Objective:To explore the role CD4+CD45RO+memory T cells in the pathogenesis of Hashimoto's thyroiditis (HT) by detecting the percentages of CD4+CD45RO+ memory T cells in peripheral blood mononuclear cells in peripheral blood of newly diagnosed HT patients. Methods:53HT patients and 43 matched healthy controls (HC) were included in this study. According to the thyroid functions,HT patients were divided into euthyroid subset(HT-A,n =15) ,subclinical hypothyroidism(HT-B,n=14) and overt hypothyroidism subset (HT-C,n=24). The percentages of CD4+CD45RO+memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,and thyroid functions,and the titers of thyroid-specific autoantibodies (TPOAb,TgAb) were respectively detected by flow cytometry,ELISA,and ECLIA. Results:The percentages of CD4+CD45RO+ memory T cells in PBMCs,as well as the level of serum IFN-γ and IL-17,the titers of TPOAb,TgAb were all significantly higher than that in HC(P<0. 01). Bivariate correlation revealed that the percentages of CD4+CD45RO+ memory T cells positively correlated with the level of serum IFN-γ,TPOAb and TgAb(P<0. 01,P=0. 015,P<0. 01) in HT patients. Conclusion:The significant increase of CD4+CD45RO+memory T cells in peripheral blood of patients with HT suggested a role of CD4+CD45RO+ memory T cells in the pathogenesis of this disease.

Purpose To explore the relationship between the change of space anterior to right portal vein and the pathological staging in liver ifbrosis/cirrhosis. Materials and Methods Plain and contrast enhanced CT scan were performed in patients with biopsy proven liver ifbrosis/cirrhosis including S1 in 17 patients, S2 in 13 patients, S3 in 15 patients, S4 in 21 patients and cirrhosis in 22 patients. Twenty subjects were included as control group. The width of anterior space of right portal vein was measured on contrast enhanced CT and correlated with ifbrosis staging. The receiver operating characteristic curve was created for cirrhosis diagnosis. Results The width of anterior space of right portal vein enlarged in patients with S3 ifbrosis to cirrhosis (P<0.05 or P<0.01). It was signiifcantly bigger in group S4 compared to other groups (P<0.01). Spearman rank correlation analysis showed significant positive correlation between the width of anterior space and liver fibrosis staging (r=0.704, P<0.01). ROC curve analysis showed the area under curve (AUC) of 0.897 with the optimum width of ≥10 mm. Conclusion The change in the space anterior to the right portal vein is positively correlated with live ifbrosis staging. CT measurement helps early diagnose and assess the severity of liver ifbrosis and cirrhosis.

Sodium channel provides a new idea for the study of painful diabetic neuropathy.Based on the research status of sodium channel and painful diabetic neuropathy at home and abroad,five sodium channels with high correlation with diabetic painful neuropathy were selected,and the characteristics of these sodium channels were summarized.The expression status of sodium channel in diabetic painful neuropathy model was summarized,and the role of sodium channel in the pathogenesis of diabetic painful neuropathy was summarized.The relationship between sodium channel and diabetic painful neuropathy was analyzed,as well as the difficulties facing the current research,in order to provide references for the research and application of sodium channel in the treatment of diabetic painful neuropathy.

Objective To investigate the features and correlation analysis of clinico-pathological and expression of phospholipase A2 receptor(PLA2R)in idiopathic membranous nephropathy. Methods A number of 244 patients of IMN proved by renal biopsy were recruited in Wuxi People's Hospital from July 2008 to February 2015. Data were restrospectively collected. Results In the 244 IMN patients(mean age 54.07 ± 15.22 years,130 males and 114 females),44.3% had hypertension and 62.7% had nephrotic syndrome. Compared with female patients ,male patients had more severe proteinuria and lower eGFR(P < 0.05). Compared with the group of proteinuria < 4 g/24 h,the groups of proteinuria 4~8 g/24 h and > 8 g/24 h had higher level of cholesterol and blood pressure ,lower eGFR and more severe tubulointerstitial lesions(P < 0.05). Pathological stage Ⅰ and Ⅱaccounted for 98%,and there were more severe tubulointerstitial lesions and lower eGFR in the patients of stage Ⅱthan that in the patients of stageⅠandⅠ~Ⅱ(P<0.05). The positive rate of PLA2R accounted for 84.3%. Lower eGFR and more severe tubulointerstitial lesions were found in PLA2R-positive patients than those in PLA2R-neg-ative patients(P < 0.05). Multiple regression analysis showed that tubulointerstitial lesions(B =-7.253),hyper-tension ratio(B=-10.726)and the level of cholesterol(B=-2.077)had negative correlations with eGFR(P<0.01, R2=0.470). Conclusions IMN patients of male gender,grave proteinuria,high pathological stage and positive PLA2R should be treated more actively , since severe tubulointerstitial lesions and kidney injury were more common in those patients.

