Objective:Non-alcoholic fatty liver disease(NAFLD)is a common metabolic disorder in overweight and obese children,and its etiology and pathogenesis remain unclear,lacking effective preventive and therapeutic measures.This study aims to explore the association between whole blood copper,zinc,calcium,magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years,providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. Methods:A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys.Fasting blood samples were collected from the subjects,and various indicators such as blood glucose,blood lipid,and mineral elements were detected.All children were divided into an overweight group(n=400)and a NAFLD group(n=202).The NAFLD group was divided into 2 subgroups according to the ALT level:A non-alcoholic fatty liver(NAFL)group and a non-alcoholic steatohepatitis(NASH)group.Logistic regression analysis was used to analyze the association between minerals(copper,zinc,calcium,magnesium,and iron)and NAFLD,NAFL and NASH. Results:A total of 602 subjects were included,of whom 73.6%were male,with a median age of 10(9,11)years,and a body mass index(BMI)of 24.9(22.7,27.4)kg/m2.The intergroup comparison results showed that compared with the overweight group,the NAFLD group had higher levels of age,BMI,diastolic blood pressure(DBP),systolic blood pressure(SBP),triglyceride(TG),low density lipoprotein(LDL),alanine transaminase(ALT)and aspartate aminotransferase(AST),and lower level of high density lipoprotein(HDL).The NAFL group had higher levels of age,BMI,DBP,SBP,ALT,and AST,and lower levels of HDL compared with the overweight group.The levels of age,BMI,DBP,SBP,TG,LDL,ALT,and AST of NASH were higher than those in the overweight group,while the level of HDL was lower than that in overweight group(all P<0.017).After adjusting for a variety of confounders,the OR of NAFLD for the highest quantile of iron was 1.79(95%CI 1.07 to 3.00)compared to the lowest quantile,and no significant association was observed between copper,zinc,calcium,and magnesium,and NAFLD.The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21(95%CI 1.26 to 3.88),while no significant association was observed between iron level and NASH.In addition,no significant associations were observed between copper,zinc,calcium,and magnesium levels and NAFL or NASH. Conclusion:High iron level increases the risk of NAFLD(more likely NAFL)in overweight and obese children,while copper,zinc,calcium,magnesium,and other elements are not associated with the risk of NAFLD in overweight and obese children.

Objective:Non-alcoholic fatty liver disease(NAFLD)has significant genetic susceptibility.Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis.However,the association between adipocytokine pathway genes and NAFLD remains unclear.This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. Methods:A case-control study was conducted,dividing obese children into NAFLD and control groups.Peripheral venous blood(2 mL)was collected from each participant for DNA extraction.A total of 14 single nucleotide polymorphisms(SNP)in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing.Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children.Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression.Generalized multifactor dimensionality reduction(GMDR)was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. Results:A total of 1 022 children were included,with 511 in the NAFLD group and 511 in the control group.After adjusting for age,gender,and BMI,multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models:heterozygote model(CG vs CC,OR=0.58,95%CI 0.36 to 0.95,P=0.029),dominant model(GG+CG vs CC,OR=0.62,95%CI 0.38 to 1.00,P=0.049),and overdominant model(CC+GG vs CG,OR=1.72,95%CI 1.06 to 2.80,P=0.028).PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models:heterozygous model(CT vs CC,OR=1.51,95%CI 1.10 to 2.07,P=0.011),dominant model(CT+TT vs CC,OR=1.50,95%CI 1.10 to 2.03,P=0.010),overdominant model(CC+TT vs CT,OR=0.67,95%CI 0.49 to 0.92,P=0.012),and additive model(CC vs CT vs TT,OR=1.40,95%CI 1.07 to 1.83,P=0.015).No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD.GMDR analysis,adjusted for age,gender,and BMI,revealed no statistically significant interactions among the 14 SNPs(all P>0.05). Conclusion:Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children.However,no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.

