There has been increasing evidence of hormonal changes during reproductive events that lead to mood changes. However, studies on the severity of psychological problems according to the menopausal stage are limited. Thus, this study aimed to investigate the association between menopausal stages, depression and suicidality.A total of 45 177 women who underwent regular health check-ups between 2015 and 2018 at Kangbuk Samsung Hospital were included. Participants were stratified into four groups  based on the Stages of Reproductive Aging Workshop Criteria. The Center for Epidemiological Studies-Depression scale (CESD) was used to evaluate depressive symptoms, and the degree of depressive symptoms was classified as moderate (CESD score 16–24) or severe (CESD score ⩾ 25). To measure suicide risk, we administered questionnaires related to suicidal ideation.p for trend <0.001), respectively.Overall, the prevalence of CESD scores of 16–24 and ⩾ 25 was 7.6 and 2.8%, respectively. Menopausal stages were positively associated with depressive symptoms in a dose-dependent manner. Multivariable-adjusted prevalence ratios  for CESD scores of 16–24 comparing the stages of the early menopausal transition (MT), late MT and post-menopause to pre-menopause was 1.28 (1.16–1.42), 1.21 (1.05–1.38) and 1.58 (1.36–1.84), respectively. The multivariable-adjusted PRs for CESD scores ⩾ 25 comparing the stages of the early MT, late MT and post-menopause to pre-menopause were 1.31 (1.11–1.55), 1.39 (1.12–1.72), 1.86 (1.47–2.37), respectively. In addition, the multivariable-adjusted PRs for suicidal ideation comparing the early MT, late MT and post-menopause stages to the pre-menopause stage were 1.24 (1.12–1.38), 1.07 (0.93–1.24) and 1.46 (1.25–1.70) (These findings indicate that the prevalence of depressive symptoms and suicidal ideation increases with advancing menopausal stage, even pre-menopause. Among the 59 940 women, 14 763 were excluded for the following reasons: history of cancer (n = 3962); history of hysterectomy or ovariectomy (n = 4422); history of premature menopause (n = 256); history of artificially-induced menopause due to radiation (n = 209), chemotherapy (n = 383) or other (n = 629); currently receiving hormone replacement therapy ; currently taking an oral contraceptive (n = 320) or currently pregnant (n = 6); history of mental illness diagnoses such as panic disorder, claustrophobia, depression and others (n = 2357); currently taking anxiety drugs (n = 703), antidepressants or other neuropsychological medications (n = 869); and missing data related to depressive symptoms and suicidality (n = 3779). As some individuals met more than one exclusion criteria, the total number of women ultimately included in the study was 45 177.The study population consisted of women aged 40–65 years who underwent comprehensive health examinations at the Kangbuk Samsung Hospital Total Healthcare Centers in Seoul and Suwon, South Korea, between 2015 and 2018 . The requirement for informed consent was waived because we used non-identified retrospective data that were routinely collected during the health screening process.et al., et al., Data on demographic factors, socioeconomic status, health behaviours, dietary intake, medical history  and medication use (including neuropsychiatric medications such as anxiety drugs and antidepressants) were collected using standardised, structured, self-administered questionnaires. Physical activity was assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form . Regarding subjective sleep quality, the response categories of the PSQI were very good, fairly good, fairly bad and very bad. The last two categories were defined as poor subjective sleep quality.2 according to the criteria for obesity in Asians. Hypertension was defined as BP ⩾ 140/90 mmHg or current use of antihypertensive medication.Anthropometric parameters and sitting blood pressure (BP) were measured by trained nurses. Obesity was defined as a body mass index (BMI) of ⩾25 kg/mFasting blood measurements included glucose, haemoglobin A1c, insulin, high-sensitivity C-reactive protein and lipid profiles. The homeostatic model assessment-insulin resistance (HOMA-IR) was calculated as follows: fasting blood insulin (uU/ml) × fasting blood glucose (mg/dl)/405. Type 2 diabetes mellitus was defined as fasting serum glucose ⩾ 126 mg/dl, haemoglobin A1c ⩾ 6.5% or current use of insulin or medications for diabetes.The participants were classified into four groups according to menopausal stage based on the Stage of Reproductive Aging Workshop + 10 criteria as follows: (1) premenopause , (2) early MT (having a persistent difference of 7 or more days in the length of consecutive cycles), (3) late MT (occurrence of amenorrhoea of ⩾60 days) and (4) post-menopause (amenorrhoea for ⩾1 year).et al., et al., The Center for Epidemiological Studies-Depression (CESD) was used to evaluate depressive symptoms within the past week using the Korean version of the CESD scale; the internal consistency of the Korean version has been reported to range from 0.84 to 0.91. The CESD is composed of 20 items, each rated on a scale from 0 to 3, with total scores ranging from 0 (lowest) to 60 (highest)  and severely depressed (⩾25 points). To test for linear trends, the number of categories was used as continuous variables in the regression models.We estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) for CESD scores of 16–24 and ⩾25 for the early MT, late MT and post-menopause stages compared to the pre-menopause stage using participants with a CESD score <16 as the reference group in multinomial logistic regression models. Moreover, to evaluate the association of suicidal ideation across menopausal stages, we used a logistic regression model to estimate the odds ratios with 95% CIs for suicidal ideation. We used three models to progressively reduce confounding associations. We initially adjusted for age and then further adjusted for the centre, year of screening examination, smoking status, alcohol intake, physical activity level, total energy intake, BMI, educational level, antihypertensive medication, parity and age at menarche. In addition, to evaluate the effects of psychological symptoms around the period of the MT, sleep duration and sleep quality were adjusted.v. ⩾25 kg/m2), age at menarche (<12 v. ⩾12 years), parity (0 v. ⩾1 time), sleep quality (good v. poor), smoking status (never smoker v. ex-smoker or current smoker), alcohol intake  and physical activity (no HEPA v. HEPA). Interactions by subgroup were tested using likelihood ratio tests comparing models with and without multiplicative interaction terms. All p values were two-tailed, and statistical significance was set at p < 0.05. We used STATA version 13.0  for the data analyses.Additionally, we performed stratified analyses in pre-specified subgroups defined by BMI (<25 The mean (standard deviation) age of the 45 177 study participants was 47.3 (6.5) years (online Supplementary Table S1). The prevalence of pre-menopause, early MT, late MT and post-menopause was 49.7, 15.5, 8.7 and 26.1%, respectively. Compared to premenopausal women, participants in the later menopausal stages were more likely to be older and engage in HEPA. They also had higher rates of hypertension and diabetes, BMI, BP, glucose level and HOMA-IR, and were more likely to take dyslipidaemia medication and have unfavourable lipid profiles.Overall, the prevalence of CESD scores of 16–24 and ⩾25 was 7.6% and 2.8%, respectively . ParticiMenopausal stages were positively associated with depressive symptoms in a dose-dependent manner . After ap for trend <0.001), respectively. Although attenuated after adjusting for sleep duration and sleep quality, the association with the early MT and post-menopause stages remained statistically significant. However, a significantly higher prevalence of suicidal ideation during late MT compared with pre-menopause was no longer observed. After further adjustment for the history of suicidal behaviour, the associations remained virtually unchanged (online Supplementary Table S3). Depressive symptoms (CESD scores ⩾25) showed a tendency towards a consistently higher prevalence of suicidal behaviour across menopausal stages (online Supplementary Table S4). In additional analyses without excluding women with a history of psychiatric diagnosis, the results were slightly attenuated but overall patterns remained similar to those of the original analyses (online Supplementary Table S5). Analyses using binary category  showed similar patterns (online Supplementary Tables S6 and S7). When we evaluated the prevalence of (i) isolated depression within the past week, (ii) isolated suicidal ideation within the past 12 months and (iii) concurrent depression and suicidal ideation  across menopausal stages, overall patterns of association were similar to the findings of the original analyses for all three dependent variables, with the post-menopause stage being associated with the highest prevalence of either isolated or concurrent depression and suicidal ideation (online Supplementary Table S8).A total of 3236 women (7.16%) reported suicidal ideation. Menopausal stages were positively associated with suicidal ideation . There w2, with a stronger association in obese women than in non-obese women (p for interaction 0.002) (online Supplementary Table S9). The association between the menopausal stage and suicidal ideation was stronger in women with alcohol intake ⩾10 v. <10 g/day (p for interaction 0.014) (online Supplementary Table S10). Otherwise, the associations did not significantly differ among the subgroups.In the subgroup analyses, the association between the menopausal stage and depressive symptoms differed by obesity, defined as BMI ⩾ 25 kg/mIn this large study of middle-aged Korean women, depressive symptoms and suicidality were significantly associated with menopausal stages and started to increase from the early transition stage. This association remained significant after adjusting for possible confounders. Our results provide the time window during which both depressive symptoms and suicidal ideation are more likely to occur among women in the early to late transition stage who may benefit from appropriate screening measures.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Previous epidemiologic studies have demonstrated that the prevalence and risk of depressive symptoms markedly rise during peri- and post-menopause (Cohen et al., et al., et al., et al., et al., et al., et al., et al., Similarly, we found the highest prevalence of suicidal ideation in postmenopausal women among all menopausal stages. There is relatively limited evidence on suicidality in peri- and post-menopausal women; however, our study findings are consistent with several prior studies (Pinto-Meza et al., et al., et al., et al., et al., et al., per se in postmenopausal women after adjustment for available confounders (Schreiber and Dautovich, et al., In our subgroup analysis, we observed a stronger association between the menopausal stage and depressive symptoms in women with a high BMI. Middle-aged women in MT are predisposed to being obese due to the ageing process, changes in hormonal status and/or mood changes that may prompt maladaptive coping behaviours such as stress eating, and obesity may also exacerbate depressive symptoms (Freeman et al., et al., et al., et al., et al., We also found that higher alcohol intake was significantly associated with a higher prevalence of suicidal ideation in the late MT and post-menopause stage. It is uncertain whether alcohol consumption is driven by existing depressive symptoms, or whether it causes or worsens depressive symptoms and leads to suicidal ideation. It has been reported that depression and alcoholism have strong reciprocal relationships and frequently co-occur (Sullivan et al., et al., et al., et al., et al., et al., The present study has several limitations. First, due to the cross-sectional design of our study, causality in the association between menopausal stages and depressive symptoms could not be determined. Second, the diagnosis of depressive symptoms was not made clinically by a physician and was based on a self-administered questionnaire. However, the CESD is one of the most widely used tools in population-based research settings to assess depressive symptoms and has good validity and reliability (Luckett The present study has several strengths. First, this was a large-scale study that examined women's psychological health across menopausal stages in Korea. To our knowledge, this is the first study to examine women's psychological health based on the four distinctive menopausal stages in an Asian population. Second, this study used the STRAW + 10, which is known to be the current standard measure for classifying the specific menopausal stages. Because most women's health studies, especially concerning menopause, are based on dichotomous classification, either menopausal or non-menopausal, our study has the great advantage of identifying the menopausal stage and the potential health complications at a certain stage. Third, a wide range of data was obtained through standardised methods, enabling us to examine independent associations between menopausal stages and depressive symptoms.In conclusion, in this study of middle-aged women, the prevalence of depressive symptoms and suicidality gradually increased with the advancing menopausal stage. Thus, psychological vulnerability around the time of MT should be considered, and a better understanding of the association between menopausal stages and women's mental health may help identify women at risk for depression and suicidality.


