Atramacronoid A induces the PANoptosis-like cell death of human breast cancer cells through the CASP-3/PARP-GSDMD-MLKL pathways.

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.

Rational design of a ratiometric fluorescent aptasensor for patulin in traditional Chinese medicine through the studies of the interaction mechanism between its DNA aptamer and the target molecule.

Patulin (PAT) is a kind of mycotoxin which must be monitored for the sake of quality and safety in traditional Chinese medicine (TCM) owing to its harm to human health. On this account, a rationally designed ratiometric fluorescent aptasensor was developed based on the studies of the interaction mechanism between PAT and its aptamer (PAT-APT). First, CD spectroscopy, molecular docking, and molecular dynamic simulation were applied to investigate the details on how PAT-APT binds with its target molecule. The results indicated that the structure of PAT-APT changed to a certain extent and was stabilized after binding with PAT. C-11, C-37 and C-38 were the key sites for the recognition and interaction between PAT-APT and its target. Second, based on these results, a ratiometric aptasensor was designed using fluorescence resonance energy transfer (FRET) and synchronous fluorescence spectroscopy. A complementary sequence (cDNA) to the aptamer with an appropriate length and hybridization position was obtained through rational design and optimization. Both PAT-APT and cDNA were labeled using a pair of fluorophores, which could generate FRET when the two single-stranded oligonucleotides hybridized. The accurate detection of PAT could be realized according to the change ratio of the fluorescence intensity at the corresponding wavelengths of the two fluorophores before and after the assay. The aptasensor achieved an ultralow limit of detection of 0.16 nM, perfect selectivity, and satisfactory practicability in complex TCM samples. To our knowledge, this is the first aptasensor for PAT designed through the interaction mechanism between its aptamer and the target molecule. Moreover, the assay for PAT is cost-effective, does not need complicated pretreatment and only takes less than an hour. In summary, this study makes a contribution to the safety control of TCM and provides a thinking mode from mechanism to rational design to conquer the problem of sensitive aptasensing of one component in a complex system.

SAR-guided development of indole-matrine hybrids as potential anticancer agents via mitochondrial stress/cytochrome c/caspase 3 signaling pathway.

Matrine is a clinically used adjuvant anticancer drug, yet its mild potency limited its application. To improve the anticancer activity of matrine, a total of 31 indole-matrine hybrids were constructed in four rounds of SAR-guided iterative structural optimization process. All of the synthesized compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines (Hela, MCF-7, SGC-7901, HepG2) and two normal cell lines (GES-1, LO2). The most active hybrid 8g exhibited the anticancer IC50 values of 0.9 to 1.2 µM, which was 3-magnitude of orders more potent than matrine. 8g also showed better selectivity towards cancer cells with the selectivity index value raised from 1.5 to 6.2. Mechanistic studies demonstrated a mitochondrial distribution for 8g by intracellular click chemistry approaches, which led to the discovery that 8g strongly induced mitochondrial stress, as evidenced by impaired energy metabolism, depolarized mitochondrial membrane potential, overload of mitochondrial calcium and escalated ROS production. 8g-induced mitochondrial stress further led to the release of cytochrome c and subsequent activation of caspase 3, which significantly promoted cellular death and inhibited colony formation.

Surgical Interventions for Congenital Ptosis: a Systematic Review and Meta-analysis of 14 Randomized Controlled Trials.

