), while the precancerous lesions were mainly superficial protruded and flat type, both accounting for 38.9% (14/36). Conclusions:After H. pylori eradication, the endoscopic atrophy range of early gastric cancer and precancerous lesions is mostly above C-2. And the lesions are mostly located in the middle and lower 1/3 part of the stomach, long diameter of lesions <20 mm. The main morphological type is superficial type, especially superficial depression type.

Objective:To explore the prevalence of gout and related factors in community population, thereby provide evidence for comprehensive prevention and control of gout in community.Methods:A stratified multi-stage cluster sampling was used to survey the permanent residents of 20 to 75 years old in the 3 selected streets (towns), univariate analysis was performed using logistic regression by SPSS statistical software.Results:The prevalences of hyperuricemia and gout were 9.82% and 5.75% respectively(male 18.88% and 7.94%, female 3.79% and 4.29%)in Jiading Shanghai. The positive rate of family history was 17.13%, and the relationship between family history and gout was significant( OR=3.140, 95% CI 2.365-4.169, P<0.01). Age( OR=1.034, 95% CI 1.021-1.047), body mass index ( OR=1.102, 95% CI 1.074-1.131), waist-hip ratio ( OR=4.876, 95% CI 1.153-20.622), sleep quality ( OR=1.310, 95% CI 1.159-1.480), other animal meat ( OR=1.117, 95% CI 1.007-1.240), fresh water fish ( OR=1.138, 95% CI 1.005-1.288), and processed meat ( OR=1.145, 95% CI 1.033-1.270) were closely related to gout ( P<0.05 or P<0.01). Sex, alcohol drinking, marine fish, and soybean milk/soymilk were related to gout ( P<0.05 or P<0.01), but showed a protective effect ( OR<1.000). Conclusion:Reducing uric acid production through less consumption of purine-rich food such as animal meat as well as processed meat and weight control would be helpful in preventing gout.

Objective:To analyze and compare the features of undifferentiated-typed early gastric cancer (UD-EGC) and gastric mucosa-associated lymphoid tissue(MALT) lymphoma under white light endoscopy (WLE) and magnifying endoscopy-narrow band imaging (ME-NBI).Methods:Data of patients with complete endoscopic images of WLE and ME-NBI in Shanghai General Hospital, Shanghai Jiao Tong University from March 2015 to July 2019 were retrospectively analyzed.Twenty-six UD-EGC patients and seven gastric MALT lymphoma patients in ⅠE1 stage were included, and the characteristics of the two diseases under WLE and ME-NBI were compared and summarized.Results:There were no significant differences in age, sex or infiltration depth of lesions between the two groups.Under WLE, UD-EGC was often manifested as a single lesion located in the lower part of the stomach, with unclear lesion boundaries. While MALT lymphoma lesions were mostly multifocal with clear boundaries, located in the middle of the stomach. Under ME-NBI, the microsurface pattern of UD-EGC showed dilation or disappearance of areas between the recesses, and the spiral microvascular pattern. However, the microsurface pattern of MALT lymphomas were characterized by " cross-road traffic sign" , " pebble sign" , and the presentation of residual glandular duct at the lesion was similar to that of Helicobacter pylori ( HP)-related gastritis. Furthermore, the microvascular pattern of MALT lymphomas often showed " tree like appearance (TLA)" . After HP eradication therapy, the morphology of microsurface pattern and microvascular pattern in the original lesion area gradually returned to normal. Conclusion:UD-EGC and gastric MALT lymphoma showed particular features in the number, site and boundary under WLE, and they showed significantly different microsurface pattern and microvascular pattern under ME-NBI. Differentiation of the two diseases will help reduce the risk of missed diagnosis and misdiagnosis.

Objective? To explore the application of three-dimensional quality assessment model of structure-process-outcome in continued nursing care for elderly patients with lung cancer after operation. Methods? By purposive sampling, 48 elderly patients discharged after radical resection of lung cancer from January to December 2016 were taken as control group and received routine continuous nursing care. Another 51 elderly patients discharged after radical resection of lung cancer from June 2017 to June 2018 were taken as the observation group. Continuous nursing program based on structure-process-outcome quality assessment model was applied for the observation group. The effect of intervention was assessed by using Strategies Used by People to Promote Health (SUPPH) and Quality of Life Questionnaire-30(QLQ-30). Results? At 6 months after discharge, the scores of each dimension of SUPPH scale in the observation group were statistically higher than those in the control group (P＜ 0.05). In the observation group the scores of "physical function", "role function", "social function" and "overall health" of QLQ-30 scale were higher than the control group, the scores of "fatigue", "pain", "insomnia", "lack of appetite", "constipation", and "diarrhea" were all lower than the control group with statistical significance (P＜0.05). Conclusions? The continuous nursing care based on the three-dimensional quality assessment model of structure-process-outcome for elderly patients with lung cancer can help to improve their sense of self-efficacy and quality of life.