The patient is a male neonate born at term. He was admitted 16 minutes after birth due to stridor and inspiratory respiratory distress. Physical examination revealed a cleft palate, and a grade II systolic ejection murmur was audible at the left sternal border. Whole exome sequencing identified a heterozygous variant in the SON gene, c.5753-5756del (p.Val1918GlufsTer87), which was absent in either parent, indicating a de novo mutation. According to the guidelines of the American College of Medical Genetics and Genomics, this was classified as a "pathogenic variant" leading to a diagnosis of Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome. Upon admission, symptomatic supportive treatment was provided. Follow-up at the age of 8 months revealed persistent stridor; the infant could only consume small amounts of milk and was unable to sit steadily. This patient represents the youngest reported case to date, and his symptoms expand the clinical spectrum of the disease, providing valuable insights for clinical diagnosis and treatment.
Humans ; Infant, Newborn ; Male ; Minor Histocompatibility Antigens/genetics* ; DNA-Binding Proteins/genetics* ; Rare Diseases/genetics* ; Neurodevelopmental Disorders/genetics*

OBJECTIVE: To investigate the effects of astragaloside IV (AS-IV) on podocyte injury of diabetic nephropathy (DN) and reveal its potential mechanism. METHODS: In in vitro experiment, podocytes were divided into 4 groups, normal, high glucose (HG), inositol-requiring enzyme 1 (IRE-1) α activator (HG+thapsigargin 1 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups. Additionally, podocytes were divided into 4 groups, including normal, HG, AS-IV (HG+AS-IV 20 µmol/L), and IRE-1α inhibitor (HG+STF-083010, 20 µmol/L) groups, respectively. After 24 h treatment, the morphology of podocytes and endoplasmic reticulum (ER) was observed by electron microscopy. The expressions of glucose-regulated protein 78 (GRP78) and IRE-1α were detected by cellular immunofluorescence. In in vivo experiment, DN rat model was established via a consecutive 3-day intraperitoneal streptozotocin (STZ) injections. A total of 40 rats were assigned into the normal, DN, AS-IV [AS-IV 40 mg/(kg·d)], and IRE-1α inhibitor [STF-083010, 10 mg/(kg·d)] groups (n=10), respectively. The general condition, 24-h urine volume, random blood glucose, urinary protein excretion rate (UAER), urea nitrogen (BUN), and serum creatinine (SCr) levels of rats were measured after 8 weeks of intervention. Pathological changes in the renal tissue were observed by hematoxylin and eosin (HE) staining. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expressions of GRP78, IRE-1α, nuclear factor kappa Bp65 (NF-κBp65), interleukin (IL)-1β, NLR family pyrin domain containing 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), and nephrin at the mRNA and protein levels in vivo and in vitro, respectively. RESULTS: Cytoplasmic vacuolation and ER swelling were observed in the HG and IRE-1α activator groups. Podocyte morphology and ER expansion were improved in AS-IV and IRE-1α inhibitor groups compared with HG group. Cellular immunofluorescence showed that compared with the normal group, the fluorescence intensity of GRP78 and IRE-1α in the HG and IRE-1α activator groups were significantly increased whereas decreased in AS-IV and IRE-1α inhibitor groups (P<0.05). Compared with the normal group, the mRNA and protein expressions of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N in the HG group was increased (P<0.05). Compared with HG group, the expression of above indices was decreased in the AS-IV and IRE-1α inhibitor groups, and the expression in the IRE-1α activator group was increased (P<0.05). The expression of nephrin was decreased in the HG group, and increased in AS-IV and IRE-1α inhibitor groups (P<0.05). The in vivo experiment results revealed that compared to the normal group, the levels of blood glucose, triglyceride, total cholesterol, BUN, blood creatinine and urinary protein in the DN group were higher (P<0.05). Compared with DN group, the above indices in AS-IV and IRE-1α inhibitor groups were decreased (P<0.05). HE staining revealed glomerular hypertrophy, mesangial widening and mesangial cell proliferation in the renal tissue of the DN group. Compared with the DN group, the above pathological changes in renal tissue of AS-IV and IRE-1α inhibitor groups were alleviated. Quantitative RT-PCR and Western blot results of GRP78, IRE-1α, NF-κ Bp65, IL-1β, NLRP3, caspase-1 and GSDMD-N were consistent with immunofluorescence analysis. CONCLUSION AS-IV could reduce ERS and inflammation, improve podocyte pyroptosis, thus exerting a podocyte-protective effect in DN, through regulating IRE-1α/NF-κ B/NLRP3 signaling pathway.
Podocytes/metabolism* ; Animals ; Diabetic Nephropathies/metabolism* ; Saponins/therapeutic use* ; Triterpenes/therapeutic use* ; Signal Transduction/drug effects* ; NF-kappa B/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Male ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Endoribonucleases/metabolism* ; Endoplasmic Reticulum Chaperone BiP ; Rats ; Diabetes Mellitus, Experimental/complications* ; Endoplasmic Reticulum/metabolism* ; Multienzyme Complexes

