OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE: To investigate the molecular epidemiological characteristics of common δβ-thalassemia/hereditary persistence of fetal hemoglobin(HPFH) in the prepregnant population in Huadu, and to provide a laboratory basis for prevention and control of thalassemia. METHODS: Blood samples of childbearing age people in Huadu District of Guangzhou who participated in free thalassemia testing from January 2016 to July 2021 were collected for hematological parameters analysis and hemoglobin electrophoresis. Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia, ^SEA-HPFH and Taiwanese deletion β-thalassemia were detected by Gap-PCR in the samples with higher HbF(≥5%). Primers were designed for the proximal HBG1 and HBG2 promoter, and the point mutations in the proximal promoter region were detected by Sanger sequencing. Hematology parameters data were statistically analyzed. RESULTS: Among 27 088 samples, Thirteen cases of Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia and thirty-three cases of ^SEA-HPFH were detected, which including 3 cases of Chinese ^Gγ⁺(^Aγδβ)⁰/β^N compounded with --^SEA/αα and three cases of ^SEA-HPFH/β^N compounded with --^SEA/αα. 6 carriers with ^Aγ-196 C>T were also detected; No Taiwanese thalassemia genetype was detected. The total detection rate of common δβ-thalassemia/HPFH was 0.19% (52/27 088). There were significant differences in the levels of MCV, MCH, HbA₂, and HbF among Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia, ^SEA-HPFH, ^Aγ-196 C>T (P<0.001). The hematological parameters of ^Aγ-196C>T combined with α⁰-thalassemia were similar to those of Chinese ^Gγ⁺(^Aγδβ)⁰-thalassemia carriers, and only HbA₂ was significantly lower than that of the latter, which was helpful for clinical identification. CONCLUSION δβ-thalassemia/HPFH should be included in the scope of thalassemia prevention program in the prepregnant population in Huadu District, and hematological parameters can provide some basis for identifying different types of δβ-thalassemia/HPFH.
Diagnosis, Differential ; Fetal Hemoglobin/genetics* ; Heterozygote ; Humans ; Thalassemia/genetics* ; beta-Thalassemia/genetics*

Objective:To analyze the phenotype and genotype of two Chinese family with inherited dysfibrinogenemia and the molecular pathogenic mechanism.Methods:In the probands and their family members, coagulation routine, fibrinogen activity(Fg∶A) and fibrinogen antigen(Fg∶Ag) were detected . To find the mutation and exclude single nucleotide polymorphisms, all the exons and exons-intron boundaries of fibrinogen genes ( FGA, FGB and FGG) were amplified by Ploymerase Chain Reaction (PCR), then sequenced. Bioinformatics prediction softwares were used to predict and score the change of function caused by the variant. PyMol were used to analyze the structure of protein caused by the variant. Clustal X software was used to analyze the conservation of the mutant amino acids. Results:The thrombin time(TT) of the two was slightly prolonged and could not be corrected by protamine sulfate, and the fibrinogen activity was significantly reduced (1.25 g/L and 1.17 g/L), but the fibrinogen antigen content was normal, respectively (3.50 g /L and 3.81 g/L). Genetic analysis showed that both probands were heterozygous missense variants( FGB exon 7 c. 1115 T>A (p.Val372Glu)), both of which originated from the paternal line. The prediction results of the four bioinformatics softwares indicate that this variant could be disease causing. Clustal X software showed that Val372 is highly conserved among homologous species. Based on the guidelines of the American College of Medical Genetics and Genomics, c. 1115 T>A was predicted to be likely pathgenic(PM2+ PP1+ PP2+ PP3+ PP4). PyMol shouwed p. Val372Glu variant changes the secondary structure and three-dimensional structure of fibrinogen protein were changed caused by p. Val372Glu variant. Conclusion:Inherited dysfibrinogenemia of the probands maybe caused by variant of FGB c. 1115 T>A(p.Val372Glu), and the variant was firstly reported.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.
Adolescent ; Betacoronavirus ; Child ; Child, Preschool ; China ; Coronavirus Infections ; Humans ; Infant ; Pandemics ; Pneumonia, Viral ; Retrospective Studies

