This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

OBJECTIVE: To study the correlation between miR-122 and early HBV infection and analyze its application value in early infection of voluntary blood donors. METHODS: A total of 150 samples from voluntary blood donors in Fujian Blood Center from May 2021 to July 2022 were collected and divided into group N (normal group), group E (ELISA single positive group), and group D (both ELISA and nucleic acid positive group), and the general information of the three groups of blood donors was collected. Total RNA was extracted from the three groups of samples, and the expression level of miR-122 was detected by qRT-PCR. The expression differences of miR-122 among the three groups of samples were statistically analyzed, and the correlation between the expression level of miR-122 in group D and its HBV DNA copy number was analyzed. The miRNA database was used to predict the potential target genes of miRNA and perform bioinformatics analysis. RESULTS: There was no statistical difference in gender, education level, and occupation distribution among the three groups, but the age distribution and number of blood donations among different groups were statistically significant. Compared with group N, the relative expression levels of miR-122 in the plasma of group E and group D were significantly downregulated (P < 0.05); the relative expression level of miR-122 in group D was more significantly downregulated than that in group E (P < 0.001). Pearson correlation analysis showed that the expression level of miR-122 in group D was negatively correlated with the HBV-DNA copy number (R ²=-0.804,P < 0.01). Two potential target genes were screened using the miRNA database: ALDOA(aldolase A) and PKM (pyruvate kinase). GO analysis results showed that the potential target genes of miRNA mainly involved in biological processes including cell homeostasis and regulation of transcriptional processes. CONCLUSION Downregulation of miR-122 expression is closely related to early HBV infection and replication activity.
Humans ; MicroRNAs ; Blood Donors ; Hepatitis B/diagnosis* ; Hepatitis B virus ; DNA, Viral/blood* ; Male ; Female ; Early Diagnosis ; Adult

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Obesity is a well-established risk factor for thrombotic events such as venous thromboembolism， and the alterations in pharmacokinetics induced by obesity pose challenges for anticoagulation management. This article systematically reviews the advances of the use of various anticoagulants in obese patients， and finds that the dosage of low-molecular-weight heparin needs to be adjusted according to preventive or therapeutic goals in severely obese patients， the preventive dose may be increased to 40 mg， q12 h or 0.5 mg/（kg·d）， while the therapeutic dose is recommended to be reduced to 0.8 mg/（kg·d）， q12 h. Direct oral anticoagulant drugs are safe and effective for general obese patients； in severely obese patients， standard doses of rivaroxaban or apixaban may be used， warranting cautious application and consideration for therapeutic drug monitoring. In special clinical scenarios such as obesity combined with trauma， pregnancy， advanced age， or bariatric surgery， anticoagulation strategies should be individualized， with close attention to monitoring. Future research should focus on optimizing anticoagulant regimens for special populations and addressing anticoagulation management in obese patients with other embolic diseases.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the predictive value of serum proprotein convertase subtilisin/kexin 9(PCSK9)level for major adverse cardiovascular events(MACE)in patients with acute myocardial infarction(AMI)after per-cutaneous coronary intervention(PCI).Methods:A total of 585 AMI patients who underwent PCI in our hospital from May 2016 to Aug 2020 were enrolled.General data and preoperative serum PCSK9 level were collected.Accord-ing to presence of MACE within one year after PCI,patients were divided into MACE group(n=152)and no MACE group(n=433).Correlation between blood lipids and serum PCSK9 level,and influencing factors for MACE within one year after PCI in AMI patients were analyzed.And the predictive value of serum PCSK9 level for MACE within one year after PCI in AMI patients was analyzed.Results:After one year follow-up,the incidence rate of MACE was 25.98％(152/585).Compared with no MACE group,there were significant rise in preoperative Gensini score,proportions of age≥60 years,multiple infarcted sites,number of diseased vessels ≥2,hypertension,diabe-tes,hyperlipidemia,LVEF＜50％and postoperative slow-flow/no-reflow,serum PCSK9 level[51.95(46.82,56.58)ng/ml vs.72.24(62.37,73.88)ng/ml]in MACE group,P＜0.01 all.Spearman correlation analysis indicated that in AMI patients,serum PCSK9 level was significant positively correlated with levels of total cholesterol(TC)and low den-sity lipoprotein cholesterol(LDL-C)(r=0.728,0.784,P=0.014,0.008).Multivariate Logistic regression analysis indi-cated that age≥60 years,preoperative Gensini score,multiple infarcted sites,number of diseased vessels≥2,hypertension,diabetes,hyperlipidemia,LVEF＜50％,slow-flow/no-reflow after PCI,serum PCSK9 level were independent risk fac-tors for MACE within one year after PCI in AMI patients(OR=2.757～6.888,P＜0.01 all).ROC curve analysis indica-ted that cut-off value,sensitivity,specificity and AUC(95％CI)of serum PCSK9 level was 59.11 ng/ml,88.72％,77.37％and 0.871(0.841～0.897)respectively for predicting MACE within one year after PCI in AMI patients,sugges-ting serum PCSK9 level possessed good predictive value for it.Conclusion:High serum PCSK9 level can increase the risk of MACE after PCI in AMI patients,which has good predictive value for it.

Thyroglobulin(Tg)is a glycoprotein with large molecular weight,which is synthesized and secreted into the bloodstream by thyroid follicular cells.The concentration level of Tg in blood is one of the important biomarkers for diagnosis of thyroid diseases such as differentiated thyroid cancer(DTC),subacute thyroiditis,etc..Radioimmunoassay(RIA),immunoradiometric assay(IRMA),and immunochemiluminescence assay(ICMA)are the main clinical methods for detecting Tg.Recently,for meeting the requirement of detecting low concentration of Tg in blood after thyroid clearance surgery,researchers have developed various high-performance analysis methods for detecting Tg concentration in blood samples,providing new assays for thyroid disease screening and efficacy evaluation.This review summarized the analysis methods of Tg,especially the new progresses in the biosensors for monitoring low concentration of Tg in blood during the past five years.The current technical challenges of these methods in clinical applications were briefly discussed,which might provide useful information for developing new liquid biopsy methods of DTC.