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BACKGROUND: This study aimed to delineate the association between menopausal-related symptoms and brain cortical hemodynamics in peri-postmenopause women. METHODS: Cross-sectional data from a total of 358 Han-Chinese women who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from August 2019 to August 2022. Menopausal-related symptoms were analyzed through Kupperman index (KMI) scale and PSQI scale, while cerebral blood flow was measured using a functional near-infrared spectroscopy (fNIRS). Multiple linear regression model was used to assess the risk factors for subregions of brain hemodynamic response. RESULTS: After adjusting for confounding factors, we identified that menopausal symptom (B = -1.575, 95 % CI (-2.661, -0.488), p = 0.005) and duration of menopause (B = -14.583, 95 % CI (-26.753, -4.192), p = 0.007) were independently associated with the lower brain hemodynamic response in the prefrontal lobe, while in the temporal lobe, overweight (BMI ≥ 24 kg/m2) was negatively associated with the lower brain cortical activity (B = -36.882, 95 % CI (-72.708, -1.056), p = 0.044) after adjusting for other confounding variables. CONCLUSIONS: Our findings proposed that menopausal symptom and overweight should be attached great importance to the postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as menopausal hormone therapy (MHT) of brain health in postmenopausal women.

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OBJECTIVE: To explore whether functional near-infrared spectroscopy (fNIRS) can aid in the early detection and diagnosis of postpartum depression. METHODS: The study was a cross-sectional survey that invited all women who sought postpartum health examination 42 days after childbirth between August 2020 and January 2021. Personal information, Edinburgh Postnatal Depression Scale (EPDS), and well as fNIRS results were collected. RESULTS: In all, 109 individuals agreed to participate and completed the examination in its entirety. The variance in integral and centroid values was not statistically significant across different subgroups of depression (P > 0.05). The difference in diagnosis of postpartum major depression between EPDS and fNIRS was statistically significant (P < 0.001). fNIRS results in postpartum depression diagnosis were substantially associated with gestational diabetes mellitus (P = 0.027), the number of pregnancies (P = 0.001), and postpartum body mass index (P = 0.035). CONCLUSION: fNIRS can provide an objective method for early detection and diagnosis of postpartum depression. Certain clinical conditions can have an effect on brain activity, which may result in postpartum depression. Additional high-quality study is required to establish strong evidence on the subject.

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BACKGROUND: The potential impact of ß cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between ß cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes. METHODS: This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on ß cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of ß cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models. RESULTS: Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for ß cell function (HOMA-ß) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-ß was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-ß. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes. CONCLUSIONS: We demonstrated a significant association of ß cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.

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Objective: To delineate the association between sleep characteristics and renal function in peri-post menopause free of Chronic kidney disease (CKD) as well as cardiometabolic and hormone indicators. Methods: Cross-sectional data from a total of 823 Han-Chinese women aged 40-67 years who visited the Menopause Clinic in the Shanghai Sixth People's Hospital from November 2011 to November 2020 were analyzed through the Pittsburgh Sleep Quality Index (PSQI) and serum cystatin C (Cys-C). Logistic regression models were used to assess the association between cumulative/each sleep parameter and renal function after adjusting for cardiometabolic variables. Results: After confounding factors, we identified that poor perceived sleep quality, shorter sleep duration (<6 h), low sleep efficiency (<75%), delayed sleep latency and worse sleep disturbance elevated more than doubled the odds ratio for declining renal function (≥0.91 mg/dL, the highest Cys-C) in postmenopause in a graded fashion. Meanwhile, multiple logistic regression analysis revealed that sleep disorder (PSQI ≥ 8), late postmenopause, highest quartile independently increased the odds ratio for declining renal function (OR 2.007, 95% CI: 1.408-2.861, OR = 3.287, 95%CI: 3.425-8.889, OR = 2.345, 95% CI: 1.310-4.199, respectively), while participants with menopausal hormone replacement (MHT) lower the odds of declining renal function (OR = 0.486, 95% CI: 0.324-0.728). Conclusion: The findings proposed that maintaining good sleep quality should be attached great importance to postmenopausal women, which provides clinical evidence for the feasible early detection and effective prevention such as MHT of renal disease progression in postmenopausal women.