The prevalence of cardiometabolic diseases has increased in Latin American and the Caribbean populations (LACP). To identify gene-lifestyle interactions that modify the risk of cardiometabolic diseases in LACP, a systematic search using 11 search engines was conducted up to May 2022.Eligible studies were observational and interventional studies in either English, Spanish, or Portuguese. A total of 26,171 publications were screened for title and abstract; of these, 101 potential studies were evaluated for eligibility, and 74 articles were included in this study following full-text screening and risk of bias assessment. The Appraisal tool for Cross-Sectional Studies (AXIS) and the Risk Of Bias In Non-Randomized Studies—of Interventions (ROBINS-I) assessment tool were used to assess the methodological quality and risk of bias of the included studies.We identified 122 significant interactions between genetic and lifestyle factors on cardiometabolic traits and the vast majority of studies come from Brazil (29), Mexico (15) and Costa Rica (12) with FTO, APOE, and TCF7L2 being the most studied genes. The results of the gene-lifestyle interactions suggest effects which are population-, gender-, and ethnic-specific. Most of the gene-lifestyle interactions were conducted once, necessitating replication to reinforce these results.The findings of this review indicate that 27 out of 33 LACP have not conducted gene-lifestyle interaction studies and only five studies have been undertaken in low-socioeconomic settings. Most of the studies were cross-sectional, indicating a need for longitudinal/prospective studies. Future gene-lifestyle interaction studies will need to replicate primary research of already studied genetic variants to enable comparison, and to explore the interactions between genetic and other lifestyle factors such as those conditioned by socioeconomic factors and the built environment. The protocol has been registered on PROSPERO, number CRD42022308488.https://clinicaltrials.gov, identifier CRD420223 08488. Cardiometabolic diseases such as hypertension and type 2 diabetes (T2D) are accountable for most non-communicable disease (NCD) deaths and impose an economic burden on low- and middle-income countries . In LatiFactors such as changes in patterns of food consumption, the process of urbanization, increased health and socioeconomic disparities, underfinanced healthcare systems, lower levels of income and productivity, and the rise in sedentary lifestyle have led to an increase in NCDs –21. MoreThe influence of gene-lifestyle interactions on obesity, T2D and cardiovascular diseases (CVDs) has been broadly studied, and there is evidence that the genetic risk of cardiometabolic traits can be modified , 24–27. Eligible for inclusion were articles that explored the interaction between genetic variations and lifestyle factors on cardiometabolic disease traits in LACP. All cardiometabolic diseases and traits were considered including CVDs, cerebrovascular diseases such as stroke, blood lipid levels, obesity-related traits such as body mass index (BMI) and T2D-related traits such as fasting glucose. The eligible articles included observational and dietary intervention studies and were in either English, Spanish, or Portuguese. Articles that did not explore gene-lifestyle interactions or were not based on LACP were excluded.via PubMed and EBSCO Host), Web of Science, ScienceDirect, SciELO, SCOPUS, Taylor & Francis Online, Cochrane library, LILACS , IBECS, Google Scholar, and ERIC (Education Resources Information Center via EBSCO Host) search engines until the 25th of May 2022. To reach literature saturation, the researchers conducted independent search strings  and the outcome (cardiometabolic traits). P-values < 0.05 were considered statistically significant. Pinteraction refers to the P-value for the interaction between the genetic variant and dietary/lifestyle factors on cardiometabolic traits. To synthesize the findings, we categorized the outcomes into four categories: obesity, diabetes, CVD, and overall cardiometabolic risk. We then coded the exposures considering major themes; proteins, carbohydrates, fats, and fiber as well as plasma fatty acids, polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), breastfeeding, smoking, alcohol, coffee, and lifestyle , macronutrients , and micronutrients . The final graphical representation of the interaction between the genetic variations, and the coded lifestyle factors on the clustered outcomes was a heat map, where the intensity of the color corresponds to the P-values of the gene-lifestyle interactions  of cross-sectional studies we used the Appraisal tool for Cross-Sectional Studies (AXIS)  Supplem, 3. CohoThe search string results had an output of 29,092 articles and from these, 101 articles were identified as potential studies. After the full-text screening, 27 articles were excluded for the following reasons: six studies were not based on LACP –40, fivep < 0.05), as shown in The 74 studies conducted in LACP encompass ethnicities from Argentina, Colombia, Chile, Costa Rica, Mexico, Brazil, and LACP diaspora, including Dominicans, Puerto Ricans, Mexicans, and other Hispanic ethnicities residing in the United States of America (USA). Most of the studies are focused on four countries: Brazil , Mexico APOE) genotype on low-density lipoprotein cholesterol (LDL) (Pinteraction = 0.028), where a high intake of olive oil (≥ once a week) was associated with lower LDL levels in men carrying the “ε2” allele but had no effect in men without the “ε2” allele. In this study . A reduction in triglyceride levels in response to a high PUFA intake was also observed in carriers of the “ε2” allele but not in participants without the “ε2” allele (Pinteraction = 0.04). A high PUFA intake was also associated with increased high-density lipoprotein cholesterol (HDL) concentration in participants without the “ε4” allele and reduced HDL levels in carriers of the “ε4” allele (Pinteraction = 0.018) . The findings of the first study  . In cont= 0.018)  observedst study  indicate of CVDs . Nonethe of CVDs  suggest nd study  was condnd study . PUFA isarticles , 69.Pinteraction = 0.019); while those with a GRS > 9 had a lower odds ratio for dyslipidaemia with an intake of BHEI-R solid fats, alcoholic beverages and added sugars (SoFAAS) component below the median (Pinteraction < 0.001). Similarly, a cross-sectional study involving 250 pregnant women (FADS) SNPs (rs174561 and rs3834458) and dietary α-linolenic acid (ALA) and linoleic/α-linolenic acid ratio (LA/ALA) on plasma concentrations of omega-3 (n-3) PUFAs. It was reported that, in women with high ALA intake, plasma ALA concentrations were higher in homozygotes for the minor allele (p < 0.05), compared to carriers of the major allele (MM and Mm) of rs174561 and rs3834458. However, the P-values given in the study (p = 0.004 for rs174561 and p = 0.028 for rs3834458) seem to represent associations stratified by genotype, instead of interactions. FADS are involved in the synthesis of PUFA and their activation is linked to inflammation and coronary artery disease   observednt women  observed disease , 71, and disease , no sign disease  and fat Pinteraction = 0.016), fasting insulin (Pinteraction = 0.017), body fat mass (Pinteraction = 0.009), and decreased insulin:glucose ratio (Pinteraction = 0.01), but the interaction did not influence homeostasis model assessment estimate of insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or waist circumference (WC). Similarly, the second BOLD study  SNP rs2241766 (Pinteraction = 0.019); arachidonic acid and ADIPOQ rs16861209 (Pinteraction = 0.044); docosapentaenoic acid and ADIPOQ rs16861209 (Pinteraction = 0.037); and SFA and ADIPOQ rs17300539 (Pinteraction = 0.019) on the risk of systemic inflammation. Carriers of the “G” allele of rs2241766 had a reduced odds ratio of having inflammatory biomarkers when plasma n-3 levels were above the median, while participants with the “CC” genotype of rs16861209 had a lower odds ratio of having inflammatory biomarkers in the 50th percentile of plasma arachidonic acid and docosapentaenoic acid. Moreover, carriers of the “A” allele of rs17300539 had a higher odds ratio of having inflammatory biomarkers in the upper 50th percentile of plasma SFA compared to those with the “GG” genotype (TLR4) SNP rs11536889, in which individuals with the “C” allele had an increased odds ratio of having inflammatory biomarkers at the higher percentile of arachidonic acid/eicosapentaenoic acid ratio (Pinteraction = 0.034). Similarly, the third study consisting of 262 participants (CRP) SNP rs1417938, where individuals with the “AA” genotype had a higher odds ratio of having inflammatory biomarkers with a plasma palmitoleic acid above the median (Pinteraction = 0.047).Five Brazilian cross-sectional studies –79 invesgenotype . In the icipants  identifiTNF-α) SNP rs180062 (−308G/A) (Pinteraction = 0.041); while a decreasing risk with increasing plasma stearic acid was found in participants with the “GG” genotype (Pinteraction = 0.046), in a sample of 281 participants from the HS-SP (IL1B) SNP rs16944 (Pinteraction = 0.043), and in response to increasing plasma arachidonic acid levels in those with the “GG” genotype of interleukin 10 (IL10) SNP rs1800896 (Pinteraction = 0.007), in a sample