Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids. Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD. Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas low-density lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different. Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

OBJECTIVE To explore the effects of trichloroisocyanuric acid(TCCA)on the prolifera-tion of spermatogonia by inducing oxidative stress and ferroptosis.METHODS GC-1 cells were cultured in DMEM-F12 medium,and cell proliferation was plotted according to the growth curve.GC-1 cells were treated with TCCA at concentrations of 0(cell control),97,194,and 387 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,apoptosis cells were stained with Hoechst 33342,cell cycle was examined by PI staining method,RT-qPCR was performed to measure the mRNA expres-sion levels of apoptosis-related genes Bax,Fas,oxidative stress-related genes superoxide dismutase 2(SOD2),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),dihydroorotate dehydrogenase(DHODH),DNA methyltransferase 3A(DNMT3A),and DNA methyltransferase 3L(DNMT3L).The Griess method was used to determine the nitric oxide(NO)content,colorimetric method for the malondialdehyde(MDA)level,DCFH-DA fluores-cence probe method for the reactive oxygen species(ROS)level,DNTB colorimetric method for the reduced glutathione(GSH)content,and WST-8 method for the reduced coenzymeⅡ(NADPH)content.RESULTS Compared with the cell control group,the cell survival rates in the TCCA 194 and 387 μmol·L-1 groups decreased significantly(P<0.01),accompanied by nuclear condensation and fragmentation,a significant increase in apoptosis rate(P<0.01),and cell arrest in the G2/M phase(P<0.05).Additionally,in the TCCA 387 μmol·L-1 group,the levels of NO,MDA and ROS increased(P<0.01),while the levels of GSH and NADPH decreased(P<0.01).Moreover,the mRNA expressions of SOD2,GPX4,Nrf2,SLC7A11,and DHODH decreased(P<0.05,P<0.01),while the expressions of Bax,Fas,DNMT3L,and DNMT3A increased(P<0.05,P<0.01).CONCLUSION TCCA exposure reduces the viability of GC-1 cells,inhibits cell proliferation,induces apoptosis of GC-1 cells.The mechanism may be related to the ability of TCCA to enhance oxidate stress,induce ferroptosis,and interfere with the methylation of GC-1 cells.

This study explores the application effect of the case-based teaching method based on Xuexitong learning platform in the online teaching of Digestive System, and analyzes the learner's emotional experience, learning behavior, and learning effect in the case-based online teaching. The results of the study show that the case-based online teaching model based on Xuexitong learning platform improves students' online learning interest, and the students have good emotional experience, high learning enthusiasm, good classroom interaction, enhanced self-learning ability before and after class, and good learning effect. In addition, precise teaching can be used for individual students who are not enthusiastic about online learning.

Objective:To differentiate hyperintense hepatocellular carcinoma (HCC) with focal nodular hyperplasia (FNH) in the hepatobiliary phase by MRI multimodal parameters.Methods:A retrospective cross-sectional study method was adopted. Clinical data on 15 cases with hyperintense HCC and 15 cases with FNH in the hepatobiliary phase admitted to the First Affiliated Hospital of the Army Medical University from January 2012 to December 2019 were collected. All patients with solitary lesions who underwent Gd-EOB-DTPA-enhanced MRI examinations were included. Surgically resected specimens were verified by pathological and immunohistochemical examination. HCC and FNH imaging features were analyzed by two radiologists.Results:(1) HCC and FNH apparent diffusion coefficient (ADC) values were 1 205.07±239.65×10 -3 mm 2/s and 1 434.73±217.6×10 -3 mm 2/s, respectively, and the SI ADC difference was statistically significant ( P<0.05) between the two groups. (2) In the dynamic contrast-enhanced MRI sequence, 15 cases of HCC were significantly enhanced in the arterial phase, of which 13 cases were characterized by continuous enhancement, and 2 cases were characterized by wash-in and wash-out enhancement. There was no statistically significant difference ( P>0.05) between the two groups. SI enhancement rate between HCC and FNH (1.39±0.60 vs. 1.33±0.50, P>0.05) had no significant difference. (3) HCC and FNH morphological features in the hepatobiliary phase included: annular hypointensity: HCC (8 cases) vs. FNH (0 cases); contrast filling defects: HCC (8 cases) vs. FNH (0 cases); linear hyposignal separation: HCC (10 cases) vs. FNH (0 cases); and stellate scars: HCC (0) vs. FNH (5 cases), and there were statistically significant differences ( P<0.05) between the two groups . Conclusion:Multimodal MRI have significant value for differentiating hyperintense HCC and FNH in the hepatobiliary phase.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective To explore the mechanism of HIF-1α promoting malignant development of nasopharyngeal carcinoma by upregulating PD-L1 expression under hypoxic conditions. Methods CNE2 cells were divided into normoxia (20%O₂), hypoxia (1%O₂), HIF-1α-siRNA+hypoxia and NC-siRNA+hypoxia groups. Cell proliferation, apoptosis, the mRNA levels of HIF-1α, STAT3 and PD-L1, the protein levels of HIF-1α, PD-L1, STAT3 and STAT3 phosphorylation were detected by MTT assay, flow cytometry, RT-PCR and Western blot, respectively. Results Cell proliferation of hypoxia group was significantly higher than that of normoxia group (P=0.000). The cell proliferation rate of HIF-1α-siRNA+hypoxia group was significantly lower than those in other groups (P=0.000). The apoptosis rate of HIF-1α-siRNA+hypoxia group was remarkably higher than those in other groups (P=0.001). RT-PCR detection showed that the mRNA levels of HIF-1α, PD-L1 and STAT3 in the HIF-1α-siRNA+hypoxia group were significantly lower than those in hypoxia group and NC-siRNA+hypoxia group. The protein expression of HIF-1α, PD-L1 and STAT3 showed similar tendency in Western blot assays compared with the mRNA levels. The pSTAT3 protein expression level in HIF-1α-siRNA+hypoxia group was significantly lower than those in hypoxia group and HIF-1α-siRNA+hypoxia group (P=0.001). Conclusion Under hypoxic microenvironment, HIF-1α may up-regulate the expression of PD-L1 through STAT3, thereby promoting the immune escape of cancer cells, leading to the malignant development of nasopharyngeal carcinoma.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

OBJECTIVE: To explore the genetic basis for a pedigree affected with X-linked mental retardation. METHODS: The proband was subjected to chromosomal karyotyping, FMR1 mutation testing and copy number variation analysis with a single nucleotide polymorphism microarray (SNP array). His family members were subjected to multiplex ligation-dependent probe amplification (MLPA) assaying. Expression of genes within the repeated region were analyzed. RESULTS: The proband had a normal chromosomal karyotype and normal number of CGG repeats within the FMR1 gene. SNP array identified a 370 kb duplication in Xq28 (ChrX: 153 027 633-153 398 515), which encompassed 14 genes including MECP2. The patient was diagnosed as Lubs X-linked mental retardation syndrome (MRXSL). MLPA confirmed the presence of copy number variation, its co-segregation with the disease, in addition with the carrier status of females. Genes from the duplicated region showed higher levels of expression (1.79 to 5.38 folds) within peripheral blood nucleated cells of the proband. CONCLUSION The patients were diagnosed with MRXSL. The expression of affected genes was up-regulated due to the duplication. Genetic counseling and prenatal diagnosis may be provided based on the results.
DNA Copy Number Variations ; Female ; Fragile X Mental Retardation Protein ; Humans ; Mental Retardation, X-Linked ; Methyl-CpG-Binding Protein 2 ; Pedigree ; Pregnancy