Diabetic retinopathy(DR)remains the leading cause of vision loss in patients with diabetes. Current anti-vascular endothelial growth factor(VEGF)therapies are limited by inadequate response in some patients and the necessity for repeated intravitreal injections, underscoring the urgent need for novel therapeutic targets. Angiopoietin-like protein 4(ANGPTL4), a multifunctional secreted protein, has emerged as a critical regulator in the pathogenesis and progression of DR, positioning it as a promising interventional target. This review systematically elaborates the biological characteristics of ANGPTL4, with a focus on its expression dynamics, molecular mechanisms, and regulatory networks rolesin the development of DR. Furthermore, the prospects of ANGPTL4-targeted therapeutic strategies are discussed, aiming to offer new insights and directions for understanding DR pathogenesis, advancing multi-target drug development, and improving clinical management.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the impact of dietary protein intake on the prevalence of type 2 diabetes in adult residents, and to provide a reference for formulating diabetes prevention and control measures. Methods The research was based on cross-sectional survey data from the Nutrition and Health Follow-up Study of Chinese Residents in Chongqing (2021). Energy and nutrient intake was calculated in combination with the Chinese food composition table. Multivariate logistic regression was used to analyze the association between dietary protein and diabetes, and then restricted cubic spline regression (RCS) was used to analyze the dose-response relationship between dietary protein intake and the development of diabetes. Results Among the 1 415 adult residents, dietary intake of total protein, animal protein, and plant protein was 69.69g/d, 26.26g/d, and 43.43g/d, respectively. The ratio of protein to energy supply was 14.31%, and the prevalence of diabetes was 18.02%. Comparing with the residents in the first percentile of total dietary protein intake, the multivariable-adjusted odds ratios of those in the second and third percentile were 1.754 and 2.453 respectively. Comparing the residents in the third percentile with those in the first percentile, the multivariable-adjusted odds ratios of diabetes were 1.592 for protein energy supply ratio, and 1.558 for animal protein intake. Conclusion High protein intake, high protein energy supply ratio and high animal protein intake may increase the risk of diabetes, and different types of protein may have different effects on diabetes.

Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To examine the expression pattern of apoptosis signal-regulating kinase 1(ASK1)in the intestinal tissues of patients with Crohn's disease(CD),and analyze its mechanistic impact on intestinal epithelial barrier function and inflammatory responses.Methods Ileal tissue samples from Crohn's disease patients and healthy controls were collected.ASK1 protein level was assessed by immunohistochemistry,and its relationship with the Crohn's disease activity index(CDAI)was analyzed.A mouse model of acute colitis was constructed using TNBS,and subjected to qRT-PCR,Western blotting and immunohistochemistry for ASK1 expression,and the association between ASK1 expression and the disease activity index was examined.Lentivirus transfection was employed to create stable Caco-2 cell lines with altered ASK1 expression,and the intestinal barrier integrity and inflammation were assessed by measuring transepithelial electrical resistance(TEER),FITC-dextran leakage,and IL-6,IL-1β levels.Furthermore,the effects of ASK1 expression on Krüppel-like factor 4(KLF4)levels was examined using qRT-PCR and Western blotting.Results ASK1 was highly expressed in the ileum of CD patients and positively correlated with CDAI.In a TNBS-induced mouse model of acute colitis,ASK1 expression was up-regulated and positively correlated with DAI.Inflammation-induced ASK1 overexpression weakened the Caco-2 cell intestinal barrier,whereas ASK1 knockdown strengthened it.Moreover,ASK1 had the capability to enhance the expression of inflammatory factors.Additionally,ASK1 knockdown increased KLF4 expression,while overexpression decreased it,indicating a negative correlation between ASK1 and KLF4.Conclusion ASK1 expression is notably higher in CD and positively correlates with disease activity.ASK1 can influence intestinal barrier integrity and inflammatory factor expression,possibly through its impact on KLF4 expression.

Objective To determine the levels of arsenic in food in Chongqing city,and to assess the levels of dietary arsenic exposure and the associated potential health risks in residents of Chongqing city.Methods By using the monitoring data on arsenic levels in food in Chongqing between 2018 and 2023 in combination with the local dietary survey data for Chongqing from the 2018 China Nutrition and Health Survey Program,and adopting the 2-dimensional Monte Carlo simulation,we made an estimate of the dietary arsenic exposure levels of Chongqing residents.The margin of exposure(MOE)method was applied to assess both non-carcinogenic risks(skin damage)and carcinogenic risks(lung cancer and urinary system cancers)associated with dietary intake of arsenic.Results Out of 4900 food samples,the detection rate of arsenic was 36.40％,with the average levels ranging from the median bound(MB)of 0.020 7 to the upper bound(UB)of 0.023 4 mg/kg.The highest average levels were found in rice and its products,with an MB of 0.0981 and a UB of 0.098 5 mg/kg.The daily average exposure to inorganic arsenic for residents of different ages,sexes,and places of residence was highest in individuals aged 3 to 6,with an MB of 1.046 μg/(kg·d)and a UB of 1.116 μg/(kg·d),and lowest among individuals aged 60 and older.Arsenic exposure was higher in males than that in females and higher in people living in rural areas compared to those in urban areas.In terms of non-carcinogenic risks,the MOE values for inorganic arsenic were always higher than 1 in various populations.As for carcinogenic risks,the MOE values were all less than 100 in various populations.Rice and its products were the main source of dietary arsenic exposure in Chongqing,accounting for 69.97％to 74.37％of the total exposure.Conclusion The non-carcinogenic risk caused by dietary arsenic exposure in Chongqing is relatively low,but there may be a certain level of carcinogenic risk.Continued attentions should be given to dietary arsenic exposure levels in young children.