of 301 participants from the HS-SP  in carriers of the “AA” genotype of fucosyltransferase 2 (FUT2) SNP rs602662. Carbohydrate intake also interacted with Catechol-O-Methyltransferase (COMT) SNP rs4680, increasing oxidized-LDL more in carriers of “AA” than “GG” genotype (Pinteraction = 0.005)   on cardip = 0.01) among participants carrying the “T” allele of FTO SNP rs79149291 with a protein intake above 12.7% TEI/day (AA” genotype of FUT2 SNP rs602662 (Pinteraction = 0.007) had increased homocysteine levels  among carriers of the “G” allele of Angiotensinogen (AGT) SNP rs699 with a higher plasma magnesium (209.3 mg). Similarly, among those with a high calcium intake (573.3 mg), carriers of the “T” allele of Bradykinin Receptor B2 (BDKRB2) SNP rs1799722 had significantly higher SBP (Pinteraction = 0.015) and diastolic BP (DBP) (Pinteraction = 0.014) than carriers of the “CC” genotype (ACE) SNP rs4646994 on the risk of hypertension, where carriers of the “I/I” genotype with a high sodium intake (>2 g/day) had an increased risk of hypertension (Pinteraction = 0.007). Furthermore, in a cross-sectional study of 1298 healthy adults  (p22phox) with more than 86.5 mEq sodium per 12 h of urine collection, had increased SBP (Pinteraction < 0.001) and DBP (Pinteraction = 0.011). Sodium is known to increase BP by reducing vasodilation  of FTO SNP rs9939609 had increased BMI (Pinteraction = 0.033). However, a cross-sectional study examining folate intake in 5914 healthy adults  SNP rs2070744 (−786 T/C) on plasma nitrite levels. Individuals carrying the “C” allele who consumed alcohol had lower plasma nitrite levels (Pinteraction = 0.033). However, there were no significant interactions between alcohol intake and rs2070744 on BP (MTHFR SNP rs1801133 (C677T), in which men with the “677TT” genotype who consumed ≥ 15 g of alcohol per day had the highest homocysteine concentration (Pinteraction = 0.002); but the interaction was not observed in women. Moreover, a prospective cohort study of 964 postmenopausal women , rs675 (Thr347Ser) and rs5110 (Gln360His), increasing BMI in individuals with the “X*2” (Pinteraction = 0.007) and “347Ser” (Pinteraction = 0.02) alleles. However, men with the “360His” allele who were non-smokers had a larger WC than homozygotes for the “Gln” allele (Pinteraction = 0.018) (APOC3 SNP rs5128 had increased triglycerides and the effect was more pronounced in women who smoked than in non-smokers (Pinteraction = 0.009). Serum APOC3 concentration has been shown to be positively associated with triglyceride levels, and smoking has been reported to lower the concentration of APOC3 but only in women without central obesity  . SimilarADRB2) SNP rs1042714, decreasing triglyceride levels and triglyceride-glucose index (Pinteraction = 0.001 for both) more in carriers of the “Glu27Glu” genotype than those carrying the “Gln27” allele. A cross-sectional study of 1701 children and adolescents (FNDC5) SNP rs16835198 compared to carriers of the “G” allele only in those with lower levels of cardiorespiratory fitness (CRF) ; and lower limb strength . Physical activity has been proposed to alter the expression of certain genes  (Pinteraction = 0.02) and DBP (Pinteraction < 0.01) in carriers of the “I” allele of ACE SNP rs4646994 compared with a non-exercise control session, but the reduction was not observed in participants with “DD” genotype. However, five studies  was shown to increase cardiometabolic risk score in carriers of “AA” genotype of = 0.047)  reported studies , 98, 99 BHMT) SNP rs492842, increasing vitamin B12 concentrations (Pinteraction = 0.034) in participants with the “TT” genotype. A case-control interventional study of 126 obese women (Pinteraction = 0.04) among carriers of the “A” allele of FTO SNP rs9939609. Furthermore, in a prospective cohort study of 3,701 women, breastfeeding (> 6 months duration) interacted with FTO SNP rs9939609, decreasing BMI (Pinteraction = 0.03), fat mass (Pinteractin = 0.03), and WC (Pinteraction = 0.04) in carriers of the “A” allele  was found to be associated with higher total cholesterol (TC) (Pinteraction = 0.016), non-HDL (Pinteraction = 0.024) and LDL (Pinteraction = 0.030) only in carriers of the “ε2” allele of APOE SNP rs7412. Similarly, interactions between MUFA intake (Pinteraction = 0.001), total fat intake (Pinteraction = 0.001), dietary cholesterol intake (Pinteraction = 0.019) and Dopamine Receptor D2/Ankyrin Repeat and Kinase Domain Containing 1 (DRD2/ANKK1) SNP rs1800497, increasing triglyceride levels in carriers of the “A2A2” genotype were observed in a cross-sectional study of 175 Mexican adults with T2D  SNP rs1137101 on TC (Pinteraction = 0.002) and triglyceride (Pinteraction = 0.02) levels. It was reported that, a SFA intake of ≥ 12 g/day was associated with a 3.8 times higher risk of hypercholesteroleamia and a 2.4 times higher risk of hypertriglycerideamia compared to an intake of < 12 g/day in participants carrying the “G” allele of rs1137101 (LEPR SNP rs1137101 on TC (Pinteraction = 0.001) was also reported in this study (GFOD2) SNP rs12449157 on TC (Pinteraction = 0.006) and LDL (Pinteraction = 0.025). Participants carrying the “G” allele had a larger decrease in TC and LDL in response to the dietary intervention compared to subjects with the “AA” genotype of rs12449157 (CAPN10) SNPs rs5030952, rs2975762, and rs3792267 on lipid traits. It has been reported that SFA of different types and from different food sources might have different effects on cardiometabolic traits  SNP rs9282541 (R230C), but not in those carrying the “R” allele (Pinteraction = 0.037). In another cross-sectional study of 215 healthy adults (Pinteraction = 0.034) and LDL (Pinteraction = 0.037) more in participants with “B1B2/B2B2” genotype than those with “B1B1” genotype of cholesteryl ester transfer protein (CETP) SNP rs708272. However, the interaction did not influence triglycerides, HDL, BMI nor waist circumference (interaction = 0.023) in carriers of the “A1”allele of DRD2/ANKK1 SNP rs1800497. These findings indicate that carbohydrate intake might modulate lipid levels in Mexicans with certain genetic variants, but the mechanism through which carbohydrates affect lipid levels are unclear. Moreover, it has been reported that, the effect of carbohydrates on lipids might be dependent on glycemic index or glycemic load, and highly processed carbohydrates are linked to unfavorable lipid profiles  but a deficient maternal folate (<400 mcg/d) was not associated with anthropometric parameters  of new-borns (Pinteraction = 0.01) in carriers of the “TT” genotype of MTHFR SNP rs1801133 in a cross-sectional study of 130 healthy women  was observed in individuals carrying the “B2” allele of CETP SNP rs708272 who did not perform physical activity, compared to those with the “B1B1” genotype. However, there were no interactions on TG, HDL, TG:HDL ratio, LDL, BMI or WC (Pinteraction = 0.0001 for both). In this study (APOB SNP rs512535 (Pinteraction = 0.004) and tumor necrosis factor (TNFA) SNP rs361525 (Pinteraction = 0.007) with low levels of ME. However, another cross-sectional study of 565 physically active participants  on glycemic traits. Moreover, the fourth cross-sectional study which consisted of 394 participants  SNP rs661 (Q192R) on serum asymmetric dimethylarginine (ADMA) was observed, where individuals carrying the “R” allele had higher ADMA levels compared to those with the “QQ” genotype in response to higher levels of urinary 1-hydroxypyrene (Pinteraction = 0.02). Increased levels of ADMA (p < 0.01) and fatty acid-binding protein 4 (p < 0.001) were also identified in individuals with the “RR” genotype of PON1 SNP rs661 with higher urinary arsenic levels (>45.0 μg/g of creatinine) in comparison with participants with the “QQ” genotype in a sample of 185 Mexican women  was associated with higher levels of very-low density lipoprotein cholesterol (VLDL) (Pinteraction = 0.03) and lower concentration of HDL (Pinteraction = 0.02) in carriers of the “ε2” allele. However, no significant interactions were identified between SFA intake and APOE genotype on lipids in a case-control study involving 1,927 participants with myocardial infarction (MI) and 1,927 matched controls (APOC3 genotype and impact on the concentration of TC (Pinteraction = 0.0004) and LDL (Pinteraction = 0.01). Homozygotes for the APOC3-455T-625T alleles had a 13% increase in TC and a 20% increase in LDL with a high SFA intake (>11% of energy intake), but the interaction was not significant in individuals with the APOC3-455C-625del allele (APOE genotype on the risk of MI (Pinteraction = 0.0157) was also reported, in which carriers of the “ε4” allele had a 49% increased risk of MI compared to a 2.2 fold increased risk in those with the “ε2” allele in response to a high SFA intake (>11.8% of energy intake).The interaction between dietary fat intake and genetic variants on CVD-related traits was examined by six Costa Rican studies –129. In controls . In anotcontrols , SFA intl allele . In the l allele , a signi4” allele which is considered a risk factor for CVDs . Individuals with the “Pro12/Pro12” genotype had a 34% reduced risk of MI per 5% increment in energy from PUFA compared to a 7% decreased risk in those carrying the “Ala12” allele (PCSK9) SNP rs11206510 on the risk of MI (Pinteraction = 0.012), where carriers of the “C” allele had an odds ratio for MI of 0.84 per 0.1% increase in total energy from LC n-3 PUFA, compared to an odds ratio of 1.02 in participants without the “C” allele (PLA2G4A) SNP rs12746200 on the risk of MI (Pinteraction = 0.005), in which participants with the “G” allele had a reduced risk of MI with an intake of n-6 PUFA above the median compared to those with the “AA” genotype. However, there were no significant interactions with n-3 PUFA intake . SSB intake also interacted with rs4977574, increasing the risk of MI in carriers of the “G” allele (Pinteraction = 0.005), but there was no interaction with fruit juice intake (CYP1A2) SNP rs762551 compared to carriers of the “AA” genotype (Pinteraction = 0.04). Similarly, in a case-control study consisting of 2,042 participants with a first non-fatal MI and 2042 control subjects (GSTT1) SNP rs17856199, lowering the risk of MI in carriers of the “*1” allele, but not in individuals with the “*0*0” genotype (Pinteraction = 0.006). These findings indicate that, dietary factors other than fat intake, might also influence the risk of MI in Costa-Ricans with certain genetic variants.Interactions between other dietary factors and genetic variants on the risk of MI were examined by three Costa Rican studies –137. In e intake . In anote intake , an incrPON1192) SNP rs661 on the risk of MI (Pinteraction = 0.04), where the PON1rg192A allele was associated with an increased risk of MI only in non-smokers. Similarly, in the case-control study discussed above . However, there were no significant interactions with GSTM1 or GSTP1 genotype on the risk of MI ; but the SNP had no effect on BMI when SFA intake was low (<22 g/day). This study also observed that, among individuals with a high SFA intake (≥22 g/d), those with the “CC” genotype had a higher risk of obesity than participants carrying the “T” allele of the SNP rs5082  (Pinteraction = 0.007), but the interaction was not observed in men. The findings of these studies indicate that micronutrients might modulate the association between genetic variants and lipid and glycemic traits, but further studies are needed to replicate and elucidate the mechanisms involved.The interaction between micronutrient intake and genetic variants on cardiometabolic traits was investigated by two studies , 159. A Pinteraction = 0.005). Significant interactions following the same pattern were observed for fat mass (Pinteraction = 0.003), fat percentage (Pinteraction = 0.003) and fat mass index (Pinteraction = 0.002) (Only one study  examined= 0.002) .In summary, research in LACP diaspora has mainly focused on Puerto Ricans residing in USA and most of this evidence (10 out of 13 studies) comes from the same study (BPRHS). Dietary fat intake has been the most frequently studied, with carbohydrate intake being examined by only two studies. Similarly, physical activity was investigated by only one study and lifestyle factors such as socioeconomic status, level of education, and the effect of rural and urban environments have not been explored.Pinteraction = 0.02), where the strongest effect was observed between the highest SSB intake (≥2 servings/day of 330 ml) and the highest wGRS. In this study (TCF7L2) SNP rs7903146 (Pinteraction = 0.002) and with the “G/G” genotype of Melatonin Receptor 1B (MTNR1B) SNP rs10830963 (Pinteraction = 0.001), increasing log-fasting glucose levels. The second Chilean study (IRS-1) SNP rs1801278 on glycemic traits. In Chile, research has been limited to diabetes traits as outcomes and simple carbohydrates as exposure, reflecting a need for further research into other dietary and lifestyle factors such as socioeconomic status, level of education and the effect of rural and urban environments.Two gene-diet interaction studies were reported in Chileans , 162. This study , SSB intUCP3) rs1800849, FTO rs17817449, and CAPN10 rs3842570) on excess weight. However, sub-group analysis showed that, a sedentary lifestyle was associated with an increased risk of excess weight only in those with the “GG” or ‘TT’ genotype of FTO rs17817449 (p = 0.0005); and ‘CC’ genotype of UCP3 rs1800849 (p = 0.0032)   . It was  0.0212) . The sec 0.0212) . As both 0.0212) , 164 werPPARγ SNP rs1801282 on the risk of MetS (Pinteraction = 0.031) where among the non-smokers, carriers of the “Pro/Ala” genotype (p = 0.0059) and the “Ala12” allele (p = 0.009) had a higher risk of MetS than non-carriers. It is unclear whether there were significant interactions between smoking status and rs1801282 genotype on the other outcomes investigated in the study (p-values given are for associations stratified by smoking status. The study adjusted for BMI and age only, but the pathophysiological mechanism of MetS is multifactorial (Only one study  was condhe study  (Table 1actorial , and hen2” allele of APOE (2” allele of APOE (DRD2/ANKK1 SNP rs1800497. A high PUFA intake was also associated with increased concentration of LDL in Brazilian carriers of the “ε4” allele, and reduced concentration of TG in those carrying the “ε2” allele of APOE (4” allele of APOE (The most commonly investigated interactions in LACP related to dietary fat intake and genetic variants on blood lipids. A high intake of olive oil was associated with lower LDL in Brazilian men with the “ε of APOE , while a of APOE . In cont of APOE . However of APOE .2” allele of APOE (APOE genotype on blood lipids in a Costa-Rican case-control study involving participants with MI (APOC3-455T-625T alleles (LEPR SNP rs1137101 (GFOD2 SNP rs12449157 (Furthermore, a high SFA intake was associated with higher VLDL and lower HDL concentrations in Costa Rican carriers of the “ε of APOE , but no  with MI . However alleles . Similars1137101 ; while a12449157 .The inconsistencies in the findings of the above studies call for further research into the interaction between sub-types of fat and genetic variants on blood lipids. The sources of dietary fat also need to be considered since SFA from different food sources have been reported to have different effects on cardiometabolic traits .FTO, examined in Colombians, Mexicans, and Brazilians, APOE explored in Costa Ricans, Mexicans, and Brazilians, and TCF7L2 investigated in Chileans, Mexicans, Brazilians and LACP diaspora. The concentration of blood lipids such as HDL and LDL was the most widely investigated trait, followed by BMI and WC; MI was examined by 11 studies and one study looked at hepatic fat accumulation, while diseases such as stroke and liver cirrhosis were not investigated. Research has identified gene-lifestyle interactions that describe effects which are population-, gender-, and ethnic-specific. The findings of this review indicate that most of the gene x lifestyle interactions were conducted once, necessitating replication to strengthen the evidence.This is the first systematic review to investigate gene-lifestyle interactions on cardiometabolic diseases in LACP, highlighting several gene-lifestyle interactions with effects being significant in Brazilians, Mexicans, Costa Ricans, Chileans, Argentinians, Colombians and LACP diaspora. The most frequently studied genes have been Another issue that could affect the results is the accuracy of the methods used to measure exposure variables such as dietary intake and physical activity , 168. SoSample size has also been highlighted as a key methodological issue in gene-lifestyle interaction studies , 168. FoOverall, the included studies are majorly cross-sectional, indicating a need for longitudinal/prospective studies. The findings reflect gaps in covering the genetic risks and the socioeconomic variables to which the LACP are exposed; 27 out of 33 LACP have not conducted gene-lifestyle interaction studies yet. Only five studies have been conducted in contexts of low socioeconomic status, and from these, only two studies investigated gene-socioeconomic status interactions , 164. MoIn conclusion, this systematic review has identified several gene-lifestyle interactions on cardiometabolic disease traits in Brazilians, Mexicans, Costa Ricans, Chileans, Argentinians, Colombians and LACP diaspora, highlighting effects which are population-, gender-, and ethnic-specific. However, the lack of replication of most of the gene-lifestyle interactions made it difficult to evaluate the evidence. Moreover, most of the studies were cross-sectional meaning that they preclude causal assumptions hence a temporal relationship cannot be established. Future gene-lifestyle interaction studies will need to replicate primary research of already studied genetic variants to enable comparison, and to explore the interactions between genetic and other lifestyle factors such as those conditioned by socioeconomic factors and the built environment. Moreover, the molecular mechanisms that underlie the gene-lifestyle interactions identified by this systematic review need to be explored.The original contributions presented in this study are included in the article/KV: conceptualization, supervision, and project administration. EV, KV, and RW: methodology, validation, investigation, writing—original draft preparation, and resources. EV and RW: software, formal analysis, data curation, and visualization. AS and KV: funding acquisition. All authors contributed to writing—review and editing and read and agreed to the final version of the manuscript.


