PET/CT study of dopamine transporter (DAT) binding with the triple reuptake inhibitor toludesvenlafaxine in rats and humans.

PURPOSE: Toludesvenlafaxine is a recently developed antidepressant that belongs to the triple reuptake inhibitor class. Despite the in vitro evidence that toludesvenlafaxine inhibits the reuptake of serotonin (5-HT), norepinephrine (NE) and dopamine (DA), there is no in vivo evidence that toludesvenlafaxine binds to DAT and increases DA level, a mechanism thought to contribute to its favorable clinical performance. METHODS: Positron emission tomography/computed tomography (PET/CT) was used to examine the DAT binding capacity in healthy rats and human subjects and microdialysis was used to examine the striatal DA level in rats. [18F]FECNT and [11C]CFT were used as PET/CT radioactive tracer for rat and human studies, respectively. RESULTS: In rats, 9 mg/kg of toludesvenlafaxine hydrochloride (i.v.) followed by an infusion of 3 mg/kg via minipump led to the binding rate to striatum DAT at 3.7 - 32.41% and to hypothalamus DAT at 5.91 - 17.52% during the 45 min scanning period. 32 mg/kg oral administration with toludesvenlafaxine hydrochloride significantly increased the striatal DA level with the AUC0 - 180 min increased by 63.9%. In healthy volunteers, 160 mg daily toludesvenlafaxine hydrochloride sustained-release tablets for 4 days led to an average occupancy rates of DAT at 8.04% ± 7.75% and 8.09% ± 7.00%, respectively, in basal ganglion 6 h and 10 h postdose. CONCLUSION: These results represent the first to confirm the binding of toludesvenlafaxine to DAT in both rats and humans using PET/CT, and its elevation of brain DA level, which may help understand the unique pharmacological and functional effects of triple reuptake inhibitors such as toludesvenlafaxine. GOV IDENTIFIERS: NCT05905120. Registered 14 June 2023. (retrospectively registered).

Population Pharmacodynamic Models of Risperidone on PANSS Total Scores and Prolactin Levels in Schizophrenia.

Currently, research predominantly focuses on evaluating clinical effects at specific time points while neglecting underlying patterns within the treatment process. This study aims to analyze the dynamic alterations in PANSS total scores and prolactin levels in patients with schizophrenia treated with risperidone, along with the influencing covariates. Using data from an 8-week randomized, double-blind, multicenter clinical trial, a population pharmacodynamic model was established for the PANSS total scores of and prolactin levels in patients treated with risperidone. The base model employed was the Emax model. Covariate selection was conducted using a stepwise forward inclusion and backward elimination approach. A total of 144 patients were included in this analysis, with 807 PANSS total scores and 531 prolactin concentration values. The PANSS total scores of the patients treated with risperidone decreased over time, fitting a proportionally parameterized sigmoid Emax model with covariates including baseline score, course of the disease, gender, plasma calcium ions, and lactate dehydrogenase levels. The increase in prolactin levels conformed to the ordinary Emax model, with covariates encompassing course of the disease, gender, weight, red blood cell count, and triglyceride levels. The impacts of the baseline scores and the course of the disease on the reduction of the PANSS scores, as well as the influence of gender on the elevation of prolactin levels, each exceeded 20%. This study provides valuable quantitative data regarding PANSS total scores and prolactin levels among patients undergoing risperidone treatment across various physiological conditions.

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients: An interim analysis of post-marketing surveillance.