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BACKGROUND: Infertility now is a public health concern and is associated with increased psychological distress. METHODS: We enrolled 1247 infertile couples and assessed their anxiety and depression status before and during assisted reproductive technology (ART) treatment using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). The Chi-square or fisher's exact test was used to analyze the prevalence of anxiety and depression in infertile couples. Multivariate logistical regression was performed to analyze the risk factors for anxiety and depression. RESULTS: The prevalence of anxiety was 13.5% and 8.7% (p < 0.05), and that of depression was 9.4% and 7.9% (p = 0.2) in female and male partners, respectively. Female SAS and SDS scores were positively associated with male SAS and SDS scores, respectively (r = 0.52 and r = 0.50, respectively, both p < 0.0001), and were positively associated with their own SDS and SAS scores, respectively (r = 0.63 and r = 0.62, respectively, both p < 0.0001). Their own depression or partners' anxiety was associated with the anxiety, and their own anxiety or partners' depression was associated with the depression in infertile couples. No children, unemployment, and low education level were also associated with female anxiety. SAS and SDS scores were significantly decreased during ART treatment. CONCLUSIONS: Females were more vulnerable to having anxiety than males in infertile couples. Anxiety and depression in infertile couples could interact, therefore, anxiety and depression would be simultaneously counseled, and their partners also should be given supportive psychotherapy. TRIAL REGISTRATION: It was an observational study and had no health care interventions on participants. So it was not registrated.

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The study examined the relationship between menopausal symptoms and sleep disturbances and the related influencing factors. Methods. We recruited women aged 40-65 years who attended the menopause clinic at Shanghai Jiao Tong University's Sixth People's Hospital from February 2011 to November 2019. The Menopause Rating Scale (MRS) was used to collect women's menopausal symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the subjects' sleep condition. We used logistic regression models to identify the relationship between menopausal symptoms and sleep quality. Results. A total of 1341 participants were recruited in this study. The most frequent three symptoms assessed by MRS were fatigue (72.9%), sleep disturbance (67%), and hot flashes with night sweats (65%). Participants' age was significantly associated with the severity of menopausal syndrome (P < 0.01). According to the PSQI sleep evaluation, 66.9 percent of participants had sleep disturbances (PSQI > 5). Logistic regression analysis revealed that women with mild, moderate, or severe menopausal syndrome had a 3-, 7-, and 17-fold increased chance of having sleep disturbances compared to women without menopausal syndrome. Conclusion. Women aged 40-65 years were found to have a significantly higher risk of menopausal syndrome and sleep disturbances.

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The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

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This study aimed to develop polymer Eudragit S100 for preparing pH-responsive liposomes-loaded betulinic acid (pH-BA-LP) to improve the therapeutic index of chemotherapy for colorectal cancer. BA-loaded liposomes were coated with Eudragit S100 by a thin film dispersion and easily scalable pH-driven method. The prepared liposomes were evaluated for size, surface morphology, entrapment efficiency, stability, in vitro drug release, and antitumor activity. In particular, pH-BA-LP showed advantages such as lower size (<100 nm), encapsulation efficiency of 90%, high stability, and stably cumulative release. By detecting the antitumor effects of pH-BA-LP in vivo, it showed that the tumor proliferation and cell migration were significantly inhibited in colorectal cancer. The pH-BA-LP also inhibited tumor growth via the regulation of Akt/TLR-mediated signalling and significantly down-regulated the expression of NFAT1 and NFAT4 proteins. It was found that pH-BA-LP can increase NK cells and CD3+ cells in tumor tissues, and the proportion of CD8+ cells in CD3+ cells was also increased, which proved that pH-BA-LP can play an antitumor effect by enhancing the autoimmunity level in tumor-bearing mice. The positive infiltration rates of CD8 and CD68 were increased and CD163 was relatively decreased by using pH-BA-LP, which proved that pH-BA-LP can regulate the immune infiltration levels in tumor-bearing mice. Therefore, the present work provides an effective method to prepare pH-responsive polymer-coated liposomes for colonic delivery with biologically active compounds.

