Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective:To describe the epidemiological characteristics of intakes of different types of preserved vegetables in participants from the China Kadoorie Biobank (CKB).Methods:The CKB project conducted baseline survey, the first resurvey, and the second resurvey during 2004-2008, 2008, and 2013-2014, respectively. According to the average intake levels of salted and sour pickled vegetables in the second resurvey, the 10 survey areas were classified as the area where people mainly consumed salted vegetables, the area where people mainly consumed sour pickled vegetables, and the area where people rarely consumed preserved vegetables. For the first two areas, logistic regression model was used to describe the temporal trends and population distribution of preserved vegetable intake and analyze the distribution of other dietary factors.Results:The area where people mainly consumed salted vegetables included Qingdao, Harbin, Suzhou, and Zhejiang (baseline participant number: 204 036), while the area where people mainly consumed sour pickled vegetables included Gansu and Sichuan (baseline participant number: 105 573). In the area where people mainly consumed salted vegetables, the average intake frequencies of preserved vegetables was 3.1, 3.3, and 1.8 days/week in the baseline survey, the first resurvey, and the second resurvey, respectively, showing a declining trend ( P<0.001). Similarly, the average intake frequencies of preserved vegetables were 2.8, 2.7, and 1.6 days/week in the baseline survey, the first resurvey and the second resurvey in the area where people mainly consumed sour pickled vegetables ( P<0.001). At baseline survey, the married and those had lower education level tended to have more preserved vegetable intakes in both areas ( P<0.001). In the area where people mainly consumed salted vegetables, the elderly had higher frequency of preserved vegetable intake ( P<0.001), which was converse in the area where people mainly consumed sour pickled vegetables. In the participants with higher frequency of preserved vegetable intake, more people consumed spicy food daily and preferred salty food ( P<0.05). Conclusions:The area and population specific differences in the type and frequency of preserved vegetable intake were observed in adults in the CKB project in China. Besides, the average level of preserved vegetable intake showed a declining trend. Preserved vegetable intake might be associated with other dietary habits.

Objective To explore the correlations of lumbar bone mineral density(BMD)and metabolic syndrome(MS)in adult males.Methods Data of low dose chest CT and quantitative CT of 13 490 adult males were retrospectively analyzed,and lumbar BMD were measured to judge whether MS existed and the degree of MS,and the correlations of lumbar BMD with MS or not and the degree of MS,as well as of lumbar BMD value and the related indicators of MS were assessed.Taken lumbar BMD as the dependent variable,the age,low density lipoprotein cholesterol(LDL-C),blood uric acid(BUA),hemoglobin(Hb)and MS or not were included in multiple linear regression analysis to observe the impact of MS and related indicators on lumbar BMD.Results Among 13 490 adult males,3 900 were found with MS(MS group),while 9 590 were found without MS(non-MS group).Significant difference of lumbar BMD was detected between groups(P=0.001).Lumbar BMD values were negatively correlated with MS(rs=-0.025,P=0.004)and the degree of MS(rs=-0.038,P＜0.001),whereas positively correlated with abdominal obesity,high triglyceride and low HDL-C or not(rs=0.024,0.061,0.036,all P＜0.001)but negatively correlated with hypertension and hyperglycemia or not(rs=-0.135,-0.104,both P＜0.05).After adjustment of age,lumbar BMD of adult males was negatively correlated with MS or not as well as LDL-C(both P＜0.05),but positively correlated with BUA and Hb(both P＜0.001).Conclusion Lumbar BMD was associated with MS in adult males.

Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.