Objective:To examine the effect of brown midle borosilicate glass ampoules on the drug safety of ambr-oxol hydrochloride injection.Methods:By simulating the storage conditions of ambroxol hydrochloride injection,experimental studies were designed using inductively coupled plasma emission spectroscopy(ICP-OES)and scan-ning electron microscopy(SEM)to investigate element migration and internal surface detachment.Results:The Si content in the injections increased over time,and after 0 to 48 months of various stages of testing,the inner surface of the glass was intact,with no detachment or erosion;the migration of various target elements,such as Cd,Pb,As,Hg,etc.,into the injections took place,but the contents were in accordance with the limits set by the relevant regulations.Conclusion:Brown middle borosilicate glass ampoule packaging for ambroxol hydrochloride injection is safe and stable for 48 months.Brown middle borosilicate glass ampoule can be used as a good container for ambr-oxol hydrochloride injection.

Pituitary neuroendocrine tumors (PitNETs) are the second common central nervous system tumors. Patients often present with headache, vision loss, visual field defects, and cognitive dysfunction. Cognitive function is the ability of the brain to acquire, analyze and process external information; once the patient has serious cognitive dysfunction, it will bring heavy burden to the family and society. This article summarizes the cognitive functions in patients with PitNETs from perspectives of hormone, anatomical structures around the pituitary, tumor volume, treatment, and cognitive function assessment, in order to provide research ideas in elucidating relevant mechanisms in the future and provide basis for formulating rehabilitation plans for patients.

In recent years, the rapid increase in cancer treatment costs in China had brought a huge economic burden to society, and it was urgent to standardize the rational application of anti-tumor drugs. In the context of the reform of group payment related to disease diagnosis, a tertiary first-class hospital focused on the needs of patients and guided by value-based healthcare, established a professional and normalized refined anti-tumor drug management system, setted up a multidisciplinary diagnosis and treatment team, and promoted " Internet plus pharmaceutical services" in December 2018.From 2019 to 2021, the proportion of hospital drugs were 30.8%, 30.1%, and 27.3%, respectively. The amount of money spent on anti-tumor drugs were 83.25 million yuan, 76.41 million yuan, and 62.48 million yuan, respectively, showing a decreasing trend year by year. The practice of refined management of anti-tumor drugs fully reflected the core concept of value based healthcare, achieving closed-loop management of the entire process of drugs, improving the level of rational drug use, reducing the economic burden on patients, and providing reference for improving the level of rational use of anti-tumor drugs in public hospitals.

Objective To investigate the effects of microRNA497 (miR-497) on the metastasis of gastric cancer and its possible molecular mechanism. Methods SGC-7901 gastric cancer parent cells were cultured in an ultra-low adhesion environment, and the anoikis resistance model of SGC-7901 cells was created after re-adhesion. Clone formation assay, flow cytometry, Transwell^TM test and scratch healing test were used to detect the differences of biological behavior compared with their parent cells. Fluorescence quantitative PCR was performed to detect the expression of miR-497. Western blot analysis was used to detect the changes of key proteins of Wnt/β-catenin signaling pathway and epithelial mesenchymal transformation (EMT) related proteins such as vimentin and E-cadherin. Parent cells and anoikis resistant SGC-7901 cells were transfected with miR-497 inhibitor or miR-497 mimic, and CCK-8 assay was used to detect the proliferation activity. Transwell^TM invasion assay was performed to detect the invasion ability of cells. Transwell^TM migration test and scratch healing assay was used to determine the migration ability. Western blot analysis was used to detect the expressions of Wnt1, β-catenin, vimentin and E-cadherin. By transfecting miR-497 mimic into the anoikis resistance SGC-7901 cells and inoculating them subcutaneously in nude mice, the changes in the volume and mass of tumor tissues were measured and recorded. Western blot analysis was used to determine the expressions of Wnt1, β-catenin, vimentin and E-cadherin of tumor tissues. Results Compared with the parent cells, the anoikis resistance SGC-7901 gastric cancer cells had faster proliferation rate, stronger colony formation, lower apoptosis rate, stronger invasion and migration ability. The expression of miR-497 was significantly decreased. After down-regulation of miR-497, the proliferation ability, invasion and migration ability were significantly enhanced. The expressions of Wnt1, β-catenin and vimentin increased significantly, while E-cadherin decreased notably. The results of up-regulation miR-497 were the opposite. The tumor growth rate, tumor volume and mass of miR-497 overexpression group were significantly lower than those of control group. The expressions of Wnt1, β-catenin and vimentin decreased significantly, while the expression of E-cadherin increased significantly. Conclusion The expression of miR-497 is low in the anoikis resistance SGC-7901 cells. miR-497 can inhibit the growth and metastasis of gastric cancer cells by blocking Wnt/β-catenin signaling pathway and EMT.
Animals ; Mice ; Humans ; beta Catenin/metabolism* ; MicroRNAs/metabolism* ; Vimentin/metabolism* ; Stomach Neoplasms/pathology* ; Anoikis/genetics* ; Wnt Signaling Pathway/genetics* ; Mice, Nude ; Cell Proliferation/genetics* ; Cadherins/genetics* ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/genetics* ; Cell Movement/genetics*