We find that WTe2 single crystals have an ultrahigh Nernst power factor of ~3 Wm−1K−2, which outperforms the conventional Seebeck power factors of the state-of-the-art thermoelectric semiconductors by 2–3 orders of magnitude. A unique band structure that hosts compensated electrons and holes with extremely high mobilities is the primary mechanism for this huge Nernst power factor. Moreover, a large Ettingshausen signal of ~5 × 10−5 KA−1m is observed at 23.1 K and 9 T. In this work, the combination of the exceptional Nernst–Ettingshausen performance and excellent mechanical transformative ability of WTe2 would be instructive for flexible micro-/nano-thermoelectric devices.Topological semimetals are well known for their interesting physical properties, while their mechanical properties have rarely received attention. With the increasing demand for flexible electronics, we explore the great potential of the van der Waals bonded Weyl semimetal WTe Flexible thermoelectrics are of great interest with increasing demand of flexible and wearable electronics. Here, the authors demonstrate that the Weyl semimetal, WTe2, has a high Nernst power factor and great mechanical flexibility. With no moving parts, thermoelectric devices avoid vibration, noise, and fatigue problems, making them highly suitable for cooling and precise temperature control of laser diodes, medical storage systems, and infrared detectors5. Recently, topological semimetals have shown large anomalous Nernst signals7. Compared with the longitudinal Seebeck–Peltier effects, transverse thermoelectric applications based on Nernst–Ettingshausen effects require only one material instead of coupled p- and n-type legs, making device construction considerably simpler9. Moreover, the output of a Nernst–Ettingshausen cooler depends on its geometry, making them suitable for use in micro- or nanodevices9.Topological semimetals are gaining increasing attention for various frontier applications including quantum computing, spintronics, and thermoelectrics, owing to their unique physical transport properties and topological states. By converting heat into electricity and vice versa in a solid state, thermoelectric technology holds great potential for power generation and solid-state cooling12. To date, the studies of flexible thermoelectrics have mainly focused on the longitudinal Seebeck effect. In contrast, flexible micro- or nanoscale Nernst–Ettingshausen coolers have rarely been investigated. One of the main challenges for flexible longitudinal and transverse thermoelectrics, is that most inorganic thermoelectric materials are inherently rigid. Present flexible Seebeck effects rely on conductive polymers such as poly: poly(styrenesulfonate) (PEDOT:PSS)13, embed conducting polymers to form organic/inorganic hybrids14, and inorganic films  grown on flexible substrates15. However, these strategies have certain disadvantages, including the low electrical conductivity of the polymer and the cumbersome process for producing thin films and hybrid materials, which induce critical device-level limitations for practical applications. Ag2X  semiconductors are rare examples of material that have the high-longitudinal thermoelectric performance as an inorganic material and the mechanical flexibility like organic materials16. Meanwhile, the development of flexible transverse thermoelectrics is still lacking, particularly based on inorganic materials. Thus, exploring materials with combined high transverse thermoelectric performance and mechanical flexibility is highly desired. Van der Waals bonded topological semimetals are considered potential candidates for achieving flexible nano-/microscale Nernst–Ettingshausen coolers.In addition to miniaturization and high thermoelectric performance, the mechanical flexibility of thermoelectric devices has become increasingly important in recent years and has driven the development of novel materials and composites2 single crystals are adopted as an example to demonstrate topological semimetals as ideal candidates for flexible transverse thermoelectric applications. Owing to the van der Waals bonding between the Te layers, WTe2 has excellent flexibility and can be twisted into different shapes. Furthermore, as a consequence of the extremely high charge-carrier mobilities and semimetallic transport behavior, large unsaturated Nernst and Ettingshausen signals with maximum values of ~7000 μVK−1 (at 11.3 K and 9 T) and ~5 × 10−5 KA−1m (at 23.1 K and 9 T), respectively, are observed. Most importantly, an ultrahigh Nernst power factor of ~3 Wm−1K−2 is achieved, which is 2–3 orders higher than the Seebeck power factors typically reported. The present work highlights the role of flexible topological semimetals for thermoelectric cooling, particularly as flexible devices, in niche applications.In this work, layered WTe2 crystallizes in an orthorhombic structure with a space group of Pmn2117. The a-axis has the smallest lattice constant, and the Te–Te layers in the ab-plane are bonded along the c-axis by van der Waals forces  of 1572  is determined by:Ne and Nh, σe and σh, μe and μh, αe and αh denote the Nernst coefficient, conductivity, mobility, and Seebeck coefficient of electrons and holes, respectively, e is the elementary charge, and B is the magnetic field28. Accordingly, the high mobilities of both electrons and holes can dramatically increase N. Moreover, with comparable mobility and concentration of the two charge carrier types, as well as a magnetic-field-independent N (i.e. linear Nernst thermopower as a function of B), the terms with B2 in Eq.  is shown in the inset of Fig. μe/μh) is shown in the inset of Fig. μe/μh ≈ 3 at approximately 30 K. The saturated decreasing trend of μe/μh at 10 K indicates again that the changeover temperature to achieve the most effective competition between electron and hole conduction is at 10 K, which is consistent with the results of the Seebeck analysis. This may explain why the maximum Syx is achieved at 10 K.The exact concentration and mobility of electrons and holes, as well as the effective masses are adopted to further reveal the thermoelectric responses. In a system with two types of charge carrier, the Hall charge-carrier concentration and mobility can be resolved by fitting the Hall conductivity mentclass2pt{minimαh than the electrons |αe|, which can be explained based on the effective masses of the charge carriers. Experimentally, the effective masses of the electron and hole pockets are revealed in the analysis of Shubnikov–de Haas (SdH) oscillations of the longitudinal resistivity. Both ρxx and ρyx show clear quantum oscillations below 10 K at higher magnetic fields above 5 T. The fast Fourier transformation (FFT) analysis of the oscillatory part reveals four main frequencies, associated with four Fermi pockets including two electron pockets and two-hole pockets, labeled e1 and e2, and h1 and h2, respectively in Fig. F = 94 T (h1), 130 T (e1), 144 T (e2), and 159 T (h2), are very close to the previously reported values34. We extracted the effective cyclotron mass m* values from fitting the temperature dependence of the FFT amplitudes AFFT, according to the Lifshitz–Kosevich formula below35Furthermore, we propose that the holes have a higher Seebeck coefficient A0 is a constant, kB is Boltzmann’s constant, T is the temperature, ℏ is the reduced Planck constant, and B1 and B2 are the starting and ending magnetic fields of the FFT field window, respectively. As shown in Fig. m0, 0.26m0, 0.29m0, and 0.31m0, respectively, in units of the free electron mass m0. Generally, the effective masses of the hole pockets are slightly higher than those of the electron pockets, leading to a larger αh than αe. This may be one of the reasons for the positive α at temperatures below 10 K and the higher μe/μh ratio.Here, 2 exhibit high mobility and even compensated electron–hole conduction, making them excellent candidates for transverse thermoelectric applications. Fig. 2, ZrTe536, NbP8, and Cd3As237, as well as Bi single crystals30. The Nernst signal strength has a positive correlation with the charge-carrier mobility. This is the reason why topological semimetals, which usually have low effective mass and even massless Fermions, are highly promising for achieving high Nernst signals. Furthermore, the compensated conduction of the electrons and holes is essential for achieving large Nernst thermopowers. Therefore, the critical Fermi energy at which the electrons and holes compensate most effectively also strongly affects the Nernst signal. For example, WTe2 and NbP8 have their maximum Nernst thermopowers at 10 K and 109 K, respectively, corresponding to the temperatures where the compensation is most effective.Owing to the sharp linear-band dispersions, topological semimetals such as WTe2 shows giant magnetoresistance, its resistivity (at 9 T) has the same order of magnitude as general thermoelectric semiconductors such as 2Te3 (at 0 T) , which is 2–3 orders higher than the general Seebeck power factors. The maximum Nernst thermoelectric figure of merit, zT = (PF/κ)T, where κ is the thermal conductivity and T is the absolute temperature, reaches around 0.2 at 10 K 2Te338. This is remarkable as few materials have been found with such high PF values to date.In addition to the high Nernst thermopower, topological semimetals usually have low resistivities. Notably, although WTeTe2 Fig.  reaches 1-xSbx is the best thermoelectric material below 300 K, showing the best performance at ~100–150 K. Rare materials have been reported to present high thermoelectric performance at extremely low temperatures. In this regard, the high transverse thermoelectric performance of WTe2 is of significant interest for solid-state cooling at low temperatures, especially for niche applications where vibration-free operation is more important than the cost of providing the magnetic field. Most importantly, it demonstrates the great potential of van der Waals bonded topological materials as a platform for developing flexible thermoelectrics.Note that the longitudinal thermoelectric materials based on the Seebeck effect have few representatives below 300 K. BiPF values of WTe2 and other topological semimetals, including NbP40, ZrTe536 and Cd3As237, with a comparison of the Seebeck PF values of most of the well-known longitudinal thermoelectric semiconductors49. The topological semimetals, particularly WTe2, have high PF values, which are even 2–3 orders of magnitude higher than those of the best thermoelectric semiconductors. For practical applications, both high PF and high zT are desirable. Since the thermal conductivities of WTe2 single crystals  and Te chunks  were mixed and then placed in an alumina crucible. Subsequently, they were sealed in a quartz tube under partial argon pressure. The sealed tube was then heated to 1100 °C in 3 days, kept at this temperature for 48 h, and then slowly cooled to 500 °C at a rate of 2 °C/h. Finally, the single crystals were separated from the flux by centrifugation. Ribbon-shaped layered crystals with shiny surfaces were obtained.WTeab-plane direction: a current or temperature gradient was applied along the a-axis (100), and the Nernst and Ettingshausen signals were measured along the b-axis (010) with a magnetic field applied along c-axis (001) direction, perpendicular to the layers. The longitudinal resistivities (ρxx) and Hall resistivities (ρyx) were measured using a physical property measurement system  in the electrical-transport mode with a standard four-probe method. The Nernst thermopower, Ettingshausen temperature gradient, Seebeck coefficient, and thermal conductivity were measured under high vacuum in the PPMS by a standard four-contact, steady-state method (Supplementary Fig. 3He insert.The transport properties were measured in the Supplementary InformationPeer Review File


