Impact of PD-L1 gene polymorphisms and interactions with cooking with solid fuel exposure on tuberculosis.

Introduction Given that PD-L1 is a crucial immune checkpoint in regulating T cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphism and its interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations. Methods A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry (MS) technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between SNPs and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions. Results Compared with genotype CC, genotypes GG and CG + GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, P<0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction (RERI) between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI 1.922,2.809), suggesting positive interactions with TB susceptibility. Conclusion The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Polymorphisms in PI3K/AKT genes and gene­smoking interaction are associated with susceptibility to tuberculosis.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.

Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study.

BACKGROUND: The current routine endometrial preparation protocol for women with polycystic ovary syndrome (PCOS) is hormone replacement treatment (HRT). Letrozole is rarely used in frozen embryo cycles. Evidence confirming whether letrozole-stimulated (LS) protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable remains lacking. METHODS: This was a retrospective cohort study involving all frozen embryo transfer cycles with LS and HRT for PCOS during the period from Jan 2019 to December 2020 at a tertiary care center. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between LS and HRT protocols after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which LS protocol was suitable. RESULTS: The results of multivariate logistic regression showed that LS was significantly associated with a higher clinical pregnancy rate (70.9% vs. 64.4%;aOR:1.41, 95%CI: 1.18,1.68), live birth rate (60.5% vs. 51.4% aOR:1.49, 95%CI: 1.27,1.76), and a lower risk of miscarriage (14.7% vs. 20.1% aOR: 0.68, 95%CI: 0.53,0.89), hypertensive disorders of pregnancy (6.7% vs. 8.9% aOR: 0.63, 95%CI: 0.42,0.95), and gestational diabetes mellitus (16.7% vs. 20.7% aOR:0.71, 95%CI: 0.53,0.93) than HRT. There were no significant differences in other outcomes such as preterm birth, cesarean delivery, small for gestational age, or large for gestational age between the two endometrial preparation protocols. Subgroup analysis showed that LS had higher live birth rates than HRT in most of the subgroups; in the three subgroups of maternal age ≥ 35 years, menstrual cycle < 35 days, and no insulin resistance, the live birth rates of the two endometrial preparation protocols were comparable. CONCLUSIONS: LS protocol could improve the live birth rate and reduce the incidence of miscarriage, hypertensive disorders of pregnancy and gestational diabetes mellitus in patients with PCOS. LS protocol is suitable for all types of patients with PCOS. LS should be considered the preferred endometrial preparation protocol for women with PCOS.

Longitudinal change of gut microbiota in hypertensive disorders in pregnancy: a nested case-control and Mendelian randomization study.

Mounting evidence has shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP), however, most studies only focused on one time point in pregnancy. In this study, we conducted a nested case-control study utilizing a follow-up cohort, resulting in the collection of 47 HDP patients and 30 healthy controls. The GM profiles were explored using 16S rRNA sequencing at three time points during pregnancy. The diversity analysis of GM showed no significant difference between HDP patients and controls, however, we found 21 differential GM during pregnancy. Trend analysis showed that there are statistical differences in the relative abundance of Thermomonas, Xanthomonas, and Phenylobacteriumat during pregnancy in the gestational hypertension group, and of Xanthomonas, Polycyclovorans, and Phenylobacterium in the control group. The correlation study found that six genera of GM are related to blood pressure. Furthermore, the MR analysis identified the causal relationship between Methanobrevibacter and pre-eclampsia (PE). This study first explored the longitudinal change of GM in HDP patients during pregnancy, found the differential GM, and detected the causal association. Our findings may promote the prevention and treatment of HDP from the perspective of GM and provide valuable insights into the pathogenesis of HDP.

Development and validation of frailty and malnutrition knowledge assessment scale for community-dwelling older adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population, two scales were developed and validated through five phases. Phase 1: the item pools were constructed through a literature review and research panel based on the symptom interpretation model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales each comprise 3 dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all >0.60, Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 min. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

Gut microbiota and hypertensive disorders in pregnancy: evidence from the Mendelian randomization study.

BACKGROUND: Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation. METHODS: We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy. RESULTS: The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of LachnospiraceaeUCG010, Olsenella, RuminococcaceaeUCG009, Ruminococcus2, Anaerotruncus, Bifidobacterium, and Intestinibacter with GH, of Eubacterium (ruminantium group), Eubacterium (ventriosum group), Methanobrevibacter, RuminococcaceaeUCG002, and Tyzzerella3 with PE, and of Dorea and RuminococcaceaeUCG010 with eclampsia, respectively. CONCLUSIONS: This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.