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Abstract: Objective　To evaluate the potential transmission risk of schistosomiasis in Yunnan Province, and to provide strategic basis for the prevention and control. Methods　Based on the prevalence of schistosomiasis, the social and environmental factors that may lead to the epidemic, 1-3 villages from 3 provincial-level and 15 county-level counties (cities and districts) were selected as the evaluated villages in 2021. The risk of schistosomiasis spread was analyzed comprehensively by consulting, reviewing and collecting routine surveillance data of schistosomiasis in the villages, combined with snail and wild feces survey. The risk level was evaluated for the positive snails, positive wild feces, resident infection, average density of live snails and snail frame occurrence rate. Results　Totally 7 snail counties schistosomiasis transmission was blocked of 18 epidemic counties and the rest were eliminated counties. A total of 152 447 snail frames were investigated and 3 043 frames with snails, 15 895 snails were captured and included 15 727 live snails in the 32 evaluated villages. The total area of snail was 58.87 hm2 and the area of reoccurrence was 34.19 hm2 with snail frame occurrence rate of 2.00% and average density of live snails 0.103 2/0.11 m2, and no positive snails were found by loop-mediated isothermal amplification (LAMP) assay. A total of 1 374 wild feces were collected in 27 evaluated villages of 14 epidemic counties, mainly from cattle, dogs, sheep, equine animals, pigs and so on, all of which were negative. According to the risk assessment of epidemic spread, Yongle Village and Yongsheng Village in Eryuan County, Zhiming Village in Chuxiong City were Ⅱ risk, and the rest were Ⅲ risk. Conclusions　Although the risk of transmission is low in Yunnan Province, the risk of transmission and spread still exists. It is necessary to strengthen the risk monitoring, control of snail and effective management of livestock to prevent the rebound of the epidemic.

Aim To explore he preventive and therapeutic effects of Tongbu-fangchan prescription on aceylcholine-calcium chloride (Ach-CaCl

Fibrosis is a repair response initiated by tissues and organs after injury, and is a self-protection mechanism of the body. It has been found that endothelium-to-interstitial transdifferentiation (EndMT) is involved in the physiological and pathological processes of various organ fibrosis, which has become a focus of the research on fibrotic diseases. In recent years, the study has found that EndMT plays an important role in many pathological processes in cardiovascular system, lungs, kidneys, liver, pancreas fibrosis, and so on. This article summarizes EndMT regulatory mechanism and its role in each organ fibrosis, as well as the related treatment progress of EndMT targets, so as to provide new targets for prevention and control of organ fibrosis.

Objective: To analyze the survival of newly diagnosed malignant tumors in cancer registration areas of Hubei Province from 2013 to 2015. Methods: From January 1, 2013 to December 31, 2015, all newly diagnosed malignant tumors were collected from cancer registration areas in Hubei Province, and patients were followed up using a combination of active and passive methods. Cancer survival was analyzed using the strs package in Stata software. Observed and expected survival were calculated using the life table and Ederer Ⅱ methods, and the difference in survival rate of patients with different sex, age, urban and rural areas and different cancer species was compared. Results: From 2013 to 2015, 83 987 new malignant tumors were diagnosed in cancer registration areas in Hubei Province, including 45 742 males (54.46%) and 38245 females (45.54%). The overall 5-year relative survival rate was 41.46%, 34.43% for men and 49.63% for women. With the increase of age, the observed survival rate and relative survival rate of patients of different genders showed a decreasing trend. The 5-year relative survival rate of patients with malignant tumors was 47.58% in urban areas and 26.58% in rural areas. The observed survival rate and relative survival rate in rural areas were significantly lower than those in urban areas. The overall 5-year relative survival rates for common malignancies were 20.61% for lung cancer, 15.36% for liver cancer, 22.89% for esophageal cancer, 34.92% for gastric cancer, and 54.87% for colorectal cancer. In addition, the 5-year relative survival rates of common malignant tumors in women were 78.65% for breast cancer and 52.55% for cervical cancer. Conclusions: In Hubei Province, the survival rate of malignant tumors is different among different genders, regions, age groups and cancer species. Prevention and treatment and health education should be strengthened for malignant tumor patients in rural areas and those with high incidence and low survival rate such as liver cancer and lung cancer, and relevant strategies should be formulated according to the gender and age distribution characteristics of different cancer species.
Humans ; Female ; Male ; Liver Neoplasms ; Uterine Cervical Neoplasms/epidemiology* ; Lung Neoplasms ; China/epidemiology* ; Urban Population ; Incidence ; Survival Analysis ; Rural Population ; Registries