BACKGROUND: Several types of surgeries have been used in the treatment of congenital ptosis, but the optimal methods and materials for this treatment are unknown. PURPOSE: The study aims to evaluate the comparative effectiveness and safety of various surgical methods and materials for treatment of congenital ptosis. METHODS: We performed comprehensive searches of five databases, two clinical trial registries and one gray literature database from inception to January 2022 for related trials to include in this study. Meta-analysis was performed to evaluate the effect of surgical methods and materials on the primary outcomes: margin reflex distance 1 (MRD1), palpebral fissure height (PFH), and degree of lagophthalmos; and secondary outcomes: undercorrection, entropion, corneal epithelial defects, wound dehiscence, recurrence, infection, and cosmetic outcomes. RESULTS: A total of 14 trials evaluating 909 eyes of 657 patients were included in our study. Compared with the levator plication, the frontalis sling significantly increased the MRD1 (MD = - 1.21; 95% CI [- 1.69, - 0.73]), and the levator resection significantly increased the PFH (MD = 1.30; 95% CI [0.27, 2.33]). For the frontalis sling surgical patterns, the fox pentagon was significantly better than the double triangle at improving the degree of lagophthalmos (MD = 0.70; 95% CI [0.32, 1.08]), while the opened pattern provided statistically better cosmetic outcome than the closed frontalis sling. Analysis of surgical material showed that absorbable sutures significantly increased the MRD1 (MD = 1.16; 95% CI [0.60, 1.72]) compared to non-absorbable sutures when used in levator plication; frontalis sling surgeries performed with silicon rods significantly increased the PFH (MD = 0.88; 95% CI [0.29, 1.47]) compared to those performed with Gore-Tex strips, while autogenous fascia lata provided statistically better aesthetic outcome for lid height symmetry and contour. CONCLUSION: Different surgical methods and materials appear to affect different aspects of the congenital ptosis treatment outcome. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Silencing Tautomerization to Isolate Unstable Physalins from Physalis minima.

The inherent structural instability of some physalins has hampered the isolation and identification of these compounds for approximately 50 years, and an effective method to overcome these challenges remains unavailable. In the present study, the unprecedented tautomerization mechanism of unstable physalins was elucidated by performing isotopic labeling experiments and DFT calculations, which led to the successful separation of tautomers and isolation of highly pure products for the first time. As a result, 15 new physalins, physaminins A-O (1-15), as well as 17 known analogues (16-32), were isolated from the whole plants of Physalis minima L. The chemical structures of the new compounds were established by performing a comprehensive analysis of spectroscopic data, and their absolute configurations were confirmed by using computational ECD calculations and/or single-crystal X-ray diffraction analyses. All obtained isolates were evaluated for their antiproliferative effects against four human cancer cell lines (A549, HepG2, MCF-7, and SCG-7901) and two noncancerous cell lines (RAW 264.7 and human normal hepatocytes L02), as well as their anti-inflammatory activities by measuring their abilities to inhibit NO production in LPS-stimulated murine RAW 264.7 cells in vitro. Compounds 1-5, 13, 16, 18, 19, 23, and 30 exerted significant antiproliferative effects on the four human cancer lines, with IC50 values ranging from 0.2(0) to 24.7(2) µM, and these compounds were not toxic to the two noncancerous cell lines at a concentration of 10 µM. Moreover, compounds 7, 10, 11, 12, 14, 17, 22, and 27 significantly inhibited NO production, with IC50 values ranging from 2.9(1) to 9.5(2) µM.

The Synthesis and Biological Evaluation of Aloe-Emodin-Coumarin Hybrids as Potential Antitumor Agents.

A series of novel aloe-emodin-coumarin hybrids were designed and synthesized. The antitumor activity of these derivatives was evaluated against five human tumor cell lines (A549, SGC-7901, HepG2, MCF-7 and HCT-8). Some of the synthesized compounds exhibited moderate to good activity against one or more cell lines. Particularly, compound 5d exhibited more potent antiproliferative activity than the reference drug etoposide against all tested tumor cell lines, indicating that it had a broad spectrum of antitumor activity and that it may provide a promising lead compound for further development as an antitumor agent by structural modification. Furthermore, the structure-activity relationship study of the synthesized compounds was also performed.

Long non-coding RNA HOTAIR regulates myeloid differentiation through the upregulation of p21 via miR-17-5p in acute myeloid leukaemia.