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OBJECTIVE: The aim of this study was to evaluate the relationship between the severity of menopausal symptoms and everyday cognitive decline in Chinese peri and postmenopausal women. METHODS: The peri and postmenopausal Chinese Han female who first visited the menopausal clinic of Shanghai Jiao Tong University Affiliated Sixth People's Hospital was selected as the study participants. The general questionnaire was used to obtain the sociodemographic characteristics of the study participants. The menopausal rating scale (MRS) was used to assess the severity of menopausal symptoms. The short version of the Everyday Cognition (ECog-12) scales was used to assess everyday cognitive performance. RESULTS: A total of 295 women were included, with an average age of 51.12 ± 5.15 years. The average ECog scores were 1.51 ± 0.49 and the average MRS scores were 6.89 ± 4.77. In multiple linear regression analysis, after adjusting for confounding factors age, body mass index (BMI), monthly income, occupational status, education level, menopausal status, parity, regular exercise, and history of chronic diseases, complaints of anxiety and physical/mental fatigue were positively correlated with everyday cognitive decline. CONCLUSIONS: Menopausal anxiety and physical/mental fatigue were the independent predictors of everyday cognition.

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Genitourinary syndrome of menopause (GSM) is a chronic and progressive condition with a series of vulvovaginal, sexual, and lower urinary tract discomforts, mainly due to hypoestrogenism. Menopausal hormone therapy (MHT) has generally been considered as the most effective treatment for GSM. In addition, vaginal microbiota is of particular significance to gynecological and reproductive illnesses and potentially has some intimate connections with GSM. Consequently, we sought to evaluate how MHT impacts the composition and structure of vaginal microbiota while alleviating GSM in Chinese menopausal women aged 45-65 years, which has not been investigated previously. 16S rRNA gene sequencing was performed to analyze microbial diversity and composition using vaginal swabs obtained from 100 menopausal women, classified as MHT women who have been taking tibolone regularly (n = 50) and non-treated women who never received any treatment (n = 50). Vaginal Health Index Score (VHIS) and GSM symptoms inquiry were also performed. We found that the vaginal microbial diversity decreased and that the abundance of Lactobacillus increased to be the dominant proportion significantly in the MHT group, in considerable contrast to vaginal microbiota of the non-treated group, which significantly comprised several anaerobic bacteria, namely, Gardnerella, Prevotella, Escherichia-Shigella, Streptococcus, Atopobium, Aerococcus, Anaerotruncus, and Anaerococcus. In this study, women without any MHT had significantly more severe GSM symptoms than those receiving tibolone, especially with regard to vulvovaginal dryness and burning, as well as decreased libido (P < 0.01). However, there was no significant difference in the severity of urological symptoms between the groups (P > 0.05). Furthermore, Lactobacillus was demonstrated to be associated with VHIS positively (r = 0.626, P < 0.001) and with GSM negatively (r = -0.347, P < 0.001). We also identified Chlamydia (r = 0.277, P < 0.01) and Streptococcus (r = 0.270, P < 0.01) as having a prominent association with more serious GSM symptoms. Our study provided an elucidation that MHT could notably alleviate GSM and conspicuously reshape the composition of the vaginal microbiota, which is of extreme importance to clinical practice for the management of GSM.

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INTRODUCTION: To gain insight into mechanisms of preeclampsia (PE)-dependent proteinuria, this study focused on whether preeclampsia serum (PES) could induce hyperpermeability in human renal glomerular endothelial cells (HRGECs) via the miRNAs-Caveolin-1 (CAV-1)-dependent pathway. METHODS: Bioinformatics approach was used to identify miRNAs targeting CAV1. Normal pregnancy serum (NPS) and severe PES were used to treat HRGECs monolayer to demonstrate if PES could induce the expression of identified miRNAs. A luciferase reporter assay was used to determine whether CAV1 was a direct target of miR-199a-5p, miR-199b-5p, and miR-204. The relationship between the expression of miR-199a-5p, miR-199b-5p, miR-204, and CAV1 in HRGECs was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. The gain-of-function and loss-of-function experiments were performed on HRGECs to investigate the effects of miR-199a-5p, miR-199b-5p, miR-204 on HRGECs permeability. RESULTS: We identified that CAV1 3'UTR has putative binding sites for miR-199a-5p, miR-199b-5p, and miR-204, whereas miR-199a-5p does not appear to be a direct regulator of CAV1. We detected that PE serum downregulated the expression of miR-199a-5p, miR-199b-5p and miR-204, increased expression of CAV1 and increased cell monolayer permeability in HRGECs. The level of CAV1 and permeability decreased when miR-199b-5p or miR-204, but not miR-199a-5p, were overexpressed. DISCUSSION: miR-199b-5p and miR-204 may play a role in PES-induced increasing permeability of HRGECs by regulating CAV1 expression.