Objective To understand the status quo of nutrition working ability in primary medical and health institutions of Chongqing City.Methods Three primary medical institutions were randomly extracted from each of 39 districts and counties of Chongqing City,and Primary Nutrition Service Capacity Survey Form and Nutrition Work Capacity Survey System were adopted to conduct the questionnaire survey.Then the sur-vey results were analyzed.Results A total of 117 primary medical institutions were surveyed,in which 86 in-stitutions(73.50％)undertook the nutritional work.The number of engaging the nutrition full-time work in the units was 0(0,0).Among the nutritional staff,the age in 164 persons was 30-＜40 years old,accounting for 48.38％,180 persons(53.10％)had the primary title,232 persons(68.44％)had the bachelor degree,287 persons(84.66％)had the medical related background,but only 2 persons had the nutritional related profes-sional background.There were 57(48.72％),75(64.10％),77(65.81％)primary medical institutions in carry-ing out the nutrition and health management of pregnant women,children aged 0-6 years old and elderly peo-ple,34 institutions(29.10％)in carrying out nutritional monitoring,and 17 institutions(14.50％)had the clinical nutrition work ability.Compared with the villages and towns,the proportion of urban area primary medical institutions in carrying out the blood routine items in children aged 0-6 years old,hemoglobin,blood routine and urine routine items in elderly people was higher,the number of published popular science works on nutrition was more,and the differences were statistically significant(P＜0.05).Conclusion The nutrition work system of primary medi-cal institutions in Chongqing City is temporarily imperfect,the specialized persons still lack and the nutritional health service level needs to be further strengthened.

Neddylation is overactivated in lung cancer, which promotes the development of lung cancer by activating its downstream CRL ubiquitin ligase and promoting the CRL tumor-suppressor protein substrate degradation. MLN4924, a small molecule inhibitor of Neddylation, plays an anti-lung cancer role by inducing cell cycle arrest, apoptosis and senescence. Furthermore, targeting the key enzymes of Neddylation and their substrates, Cullin family proteins, can inhibit the development of lung cancer.

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in colorectal cancer patients.Methods:From January 2017 to December 2018, 60 patients with colorectal cancer who admitted to the Second People′s Hospital of Lianyungang were selected and divided into ERAS group and control group according to the random digital table method, with 30 patients in each group.The inflammation, nutritional indicators, immune indicators and clinical manifestations before and after surgery in the two groups were compared.Results:At 1 d and 3 d after surgery, the C-reactive protein (CRP) levels in the ERAS group were (70.2±10.3)mg/L, (82.5±8.2)mg/L, respectively, which were lower than those in the control group [(81.5±9.9)mg/L, (110.2±12.9)mg/L] ( t=4.324, 9.911, all P<0.05). On the third day after operation, the levels of albumin and prealbumin in the ERAS group were (31.6±4.8)g/L, (196.8±40.6)g/L, respectively, which were higher than those in the control group [(28.0±5.8)g/L, (172.1±38.8)g/L]( t=2.621, 2.409, all P<0.05). The immune parameters(IgA, IgM, IgG, CD 4+, CD 4+ /CD 8+) in the ERAS group were higher than those in the control group( t=2.132, 2.223, 6.063, 4.253, 2.828, all P<0.05). The number of cases with thirsty and hunger on the day of surgery in the ERAS group was 3 cases and 7 cases, respectively, which were less than 21 cases and 25 cases of the control group(χ 2=22.500, 21.696, all P<0.05). The first exhaust time, defecation time and hospital stay time in the ERAS group were (36.2±12.1)h, (63.4±13.4)h and (9.5±3.2)d, respectively, which were shorter than those in the control group [(54.7±13.8)h, (96.5±18.8)h and (12.1±4.0)d] ( t=5.513, 7.845, 2.761, all P<0.05). The incidence of complications between the two groups had no statistically significant difference ( P>0.05). Conclusion:ERAS can significantly reduce the physical and psychological traumatic stress of patients with colorectal cancer, achieve rapid recovery, improve the treatment effect, shorten the length of hospital stay, reduce social and family burden, and provide a basis for the choice of clinical treatment program.