Long non-coding RNA HOTAIR has been reported to play a key role in regulating various biological processes in various cancers. However, the roles and mechanisms of HOTAIR in acute myeloid leukaemia (AML) are still unclear and need to be investigated. In this study, we induced differentiation of four AML cell lines by all-trans retinoic acid (ATRA) and found HOTAIR was significantly upregulated in the process. Chromatin immunoprecipitation (ChIP) assays indicated that C/EBPß upregulated HOTAIR during ATRA induced differentiation in HL-60 cells. By gain- and loss-of-function analysis, we then observed that HOTAIR expression was positively correlated with ATRA-induced differentiation and negatively regulated G1 phase arrest in HL-60 cells. In addition, we found that HOTAIR promoted ATRA-induced differentiation via the regulation of the cell cycle regulator p21 via miR-17-5p. Moreover, we detected the expression of HOTAIR in 84 de novo AML patients, HOTAIR was found significantly downregulated in the AML patients compared to the iron deficiency anaemia (IDA) control group, negatively correlated with the platelet level in M2 patients. In all, our data suggest that HOTAIR may be subtype-specific in AML-M2 patients, also HOTAIR regulates AML differentiation by C/EBPBß/HOTAIR/miR-17-5p/p21 pathway. The findings of the present study provide a novel insight into the mechanism of lncRNA-mediated differentiation and indicate that HOTAIR may be a promising therapeutic target for leukaemia, especially for AML with M2 type.Abbreviation: AML: acute myeloid leukaemia; APL: acute promyelocytic leukaemia; ATRA: all-trans retinoic acid; CCK8: cell Counting Kit-8; CDKs: cyclin-dependent kinases ; CeRNA: competing endogenous RNAs; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; FAB: French-American-British; FCM: flow cytometry; HOTAIR: HOX transcript antisense RNA; IDA: iron-deficiency anemia; lncRNA: long non-coding RNA; 3'UTR: 3'untranslated region; MT: Mutation type; WT: Wild type; qRT-PCR: Quantitative real-time PCR.

CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy.

The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. We showed that CS1003 bound to recombinant human, cynomolgus monkey, and mouse PD-1 with EC50 values of 0.1757, 0.2459, and 0.3664 nM, respectively. CS1003 blocked PD-1 interaction with its ligands, dose-dependently enhanced T cell proliferation and secretion of cytokines (IL-2 and IFN-γ) to the levels comparable to the reference antibody pembrolizumab. Intraperitoneal administration of CS1003 (0.1, 0.5, 2.5 mg/kg, once every 3 days) dose-dependently suppressed the growth of MC38-hPD-L1 colon cancer in hPD-1 knock-in mice. Pharmacokinetics (PK) study revealed a linear PK profile within the dose range of 2-18 mg/kg following single intravenous administration in cynomolgus monkey. These data provide a comprehensive preclinical characterization of CS1003 that supports its clinical development for cancer immunotherapy.

Performance of atherosclerotic cardiovascular risk prediction models in a rural Northern Chinese population: Results from the Fangshan Cohort Study.

BACKGROUND: Performance of Pooled Cohort Equations (PCEs) for atherosclerotic cardiovascular disease (ASCVD) risks varied across populations. Whether the recently developed Prediction for ASCVD Risk in China (China-PAR) model could accurately predict cardiovascular risks in real practice remains unclear. METHODS: A population-based cohort study in rural Beijing in the "stroke belt" in North China was used to externally validate PCE and China-PAR models for 5-year ASCVD risk prediction. Expected 5-year prediction risk using China-PAR model was compared with PCE (white). The models were assessed for calibration, discrimination, and reclassification. RESULTS: Among 11,169 adults aged 40 to 79 years over a median 6.44 years of follow-up, 1,921 participants developed a first ASCVD event during total 70,951 person-years. China-PAR model fairly predicted ASCVD risk in men but overestimated by 29.4% risk in women (calibration χ2 = 81.4, P < .001). Underestimations were shown by PCE as 76.2% in men and 88.2% in women with poor calibration (both P < .001). However, discrimination was similar in both models: C-statistics in men were 0.685 (95% CI 0.660-0.710) for China-PAR and 0.675 (95% CI 0.649-0.701) for PCE; C-statistics in women were 0.711 (95% CI 0.694-0.728) for China-PAR and 0.714 (95% CI 0.697-0.731) for PCE. Moreover, China-PAR did not substantially improve accuracy of reclassification compared with PCE. CONCLUSIONS: China-PAR outperformed PCE in 5-year ASCVD risk prediction in this rural Northern Chinese population at average population risk level, fairly predicted risk in men, but overestimated risk in women; however, China-PAR did not meaningfully improve the accuracy of discrimination and reclassification at individual risk level.

Red blood cell distribution width and platelet counts are independent prognostic factors and improve the predictive ability of IPI score in diffuse large B-cell lymphoma patients.