The use of total laparoscopic hysterectomy is increasing. However, as with conventional abdominal hysterectomy, vaginal bacteria-related postoperative complications need to be managed in total laparoscopic hysterectomy. Therefore, we started to combine metronidazole vaginal tablets with intravenous administration of cephem antibiotics immediately before starting surgery to reduce complications. To evaluate the effect of this combination, and to determine the risk factors for these complications, we retrospectively collected medical records from our hospital and performed a multivariate analysis.We reviewed the medical records of 520 patients who underwent total laparoscopic hysterectomy from 1 January 2015 to 31 December 2021. Among these cases, we identified 16 cases as having vaginal bacteria-related postoperative complications, defined as needing more than one additional day for treatment of postoperative complications, namely postoperative infection (10 cases) and vaginal dehiscence (6 cases). First, we evaluate the effect of metronidazole vaginal tablets by dividing the patients into two groups according to whether metronidazole vaginal tablets were used, and comparing the vaginal bacteria-related postoperative complication rates and other indices. Second, we performed a multivariate logistic regression analysis to assess the influence of each of 17 representative factors, including patient characteristics and symptoms, uterus and leiomyoma sizes, concomitant procedures such as laparoscopic cystectomy and pelvic lymphadenectomy, and others.In the multivariate analysis of the 520 cases, we confirmed that the use of metronidazole vaginal tablets could reduce the vaginal bacteria-related postoperative complications rate by more than half . In addition to metronidazole vaginal tablets use, concomitant laparoscopic cystectomy and blood transfusion were associated with significant increases in the vaginal bacteria-related postoperative complication rate.The effect of the addition of metronidazole vaginal tablets to pre- and postsurgical treatment on the reduction of vaginal bacteria-related postoperative complications was confirmed. This easy, safe, and low-cost method may improve the management of total laparoscopic hysterectomy. Since total laparoscopic hysterectomy (TLH) is associated with less pain and a quicker recovery than conventional abdominal hysterectomy (AH), the number of indications for TLH has increased, and TLH has become more widespread –3. TLH iEnterococcus faecalis, Prevotella loescheii, and Group B Streptococcus, for only 6 out of the 16 patients; therefore, postoperative infection was instead defined as C-reactive protein positivity (> 0.30 mg/dL)  and antibiotic administration. At that time, we excluded three patients, in which bleeding, hemorrhage, or an abscess was present in the trocar sites.This study was reviewed and approved by the Human Ethical Committee of the University of Teikyo Hospital . The deidentified medical records of 520 female patients who underwent TLH from 1 June 2015 to 31 December 2021 were reviewed retrospectively. In these cases, bilateral salpingectomy (BS) or bilateral salpingo-oophorectomy (BSO) was performed during TLH. This study also included 26 cases with concomitant pelvic lymphadenectomy (PLA), and 29 cases with concomitant laparoscopic cystectomy (LC), including 4 bilateral LCs and 25 unilateral LCs. All operations were performed under the direct supervision of at least one of two laparoscopic surgery experts (A.F. and O.N.). Most indications for TLH were leiomyoma (403 cases) or adenomyoma (60 cases). However, since we focused mainly on vaginal disinfection, we did not exclude other indications, including early-stage endometrial carcinoma (31 cases), cervical intraepithelial neoplasia (11 cases), atypical endometrial hyperplasia (8 cases), uterine cervical tumor (4 cases), vaginal atresia with menstrual molimen (1 case), cesarean scar pregnancy (1 case), or cesarean scar syndrome (1 case). We extracted data on patient characteristics, such as age, delivery history, presenting symptoms, and physical examination findings, from medical records, since these factors were considered to be related to TLH outcomes. Surgical history and intraoperative findings were also included, since these factors might have an influence on the difficulty of performing a TLH, especially the process of suturing the vaginal wall. To evaluate the effect of MVT on TLH, we extracted data on the vaginal bacteria-related postoperative complications (VBRPC) of patients, including postoperative infection (ten cases) and vaginal dehiscence (six cases), for whom the diagnosis was made within 30 days after the operation [t-test and Pearson’s chi-square test. Second, to confirm the effect of vaginal tablets on VBRPC, we tried to identify risk factors for VBRPC. To control confounding factors, we divided the patients into two groups according to the presence or absence of each factor, and performed multivariate logistic regression analysis. In this analysis, we assessed the influence of the following 17 factors: (1) advanced age, defined as an age ≥ 50 years; (2) high body mass index (BMI), defined as a BMI ≥ 25 (kg/m2); (3) nulliparity, defined as no previous delivery; (4) gynecological operation history; (5) menstrual disorder, defined as patients with menstruation-related symptoms such as dysmenorrhea, menostaxis, menorrhagia, anemia or abnormal vaginal bleeding; (6) abdominal distension, defined as patients with abdominal symptoms such as abdominal pressure, pelvic pain, dysuria, or dyschezia; (7): GnRH analog, defined as treatment with gonadotropin-releasing hormone analog (GnRHa) before TLH; (8) concomitant LC; (9) concomitant PLA; (10) long-time operation, defined as an operation lasting over 240 minutes according to the average and standard deviation of 520 cases; (11) massive blood loss, defined as loss of over 500 mL of blood; (12) heavy uterus, defined as a resected uterine weight ≥ 500 g; (13) abdominal adhesion, defined as abdominal adhesion detected by laparoscopic inspection immediately after the start of surgery; (14) blood transfusion, defined as the need for blood transfusion, including both autologous and allogeneic blood transfusion, during or after the operation; (15) large leiomyoma, defined as a dominant leiomyoma ≥ 8 cm by magnetic resonance imaging (MRI); (16) large uterus, defined as an average uterine length ≥ 10 cm by transvaginal ultrasound (TVUS) before surgery; and (17) MVT use, defined as treatment with vaginal tablets. The criteria for “massive blood loss,” “large leiomyoma,” and “heavy uterus” were determined on the basis of past reports [p < 0.05 was considered statistically significant.First, to evaluate the effect of MVT , we divided the patients into two groups according to the presence or absence of the use of this tablet (425 versus 95 cases). In our hospital, we administered three vaginal tablets to the former patients, timed at 1 day before TLH, immediately after completion of the operation, and 3 days after the operation. In these two groups, we compared the 17 indices presented in Table 0 cases;  massive ≥ 500 g;  abdomina2, 1.1 ± 1.0 (0–4), and 6.1 ± 2.0 (4–40) days, respectively. In total, 108 patients had a gynecological operation history, including patients with only cesarean section (36 cases), and 353 patients treated with GnRHa before surgery. The overall average operation time of the 520 patients was 204.6 ± 55.6 (94–504) minutes, the average blood loss volume was 124.1 ± 198.1 (0–2003) mL, and the average weight of the resected uterus was 312.3 ± 223.9 (28–1454) g. Of the 520 patients, 60 had no complaints, but the other 460 patients had various symptoms, such as menstrual disorder and abdominal distension; one patient reported multiple symptoms. By MRI, the average size of the dominant leiomyoma in 447 patients was 6.3 ± 3.0 (1.1–20.0) cm, and submucous leiomyoma was found in 108 cases. The average hemoglobin concentrations before and after the operation were 13.0 ± 1.2 (6.6–16.7) and 11.5 ± 1.3 (5.1–15.2) g/dL, respectively. Autologous blood donation was performed in 271 patients, and blood transfusion was performed in 24 patients, including 21 patients who required only autologous blood transfusion, 1 patient who required allogeneic blood transfusion, and 2 patients who required both.The average age, BMI, parity, and hospitalization duration of the included patients were 47.4 ± 5.9 (34–81) years, 23.0 ± 3.8 (15.1–46.5) kg/mp < 0.05). Apart from this result, concomitant LC  and blood transfusion  showed significant differences. Due to the above-mentioned results, we confirmed the effectiveness of MVT.To evaluate the effect of MVT, we compared two groups of patients classified according to whether they received MVT. As expected, the rate of VBRPC was significantly lower in patients who received MVT Table . Howevern 16). However, we observed a retrospective study-specific limitation, and could not strictly detect a causal relationship with infection by performing a microbiological culture test of vaginal discharge. The rate of VBRPC reached approximately 3% (n 16/520) and was approximately equal to those of previous reports [Since surgeons must cope with both skin and vaginal bacteria when performing hysterectomy , 9, 10,  reports , but we  reports , 18. On This study assessed the effect of the additional administration of MVTs on reducing vaginal bacteria-related postoperative complications. This easy, safe, and low-cost method has the possibility of improving the management of preventing TLH-related infections.