BACKGROUND: Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms. Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d. However, post-market surveillance (PMS) with an adequate sample size is required for further validation of the drug's safety profile and effectiveness. AIM: To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population. METHODS: A prospective, multicenter, open-label, 12-wk surveillance was conducted in mainland China. All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment. Safety assessments included adverse events (AEs), adverse drug reactions (ADRs), extrapyramidal symptoms (EPS), akathisia, use of EPS drugs, weight gain, and laboratory values as metabolic parameters and the QTc interval. The effectiveness was assessed using the brief psychiatric rating scale (BPRS) from baseline to the end of treatment. RESULTS: A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis. The average daily dose was 61.7 ± 19.08 mg (mean ± SD) during the treatment. AEs and ADRs were experienced by 101 patients (11.3%) and 78 patients (8.7%), respectively, which were mostly mild. EPS occurred in 25 individuals with a 2.8% incidence, including akathisia in 20 individuals (2.2%). Moreover, 59 patients received drugs for treating EPS during the treatment, with an incidence of 6.6% which dropped to 5.4% at the end of the treatment. The average weight change was 0.20 ± 2.36 kg (P = 0.01687) with 0.8% of patients showing a weight gain of ≥ 7% at week 12 compared with that at the baseline. The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges. The mean changes in total BPRS scores were -8.9 ± 9.76 (n = 959), -13.5 ± 12.29 (n = 959), and -16.8 ± 13.97 (n = 959) after 2/4, 6/8, and 12 wk, respectively (P < 0.001 for each visit compared with the baseline) using the last-observation-carried-forward method. CONCLUSION: The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population. No new safety or efficacy concerns were identified.

Comparing the efficacies of transcranial magnetic stimulation treatments using different targeting methods in major depressive disorder: protocol for a network meta-analysis.

INTRODUCTION: Transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (lDLPFC) has been widely used as a treatment for major depressive disorder (MDD) in the past two decades. Different methods for localising the lDLPFC target include the '5 cm' method, the F3 method and the neuro-navigational method. However, whether TMS efficacies differ between the three targeting methods remains unclear. We present a protocol for a systematic review and network meta-analysis (NMA) to compare the efficacies of TMS treatments using these three targeting methods in MDD. METHODS AND ANALYSIS: Relevant studies reported in English or Chinese and published up to May 2023 will be identified from searches of the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, China National Knowledge Infrastructure, Wan Fang Database, Chinese BioMedical Literature Database, and China Science and Technology Journal Database. We will include all randomised controlled trials assessing the efficacy of an active TMS treatment using any one of the three targeting methods compared with sham TMS treatment or comparing efficacies between active TMS treatments using different targeting methods. Interventions must include a minimum of 10 sessions of high-frequency TMS over the lDLPFC. The primary outcome is the reduction score of the 17-item Hamilton Depression Rating Scale, 24-item Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale. The dropout rate is a secondary outcome representing the TMS treatment's acceptability. Pairwise meta-analyses and a random-effects NMA will be conducted using Stata. We will use the surface under the cumulative ranking curve to rank the different targeting methods in terms of efficacy and acceptability. ETHICS AND DISSEMINATION: This systematic review and NMA does not require ethics approval. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410273.

Matched-pair analysis of the impact of low-dose postoperative radiotherapy on prognosis in patients with advanced hypopharyngeal squamous cell carcinoma without positive surgical margins and extracapsular extension.

Background: We conducted a comparative analysis between low and high-dose postoperative radiotherapy in patients with hypopharyngeal squamous cell carcinoma (HPSCC) in stage III or IV without positive surgical margins and extracapsular extension (ECE). Propensity score matching (PSM) was used to eliminate confounding factors and reduce bias. Methods: The matched-pair analysis included 156 patients divided into two groups: the low-dose radiotherapy group (LD-RT 50 Gy, 78 cases) and the high-dose radiotherapy group (HD-RT 60 Gy, 78 cases). Both cohorts were statistically comparable in terms of age, gender, subsite, and TNM classification. Results: The median follow-up time was 49 months (ranging from 5 to 100 months). The overall survival (OS) rate, progression-free survival (PFS) rate, locoregional control rate (87% vs. 85.7%; p = 0.754), distant metastases-free survival (79.2% vs. 76.6%; p = 0.506), and the occurrence of second primary tumors (96.1% vs. 93.5%; p = 0.347) showed no significant differences between the LD-RT group and the HD-RT group. The 3-year OS was 64.9% and 61% in the low-dose and high-dose group, respectively, and 63% in the entire group (p = 0.547). The 3-year PFS was 63.6% and 54.5% (p = 0.250), respectively, and the 3-year PFS of the entire group was 59.1%. Multivariate analyses revealed that pathological T and N classification, and pathological differentiation were associated with 3-year OS, PFS, and LRFS and were independent prognostic factors (p < 0.05). LD-RT was not associated with an increased risk of death and disease progression compared to HD-RT. Conclusion: The results of postoperative low-dose radiotherapy did not show inferiority to those of high-dose radiation for patients with advanced hypopharyngeal cancer without positive surgical margins and ECE in terms of OS, PFS, locoregional control, and metastases-free survival.