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BACKGROUND: Little attention has been paid to whether snoring frequency is associated with body composition in menopausal women, particularly in China. This study objected to investigate the association between self-reported snoring and body composition in (peri-post) menopausal Chinese women as well as metabolic indicators. METHODS: This cross-sectional study enrolled 715 participants aged 40-67 years from the Menopause Clinic in the Shanghai Sixth People's Hospital. Participants were categorized into four subgroups stratified by self-reported snoring frequency: never, rarely (< 1 night per week), occasionally (1-2 nights per week), regularly (≥3 nights per week), while body composition was measured using bioelectrical impedance analysis (BIA). Besides, blood sample were collected to test the glycolipid indicators. RESULTS: In our sample of investigation, regular snoring (≥3 nights per week) was found to be an independent risk factor for higher fat mass (total, upper limbs, trunk), with the highest risk of 2.4 times for fat mass of trunk after adjusting for metabolic confounders(p = 0.003). Meanwhile, regular snoring was independently associated with higher fat mass (total and each segment) only in menopausal transition (p = 0.023). CONCLUSIONS: We suggested that self-reported regular snoring may be taken as a simple alternative to predict higher fat mass (≥17.11 kg, upper quartile) in menopausal women. Similarly, body composition should be attached to the great importance to those who in menopausal transition in order to help to prevent obstructive sleep apnea (OSA).

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OBJECTIVE: To evaluate patterns of insulin secretion in pregnancy and analyze the association between insulin patterns and risks of gestational diabetes mellitus (GDM). METHODS: A prospective study was conducted to collect and analyze pregnant women's materials from January 2015 to December 2018. Pregnant women were grouped according to results of 75-g oral glucose tolerance test at 24-28 weeks of pregnancy: normal glucose tolerance (NGT) and GDM. Insulin secretion patterns were based on the time of peak(s) and shape of insulin secretion curve. The relationship between insulin secretion patterns and pregnant outcomes was analyzed. RESULTS: A total of 2432 pregnant women met the inclusion criteria during the study period. Among them, 737 (30.3%) women were grouped as GDM and 1695 (69.7%) as NGT. Type I insulin secretion represented the early phase of insulin secretion (peak time at 30 or 60 minutes), while type II represented the delayed peak of insulin secretion (peak time at 120 or 180 minutes). Logistic regression analysis showed that type II insulin secretion was a risk factor of pre-eclampsia, large-for-gestational-age, and neonatal hypoglycemia. CONCLUSION: The delayed insulin peak is a useful marker for risk of GDM and adverse pregnant outcomes in women with GDM.

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Objective: We aimed to investigate the association between maternal glycemic parameters and adverse pregnancy outcomes among high-risk pregnant women. Research design and methods: A total of 1976 high-risk pregnant women were enrolled between 2015 and 2017. All participants received a 75 g oral glucose tolerance test during the 24-30 gestational weeks and complete birth and delivery information was collected. Adverse pregnancy outcomes were defined as premature birth, birth weight >90th percentile, primary cesarean section, and pre-eclampsia. Logistic regression models were used to assess the association between five maternal glycemic parameters during pregnancy (fasting glucose, 1-hour glucose, 2-hour glucose, HbA1c, and serum 1,5-anhydroglucitol (1,5-AG)) and adverse pregnancy outcomes. Results: Of 1976 participants, 498 were diagnosed with gestational diabetes. The multivariable-adjusted ORs of adverse pregnancy outcomes for each one unit increase (1 mmol/L, 1%, or 1 µg/mL) were 2.32 (95% CI 1.85 to 2.92) for fasting glucose, 1.07 (95% CI 1.01 to 1.15) for 1-hour glucose, 1.03 (95% CI 0.96 to 1.10) for 2-hour glucose, 1.77 (95% CI 1.34 to 2.33) for HbA1c, and 0.96 (95% CI 0.94 to 0.98) for 1,5-AG, respectively. When all five glycemic parameters were simultaneously entered into the multivariable-adjusted model, only fasting glucose was significantly associated with total and individual adverse pregnancy outcomes. Receiver operating characteristic curve showed that fasting glucose plus any one of other four glycemic parameters had significantly enhanced the sensitivity of detecting adverse pregnancy outcomes. Conclusions: Fasting glucose at 24-30 gestational weeks was strongly associated with adverse pregnancy outcomes. Fasting glucose combined with one additional glycemic measurement showed non-inferiority indicating that post-load glycemic measurement was not necessary in detecting adverse pregnancy outcomes among high-risk pregnant women.