BACKGROUND: Elevated red blood cell distribution width (RDW) and decreased platelet count (PLT) can be clinically relevant to the prognosis in cancer patients. However, their prognostic values in patients with diffuse large B-cell lymphoma (DLBCL) need to be further explored. METHODS: Healthy donors (n = 130) and patients with DLBCL (n = 349) were included and evaluated retrospectively in this study. The prognostic influence of clinical and pathological factors including RDW and PLT on overall survival (OS) and progression-free survival (PFS) were studied by Kaplan-Meier curves. To evaluate the independent prognostic relevance of RDW and PLT, univariate and multivariate Cox proportional hazards regression models were applied. The adjusted IPI model was established based on the results of multivariate analysis, and verified by Harrell's C statistical analysis. RESULTS: Kaplan-Meier curves indicated that an elevated RDW value and thrombocytopenia are poor factors for OS (P < 0.001, P = 0.006) and PFS (P = 0.003, P < 0.001) in DLBCL patients. Multivariate analysis confirmed that elevated RDW value (HR = 2.026, 95%CI = 1.263-3.250, P = 0.003) and decreased PLT count (HR =1.749, 95%CI = 1.010-3.028, P = 0.046) were both independent prognostic factors. The c-index of IPI and NCCN-IPI were increased when RDW level and PLT were supplemented in our cohort. CONCLUSIONS: Our study shows that elevated RDW level and decreased PLT are independent poor prognostic factors in newly diagnosed DLBCL patients. Adding RDW and PLT to the IPI score may improve its predictive ability, and the adjusted IPI may be more powerful in predicting the survival of DLBCL patients in the rituximab era.

Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors.

Neratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4'-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4'-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4'-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to obtain B1-B7 and replaced indoline with benzmorpholine to get C1-C4 and D1-D2. We synthesized these compounds and evaluated their residual activities under 0.5 M drug concentration on EGFR and ERBB2. Most of compounds showed stronger inhibition on EGFR-wt and ERBB2, in which A1-A4 showed excellent inhibitory activity with inhibition percentage on EGFR-wt kinase of 7%, 6%, 19%, 27%, respectively and 9%, 5%, 12%, 34% on ERBB2 kinase compared with 2% and 6% of Neratinib.

Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

Motion-generated optical information allows event perception despite blurry vision in AMD and amblyopic patients.

Events consist of objects in motion. When objects move, their opaque surfaces reflect light and produce both static image structure and dynamic optic flow. The static and dynamic optical information co-specify events. Patients with age-related macular degeneration (AMD) and amblyopia cannot identify static objects because of weakened image structure. However, optic flow is detectable despite blurry vision because visual motion measurement uses low spatial frequencies. When motion ceases, image structure persists and might preserve properties specified by optic flow. We tested whether optic flow and image structure interact to allow event perception with poor static vision. AMD (Experiment 1), amblyopic (Experiments 2 and 3), and normally sighted observers identified common events from either blurry (Experiments 1 and 2) or clear images (Experiment 3), when either single image frames were presented, a sequence of frames was presented with motion masks, or a sequence of frames was presented with detectable motion. Results showed that with static images, but no motion, events were not perceived well by participants other than controls in Experiment 3. However, with detectable motion, events were perceived. Immediately following this and again after five days, participants were able to identify events from the original static images. So, when image structure information is weak, optic flow compensates for it and enables event perception. Furthermore, weakened static image structure information nevertheless preserves information that was once available in optic flow. The combination is powerful and allows events to be perceived accurately and stably despite blurry vision.

Strategy to rapidly discriminate trace isomeric lignan compounds from Gymnotheca chinensis by probe electrospray ionization tandem mass spectrometry.

Probe electrospray ionization (PESI) is a recently developed ionization technique based on electrospray ionization (ESI) that generates electrospray from the tip of a solid needle. High tolerance to salts, requirements of a trace amount of sample and direct ambient sampling- are major advantages of PESI compared with conventional ESI. In this report, three pairs of isomeric lignans bearing tetra-hydrofuran with variable conformations from Gymnotheca chinensis were investigated by probe electrospray tandem mass spectrometry (PESI-MS/MS) in the positive ion mode. The diagnostic characteristics of these compounds were obtained and the isomers could be successfully distinguished by comparison with their breakdown curves, even though the isomers differed only in the conformation of some groups of the isomer pairs. This report provides a rapid and reliable method for the identification of trace amounts of isomeric lignans by PESI-MS/MS. Furthermore, application of PESI and breakdown curves should have value in mass spectrometry studies of isomeric natural products compounds.

