Objective:To investigate the relationship between thyroid-stimulating hormone(TSH) levels and 10-year mortality in women aged 40 years and older.Methods:Residents aged 40 and over in urban areas of Guiyang City who participated in the " Epidemiological Study of Cancer Risk in Patients with Type 2 Diabetes in China(REACTION)" were followed up in 2011. Finally, 5 614 people were enrolled, and the baseline general information, physical examination and TSH detection were carried out. The average follow-up was(9.77±1.55) years, and the treatment and death of thyroid-related diseases were recorded. The Cox proportional hazards model was used to analyze the relationship between TSH level and 10-year mortality in middle-aged and elderly women, and plotting survival time curves(Kaplan-Meier curves) to study the association between elevated TSH levels and lifespan in subjects under 65 years old. Results:The multivariate Cox proportional hazards model showed that compared with the normal group, after multivariate adjustment, the risk of death in the TSH increased group was decreased( HR=0.644, 95% CI 0.478-0.868, P<0.05); after stratifying the elevated TSH group, the risk of death was decreased in the slightly elevated TSH group( HR=0.566, 95% CI 0.405-0.791, P<0.001); the elevated TSH group was further stratified by age. In the group under 65 years old, compared to the normal group, the mildly elevated group showed a reduced risk of mortality( HR=0.429, 95% CI 0.245-0.751, P=0.003). In the group aged 65 and above, there were no statistically significant differences in mortality risk between the mildly elevated group, severely elevated group, and the normal group( P>0.05). In the group under 65 years old, the K-M curve indicated that the survival rate of the mildly elevated TSH group was significantly higher than that of the normal group( χ2=11.931, P=0.003), the difference was statistically significant. Conclusion:Mildly elevated TSH levels in women aged 40-65 years are associated with a reduced risk of all-cause death and longer lifespan.

Objective:To investigate the 10-years risk for cardiovascular diseases(CVD) among different subtypes of pre-diabetes(Pre-DM) residents aged 40 and above in Guiyang urban area and to analyze the influencing factors.Methods:A total of 5 798 residents who participated in the " Risk Evaluation of cAncers in Chinese diabe Tic Individuals: a lONgitudinal(REACTION) Study" were selected to undergo oral glucose tolerance test and glycated hemoglobin test. According to the Pre-DM diagnostic criteria, normal glucose tolerance(NGT), impaired fasting glucose(IFG), impaired glucose tolerance(IGT), and diabetes mellitus were defined based on glycated hemoglobin(IA1C), and were combined into four groups: NGT group, single subtype group(IFG, IGT, IA1C), two-subtype combination group(IFG+ IGT, IFG+ IA1C, IGT+ IA1C), and three-subtype combination group(IFG+ IGT+ IA1C). Ten-year cardiovascular disease occurrence was investigated. The logistic regression model was used to analyze the risk of CVD occurrence in different subtypes of Pre-DM residents. Results:(1)The incidence in the single subtype group, two subtypes group and three subtypes group of CVD was 6.6%(182/2 752), 8.4%(135/1 613) and 9.6%(53/551) , respectively, all higher than NGT group at 5.2%(46/882). (2) Regardless of diagnosed by fasting blood glucose, 2 h blood glucose, or glycated hemoglobin, the 10-year CVD incidence rates(8.7%, 8.6%, 7.6%) in Pre-DM were higher than that in the NGT group(5.2%; all P<0.05). (3)After multivariate adjustment, compared with the NGT group, the 10-year CVD risk gradually increased in the single subtype group, two-subtype group, and three-subtype group, with OR of 1.03(95% CI 0.74-1.45), 1.08(95% CI 0.75-1.54), and 1.16(95% CI 0.75-1.78), respectively. Conclusion:The Pre-DM population has a higher 10-year risk for CVD, and the risk increases gradually with the accumulation of subtypes. Therefore the prevention and treatment of CVD should focus on the management of the Pre-DM population.

Objective:To investigate the effect of the interaction between metabolic syndrome and smoking on the risk of subsequent cardiovascular events.Methods:Urban residents aged 40 and above in the Yunyan District of Guiyang City were selected from " Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) Study". The baseline survey started in 2011 and general information including gender, age, medical history, lifestyle habits, and smoking status were collected. Additionally, biochemical indicators related to metabolic syndrome(MS) were measured. The study participants were then followed up, and the first cardiovascular events occurring after the initial survey were recorded. The average follow-up period was 10.07±1.49 years. The interaction between metabolic syndrome and smoking on subsequent cardiovascular events was analyzed using Cox proportional hazards models.Results:The study included a total of 7 275 individuals, among whom 639 experienced cardiovascular events. After adjusting for multiple variables, compared to non-smokers without metabolic syndrome(MS), smokers with MS showed a higher risk of cardiovascular events, with a hazard ratio( HR) of 6.54(95% CI 4.88, 8.78). This risk was higher than that of individuals with MS who never smoked [ HR 1.39(95% CI 1.11, 1.75)] and non-MS smokers [ HR 2.48(95% CI 1.77, 3.49)]. There was an additive interaction between MS and smoking on the occurrence of cardiovascular events, with a relative excess risk due to interaction(RERI) of 3.30(95% CI 1.89, 4.70), an attributable proportion(AP) of 0.55(95% CI 0.43, 0.59), and a synergy index(S) of 3.07(95% CI 1.94, 4.84). Furthermore, when stratifying the duration of smoking cessation, long-term quitters(≥8 years) showed a lower risk of cardiovascular events compared to current smokers, regardless of whether they had MS. The hazard ratios were 0.45(95% CI 0.26, 0.78) for individuals with MS and 0.42(95% CI 0.19, 0.95) for individuals without MS. Conclusions:There is an additive interaction between smoking and MS on the risk of cardiovascular events. The coexistence of both factors significantly increases the risk of cardiovascular events.