Objective:To analyze the distribution of body fat with quantitative computed tomography (QCT) in people with normal body mass index (BMI).Methods:A cross-sectional study was conducted in the physical examination population who underwent chest CT and QCT examination in the Department of Health Management, Henan Provincial People′s Hospital from January to December in 2021, and 1 395 physical examination subjects who met the inclusion criteria were selected as the research subjects. The subjects were divided into five groups according to their age. The general data of the subjects were collected. The total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), total abdominal muscle area (TMA) and muscle fat content (MFC) in the subjects were measured by QCT. One-way analysis of variance, Welch test and Kruskal-Wallis test were used to compare the above QCT measurement indexes between the two genders among different age groups with normal BMI. Pearson correlation analysis was used to analyze the correlation between VFA and sarcopenia indexes. Multivariate linear regression was used to analyze the relationship between VFA and linear correlation variables in the related indicators of sarcopenia.Results:There were significant differences in TFA, VFA, TMA and SMI among different age groups in subjects with normal BMI (all P<0.05). Pearson correlation analysis showed that VFA was negatively correlated with TMA in some age groups (male: 18-39 years group: r=-0.351; 40-49 years group: r=-0.278; 60-69 years group: r=-0.245; female:40-49 years group: r=-0.251; 50-59 years group: r=-0.270;≥70 years group: r=-0.391; all P<0.01); it was negatively correlated with SMI (male: 18-39 years group: r=-0.352; 40-49 years group: r=-0.340; 50-59 years group: r=-0.266; 60-69 years group: r=-0.316; female: 40-49 years group: r=-0.240; 50-59 years group: r=-0.284; all P<0.001); it was positively correlated with MFC (male: 18-39 years group: r=0.342; 40-49 years group: r=0.291; female: 50-59 years group: r=0.133; 60-69 years group: r=0.284; all P<0.05). Multivariate linear regression analysis showed that VFA was independently and negatively correlated with SMI in both men and women after adjusting for age interference factors (male B=-1.881, t=-6.025, P<0.001; female B=-0.603, t=-2.887, P=0.004), and it was independently positively correlated with MFC (male B=1.230, t=4.271, P<0.001;female B=0.893, t=3.836, P<0.001). There was an independent negative correlation between VFA and TMA in male subjects ( B=0.263, t=2.478, P=0.013). Conclusions:VFA is correlated with TMA, SMI and MFC in people with normal BMI. Regardless of gender, SMI has a negative effect on VFA, and MFC has a positive effect on VFA.

Objective To investigate the clinical efficacy of angiotensin converting enzyme inhibitors(ACEI)or angiotensin Ⅱ receptor blockers(ARB)combined with glucocorticoid in treating IgA nephropathy patients.Methods A total of 125 IgA nephropathy patients admitted to Anyang District Hospital from October 2019 to October 2022 were selected as the research subjects.The patients were randomly divided into the control group(n=62)and the observation group(n=63).Patients in the control group were given ACEI or ARB treatment,while patients in the observation group were given ACEI or ARB combined with fluticasone propionate inhalation aerosol.All patients were treated continuously for 3 months.The treatment effect was compared between the two groups.The 24-hour urinary protein quantitation,serum creatinine(Scr),glomerular filtration rate(GFR),white blood cell(WBC)count,hemoglobin(HGB)level,and platelet(PLT)count of patients in the two groups were measured before and after treatment.The occurrence of adverse reactions during treatment in the two groups was recorded.Results The overall effective rates of patients in the control group and the observation group were 54.84％(34/62)and 84.13％(53/63),respectively;the overall effective rate of patients in the observation group was significantly higher than that in the control group(x2=12.669,P＜0.05).Before treatment,there was no significant difference in 24-hour urinary protein quantitation,Scr and GFR between the two groups(P＞0.05).There was no significant difference in 24-hour urinary protein quantitation of patients before and after treatment in the control group(P＞0.05),and the 24-hour urinary protein quantitation of patients after treatment in the observation group was significantly lower than that before treatment(P＜0.05).After treatment,Scr in the two groups was significantly lower than that before treatment,and GFR was significantly higher than that before treatment(P＜0.05).After treatment,24-hour urinary protein quantitation in the observation group was significantly lower than that in the control group(P＜0.05);and there was no significant difference in Scr and GFR between the two groups(P＞0.05).There was no significant difference in WBC,HGB and PLT of patients before and after treatment in the two groups(P＞0.05).No adverse reactions,such as abnormal glucose tolerance,steroid diabetes and elevated blood pressure,occurred in the two groups during treatment.Conclusion Fluticasone propionate inhalation aerosol combined with ACEI or ARB can re-duce the 24-hour urinary protein quantitation and improve the renal function of IgA nephropathy patients,without the risk of causing blood system damage.It is a safe approach with significant efficacy.

