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 report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

Humans ; Factor XIII/genetics* ; Factor XIII Deficiency/genetics* ; Mutation ; Pedigree

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To study the value of serum procalcitonin (PCT) combined with soluble triggering receptor expressed on myeloid cells-1 (STREM-1) in the differential diagnosis of bacterial diarrhea and viral diarrhea in children. METHODS: A retrospective analysis was performed on the medical data of 73 children with bacterial infectious diarrhea (bacteria group) and 68 children with viral infectious diarrhea (virus group) who were treated from February 2018 to May 2019. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum PCT and STREM-1 for bacterial infectious diarrhea and viral infectious diarrhea. RESULTS: Compared with the virus group, the bacteria group had significantly higher detection rates of fecal red blood cells (79% vs 43%, P<0.05) and pus (51% vs 19%, P<0.05), as well as significantly higher serum levels of PCT and STREM-1 (P<0.05). The ROC curve analysis showed that in the differential diagnosis of bacterial infectious diarrhea and viral infectious diarrhea, serum PCT had a cut-off value of 0.97 ng/mL and an area under the ROC curve (AUC) of 0.792, and STREM-1 had a cut-off value of 15.66 ng/mL and an AUC of 0.889. Serum PCT combined with STREM-1 had an AUC of 0.955, which was significantly higher than that of each index alone (P<0.05). CONCLUSIONS Children with bacterial diarrhea have increased serum levels of PCT and STREM-1 than those with viral diarrhea. Both serum PCT and STREM-1 can be used as the indices for the differential diagnosis of bacterial diarrhea and viral diarrhea in children, and the combined measurement of PCT and STREM-1 can improve the efficiency of differential diagnosis.
Bacteria ; Biomarkers ; C-Reactive Protein ; Child ; Diagnosis, Differential ; Diarrhea ; Humans ; Procalcitonin ; blood ; Prospective Studies ; Retrospective Studies ; Triggering Receptor Expressed on Myeloid Cells-1 ; blood

Objective　Pulmonary function testing is a commonly used indicator for clinical evaluation of the degree of pulmonary fibrosis in patients. This paper aims to investigate the dynamic changes of lung function in mice with pulmonary fibrosis and to establish a range of reference values for lung function parameters in normal Kunming mice.　Methods　Twenty-eight SPF Kunming mice were randomly divided into normal control group (n=14) and model group (n=14). After anesthesia with 10% chloral hydrate, the normal control group only underwent tracheal puncture. The model group received intratracheal puncture and injection of bleomycin (BLM) (5 mg/kg body weight), and the lung function indicators of all mice were detected in the same order on the 1st, 2nd, 3rd and 4th weekends after modeling: Ti, Te, PIF, PEF, TV, EV, RT, MV, f, Penh and EF50.　Results　After intratracheal BLM injection, mice in the model group showed decreased hair softness and smoothness, hair loss and decreased activity after the 2nd week. Compared with the control group, Ti, Te and RT values in the model group significantly increased at week 4 (P<0.05), while the values of PEF, RT, MV, f and EF50 decreased significantly at the same week (P<0.05). Compared with the model group at week 1, the differences in Ti, Te, RT and f values at week 2, 3 and 4 were statistically significant (P<0.05); the differences in MV and EF50 values at week 3 and 4 were statistically significant (P<0.05); while the PIF values only showed differences at week 4 (P<0.001). Compared with the Penh values in the control group at week 2, 3 and 4 (0.553±0.189, 0.662±0.164, 0.712±0.189), the differences of the model group (0.820±0.205, 0.936±0.188, 1.053±0.236) showed statistical significance (P<0.001). Compared with the model group at week 1, the differences of Penh values in the model group only showed statistical significance at week 3 and 4 (P<0.05). Through four-week lung function test, various parameters were obtained, among which the normal range of the main index Penh value was 0.27-0.88.　Conclusion　The lung function detected by the non-invasive whole body plethysmography system was stable and reliable with good effects; the lung function in mice with the BLM-induced pulmonary fibrosis continued to decrease within four weeks. Penh, which reflects airway resistance, can be used for overall screening of the lung function among the test mice after two weeks of modeling.