Investigating causal associations among gut microbiota, gut microbiota-derived metabolites, and gestational diabetes mellitus: a bidirectional Mendelian randomization study.

BACKGROUND: Previous studies have shown that gut microbiota (GM) and gut microbiota-derived metabolites are associated with gestational diabetes mellitus (GDM). However, the causal associations need to be treated with caution due to confounding factors and reverse causation. METHODS: This study obtained genetic variants from genome-wide association study including GM (N = 18,340), GM-derived metabolites (N = 7,824), and GDM (5,687 cases and 117,89 controls). To examine the causal association, several methods were utilized, including inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS. Additionally, reverse Mendelian Randomization (MR) analysis and multivariable MR were conducted to confirm the causal direction and account for potential confounders, respectively. Furthermore, sensitivity analyses were performed to identify any potential heterogeneity and horizontal pleiotropy. RESULTS: Greater abundance of Collinsella was detected to increase the risk of GDM. Our study also found suggestive associations among Coprobacter, Olsenella, Lachnoclostridium, Prevotella9, Ruminococcus2, Oscillibacte, and Methanobrevibacter with GDM. Besides, eight GM-derived metabolites were found to be causally associated with GDM. For the phenylalanine metabolism pathway, phenylacetic acid was found to be related to the risk of GDM. CONCLUSIONS: The study first used the MR approach to explore the causal associations among GM, GM-derived metabolites, and GDM. Our findings may contribute to the prevention and treatment strategies for GDM by targeting GM and metabolites, and offer novel insights into the underlying mechanism of the disease.

Development and validation of knowledge assessment scales on sarcopenia and fall for Chinese community-dwelling older adults.

AIM: This study aimed to develop and validate sarcopenia and fall knowledge assessment scales for community-dwelling older adults. METHODS: A five-phase, systematic and standardized process was used. Phase 1: item pools were constructed based on the Symptom Interpretation Model. Phase 2: the Delphi expert consultation was carried out for items selection and revision. Phase 3: a pilot survey was carried out to further select and revise the items. Phase 4: older adults were surveyed to finalize the items. Phase 5: older adults were surveyed to test the psychometric properties of the two developed scales, including construct validity, reliability and acceptability. RESULTS: Both scales comprise three dimensions (symptom, risk factor and management strategy), with 10 items for the sarcopenia knowledge assessment scale and 14 items for the fall knowledge assessment scale. They had acceptable construct validity, with all indicators meeting their specific criteria. Their reliability was acceptable, with the Cronbach's α coefficients being 0.82 for both scales, the value of spilt-half reliability being 0.86 for the sarcopenia knowledge assessment scale and 0.85 for the fall knowledge assessment scale. Their acceptability was good, with both scales having a completion rate of 94.35% and an average completion time of 5 min. DISCUSSION: Two Chinese knowledge assessment scales with acceptable validity, reliability and acceptability have been developed, which will facilitate the assessment of the knowledge on sarcopenia and fall among community-dwelling older adults, especially for large-scale surveys. Geriatr Gerontol Int 2023; 23: 430-436.

Comparative effectiveness of non-pharmacological interventions for frailty: a systematic review and network meta-analysis.

BACKGROUND: Frailty endangers the health of older adults. Furthermore, the prevalence of frailty continues to increase as the global population ageing. OBJECTIVE: To update evidence on the effectiveness of non-pharmacological interventions for frailty by conducting a network meta-analysis (NMA) of randomised controlled trials (RCTs). METHODS: Eight databases were searched from January 1, 2000, until September 24, 2021. RCTs of interventions for frailty among participants aged ≥60 years were considered eligible. The primary outcome was frailty. Pairwise meta-analysis and NMA were performed, with the pooled standardised mean difference (SMD) and 95% confidence interval (CI) being reported. RESULTS: A total of 69 RCTs were included after screening 16,058 retrieved citations. There were seven types of interventions (11 interventions) for frailty among the included RCTs. Physical activity (PA) (pooled SMD = 0.43, 95% CI: 0.34-0.51), multicomponent intervention (pooled SMD = 0.34, 95% CI: 0.23-0.45) and nutrition intervention (pooled SMD = 0.21, 95% CI: 0.06-0.35) were associated with reducing frailty compared to control, of which PA was the most effective type of intervention. In terms of specific types of PA, resistance training (pooled SMD = 0.58, 95% CI: 0.33-0.83), mind-body exercise (pooled SMD = 0.57, 95% CI: 0.24-0.90), mixed physical training (pooled SMD = 0.47, 95% CI: 0.37-0.57) and aerobic training (pooled SMD = 0.36, 95% CI: 0.09-0.62) were associated with a reduction in frailty compared to usual care. Resistance training was the most effective PA intervention. CONCLUSION: Resistance training has the best potential to reduce frailty in older adults. This finding might be useful to clinicians in selecting interventions for older adults with frailty.