Objective To measure and compare the cerebral blood flow(CBF)of children with autism spectrum disorder(ASD),global developmental delay(GDD),and ASD with GDD groups via arterial spin labeling(ASL)technique,and to evaluate the diag-nostic value of CBF values.Methods ASL images of ASD,GDD,and ASD with GDD groups of children were firstly acquired,and the CBF values of frontal lobe,temporal lobe,parietal lobe,occipital lobe,striatum and thalamus region of interest(ROI)were fur-ther measured,respectively.One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences in CBF values among these three groups,and the receiver operating characteristic(ROC)curve was used to analyze the efficacy of CBF values in distinguishing ASD with GDD from without GDD.Results ASD with GDD had significantly lower CBF values in the left and right frontal lobes than those with ASD or GDD alone,and the differences were statistically significant(P<0.05).The CBF values in the left and right frontal lobes effectively distinguished ASD with GDD from without GDD[area under the curve(AUC)>0.7].Conclusion ASL technique can noninvasively assess CBF in children with or without GDD,helping to understand the pathophysiology of ASD with GDD and improving diagnostic accuracy.

Objective:To analyze the association between visceral fat area (VFA) and fatty liver based on quantitative CT (QCT) in people receiving health examination with normal body mass index (BMI).Methods:A cross-sectional study. A total of 1 305 physical examiners who underwent chest CT and QCT examination in the Department of Health Management of Henan Provincial People′s Hospital from January to December 2021 were retrospectively selected as subjects. The physical components at the central level of the lumbar two cone were measured with QCT, including subcutaneous fat area (SFA), VFA and liver fat content (LFC). And the metabolic indexes, such as blood lipids and blood glucose, were collected. The t-test and χ2 test were used to analyze the correlation between the detection rate of fatty live and LFCr and age and gender. According to level of VFA (<100 cm 2, 100-150 cm 2 and≥150 cm 2), the subjects were divided into three groups, and one-way ANOVA and χ2 test were used in comparison between groups. Multiple linear regression was used to analyze the correlation between VFA and metabolic indexes and LFC. Results:Of the 1 305 subjects, there were 634 males and 671 females. The detection rate of fatty liver in normal BMI population was 65.67%, and it was 72.71% and 59.02% respectively in men and women ( χ2=27.12, P<0.001), and the detection rate of fatty liver and LFC increased with age (both P<0.05). With the increase of VFA, the age, BMI, SFA, LFC, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), blood uric acid and prevalence of fatty liver increased (all P<0.05), and the low-density lipoprotein cholesterol (HDL-C) decreased ( P<0.001). Multiple linear regression analysis showed that after adjustment for age factors, regardless of male or female, LFC was independently positively related with VFA, BMI, and ALT (male β=0.206, 0.145, 0.174, female β=0.194, 0.150, 0.184; all P<0.05). FBG was positively correlated with male independently ( β=0.134; P<0.001). The indicators related to female independently were TC, TG, and blood uric acid ( β=-0.121, 0.145, 0.141, all P<0.05) Conclusion:In the population receiving health examination with normal BMI, the VFA measured by QCT technique is closely related to fatty liver.