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BACKGROUND: The long non-coding RNA UCA1 is reportedly increased in several human tumors and critical for the cell migration, invasion, or proliferation of several cancer cells. However, the potential roles of UCA1 in trophoblasts at early pregnancy still poorly understood. Here, we sought to unravel the roles of UCA1 in the occurrence of the recurrent miscarriage (RM) disorders. RESULTS: The knockdown of UCA1 in human HTR-8 trophoblast cell line reduced their cell proliferative and invasive ability. Conversely, the UCA1 overexpression promoted the cell proliferation and invasion of HTR-8 cells. Quantitative RT-PCR screening revealed that UCA1 overexpression significantly enhanced MMP9, but not MMP2, mRNA expression in trophoblast cells. The overexpression of UCA1 also promoted trophoblast invasion by upregulating MMP9 expression and activity both in vitro and ex vivo. Consistently, UCA1 and MMP9 mRNA expression level was notably reduced in placental villi derived from patients with RM diseases. CONCLUSION: This study revealed that UCA1 is critical for the regulation of invasive ability in trophoblasts. The abnormal UCA1/MMP9 pathway might result in the impaired trophoblast activities and lead to the development of RM. Our data may also provide a novel angle for the treatment in RM patients.

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BACKGROUND: Metal ions are essential for numerous life processes. This study aims to investigate the relationship between seminal quality and ion levels in seminal plasma. BASIC PROCEDURES: A total of 205 semen samples were collected and seminal plasma ion levels were examined with inductively-coupled plasma-mass spectrometry. The nickel function was demonstrated by in vitro assay and cell growth. MAIN FINDINGS: The low sperm motility group showed distinctively reduced nickel concentration in seminal plasma compared with the normal sperm motility group. However, arsenic, sulfur, selenium, magnesium and zinc were negatively associated with sperm quality. No significant relationship between other examined cations and semen quality was observed. In vitro assay suggested low concentration of nickel significantly increased sperm total motility and progressive motility. Cell growth assay further confirmed nickel promoted eukaryotic yeast cell growth. Nickel level in seminal plasma may play important functions to determine sperm quality. PRINCIPAL CONCLUSIONS: Our study reveals a strong correlation between S, Mg, Se, Zn, As, Ni and seminal quality as well as discovers a novel functional role of nickel in sperm motility and eukaryotic cell growth. These findings may provide a potential avenue for assessment of sperm quality and treatment of reproduction disorders.

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AIM: To investigate the prevalence and predictors of sexual frequency, sexual desire in midlife partnered Chinese women. METHODS: Sexual frequency, sexual desire over the past 3 months, menopausal symptoms and other socioeconomic information were assessed for women aged 40-65 years in the Shanghai Sixth People's Hospital. RESULTS: Among 3485 eligible partnered participants, the prevalence of low sexual frequency (less than once per week) and low sexual desire (less than 5 scores) were 72.74% (95% confidence interval (CI) = 71.16%-74.23%) and 71.79% (95% CI = 70.30-73.17%), respectively. Multivariable logistic regression analysis revealed that age (odds ratio (OR) = 1.20, 95% CI = 1.17-1.23), more educated (>15 years) (compared with<10 years, OR = 0.62, 95% CI = 0.48-0.82), perimenopause, postmenopause (compared with premenopause, OR = 1.48, 95% CI = 1.02-2.15, OR = 2.76, 95% CI = 1.80-4.23), sleep disorder (OR = 1.24, 95% CI = 1.02-1.50), unemployment (OR = 2.05, 95% CI = 1.45-2.92) were independently associated with low sexual frequency, while multiple linear regression revealed that age ß = -0.126, 95% CI = -0.139--0.114), unemployment (ß = -0.792, 95% CI = -0.954 to -0.629),chronic diseases (compared with no disease, single disease (ß = -0.200, 95% CI = -0.020 to -0.077, multiple diseases (ß = -0.792, 95% CI = -0.859 to -0.372), body mass index (ß = -0.615, 95% CI = -0.859 to -0.372), postmenopause (ß = -0.915, 95% CI = -1.143 to -0.759) were independent indicators for low sexual desire after adjusting for confounders. CONCLUSION: Low sexual frequency and low sexual desire were quite prevalent in midlife Chinese partnered women. Some factors, such as sleep disorder, obesity are modifiable or can be prevented or treated with safe and effective therapies.

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