Objective:To investigate the serum level and significance of complement factor B (CFB) and complement factor D (CFD) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN).Methods:From October 2019 to October 2020, 110 patients with T2DM in the endocrinology department of Affiliated Hospital of Jining Medical College were divided into DPN group ( n=60) and simple T2DM group ( n=50) according to whether or not DPN was combined. In addition, 52 cases of physical examination population in the physical examination center in the same period were selected as the normal control group ( n=52). The serum levels of CFB, CFD and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA). The correlation between CFB, CFD and clinical indexes was analyzed, and the influencing factors of DPN were analyzed by logistic regression. Results:The serum levels of CFB and CFD in DPN group were higher than those in T2DM group and normal control group [CFB: (845.43±101.10)μg/ml vs (792.19±116.59)μg/ml, (739.20±123.43)μg/ml, P<0.05], [CFD: (491.71±41.03)mg/L vs (467.58±45.16)mg/L, (445.16±50.47)mg/L, P<0. 05]. Pearson correlation analysis showed that the serum level of CFB was positively correlated with glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG) and TNF-α (all P<0.05) and negatively correlated with triiodothyronine (FT3) and total bilirubin (TBIL) (all P<0.05). Serum CFD level was positively correlated with systolic blood pressure, HbA 1c, FPG and TNF-α (all P<0.05), but negatively correlated with FT3 and TBIL (all P<0.05). Logistic regression analysis showed that CFB and CFD were still influential factors for the occurrence and development of DPN after excluding confounding factors such as systolic blood pressure, HbA 1c, FPG, FT3, DBIL, TBIL and TNF-α. Conclusions:(1) Serum CFB and CFD levels were significantly increased in DPN patients, suggesting that CFB and CFD may be involved in the occurrence and development of DPN. (2) Serum TNF-α level was significantly increased in DPN patients, confirming the role of TNF-α in the pathogenesis of DPN.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective To investigate the clinico-pathological features of idiopathic membranous nephropathy (IMN ) and the expression of phospholipase A2 receptor (PLA2R ) in elderly patients. Methods A total of 109 elderly patients with IMN confirmed by renal biopsy at Wuxi People's Hospital from July 2008 to February 2015 were included.Data were retrospectively collected. Results (1)Participating patients with IMN had a mean age of (67.3 ± 5.4)years ,and 67.9% of them had hypertension and 65.1% had nephrotic syndrome.Compared with non-elderly patients ,elderly patients had a higher proportion with hypertension (67.9% vs.25.2%)(P＝0.000) ,higher systolic pressure[(143.1 ± 15.2)mmHg vs. (127.3 ± 13.3)mmHg](P＝ 0.000) ,higher diastolic pressure [(88.4 ± 10.0)mmHg vs. (80.2 ± 8.4)mmHg](P＝ 0.000) ,more severe tubulointerstitial lesions [(3.1±1.9)points vs.(2.0±1.9)points](P＝0.000),and lower eGFR[(70.9±22.9)ml·min－1· 1.73 m －2vs. (90.6 ± 27.1 ) ml·min－1·1.73 m －2] ( P ＝ 0.000 ). (2 ) There were more severe tubulointerstitial lesions[(4.7 ± 1.8)points vs. (2.4 ± 1.7)points ,2.9 ± 1.6 points](P ＝ 0.000 , 0.000)and lower eGFR[(50.4 ± 17.4)ml·min－1·1.73 m －2vs. (80.3 ± 19.7)ml·min－1·1.73 m －2, (72.3 ± 21.4)ml·min－1·1.73 m －2](P＝0.000 ,0.000)in elderly patients of pathological stage Ⅱ, compared with patients of pathological stages Ⅰ and Ⅰ-Ⅱ. (3)The rate of positive PLA2R was 82.4%.Patients with positive PLA2R had higher proteinuria[(4.5 ± 2.3)g vs. (2.9 ± 1.1)g](P＝0.042) ,lower eGFR[(66.8 ± 21.8)ml·min－1·1.73 m －2vs. (97.7 ± 16.0)ml·min－1·1.73 m －2](P＝0.000) ,and more severe tubulointerstitial lesions [(3.1 ± 2.0)points vs. (1.7 ± 1.1)points](P＝0.037)than patients with negative PLA2R. (4)Multiple regression analysis showed that PLA2R positive rate(P＝0.008) ,tubulointerstitial lesion(P＝0.000) ,and level of cholesterol(P＝0.025)were negatively correlated with eGFR (R2＝0.572). Conclusions Compared with non-elderly patients , elderly patients with IMN have poorer prognosis as a result of higher blood pressure and more severe tubulointerstitial lesions.Elderly patients with IMN of advanced pathological stages and positive PLA2R have more severe kidney injury and tubulointerstitial lesions ,resulting in poor prognosis.