Molecular ferroelectrics offer the advantage of structural diversity and tunability, easy fabrication, and mechanical flexibility. Organic–inorganic hybrid materials are new low-symmetry emerging materials that may be used as energy harvesters because of their piezoelectric or ferroelectric properties. Among these, ferroelectric metal-free perovskites are a class of recently discovered multifunctional materials. The doped nanofibers, which are very flexible and have a high Young modulus, behave as active piezoelectric energy harvesting sources that produce a piezoelectric voltage coefficient up to geff = 3.6 VmN−1 and show a blue intense luminescence band at 325 nm. In this work, the pyroelectric coefficient is reported for the MDABCO-NH4I3 perovskite inserted in electrospun fibers. At the ferroelectric–paraelectric phase transition, the embedded nanocrystals display a pyroelectric coefficient as high as 194 × 10−6 Cm−2k−1, within the same order of magnitude as that reported for the state-of-the-art bulk ferroelectric triglycine sulfate (TGS). The perovskite nanocrystals embedded into the polymer fibers remain stable in their piezoelectric output response, and no degradation is caused by oxidation, making the piezoelectric perovskite nanofibers suitable to be used as flexible energy harvesters.In this work, we introduce lead-free organic ferroelectric perovskite N-methyl-N′-diazabicyclo[2.2.2]octonium)–ammonium triiodide (MDABCO-NH Mechanical energy harvesting at low frequencies from materials that are environmentally friendly and scavenging energy from multiple sources, for example, human body movements, are at the forefront of research ,2.Ferroelectrics are inherently piezoelectric and pyroelectric materials; that is, they are able to produce an intrinsic electrical potential difference in response to an applied force  and a temperature gradient, respectively.4H4O6] (4H2O) in 1920 and was, in fact, the first semiorganic molecular ferroelectric crystal that is also nontoxic octonium)–ammonium triiodide  incorporated in PVDF polymer fibers made by electrospinning; an output voltage of approximately 220 mV at 4 Hz, under an applied force of approximately 7.5 N, a maximum output power of 0.8 mW/m2 was generated 1⁄2] = α(hv − Eg), where hv represents the energy of the incident photon, Eg corresponds to the energy of the bad gap, and F(R) is called the Kubelka–Munk function directly determined from the total reflectance coefficient of the material (R) through the equation F(R) = (1 − R)2/2R  direction of the crystal octonium)–ammonium triiodide  single crystal. Additionally, the nanocrystals maintain their optical, piezoelectric, and pyroelectric properties for long periods when embedded into electrospun fibers, inhibiting perovskite oxidation, which is promoted by the polymer matrix that acts as a shielding.A piezoelectric nanogenerator (PENG) fabricated using an MDABCO-NH


Background: EMILIN2 is a platelet-associated elastin that regulates angiogenesis. It has recently been found to play an essential role in various tumors. Nevertheless, the mechanism of action of EMILIN2 in clear cell renal cell carcinoma (ccRCC) remains unclear.Methods: Samples from 33 cancers were obtained from UCSC Xena and The Cancer Genome Atlas (TCGA) database. The relationship between EMILIN2 expression and the clinicopathological characteristics and immune infiltration of ccRCC was investigated. Nonnegative matrix factorization (NMF) was used to classify ccRCC patients. A multigene risk prediction model of ccRCC was constructed using LASSO regression and multivariate regression analysis. A nomogram survival probability prediction map and calibration curve were constructed based on clinical information.Results: EMILIN2 is significantly overexpressed in ccRCC, a phenomenon that is associated with poor prognosis. Meanwhile, EMILIN2 expression is closely related to tumor immune infiltration in ccRCC. Patients with clear cell renal cell carcinoma were divided into two subtypes using NMF, with subtype 2 showed poor prognosis. Next, we established a risk score model for ccRCC based on the common differentially expressed genes (DEGs) between subtypes and groups based on EMILIN2 expression. The results indicated poor prognosis in the high-risk group in the training set and were confirmed in the validation set.Conclusion: Our findings suggest that EMILIN2 expression is closely associated with immune infiltration in ccRCC. EMILIN2 expression is negatively correlated with the prognosis of ccRCC patients. Here, we developed a tool that could predict the prognosis of ccRCC patients. Clear cell renal cell carcinoma is the most common form of renal cancer. The occurrence of ccRCC is associated with multiple factors, such as smoking, drugs, obesity and others . PatientThe degree of immune infiltration in ccRCC is also high among various cancers. Because the complex tumor microenvironment plays a critical role in the treatment of patients, the study of the tumor microenvironment is closely related to the identification of relevant factors and the development of drugs. Commonly used immune checkpoint inhibitors (ICI) that block the inhibitory receptor on PD-1/PD-L1 or CTLA-4 T cells have been shown to be very effective against this cancer type .EMILIN2 is located on the short arm of human chromosome 18, encoding an extracellular matrix glycoprotein with a relative molecular mass of 116 kD and five protein domains: C-terminal C1q domain, proline-rich domain, collagenous domain, coiled-coil domain, and N-terminal cysteine-rich domain (EMI domain) . EMILIN2Although large body of evidence indicates that EMILIN2 is associated with tumor immunity and angiogenesis in various cancers, the role of EMILIN2 in ccRCC remains elusive. Investigation into the role of EMILIN2 in ccRCC may help improve our understanding of the occurrence, progression, and metastasis of ccRCC and aid the development of new therapeutic strategies. In this study, we identified EMILIN2 as an independent prognostic factor in ccRCC patients. High EMILIN2 expression was found to predict poor prognosis in ccRCC patients. EMILIN2 expression is strongly associated with cancer progression in ccRCC patients. Immune checkpoint, immune infiltration and enrichment analyses revealed that EMILIN2 expression was significantly associated with the immunity of ccRCC patients. And we developed a comprehensive prognostic model of ccRCC with good performance.https://xenabrowser.net/datapages/) and TCGA database , including age, gender, tumor stage and survival data. The gene expression dataset format is TPM. The data set of ccRCC contained 531 cancer tissue samples and 72 adjacent tissue samples. The immune, matrix and ESTIMATE scores of patients were calculated by ESTIMATE (https://bioinformatics.mdanderson.org/estimate/rpackage.html).We obtained the RNA-sequencing data and clinical data of 33 types of cancer patients from UCSC Xena  cell, central memory CD4+ T cell, central memory CD8+ T cell, NK cell, NK T cell, type 1 T helper cell, type 17 T helper cell, CD56 dim NK cell, immature dendritic cell, macrophage, myeloid derived suppressive cell (MDSC), neutrophil, plasmacytoid dendritic cell, regulatory T cell (Treg), type 2 T helper cell, activated B cell, eosinophil, gamma delta T cell, immature B cell, mast cell, memory B cell, monocyte and T follicular helper cell . Following this, the NMF clustering algorithm was used to cluster ccRCC samples based on the screened genes .We selected the immunohistochemical staining images of these model genes in normal tissues and ccRCC tissues from the Human Protein Atlas database  and human renal epithelial cell line (293T) used for reverse-transcription-quantitative polymerase chain reaction (RT-qPCR) in this study were purchased from Procell . Total RNA was isolated using Trizol . HiScript III RT SuperMix for qPCR (+gDNA Wiper)  was used for cDNA synthesis. qPCR was performed using the SYBR Green assay according to the manufacturer’s protocol. Then the mRNA expressions of TNNT1, SAA1, IL20RB, COL22A1, B3GALT5, and C10orf99 were analyzed.The following primers were used for RT-qPCR:TNNT1, forward:5′-TGATCCCGCCAAAGATCCC-3′; TNNT1, reverse:5′- TCTTCCGCTGCTCGAAATGTA-3′; SAA1, forward:5′- GATCACCGATGCCAGAGAGA-3′; SAA1, reverse:5′- TTTGTATCCCTGCCCTGAGG-3′; IL20RB, forward:5′- GGCCACTGTGCCATACAAC-3′; IL20RB, reverse:5′- TCTTTGGTGATCTCCATCCCA -3′; COL22A1, forward:5′- CCTAGCGTTCGTGTAGAAGGA-3′; COL22A1, reverse:5′- CCCATCCGTACATAGGAACTCT-3′; B3GALT5, forward:5′- AAGCTCCCAGATACAGACTGC-3′; B3GALT5, reverse:5′- TGGTCCACCTCTTTCGTTTCC-3′; C10orf99, forward:5′- CCGGTCACAGCTACAAATCC-3′; C10orf99, reverse:5′- TCAGGAGGCTAGGAAGGGAT-3′; G