Magnetic-encoded fluorescent multifunctional nanospheres for simultaneous multicomponent analysis.

In this study, magnetic-encoded fluorescent (CdTe/Fe3O4)@SiO2 multifunctional nanospheres were constructed by adjusting the initial concentration of Fe3O4 in a fabrication process based on reverse microemulsion. The resultant multifunctional nanospheres were characterized by transmission electron microscopy, X-ray diffraction measurements, fluorescence spectrophotometry, and vibrating sample magnetometry. They showed good fluorescence properties, gradient magnetic susceptibility (weak, moderate, and strong), and easy biofunctionalization for biomolecules, such as immunoglobulin G (IgG), protein, and antibody. Then the capture efficiency of the (CdTe/Fe3O4)@SiO2 nanospheres were investigated by using the fluorophore-labeled IgG-conjugated nanospheres as a model. Further studies demonstrated the ability of these (CdTe/Fe3O4)@SiO2 multifunctional nanospheres to accomplish sequentially magnetic separation, capture, and fluorescent detection for each corresponding antigen of CA125, AFP, and CEA with a detection limit of 20 KU/L, 10 ng/mL, and 5 ng/mL, respectively, from a mixed sample under a certain external magnetic field within a few minutes. The strategy of combining magnetic-encoding-based separation and fluorescence-based detection proposed in this study shows great potential to achieve easy, rapid, economical, and near-simultaneous multicomponent separation and analysis for a variety of targets such as drugs, biomarkers, pathogens, and so on.

Cyclovirobuxinum D suppresses lipopolysaccharide-induced inflammatory responses in murine macrophages in vitro by blocking JAK-STAT signaling pathway.

AIM: Cyclovirobuxinum D (CVB-D), an alkaloid isolated from the Chinese medicinal plant Buxus microphylla, has been found to be effective to treat cardiac insufficiency, arrhythmias and coronary heart disease. In the present study, we investigated the effects of CVB-D on the inflammatory responses in lipopolysaccharide (LPS)-stimulated murine macrophages in vitro and the underlying mechanisms. METHODS: Murine macrophage cell line RAW264.7 cells were incubated in the presence of LPS (0.1 µg/mL) for 24 h. The cell viability was measured using MTT assay. The release of NO and cytokines were detected using the Griess test and ELISA, respectively. The mRNA and protein levels were determined using RT-PCR and Western blot, respectively. Reporter gene assays were used to analyze the transcriptional activity of NF-κB. RESULTS: Treatment of RAW264.7 cells with CVB-D (25-300 µmol/L) did not affect the cell viability. Pretreatment with CVB-D (50, 100 and 200 µmol/L) concentration-dependently decreased NO release and iNOS expression in LPS-treated RAW264.7 cells (its IC50 value in inhibition of NO production was 144 µmol/L). CVB-D also concentration-dependently inhibited the secretion and mRNA expression of IL-1ß and IL-6 in LPS-treated RAW264.7 cells. Furthermore, CVB-D remarkably inhibited the phosphorylation of STAT1 and STAT3, as well as JAK2 in LPS-treated RAW264.7 cells, but did not affect the activation of NF-κB and MAPKs pathways. Pretreatment with the JAK2 specific inhibitor AG490 (30 µmol/L) produced similar effects on NO release and iNOS expression in LPS-treated RAW264.7 cells. CONCLUSION: CVB-D exerts anti-inflammatory effects in LPS-stimulated murine macrophages in vitro at least in part by blocking the JAK-STAT signaling pathway. The anti-inflammatory actions of CVB-D may contribute to its cardioprotection.

Cohort profile: the Fangshan Cohort Study of cardiovascular epidemiology in Beijing, China.