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.
Antithrombin III/genetics* ; Antithrombin III Deficiency/genetics* ; DNA Mutational Analysis ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Objective: To evaluate the diagnostic value of bronchoalveolar lavage (BAL) for pulmonary complications in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its safety. Methods: Patients with pulmonary complications after allo-HSCT underwent BAL. Microbiological smears, culture, PCR of CMV-DNA, EBV-DNA and TB-DNA, macro genomes new generation sequencing (mNGS) techniques were performed to detect pathogens in BAL fluid (BALF) . Results: A total of 73 allo-HSCT patients with 86 times of pulmonary complications enrolled this prospective study. They underwent 132 times of BAL procedures. The clinical diagnoses of 88.4% cases were made based on BALF analysis. Of them, 67 cases (77.9%) had infectious pulmonary complications, including 29 cases (33.7%) of fungal infection, 18 cases (20.9%) of mixed infection, 11 cases (12.8%) of viral infection and 9 cases (10.5%) of bacterial infection. The other 9 cases (10.5%) of non-infectious pulmonary complications included 8 cases (9.3%) of idiopathic pneumonia syndrome (IPS) and 1 case (1.2%) of pulmonary infiltration of lymphoma. The diagnoses of the remaining 10 cases (11.6%) were not determined. The platelet counts of 33 patients were less than 50×10(9)/L before BAL. None of them developed severe bleeding complications during or after BAL. Transient fever occurred in 10 patients after BAL. Blood cultures showed staphylococcal bacteremia in them and anti-infection therapies were effective. No life-threatening complications occurred in all of the patients during or after BAL. Conclusion: BALF analysis was informative for the diagnosis of pulmonary complication and safe for patients with pulmonary complications after allo-HSCT.
Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Pneumonia/etiology* ; Prospective Studies

Genistein is a kind of isoflavone compounds， also called phytoestrogens， with clinical effects on cardiovascular disease， cancer and postmenopausal-related gynecological diseases， and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study， the protective effect of genistein on Aβ₂₅₋₃₅-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aβ₂₅₋₃₅ were screened by MTT assay. After being pretreated with different concentrations of genistein(25， 50， 100 μmol·L⁻¹) on PC12 cells， the AD model of PC12 cells was induced by Aβ₂₅₋₃₅. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope， and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were detected by qRT-PCR and Western blot assay， respectively. The results showed that as compared with the blank group， the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate， reduce the cell damage and apoptosis of AD cell model， and significantly down-regulate the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aβ₂₅₋₃₅， and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression.
Amyloid beta-Peptides ; Animals ; Apoptosis ; Calcium-Calmodulin-Dependent Protein Kinase Type 4 ; metabolism ; Calmodulin ; metabolism ; Cell Survival ; Genistein ; pharmacology ; PC12 Cells ; Peptide Fragments ; Protective Agents ; pharmacology ; Rats ; Signal Transduction ; drug effects

The loss of hippocampal neurons is one of the main pathological features of Alzheimer's disease (AD), which is related to the apoptosis of hippocampal neurons. Huangpu Tongqiao capsule is used for the treatment of AD, but the underlying mechanism is still unclear. This study is to investigate the mechanism of neuroprotective effect of Huangpu Tongqiao capsule in the treatment of AD, through observing the effect of Huangpu Tongqiao capsule containing serum on cell injury of primary cultured hippocampal neurons induced by Aβ₂₅₋₃₅ via inhibiting the cell apoptosis. Primary cultured hippocampal neurons were cultured and identified by MAP-2 immunofluorescence staining, and cell growth state was observed by inverted microscope. The Huangpu Tongqiao capsule containing serum was prepared using the method of serum pharmacology. MTT assays were used to measure the optimum concentration range of Huangpu Tongqiao capsule containing serum, and optimum Aβ concentration for establishing the AD model. After primary cultured hippocampal neurons AD cell model was induced by Aβ₂₅₋₃₅, cell survival rate was detected by MTT, cell apoptosis rate was assayed by flow cytometry, and protein expressions of Bax, Cyt C and caspase-3 were determined by Western blot analysis. The results showed that the primary cultured hippocampal neurons were cultured successfully, and cells grew mature at seventh days; Compared with normal group, the survival rate of hippocampal neurons in AD cell model group was decreased, the apoptosis rate of hippocampal neurons was increased, and the protein expressions of Bax, Cyt C and caspase-3 were increased (<0.05, <0.01); Compared with AD cell model group, the survival rate of hippocampal neurons in Huangpu Tongqiao capsule containing serum group was increased, the apoptosis rate of hippocampal neurons was decreased, and the protein expressions of Bax, Cyt C and caspase-3 were decreased (<0.05, <0.01). These findings suggest that Huangpu Tongqiao capsule containing serum has a neuroprotective effect on cell injury of the primary cultured hippocampal neurons induced by Aβ₂₅₋₃₅, and its effect on the treatment of AD is associated with the inhibition the apoptosis of hippocampal neurons.