Genome-wide association study using whole-genome sequencing identifies risk loci for Parkinson's disease in Chinese population.

Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson's disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (Pcombined = 1.47 × 10-9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P < 5 × 10-8) for PD in Chinese population. Moreover, of the reported genome-wide significant risk variants found mostly in European ancestry populations, the correlation coefficient (rb) of effect size accounting for sampling errors was 0.91 between datasets and 63.6% attained P < 0.05 in Chinese population. Accordingly, we estimated a heritability of 0.14-0.18 for PD, and a moderate genetic correlation between European ancestry and Chinese populations (rg = 0.47, se = 0.21). Polygenic risk score (PRS) analysis revealed that individuals with PRS values in the highest quartile had a 3.9-fold higher risk of developing PD than the lowest quartile. In conclusion, the present GWAS identified PD-associated variants in Chinese population, as well as genetic factors shared among distant populations. Our findings shed light on the genetic homogeneity and heterogeneity of PD in different ethnic groups and suggested WGS might continue to improve our understanding of the genetic architecture of PD.

The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study.

AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.

The impact of blastocyst freezing and biopsy on the association of blastocyst morphological parameters with live birth and singleton birthweight.

OBJECTIVE: To explore whether the associations of 3 blastocyst morphological parameters, namely, degree of blastocyst expansion (expansion), appearance of trophectoderm (TE) and inner cell mass, with live birth and singleton birth weight are influenced by blastocyst freezing and biopsy. DESIGN: A retrospective study. SETTING: An assisted reproductive technology center. PATIENT(S): 28,515 single blastocyst transfer cycles between January 2014 and August 2019. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Live birth and singleton birth weight. RESULT(S): Blastocyst transfer cycles were divided into 4 groups: biopsied blastocyst cycles (biopsied-blast), thawed blastocyst cycles (thawed-blast), blastocyst from thawed cleavage embryo cycles (blast-thawed-D3), and fresh blastocyst cycles (fresh-blast). Subgroup analyses by blastocyst stage (day 5 and day 6) were performed in thawed-blast and blast-thawed-D3. Because almost all blastocysts were biopsied on day 6 and fresh blastocysts were transferred on day 5, the biopsied-blast and fresh-blast were not divided into subgroups. First, the associations between blastocyst morphological parameters and live birth were analyzed. To explore the effect of freezing, we compared day-5 frozen cycles (thawed-blast) vs. day-5 fresh cycles (including fresh-blast and blast-thawed-D3) and day 6 frozen cycles (thawed-blast) vs. day-6 fresh cycles (blast-thawed-D3). Inner cell mass and TE were associated with live birth for day 5 embryos, and only TE affected live birth for day-6 embryos. The associations were the same in frozen cycles and fresh cycles. To explore the effect of biopsy, we compared day-6 biopsied cycles (biopsied-blast) vs. day-6 nonbiopsied cycles (including thawed-blast and blast-thawed-D3). All the 3 parameters were associated with live birth in biopsied-blast, whereas only TE was associated with live birth in nonbiopsied cycles. In addition, the associations between blastocyst morphological parameters and singleton birthweight were analyzed. In the 6 subgroups, expansion stage of day-6 embryos in biopsied-blast and TE grade of day-6 embryos in thawed-blast were associated with birth weight, and there are no associations in other subgroups. CONCLUSION(S): The association of blastocyst morphological parameters with live birth may be affected by blastocyst biopsy and/or genetic testing, and its association with birth weight may be affected by blastocyst freezing and biopsy and/or genetic testing.

The association between pre-gravid and first trimester maternal weight and its implications for clinical research studies.