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.
Adolescent ; Adult ; Child ; Deamino Arginine Vasopressin ; Female ; Hemostatics ; Humans ; Male ; Middle Aged ; Young Adult ; von Willebrand Diseases ; von Willebrand Factor

Objective The active ingredient was used as index to optimize the extraction and enrichment process of anti-in-flammatory and analgesic active-fraction(ARF)of Dianbaizhu. Methods Methyl salicylate triglycoside-B was chosen as index com-ponent to extract and enrich methyl salicylate glycosides. Extraction and elution solvents were optimized. The HPLC fingerprint was ob-tained with Thermo Hypersil Gold C18(250 mm×4.6 mm,5μm)column and a gradient elution with the mobile phase consisting of ace-tonitrile(A)-0.2％acetic acid(B)at a flow rate of 1.0 ml/min. And the detection wavelength was set at 294 nm. Results The opti-mized extraction solvent of Dianbaizhu was the 30％ethanol and the optimized elution solvent of ARF enriched by AB-8 macroporous resins was the 35％ethanol. The methodological study on similarity and RSD in ARF HPLC fingerprint of three batches of samples cor-responded to related regulations. Conclusion The extraction and enrichment process of ARF is stable and repeatable.

OBJECTIVETo investigate the genetic defect and its mechanism in a patient with congenital afibrinogenemia.

METHODSThe plasma fibrinogen activity and antigen of the patient was determined using the Clauss method and immuno-nephelometric assay, respectively. Genomic DNA was isolated from peripheral blood of the proband and his related family members. All exons and exon-intron boundaries of the three fibrinogen genes (FGA, FGB, FGG) were amplified by PCR followed by direct sequencing. Thrombin fibrin aggregation curve were detected in the plasma of the patient. Wild-type and mutation type fibrinogen vectors were constructed, and then transfected into COS-7 cells. The wild-type and mutant proteins from the culture media and cell lysates were tested by Western blot and ELISA.

RESULTSAPTT, PT, TT were significantly longer in the proband. Plasma fibrinogen activity and antigen of the patient could not be detected using the Clauss method and immuno-nephelometry, respectively. Gene analysis revealed that a novel homozygous GTTT insertion between nucleotides 2833 and 2834 in FGB exon 2 in the proband. The proband's father, mother, brother and son were heterozygous. The polymerization curves of the patient did not show a lag phase or final turbidity, compared with the normal controls. Western blot analysis showed the lack of complete half-molecules of the fibrinogen molecule and fibrinogen in patient's plasma under non-reducing conditions. It also could not detect the truncated Bβ chain under reducing conditions. Abnormal fibrinogen molecule (molecule weight>340 000) were found in transfected COS-7 cells by Western blot, which indicated that the mutation caused the abnormal intracellular fibrinogen molecule assembly. The fibrinogen band was absent in culture media transfected by the mutation. Fibrinogen levels of mutant fibrinogen were no significant different from those of wild-type fibrinogen in cell lysates by ELISA analysis [(2.47 ± 0.30) μg/ml vs (2.65±0.60) μg/ml, P=0.0889]; However, the levels of the mutant fibrinogen were statistically significant lower than those of wild type fibrinogen in culture media [(0.01 ± 0.01) μg/ml vs (3.80±0.80) μg/ml, P=0.0001].

CONCLUSIONCongenital afibrinogenemia was caused by this frameshift mutation in exon 2 of FGB. This novel mutation impaired fibrinogen assembly and secretion.

Afibrinogenemia ; congenital ; etiology ; genetics ; Fibrinogen ; genetics ; Frameshift Mutation ; Humans ; Male ; Mutagenesis, Insertional ; Pedigree ; Young Adult