Impact of vaccine measures on the transmission dynamics of COVID-19.

In many nations, efforts to prevent and control COVID-19 have been significantly impeded by the SARS-CoV-2 virus ongoing mutation. The Omicron strain, a more recent and prevalent strain, has had more significant detrimental effects in countries worldwide. To investigate the impact of the Omicron BA.2 strain on vaccine efficacy, we proposed a model with vaccination and immunological decline in this research. Then, we fitted our model based on the number of daily new instances reported by the government in Jilin and Shanghai, China. We estimated the effective reproduction number Re = 4.71 for the Jilin and Re = 3.32 for Shanghai. Additionally, we do sensitivity analysis to identify the critical factors affecting the effective reproduction number Re. It was found that vaccination rate, effectiveness rate, and declining rate had a significant effect on Re. Further, we investigate the relevant parameter thresholds that make Re lower than unity. Finally, rich numerical experiments were then carried out. We observed that even when vaccine efficiency was not high, increasing vaccination rates had a significant effect on early disease transmission, that limiting social distance was the most economical and rational measure to control the spread of disease, and that for a short period, reducing immune decline was not significant in curbing disease transmission.

Overexpression of IGF2 affects mouse weight and glycolipid metabolism and IGF2 is positively related to macrosomia.

Objective: To investigate the effects of insulin-like growth factor 2 (IGF2) on growth and glycolipid metabolism, as well as the underlying mechanism. Methods: A mouse model of IGF2 overexpression was constructed to measure weight gain before adulthood, to obtain the values of adult glycolipid metabolism indicators in the peripheral blood and to detect the expression of genes in the IGF2 signaling pathway in different mouse tissues. The present study also explored the independent association between the IGF2 gene and macrosomia by detecting and comparing the expression levels of IGF2 mRNA/H19 RNA in maternal peripheral blood and fetal cord blood of 26 human pregnancies. Results: In the mouse model, weights of the IGF2-overexpressing mice were significantly higher than those of the control mice at the age of 5-10 weeks. The glucose concentration, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels of IGF2-overexpressing mice were significantly lower than those of wild-type (WT) mice. Compared with the WT mice, the expression of H19 was significantly decreased in the pancreas and IGF1R was significantly decreased in the muscle of mice with IGF2 overexpression. The expression levels of STAT3 and AKT2 showed significant decrease in liver, muscle and increase in muscle of IGF2-overexpressing mice, respectively. GLUT2 expression showed significant increase in liver, kidney, muscle and decrease in pancreas of mice with IGF2 overexpression. This study also found that in normal mothers with the similar clinical characteristics, IGF2 expression in the maternal peripheral blood and fetal cord blood is an independent factor influencing macrosomia. Conclusion: IGF2 expression was independently correlated with the occurrence of macrosomia, and overexpression of IGF2 significantly increased the weights of mice at the age of 5-10 weeks and significantly affected the values of adult glycolipid metabolism indicators, which might be the result of changes in the IGF2-IGF1R-STAT3/AKT2-GLUT2/GLUT4 pathway. These findings might suggest that IGF2 plays an important role in growth and glycolipid metabolism during both pregnancy and postnatal development.

Cheilolejeunea zhui (Lejeuneaceae, Marchantiophyta), a new species with moniliate ocelli from Guangxi, China.

A new ocellate liverwort species, Cheilolejeunea zhui (Lejeuneaceae), is described from Guangxi, China. The new species is similar to the neotropical C. urubuensis in having moniliate ocelli in the leaf lobes and in general appearances but differs in having obliquely spreading leaves, obtuse to subacute leaf apex, thin-walled leaf cells with distinct trigones, shallowly bifid female bracteole apex, and numerous ocelli in its perianths. Molecular phylogeny of data from three regions (nrITS, trnL-F, and trnG) confirmed the systematic position of this new species to be sister to C. urubuensis, well apart from the remaining members of the genus. Based on morphological and molecular evidence, Cheilolejeunea sect. Moniliocella sect. nov. is proposed to accommodate C. urubuensis and C. zhui. The discovery of C. zhui represents the fourth known species in Cheilolejeunea with linearly arranged ocelli.