Humans ; Sjogren's Syndrome/diagnosis* ; Castleman Disease/diagnosis* ; Case-Control Studies

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

To review and investigate the diagnosis results of local anesthetics (LA) allergy and improve the understanding of LA allergy in clinician. From March 2017 to February 2022, a total of 24 patients were investigated in Allergy Center of West China Hospital,Sichuan University on suspicion of LA allergy. Clinical data and results of skin tests and drug provocation tests (DPT) with the suspected drugs were retrospectively evaluated. The value of standardized diagnostic protocol in the LA allergy were analyzed. The results showed that 24 patients (3 men/21 women) were included with age range from 20 to 74 years. Three cases (12.5%) were positive in previous LA skin tests and proved to be tolerated through standardized tests. Twenty-one patients were initially diagnosed as "LA allergy" because of adverse reactions after previous use of LA, including 20 cases of immediate-type reaction and 1 case of delayed-type reaction. Three cases were considered LA allergy through standardized diagnosis approaches, including skin tests and DPT. One patient was diagnosed with anaphylaxis caused by chlorhexidine. Of the remaining 17 patients, 7 were considered as psychosomatic reactions (29.1%), 3 of sympathetic nervous system conditions (12.5%), 1 of spontaneous urticaria (4.2%), 2 of vasovagal syncope (8.3%), drug side effects (8.3%), skin irritation (8.3%), respectively. In conclusion, true allergic reactions to LA are rare. Through standardized skin tests and DPT, allergy can be ruled out in the vast majority of patients who complain of "LA allergy". For patients who are highly suspected of LA inducing anaphylaxis, other local anesthetics that can be used as safe alternatives should be determined by diagnostic tests according to future needs.
Male ; Humans ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Anesthetics, Local/adverse effects* ; Anaphylaxis/diagnosis* ; Retrospective Studies ; Drug-Related Side Effects and Adverse Reactions ; Chlorhexidine

To review and investigate the diagnosis results of local anesthetics (LA) allergy and improve the understanding of LA allergy in clinician. From March 2017 to February 2022, a total of 24 patients were investigated in Allergy Center of West China Hospital,Sichuan University on suspicion of LA allergy. Clinical data and results of skin tests and drug provocation tests (DPT) with the suspected drugs were retrospectively evaluated. The value of standardized diagnostic protocol in the LA allergy were analyzed. The results showed that 24 patients (3 men/21 women) were included with age range from 20 to 74 years. Three cases (12.5%) were positive in previous LA skin tests and proved to be tolerated through standardized tests. Twenty-one patients were initially diagnosed as "LA allergy" because of adverse reactions after previous use of LA, including 20 cases of immediate-type reaction and 1 case of delayed-type reaction. Three cases were considered LA allergy through standardized diagnosis approaches, including skin tests and DPT. One patient was diagnosed with anaphylaxis caused by chlorhexidine. Of the remaining 17 patients, 7 were considered as psychosomatic reactions (29.1%), 3 of sympathetic nervous system conditions (12.5%), 1 of spontaneous urticaria (4.2%), 2 of vasovagal syncope (8.3%), drug side effects (8.3%), skin irritation (8.3%), respectively. In conclusion, true allergic reactions to LA are rare. Through standardized skin tests and DPT, allergy can be ruled out in the vast majority of patients who complain of "LA allergy". For patients who are highly suspected of LA inducing anaphylaxis, other local anesthetics that can be used as safe alternatives should be determined by diagnostic tests according to future needs.
Male ; Humans ; Female ; Young Adult ; Adult ; Middle Aged ; Aged ; Anesthetics, Local/adverse effects* ; Anaphylaxis/diagnosis* ; Retrospective Studies ; Drug-Related Side Effects and Adverse Reactions ; Chlorhexidine

Axial myopathy is a general term for a group of myopathy involving the axial muscles. It refers to a group of skeletal myopathy in which paraspinal muscles are individually or significantly affected, with or without the involvement of whole body skeletal muscles. Axial muscle weakness is often ignored in clinical practice. The evaluation of axial muscle is mainly the evaluation of the paraspinal muscles (erector spinae) in current literature. The clinical manifestations of paraspinal muscle weakness are dropped head syndrome and camptocormia. Physical examination and skeletal muscle magnetic resonance imaging, especially the whole body muscle magnetic resonance scan, are vital for the evaluation of axial muscle. It is of great clinical significance to increase attention to the diagnosis and differentiation of axial myopathy, which is helpful to avoid missing treatable diseases and improve the understanding and early recognition of associated myopath.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 β, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.
Animals ; Apoptosis ; Drugs, Chinese Herbal ; Inflammation/metabolism* ; Myocardial Infarction/pathology* ; NF-kappa B/metabolism* ; Nerve Tissue Proteins ; Rats ; Rats, Wistar ; Sirtuin 1/genetics*