In clinical research, weight measurement in first trimester is often treated as a surrogate for pre-pregnancy weight. The validity of this critical assumption, however, is uncertain. Thus, we sought to prospectively evaluate the relationship between pre-gravid weight and first trimester weight. In this prospective preconception observational cohort study, 474 newly-married women in Liuyang, China, underwent pre-gravid evaluation at median 17.7 weeks before a singleton pregnancy, during which they had weight measurement in first trimester. The relationship between pre-gravid and first trimester weight was assessed by Bland-Altman analysis, Concordance Correlation Coefficient, and Pearson correlation. Mean pre-gravid weight was 49.8 ± 6.4 kg and mean weight in first trimester was 51.1 ± 7.0 kg. The Concordance Correlation Coefficient between pre-gravid and first trimester weight was 0.76 (95% limits of agreement: 0.72-0.80) and Pearson correlation was r = 0.78 (p < 0.0001), indicative of good concordance and correlation. As the timing of the weight measurement in first trimester increased in weekly increments from < 8 weeks to 14 weeks, the Concordance Correlation Coefficient ranged between 0.69 to 0.76 and the Pearson correlation ranged from 0.71 to 0.78 (all p < 0.0001). In conclusion, the observed concordance between pre-gravid weight and weight measured at any point in the first trimester provides a measure of validation for the widespread practice in clinical research of treating first trimester weight measurement as a surrogate for maternal weight before pregnancy.

Combination effect between gut microbiota and traditional potentially modifiable risk factors for first-ever ischemic stroke in Tujia, Miao and Han populations in China.

China has had explosive growth in ischemic stroke (IS) burden with significant ethnic and geographic disparities. The aim of this study was to explore the possible combination effect between gut microbiota and traditional potentially modifiable risk factors for IS among two ethnic minorities (Tujia and Miao) and the Han population. Herein, we first used the 16 S rRNA sequencing to compare the gut microbial compositions of 82 patients with first-ever IS vs. 82 normal controls (NCs) among Han, Tujia, and Miao people between 1 May 2018 and 30 April 2019, from Xiangxi Tujia and Miao Autonomous Prefecture in China. An additive model was used to study the interaction between traditional risk factors and gut microbiota with R software. Linear discriminant analysis (LDA) and LDA effect size (LEfSe) results showed that the identified key gut microbiota's taxonomic composition varied in different ethnicity between the IS patients and NCs. Furthermore, families Lactobacillaceae, Enterococcaceae, Streptococcaceae, and Enterobacteriaceae were found to be positively correlated with high-risk factors and negatively correlated with preventive factors in the IS patients, but families Ruminococcaceae and Lachnospiraceae were just the opposite in the NCs. There were additive interactions between traditional risk factors (systolic blood pressure, diastolic blood pressure, and high-sensitive C-reactive protein) and family Enterococcaceae for first-ever IS with the attributable proportion due to the interaction was 0.74, 0.71, and 0.85, respectively; and the synergy index was 4.45, 3.78, and 7.01, respectively. This preliminary but promising study showed that the gut microbiota disturbances may potentially interact to IS with different ethnic host's traditional risk factors.

The Association between Gut Microbiome and Pregnancy-Induced Hypertension: A Nested Case-Control Study.

(1) Background: Pregnancy-induced hypertension (PIH) is associated with obvious microbiota dysbiosis in the third trimester of pregnancy. However, the mechanisms behind these changes remain unknown. Therefore, this study aimed to explore the relationship between the gut microbiome in early pregnancy and PIH occurrence. (2) Methods: A nested case-control study design was used based on the follow-up cohort. Thirty-five PIH patients and thirty-five matched healthy pregnant women were selected as controls. The gut microbiome profiles were assessed in the first trimester using metagenomic sequencing. (3) Results: Diversity analyses showed that microbiota diversity was altered in early pregnancy. At the species level, eight bacterial species were enriched in healthy controls: Alistipes putredinis, Bacteroides vulgatus, Ruminococcus torques, Oscillibacter unclassified, Akkermansia muciniphila, Clostridium citroniae, Parasutterella excrementihominis and Burkholderiales bacterium_1_1_47. Conversely, Eubacterium rectale, and Ruminococcus bromii were enriched in PIH patients. The results of functional analysis showed that the changes in these different microorganisms may affect the blood pressure of pregnant women by affecting the metabolism of vitamin K2, sphingolipid, lipid acid and glycine. (4) Conclusion: Microbiota dysbiosis in PIH patients begins in the first trimester of pregnancy, and this may be associated with the occurrence of PIH. Bacterial pathway analyses suggest that the gut microbiome might lead to the development of PIH through the alterations of function modules.

AST-to-ALT ratio in the first trimester and the risk of gestational diabetes mellitus.