The axon initial segment (AIS) is a specialized structure that controls neuronal excitability via action potential (AP) generation. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI (chicken ovalbumin upstream promotor-transcription factor 1) is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation. Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation, they strengthen and weaken, respectively, the receiving spontaneous network in mutant neurons. In contrast, overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation, but decreases the receiving spontaneous network. Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.
Action Potentials ; Animals ; Axon Initial Segment ; COUP Transcription Factor I ; DNA-Binding Proteins/physiology* ; Mammals ; Mice ; Transcription Factors

Objective:To investigate the changes of CPT1A and CPT1B protein expression in rat intestinal epithelial cells (IEC-6) after 60Co γ-ray irradiation, and the mechanism of the influence of carnitine palmitoyltransferase 1 (CPT1) on the proliferation of irradiated IEC-6 cells. Methods:IEC-6 cells were cultured in serum-normal medium or in serum-starved medium overnight, and pretreated with 20 μmol/L palmitic acid (PA) before irradiation with 0, 5, 10, and 15 Gy. At 24 h after irradiation, the cellular protein was collected for the measurement of CPT1A and CPT1B proteins by Western blot. The influences of ETO, an inhibitor of CPT1, on the survival and proliferation of irradiated IEC-6 cells were analyzed by colony formation assay and CCK-8 assay. The protein expressions and phosphorylation levels of the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in 5 Gy irradiated IEC-6 cells pre-treated with ETO were analyzed by Western blot at 48 h after radiation.Results:When IEC-6 cells were cultured in serum-normal medium together with PA, the protein level of CPT1A was significantly increased after 15 Gy irradiation ( t=-2.82, P<0.05). When IEC-6 cells were cultured in serum-starved medium, the protein level of CPT1A was significantly increased at 5, 10, and 15 Gy ( t=-3.28, -8.72, -8.67, P<0.05). When IEC-6 cells were cultured in serum-starved medium together with PA, the protein levels of CPT1A were significantly increased at 5, 10 and 15 Gy ( t=-10.69, -7.02, -8.23, P<0.05), the protein levels of CPT1B were significantly increased at 10 and 15 Gy ( t=-3.73, -5.05, P<0.05). After irradiation, the survival and proliferation of IEC-6 cells in ETO group were significantly lower than those in control group ( t=5.46, 13.22, P<0.05), and the protein level of ERK1/2 and p-JNK in ETO group were significantly lower than those in control group ( t=4.01, 3.29, 10.68, 14.44, P<0.05). Conclusions:CPT1 promoted radiation-induced IEC-6 injury cells survival and proliferation by enhancing the expression level of ERK1/2 protein and the activity of JNK.

