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 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

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.

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

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

Objective:To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM).Methods:A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP +) group, anti-HMGCR antibody positive (HMGCR +) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result:(1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP +, 8 (25.0%) with HMGCR +, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP +group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb ( P<0.01). The axial muscle score was lower than the distal limb score ( P<0.05).(3) Extramuscular manifestations of HMGCR + group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups ( P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP + group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR + group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion:IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP + group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR +group were more prone to myotonia potential and CRDs.

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*