OBJECTIVETo investigate the gene frequencies and mutation patterns of alpha thalassemia (alpha-thal) and beta thalassemia (beta-thal) in Liuzhou city of Guangxi Zhuang Autonomous Region.

METHODSCluster sampling was used. A total of 1 028 of umbilical blood samples were collected for a prevalence study of alpha-thal and a total of 1 312 healthy young people when receiving pre-marriage consultation were recruited for a beta-thal prevalence survey. Individuals live in city or town area of Liuzhou. A complete blood count as well as hemoglobin electrophoresis analysis were done in all of samples for phenotyping of alpha and beta-thals. Those with Hb Bart's for alpha-thal indicator and those with both microcytosis (MCV < 85 fl) and elevated levels of Hb A(2) (>/=4.0%) for beta-thal were further studied by DNA analysis. PCR-based methodologies were used to characterize the mutation contributions of alpha and beta-thals. All the subjects were tested for the state of carrying beta-thala alleles for evaluating the situation of the compound heterozygotes of alpha-thal with beta-thal.

RESULTSOf 1 028 random samples of umbilical blood screened, 112 of subjects were defined to be the gene carriers of alpha-thal. The alpha-thal carrier rate was as high as 11.19% including 3 compound heterozygotes. Five well-known types of alpha-thal alleles were detected with gene contributions of 37.4% (--(SEA) deletion), 31.3% (-alpha(3.7) deletion), 17.4% (-alpha(4.2) deletion), 12.1% (alpha(CS)alpha mutation), and 0.9% (alpha(QS)alpha mutation), successively. Of the 1 312 adult specimens studied, 89 with beta-thal including 14 of the compound higher Hb F subjects were detected. All of the 89 phenotypic beta-thal carriers had the mutations in the beta-globin gene, making the overall prevalence 6.78%. The commonly seen three mutations, beta CD41 - 42 (-CTTT) frameshift, beta CD17 (T-A) nonsense mutation and beta-28 (A-G) promoter variation were accounted for 90% of the beta-thal alleles in Liuzhou. Of these beta-thal subjects, 16 (accounting for 18%) were found to be the compound heterozygosity for a beta-thal and an alpha-thal with 9 different types of gene defects with a detection rate 1.22%.

CONCLUSIONData from ecidation of alpha and beta-thal gene frequencies and mutation spectrum in Liuzhou city was useful for genetic counselling and prenatal diagnosis of this disease.

Adult ; China ; epidemiology ; Female ; Gene Frequency ; Genetic Counseling ; Humans ; Male ; Prevalence ; alpha-Thalassemia ; epidemiology ; genetics ; beta-Thalassemia ; epidemiology ; genetics

Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.

Objective To establish a time-resolved fluoroimmunoassay (TRFIA) method for detecting M-type phospholipase A2 receptor (PLA2R) antibody and to investigate the diagnostic value of serum PLA2R antibody for idiopathic membranous nephropathy (IMN).Methods The microplates coated with recombined PLA2R antigen and Eu3+-streptavidin labeled PLA2R antigen were used to establish a dual-antigen sandwich-type TRFIA for PLA2R antibody detection (anti-PLA2R-TRFIA).The serum concentrations of PLA2R antibody in 63 IMN patients (36 males,27 females,age 25-75 years) and 90 healthy volunteers (30 males,60 females,age 22-53 years) were quantitatively analyzed.Kruskal-Wallis H test and MannWhitney u test were used to analyze the data.Results The range of anti-PLA2R-TRFIA was 0-10 mg/L and the sensitivity was 5 μg/L,while ED20,ED50 and ED80 of the standard curve were (0.144±0.012),(0.707±0.029) and (3.466±0.098) mg/L,respectively.The CV of inter-and intra-assay were 4.7％ and 5.1％,respectively.The average concentration of serum PLA2R antibody in healthy volunteers was 0.455(0.320,0.593) mg/L,but in IMN patients it was 2.690(0.717,7.750) mg/L (z=-3.688,P＜0.05).Meanwhile,the serum levels of PLA2R antibody in IMN patients were significantly different between different stages and ages (x2 values:10.328,9.716,both P＜0.05).According to the receiver operating characteristic (ROC) curve,when the diagnostic cut-off was set at 0.80 mg/L for IMN detection,the sensitivity and specificity of anti-PLA2R-TRFIA were 73.0％ (46/63) and 95.6％ (86/90),respectively.Conclusions AntiPLA2R-TRFIA has been well established.This quick and easy-performance method could increase the diagnostic accuracy for IMN.