A P D H, f o r w a r d: 5′-GGAGCGAGATCCCTCCAAAAT-3′; and GAPDH, reverse:5′-GGCTGTTGTCATACTTCTCATGG-3′.t-test to calculate the significance of the difference between the two groups. p-value greater than 0.05 was considered significant.All data analyses were based on R software (software version 4.0.2). We then used Student’s p < 0.05). For example, EMILIN2 expression was significantly up-regulated in cholangiocarcinoma, colon adenocarcinoma, and ccRCC (p < 0.05) (p < 0.0001) and showed prognostic power. In order to study the relationship between ELIMIN2 expression and tumor stage, we analyzed the EMILIN2 expression in ccRCC patients using TNM stage information. The results showed that the EMILIN2 expression was significantly different in different tumor pathological stages. For example, EMILIN2 expression is significantly higher in patients with distant metastasis   . Interes< 0.001) . These r< 0.001) .The study of immune checkpoint is crucial for the treatment of cancer. To analyze the relationship between EMILIN2 and immune checkpoints, ccRCC patients were divided into high and low groups according to the median EMILIN2 expression. The results showed that several checkpoints including CTLA-2, PDCD1, LAG3, and TIGIT were significantly overexpressed in the EMILIN2 high expression group . This inp < 0.0001)  . These ep < 0.05)  . These eWe obtained the gene sets of 27 immune cell types  that showed a significant positive correlation with EMILIN2. Next, we conducted multivariate regression analysis using the CancerSubtypes package for feature screening and identified 285 genes. Based on TCGA data, ccRCC patients were classified according to the genes expressed using the NMF package. The best value of K was 2 . Finally+ T cells, macrophages, natural killer T cells, effector memory CD4+ T cells, type 1 T helper cells, t follicular helper cells, regulatory T cells, activated dendritic cells, effector memory CD8+ T cells, central memory CD8+ T cells, activated CD8+ T cells, gamma delta T cells, monocytes, MDSCs and central memory CD4+ T cells were more enriched in subtype 2 than subtype 1. Meanwhile, only a few immune cells were enriched in subtype 1, such as neutrophils, memory B cells and immature dendritic cells  were divided into high and low expression groups according to the median expression of EMILIN2. Using the limma package, 366 DEGs were obtained, of which 235 genes were upregulated and 131 genes were downregulated. To explore the potential functions of these DEGs, we analyzed the biological pathways that these genes are associated with using the clusterProfiler package. In KEGG pathway analysis, cytokine-Cytokine_receptor_interaction, TCR signaling pathway, IL-17 signaling pathway, and natural killer cell-mediated cytotoxicity were significantly upregulated . GO analClear cell renal cell carcinoma, the most common type of renal cancer, is a tumor highly dependent on vascular survival. At present, surgical treatment and immunotherapy are the major approaches used to treat patients with this cancer type . SeveralIn this study, bioinformatics analysis showed that EMILIN2, a gene that regulates angiogenesis, was significantly upregulated in ccRCC patients and had prognostic potential. Concurrently, EMILIN2 expression was found to be closely related to the immune status of ccRCC patients. EMILIN2 expression was found to be significantly correlated with multiple immune markers and immune cells. We then obtained the gene sets of these immune cells and performed the molecular typing of ccRCC patients using the NMF algorithm. Patients with clear cell renal cell carcinoma were grouped according to EMILIN2 expression, and the intersection of genes showing differential expression in different groups and subtypes was obtained. Based on this, a six-gene model was constructed and verified by LASSO regression and multivariate regression analysis. We then developed and validated a comprehensive nomogram model by combining risk scores and clinical data.We first analyzed the EMILIN2 expression in 33 cancer types and its ability to predict patient survival. EMILIN2 showed a significant differential expression in ccRCC and indicated poor prognosis. Thus, EMILIN2 expression was closely related to the prognosis of ccRCC. Following this, we investigated the association between EMILIN2 and immune checkpoints, and found that the group with high EMILIN2 expression showed the up-regulation of immune checkpoints. This implies that EMILIN2 expression has some potential effect on the immunotherapy of patients. We then calculated the immune, stromal and ESTIMATE scores of ccRCC patients using ESTIMATE, which is often used to study the tumor microenvironment and explore immune and stromal cells in the tumor microenvironment of different patients. Patients with high EMILIN2 expression also showed a significant increase in immune and stromal scores. This indicates that EMILIN2 expression affects the tumor microenvironment in ccRCC. The study of the complex tumor microenvironment is of great significance in the treatment of patients with tumor. These findings suggest that EMILIN2 may play an important role in tumor development, metastasis and immune response.+ T cells. The interaction of T cell receptors with MHC antigenic peptide complexes leads to changes in T cells at the molecular and cellular levels and mediates the activation of various genes (To explore the immune cells EMILIN2 might be associated with, we used ssGSEA to calculate the scores for 27 types of immune cells in ccRCC patients. Interestingly, EMILIN2 expression was positively correlated with the scores of 27 immune cell types, especially T cells. Thus, EMILIN2 expression affects the extent of infiltration of various immune cells in tumors. The tumor infiltration level of immune cells is an important index for prognostic judgment and evaluating therapeutic effects. Therefore, EMILIN2 has extremely important research value in the study of immune invasion of tumors. Next, we identified DEGs between the high and low EMILIN2 expression groups. KEGG pathway enrichment results revealed that these DEGs were significantly enriched in immune and vascular pathways, such as the TCR signaling pathway and IL-17 signaling pathway. Many studies have shown that the TCR signaling pathway plays an important role in tumor immunity, and the downstream signaling pathway mediated by the TCR signaling pathway plays a key role in promoting the anti-tumor immunity of CD8us genes . The IL-us genes . Previouus genes . CollectWe divided ccRCC patients into two subtypes by screening signature genes from the gene set of 27 immune cell types. We identified 835 DEGs while analyzing differences in the expression between subtypes.To further investigate the factors affecting the survival of ccRCC patients, we studied the intersection of the DEGs with the DEGs in the high and low EMILIN2 expression groups. These DEGs was associated with the TGF−beta signaling pathway, Cytokine−cytokine receptor interaction, Viral protein interaction with cytokine and cytokine receptor, IL−17 signaling pathway and Transcriptional misregulation in cancer were significantly correlated. In the training set, we constructed a 6-gene risk score model based on the 59 genes by combining lasso regression and multivariate regression. We then confirmed the predictive ability in the validation set. TNNT1, SAA1, IL20RB, and COL22A1 are risk factors for ccRCC, whereas B3GALT5 and C10orf99 act as protective factors when these six genes are expressed at high levels. TNNT1 was shown to be associated with various cancers, such as colorectal cancer . It was However, our study may have had certain limitations, primarily because of the limited number of samples. Thus, further experiments are needed to verify the role of these six model genes. Although EMILIN2 was shown to affect angiogenesis, further experimental investigation is needed to confirm whether it affects tumor immunity by regulating angiogenesis in ccRCC.The strengths of our study are the detailed analysis of the association of EMILIN2 in tumor immunity, the molecular typing of ccRCC, and the development of a 6-gene prognostic model with a high AUC value. Then a comprehensive nomogram model was established to predict the 1/3/5-year survival rate of ccRCC patients combined with clinical information. In conclusion, our study suggests that EMILIN2, a gene that regulates angiogenesis, may be a potential target and candidate marker for the treatment of ccRCC patients.