BACKGROUND: Biliary tract carcinomas (BTCs) are relatively rare but lethal primary malignant tumors derived from the biliary tract system. The burden of BTCs varies according to sex, age, region, and country, but limited attention has been paid to the burden of BTCs. We sought to explore the up-to-date data from the Global Burden of Disease Study (GBD) and expand findings by accessing the demographic features of BTC disease burden. METHODS: Using the latest data from the GBD 2021, we evaluated and analyzed the distributions and patterns of BTC disease burden in various age groups, sexes, regions, and countries. RESULTS: The number of incident cases, deaths, and disability-adjusted life-years (DALYs) tended to increase and peaked at 216,770 (95% uncertainty interval [UI]: 181,890-245,240), 171,960 (95% UI: 142,350-194,240), and 3,732,100 (95% UI: 3,102,900-4,317,000) person-years, respectively, in 2021. However, the average global age-standardized rates (ASRs) of incident cases, deaths, and DALYs shrunk by -11.46% (95% UI: -21.91 to 3.35%), -24.09% (95% UI: -33.19 to 16.88%), and -26.25% (95% UI: -35.53 to 18.36%), respectively, from 1990 to 2021. Meanwhile, the male/female ratio (male per 100 female) of incidence, deaths, and DALYs changed from 76.40, 75.41, and 74.72 to 86.89, 79.11, and 82.29, respectively. In 2021, the highest number of incident cases, deaths, and DALYs occurred in East Asia. The top three highest incidences, deaths, and DALYs were observed in China, India, and Japan, and the highest ASRs were observed in Chile in 2021. Analysis of the Human Development Index along with disease burden estimates of BTCs also suggests that the burden of the disease is related to the level of comprehensive development of the society. CONCLUSION This study provided a comprehensive comparison of differences in the burden of disease across populations and over time, and further presented evidence concerning the formulation of prevention and control policies and etiologic studies for BTCs and proposed logical hypotheses to investigate.
Humans ; Global Burden of Disease ; Biliary Tract Neoplasms/epidemiology* ; Male ; Female ; Disability-Adjusted Life Years ; Middle Aged ; Aged ; Adult ; Incidence ; Aged, 80 and over ; Quality-Adjusted Life Years ; Cost of Illness

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is a malignant tumor with remarkable proliferative and invasive ability, which has very poor clinical prognosis due to lack of effective treatments. This study aims to evaluate the efficacy and synergistic effects of radiotherapy (RT) combined with immunotherapy (IT) and chemotherapy (CT) in patients with ES-SCLC. METHODS: A retrospective analysis was performed on 145 ES-SCLC patients treated with first-line CT. Kaplan-Meier analysis and Log-rank tests were used to evaluate survival outcomes, while propensity score matching (PSM) was applied to reduce confounding factors. RESULTS: The median overall survival (mOS) and median progression-free survival (mPFS) for the entire cohort were 15.7 and 6.9 mon, respectively. The IT+CT group had a significantly longer mOS compared to the CT group (17.2 vs 13.5 mon, P=0.047). Similarly, the RT+CT group demonstrated superior mOS (18.5 vs 12.3 mon, P<0.001) and mPFS (7.1 vs 6.2 mon, P=0.006) compared to the CT group. Multivariate analysis identified RT, IT, and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for mOS (P<0.05), while gender and ECOG PS were independent predictors for mPFS (P<0.05). Following PSM, the RT+CT group continued to exhibit significant advantages in mOS (18.0 vs 12.1 mon, P<0.001) and mPFS (7.1 vs 5.5 mon, P=0.037) compared to the CT group. Notably, the RT+IT+CT group achieved a markedly longer mOS than the IT+CT group (28.5 vs 15.8 mon, P=0.017). Grade 3-4 adverse events occurred in 27.6% of patients, with no grade 5 adverse events reported. CONCLUSIONS The combination of RT, IT, and CT significantly enhances the prognosis of ES-SCLC patients. RT plays a key role in their synergistic effects and demonstrates good safety, warranting further research and clinical application.
Humans ; Small Cell Lung Carcinoma/mortality* ; Male ; Female ; Middle Aged ; Lung Neoplasms/mortality* ; Retrospective Studies ; Aged ; Immunotherapy ; Prognosis ; Combined Modality Therapy ; Adult ; Neoplasm Staging ; Aged, 80 and over