Background: Aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) has been reported affect the risk of type 2 diabetes (T2DM), but it is uncertain if it has relationship with gestational diabetes mellitus (GDM). Objectives: Our study aimed to investigate the association between AST/ALT ratio in the first trimester and the risk of subsequent development of GDM. Method: This prospective cohort study enrolling 870 pregnant women, 204 pregnant women with missing data or liver diseases were excluded, 666 pregnant women were included in this study containing 94 GDM women. Blood samples were collected in the first trimester. Univariate analysis and multivariate logistic regression were used to evaluate the association between AST/ALT and GDM. Nomogram was established based on the results of multivariate logistic analysis. Receiver Operating Characteristic (ROC) curves and calibration curves were used to evaluate the predictive ability of this nomogram model for GDM. Decision curve analysis (DCA) was used to examine the clinical net benefit of predictive model. Results: AST/ALT ratio (RR:0.228; 95% CI:0.107-0.488) was associated with lower risk of GDM after adjusting for confounding factors. Indicators used in nomogram including AST/ALT, maternal age, preBMI, waist circumference, glucose, triglycerides, high density lipoprotein cholesterol and parity. The area under the ROC curve (AUC) value of this predictive model was 0.778, 95% CI (0.724, 0.832). Calibration curves for GDM probabilities showed acceptable agreement between nomogram predictions and observations. The DCA curve demonstrated a good positive net benefit in the predictive model. Conclusions: The early AST/ALT level of pregnant women negatively correlated with the risk of GDM. The nomogram including AST/ALT at early pregnancy shows good predictive ability for the occurrence of GDM.

Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.

BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.

Betel quid chewing and oral potential malignant disorders and the impact of smoking and drinking: A meta-analysis.

BACKGROUND: Oral potential malignant disorders (OPMDs) are a precancerous condition of oral disease. Several studies have found that betel quid chewing, smoking and alcohol drinking might be the risk factors of OPMDs. But the relationships of them, especially their interaction are still inconclusive. AIM: To evaluate the relationship between betel quid chewing and OPMDs and to explore the interaction of smoking and alcohol drinking on the relationship. METHODS: We searched PubMed, Web of Science, Embase and the Cochrane Library databases with items complete until January 2021 for relevant studies. The research data were extracted according to the inclusion criteria. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the effect size. Subgroup analysis was performed to assess interactions between exposures and OPMDs. Relative excess risk of interaction (RERI) was used to estimate the size of interaction. RESULTS: Nine articles were selected in the final meta-analysis. The results showed that betel quid chewing (pooled OR: 8.70, 95%CI: 5.18-14.61), alcohol consumption (pooled OR: 1.95, 95%CI: 1.5-2.55), and smoking (pooled OR:4.35, 95%CI: 3.06-6.2) could significantly increase the risk of OPMDs compared to individuals without these behaviors. Smoking and alcohol drinking synergistically increased the association between betel quid chewing and OPMDs (pooled OR(BQ+SM):14.38, 95%CI: 7.14-28.95; pooled OR(BQ+DK): 11.12, 95%CI: 8.00-15.45, respectively). The RERI(BQ+SM) and RERI(BQ+DK) were 2.33 and 1.47, respectively. CONCLUSION: The synergistic effects between smoking/drinking and betel quid highlights the importance of focusing on individuals with multiple exposures. Further study should be conducted to confirm these interactions.

hsa-miR-9-5p-Mediated TSPAN9 Downregulation Is Positively Related to Both Poor Hepatocellular Carcinoma Prognosis and the Tumor Immune Infiltration.

Tetraspanins (TSPANs) play crucial roles in cell adhesion, migration, and metastasis of human cancer. However, there is no study in revealing the aspects of TSPAN9 traits and its functions in hepatocellular carcinoma (HCC) prognosis. Our study is the first to portray the TSPAN9 expression in HCC tissues with immunohistochemistry (IHC) analysis. Subsequently, a series of bioinformatics analyses such as expression estimation, survival assessment, and correlation analysis were implemented to dig out the possible upstream noncoding RNAs (ncRNAs) for TSPAN9 in HCC. In this way, the relevance within TSPAN9 and tumor immunity was then explored. We found that the TSPAN9 was downregulated in HCC tissues and had a correlation with HCC prognosis. Furthermore, we identified that the AL139383.1-hsa-miR-9-5p axis was the upstream ncRNA-related pathway most associated with TSPAN9 in HCC. Besides that, expression of TSPAN9 held a significantly negative correlation with tumor immunocyte infiltration as well as immune checkpoint CTLA4. TSPAN9-related immunomodulators were mainly enriched in T cell activation, leukocyte cell-cell adhesion, regulation of T cell activation, and regulation of leukocyte cell-cell adhesion signaling pathway. In conclusion, our results indicated that hsa-miR-9-5p-mediated downregulation of TSPAN9 was associated with poor HCC prognosis, immune-related signaling pathway, and tumor immune infiltration.