Objective: To analyze the survival of newly diagnosed malignant tumors in cancer registration areas of Hubei Province from 2013 to 2015. Methods: From January 1, 2013 to December 31, 2015, all newly diagnosed malignant tumors were collected from cancer registration areas in Hubei Province, and patients were followed up using a combination of active and passive methods. Cancer survival was analyzed using the strs package in Stata software. Observed and expected survival were calculated using the life table and Ederer Ⅱ methods, and the difference in survival rate of patients with different sex, age, urban and rural areas and different cancer species was compared. Results: From 2013 to 2015, 83 987 new malignant tumors were diagnosed in cancer registration areas in Hubei Province, including 45 742 males (54.46%) and 38245 females (45.54%). The overall 5-year relative survival rate was 41.46%, 34.43% for men and 49.63% for women. With the increase of age, the observed survival rate and relative survival rate of patients of different genders showed a decreasing trend. The 5-year relative survival rate of patients with malignant tumors was 47.58% in urban areas and 26.58% in rural areas. The observed survival rate and relative survival rate in rural areas were significantly lower than those in urban areas. The overall 5-year relative survival rates for common malignancies were 20.61% for lung cancer, 15.36% for liver cancer, 22.89% for esophageal cancer, 34.92% for gastric cancer, and 54.87% for colorectal cancer. In addition, the 5-year relative survival rates of common malignant tumors in women were 78.65% for breast cancer and 52.55% for cervical cancer. Conclusions: In Hubei Province, the survival rate of malignant tumors is different among different genders, regions, age groups and cancer species. Prevention and treatment and health education should be strengthened for malignant tumor patients in rural areas and those with high incidence and low survival rate such as liver cancer and lung cancer, and relevant strategies should be formulated according to the gender and age distribution characteristics of different cancer species.
Humans ; Female ; Male ; Liver Neoplasms ; Uterine Cervical Neoplasms/epidemiology* ; Lung Neoplasms ; China/epidemiology* ; Urban Population ; Incidence ; Survival Analysis ; Rural Population ; Registries

Objective To compare the safety and efficacy of decitabine combined with unrelated umbilical cord blood transplantation and traditional regimen in the elderly patients with acute myeloid leukemia(AML)after achieving complete remission with induction therapy.Methods Fifty-two elderly AML patients who obtained complete remission(CR)after 1-2 cycles of induction therapy in the Department of Hematology of Yancheng First People's Hospital and the Huai'an First Hospital Affiliated to Nanjing Medical University from January 2019 to January 2022 were enrolled,and were divided into the observation group(n=24)and the control group(n=28).The observation group received decitabine combined with unrelated umbilical cord blood transplantation,and the control group received traditional consolidation therapy,including azacitidine+vinblastine,idarubicin+cytarabine(IA),or aclarubicin+cytarabine+granulocyte colony-stimulating factor,and so on.The hematopoietic recovery time,adverse reactions,relapse-free survival(RFS),and overall survival(OS)were compared between the two groups.Results The median recovery time of neutrophils was 12.54 d in the observation group and wes 18.64 d in the control group(P＜0.001);the median recovery time of platelets was 12.67 d in the observation group and was 19.71 d in the control group(P＜0.001).There was no difference in incidences of grade Ⅲ-Ⅳ myelosuppression and non-hematological toxicity between the two groups.There were statistical differences in the median RFS(33 months vs 11 months)and OS(36 months vs 24 months)between the observation group and the control group(P＜0.05).Conclusions Compared with the traditional consolidation regimen,decitabine combined with unrelated umbilical cord blood transplantation for consolidation of AML after achieving remission is more effective in elderly patients,could prolong survival,and has similar safety.