BACKGROUND: Urbanizing rural areas in China face a rapidly growing cardiovascular disease burden. Epidemiologic studies and effective preventive strategies are urgently needed. METHODS: The Fangshan Cohort Study is a prospective study that began in 2008 and targets local residents aged 40 years or older living in 3 towns in the Fangshan district of Beijing. The baseline examination included a questionnaire on medical history, health knowledge, and behaviors related to cardiovascular disease, as well as physical and blood biochemical examinations. The questionnaire survey will be readministered every 2 years. A system for surveillance of mortality and morbidity of cardiovascular disease is under development. RESULTS: A total of 20 115 adults (6710 men and 13 405 women) were investigated at baseline (participation rate = 84.5%). The data indicate that overweight/obesity is a serious public health issue in Fangshan: average body mass index was 25.4 kg/m(2) among men and 26.5 kg/m(2) among women, and the prevalences of overweight and obesity were 43.6% and 10.3% among men and 47.0% and 17.7% among women. CONCLUSIONS: The Fangshan Cohort Study will provide data on cardiovascular risk factors and disease profile, which will assist in developing appropriate prevention and control strategies for cardiovascular disease in rural Chinese communities.

Relationship between menopause and health-related quality of life in middle-aged Chinese women: a cross-sectional study.

BACKGROUND: Chinese menopausal women comprise a large population and the women in it experience menopausal symptoms in many different ways. Their health related quality of life (HRQOL) is not particularly well studied. Our study intends to evaluate the influence of menopause on HRQOL and explore other risk factors for HRQOL in rural China. METHODS: An interview study was conducted from June to August 2010 in Beijing based on cross-sectional design. 1,351 women aged 40-59 were included in the study. HRQOL was measured using the EuroQol Group's 5-domain (EQ5D) questionnaire. Comparison of HRQOL measures (EQ5D index and EQ5D-VAS scores) was done between different menopausal groups. Logistic regression and multiple regression analysis were performed to adjust potential confounders and explore other risk factors for health problems and HRQOL measures. RESULTS: Postmenopausal women who had menopause for 2-5 years (+1b stage) were more likely to suffer mobility problems (OR = 1.835, p = 0.008) after multiple adjustment. Menopause was also related to impaired EQ5D index and EQ5D-VAS scores after adjustment for age. Among menopausal groups categorized by menopausal duration, a consistent decrement in EQ5D index and EQ5D-VAS scores, that is, worsening HRQOL, was observed (p < 0.05). Multiple regression analysis revealed low education level and physical activity were associated with EQ5D index (ß = -0.080, p = 0.003, and ß = 0.056, p = 0.040, respectively). Cigarette smoking and chronic disease were associated with EQ5D index (ß = -0.135, p < 0.001 and ß = -0.104, p < 0.001, respectively) and EQ5D-VAS (ß = -0.057, P = 0.034 and ß = -0.214, p < 0.001, respectively). CONCLUSIONS: Reduction in physical function was found within the first five years after menopause. Worsening EQ5D index and EQ5D-VAS scores were related to menopause. Education level, physical activity, cigarette smoking, and chronic disease history were associated with HRQOL in middle aged Chinese rural women.

Research on the effect of environmental regulation to the green water resource efficiency in China-based on the perspectives of high pressure and low suction.

Environmental regulation with spatial spillover effect is an important way to accelerate the transformation and upgrading of modern water resources structure, and then achieve sustainable development of China's water resources. How does environmental regulation affect the GWRE to alleviate or solve China's water shortage? In this paper, the GWRE is measured based on panel data from 31 provinces in China from 2000-2020, and the impact of high pressure (low suction) and heterogeneity on GWRE by environmental regulations is explored. The results revealed that the high pressure of environmental regulation significantly promoted the improvement of GWRE, but the improvement effect of low suction power was not significant. Similar conclusions are drawn under the tests of population size-economic distance and population size-technology distance. The high pressure of market-type and autonomous-type environmental regulation has a significant effect on GWRE, while the improvement effect of command-type environmental regulation is weak. The high pressure of environmental regulation in the eastern, central, western, and northeastern regions has a decreasing effect on GWRE. It is recommended to break the principle of GDP performance appraisal, establish and improve the "green performance" evaluation system, adopt regional differentiated environmental regulation policies, and establish a modern green water resources industrial structure system.