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*

The compounds were isolated and purified by silica gel, MCI, Sephadex LH-20 and semi-preparative high performance liquid chromatography. The structures of the compounds were determined by NMR and MS spectroscopic data. Twenty monomer compounds were isolated from the ethyl acetate extract of Lindera reflexa root from Hunan province, and identified as: (1″S,3″S,6″R)-2′,4′,6′-trihydroxy-3′-[1″-(3″-hydroxy)-p-menthanyl]-chalcone (1), sumadain D (2), quercetin (3), catechin (4), epicatechin (5), N-cis-feruloyltyramine (6), N-trans-feruloyltyramine (7), N-trans-feruloyl-3-methoxytyramine (8), flavifloramides B (9), northalifoline (10), isolariciresinol (11), syringaresinol (12), pinoresinol (13), medioresinol (14), dehydroconiferyl alcohol (15), 4-methoxyl-denudaquinol (16), miliusanal (17), syringic acid (18), abscisic acid (19), (E)-cinnamyl-(E)-cinnamate (20). Compound 1 is a new compound, and compounds 2‒20 have been isolated from Lindera reflexa for the first time. The results showed that compounds 1, 2, 3 and 16 could significantly reduce the survival ability of MGC-803 cells with IC₅₀ values of 5.58, 23.41, 25.72 and 20.96 μmol·L^-1, respectively. Compounds 5 and 20 can reduce the survival ability of MGC-803 cells with IC₅₀ values of 98.83 and 89.26 μmol·L^-1, respectively.

AIM:To investigate the effects of the three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanisms.METHODS:SPF-grade SD rats were randomly divided into control,COPD,pyrrolidinedithiocarbamate ammonium(PDTC),Bufei-Jianpi formula(BJF),Bu-fei-Yishen formula(BYF),Yiqi-Zishen formula(YZF),BJF combined with PDTC(BJF+PDTC),BYF combined PDTC(BYF+PDTC),and YZF combined PDTC(YZF+PDTC)groups.Cigarette smoke exposure combined with bacterial infec-tion were used to develop a stable-phase rat model of COPD,and kidney-injured rats were screened for subsequent treat-ment.Pulmonary and renal functions,pathological changes in lung and kidney tissues,24 h urine volume,urine biochem-ical indexes,aquaporin(AQP)levels,ratio of inflammatory cells in the bronchoalveolar lavage fluid(BALF),serum in-flammatory factor levels,and mRNA and protein expressions of IκB kinase(IKK)and nuclear factor-κB(NF-κB)were observed at the end of the 16th week.RESULTS:Compared with control group,the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity(FVC),forced expiratory volume in 0.1 second(FEV0.1)and FEV0.1/FVC(P<0.05).The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration.The renal function indexes serum creatinine,blood urea nitrogen and serum cystatin C(Cys-C)were signifi-cantly increased(P<0.01).The renal histopathology showed swollen and disorderly arranged tubular epithelial cells.The 24 h urine volume decreased(P<0.01).The urinary biochemical indexes 24 h urinary total protein,urinary kidney injury molecule-1(KIM-1),urinary Cys-C,and urinary N-acetyl-β-D-glucosaminidase significantly increased(P<0.01).The protein levels of AQP1～4 were significantly increased(P<0.01).The ratio of neutrophils and lymphocytes in the BALF were increased(P<0.01).The ratio of monocytes was decreased(P<0.01).The serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-13,IL-1β,and transforming growth factor-β1(TGF-β1)were significantly increased(P<0.01).And the mRNA and protein expression levels of IKK,NF-κB were significantly elevated in the renal tissue(P<0.05).Compared with COPD group,the above symptoms and indexes of the rats were improved to different degrees after the intervention in treatment groups,among which BJF,BYF and YZF demonstrated similar effects to PDTC,and BJF+PDTC,BYF+PDTC and YZF+PDTC exhibited better improvements than the corresponding monotherapy.CONCLU-SION:The three Tiao-Bu Fei-Shen therapies can reduce the airway and systemic inflammatory response,improve renal function and attenuate renal injury in COPD rats.The mechanism may be related to the inhibition of NF-κB signaling path-way.

Objective: To compare digital polymerase chain reaction (dPCR) and real-time quantitative PCR (qPCR) measurements of BCR::ABL (P210) mRNA expression in patients with chronic myeloid leukemia (CML) . Methods: In this non-interventional, cross-sectional study, BCR::ABL (P210) mRNA was simultaneously measured by dPCR and qPCR in peripheral blood samples collected from patients with CML who underwent tyrosine kinase inhibitor therapy and who achieved at least a complete cytogenetic response from September 2021 to February 2023 at Peking University People's Hospital. The difference, correlation, and agreement between the two methods were evaluated using the Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman analysis, respectively. Results: In total, 459 data pairs for BCR::ABL mRNA expression measured by dPCR and qPCR from 356 patients with CML were analyzed. There was a significant difference in BCR::ABL mRNA expression between the two methods (P<0.001). When analyzed by the depth of the molecular response (MR), a significant difference only existed for patients with ≥MR4.5 (P<0.001). No significant difference was observed for those who did not achieve a major MR (no MMR; P=0.922) or for those who achieved a major MR (MMR; P=0.723) or MR4 (P=0.099). There was a moderate correlation between the BCR::ABL mRNA expression between the two methods (r=0.761, P<0.001). However, the correlation gradually weakened or disappeared as the depth of the MR increased (no MMR: r=0.929, P<0.001; MMR: r=0.815, P<0.001; MR4: r=0.408, P<0.001; MR4.5: r=0.176, P=0.176). In addition, the agreement in BCR::ABL mRNA expression between the two methods in those with MR4.5 was weaker than other groups (no MMR: ▉= 0.042, P=0.846; MMR:▉=0.054, P=0.229; MR4:▉=-0.020, P=0.399; MR4.5:▉=-0.219, P<0.001) . Conclusions: dPCR is more accurate than qPCR for measuring BCR::ABL (P210) mRNA expression in patients with CML who achieve a stable deep MR.
Humans ; Cross-Sectional Studies ; Cytogenetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger/genetics*

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.
Animals ; Male ; Rats ; Apoptosis ; Brain Ischemia/metabolism* ; Caspase 3 ; Interleukin-1 ; Interleukin-6 ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Flavonoids/pharmacology* ; Rhododendron/chemistry*

Humans ; Male ; Semen ; Sperm Motility ; Mediation Analysis ; East Asian People ; Microcystins/toxicity* ; Spermatozoa ; Sperm Count ; Infertility, Male

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Objective To investigate the effect of Angelica Sinensis polysaccharide (ASP) on proliferation, differentiation and transplantation of human leukemia stem cells (LSCs) . Methods 1. Effect of angelica sinensis polysaccharides on proliferation of CD34

Adult ; Anemia, Iron-Deficiency ; diagnosis ; metabolism ; Female ; Hemoglobins ; analysis ; Humans ; Male ; Middle Aged ; Reference Values ; Reticulocytes ; chemistry ; Young Adult