Objective:To analyze Helicobacter pylori ( Hp) resistance in Xiaoshan area from 2013 to 2020 and to provide reference for the selection of clinical antibiotics for the eradication of Hp in this area. Methods:Non-repetitive Hp strains isolated from patients treated in the First People′s Hospital of Xiaoshan District, Hangzhou from January 2013 to December 2020 and the drug susceptibility test results of these strains were collected. The patients were grouped by every 10 years of age to analyze the drug resistance of Hp in different groups and its changing trends. Results:A total of 54 912 Hp strains were isolated and cultured. The resistance rates of Hp isolates to amoxicillin, metronidazole, clarithromycin and levofloxacin were 0.42%, 92.94%, 22.41% and 29.83%, respectively. The drug resistance rates to clarithromycin and levofloxacin were increasing year by year. The resistance rates to levofloxacin, clarithromycin and metronidazole increased with age. The resistance rates to clarithromycin, levofloxacin and metronidazole in women were higher than those in men, especially in the 21-60 age group. The resistance rate to clarithromycin was significantly higher in people under 20 years old. In 2017 to 2019, the resistance rate to amoxicillin was higher in people under 20 years old than in other age groups. In 2020, the resistance rates to levofloxacin and clarithromycin in people over 70 years old both exceed 57% and increased rapidly. Conclusions:The resistance rates of Hp to levofloxacin, clarithromycin and metronidazole in Xiaoshan area were all at a high level. It was recommended to use individualized treatments for the eradication of Hp. In addition, attention should be paid to the young and older people.

Objective To investigate the characteristics of ocular surface inflammation index after pterygium excision by using Oculus Keratograph(R) 5M and Visual analogue scale and evaluated the effectiveness of antiinflammatory treatment.Methods A prospective case control study was performed.Eighteen patients (6 males and 12 females) who suffered from primary pterygium were recruited in Zhongshan Ophthalmic Center from June to September 2016.All patients were treated with monocular pterygium excision combined with amniotic membrane transplantation.Anti-inflammatory treatment was given after surgery,and the ocular inflammation index was evaluated at preoperative and 1st,3rd,7th,10th,30th and 60th day postoperative.The temporal conjunctival hyperemia index (TCHI) was assessed by Oculus Keratograph(R) 5M with a red eye index analysis software.Ocular symptom scores (OSS) and visual analogue scale (VAS) were used to analyze the subjective symptoms of the patients.Fluorescein staining was used to detect the epithelization of corneal and scleral wound.The best corrected visual acuity (BCVA),intraocular pressure and complications were evaluated in this study.This study was approved by the Medical Ethics Committee of Zhongshan Ophthalmic Center of Sun Yat-sen University (2016KYPJ024).All patients signed informed consent for clinical research.Results No drug-related ocular and systemic adverse events were found during the follow-up.Corneal epithelial defect was recovered on 10th day,and conjunctival epithelization was observed in sclera exposed area on 30th day.The BCVA on the 60th day was 0.12±0.17,which was significantly lower than 0.34±0.36 preoperatively (t =3.401,P =0.003).Compared with those before surgery,OSS and VAS were significantly increased on 1 st day (OSS:Z =-4.255,P =0.000;VAS:Z =-5.256,P =0.000).The OSS on 7th day was not significantly different from that before surgery (Z=-0.958,P=0.372).VAS decreased to baseline on 30th day.The OSS on 60th day after surgery was significantly lower than that before surgery (Z =-2.397,P =0.037).TCHI was higher than 1.2 preoperatively,and increased to the highest on 1 st day after surgery,with significant difference between them (t=-6.620,P=0.000).The TCHI decreased to baseline on 7th day,no significant difference were obtained when compared with preoperative TCHI (t =-1.050,P =0.310),and TCHI on 60th day after surgery was lower than that before surgery,with significant difference between them (t =2.758,P =0.020).Conclusions The subjective symptoms combined with conjunctival hyperemia can be more accurate assessment of ocular surface inflammation in the perioperative period of pterygium surgery,which can be used as an evaluation index to assess the effectiveness of anti-inflammatory treatment.