Plasma biomarker panel for major depressive disorder by quantitative proteomics using ensemble learning algorithm: A preliminary study.

Major depressive disorder (MDD) is a major international public health issue; thus, investigating its underlying mechanisms and identifying suitable biomarkers to enable its early detection are imperative. Using data-independent acquisition-mass spectrometry-based proteomics, the plasma of 44 patients with MDD and 25 healthy controls was studied to detect differentially expressed proteins. Bioinformatics analyses, such as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, Protein-Protein Interaction network, and weighted gene co-expression network analysis were employed. Moreover, an ensemble learning technique was used to build a prediction model. A panel of two biomarkers, L-selectin and an isoform of the Ras oncogene family was identified. With an area under the receiver operating characteristic curve of 0.925 and 0.901 for the training and test sets, respectively, the panel was able to distinguish MDD from the controls. Our investigation revealed numerous potential biomarkers and a diagnostic panel based on several algorithms, which may contribute to the future development of a plasma-based diagnostic approach and better understanding of the molecular mechanisms of MDD.

Liverworts show a globally consistent mid-elevation richness peak.

The study of elevational gradients allows to draw conclusions on the factors and mechanisms determining patterns in species richness distribution. Several earlier studies investigated liverwort diversity on single or few elevational transects. However, a comprehensive survey of the elevational distribution patterns of liverwort richness and their underlying factors is lacking so far. This study's purpose was to fill this gap by compiling an extensive data set of liverwort elevational patterns encompassing a broad diversity of mountains and mountain ranges around the world. Using polynomial regression analyses, we found a prevalence of hump-shaped richness patterns (19 of 25 gradients), where liverwort species richness peaked at mid-elevation and decreased towards both ends of the gradient. Against our expectation and unlike in other plant groups, in liverworts, this pattern also applies to elevational gradients at mid-latitudes in temperate climates. Indeed, relative elevation, calculated as the percentage of the elevational range potentially inhabited by liverworts, was the most powerful predictor for the distribution of liverwort species richness. We conclude from these results that the admixture of low- and high-elevation liverwort floras, in combination with steep ecological gradients, leads to a mid-elevation floristic turnover shaping elevational patterns of liverwort diversity. Our analyses further detected significant effects of climatic variables (temperature of the warmest month, potential evapotranspiration, and precipitation of the warmest month) in explaining elevational liverwort richness patterns. This indicates that montane liverwort diversity is restricted by high temperatures and subsequent low water availability especially towards lower elevations, which presumably will lead to serious effects by temperature shifts associated with global warming.

Stability and Hopf bifurcation of an SIR epidemic model with density-dependent transmission and Allee effect.

In this paper, an SIR model with a strong Allee effect and density-dependent transmission is proposed, and its characteristic dynamics are investigated. The elementary mathematical characteristic of the model is studied, including positivity, boundedness and the existence of equilibrium. The local asymptotic stability of the equilibrium points is analyzed using linear stability analysis. Our results indicate that the asymptotic dynamics of the model are not only determined using the basic reproduction number ${R_0}$. If ${R_0} < 1$, there are three disease-free equilibrium points, and a disease-free equilibrium is always stable. At the same time, the conditions for other disease-free equilibrium points to be bistable were determined. If ${R_0} > 1$ and in certain conditions, either an endemic equilibrium emerges and is locally asymptotically stable, or the endemic equilibrium becomes unstable. What must be emphasized is that there is a locally asymptotically stable limit cycle when the latter happens. The Hopf bifurcation of the model is also discussed using topological normal forms. The stable limit cycle can be interpreted in a biological significance as a recurrence of the disease. Numerical simulations are used to verify the theoretical analysis. Taking into account both density-dependent transmission of infectious diseases and the Allee effect, the dynamic behavior becomes more interesting than when considering only one of them in the model. The Allee effect makes the SIR epidemic model bistable, which also makes the disappearance of diseases possible, since the disease-free equilibrium in the model is locally asymptotically stable. At the same time, persistent oscillations due to the synergistic effect of density-dependent transmission and the Allee effect may explain the recurrence and disappearance of disease.

Hydroxychloroquine significantly decreases the risk of preeclampsia in pregnant women with autoimmune disorders: a systematic review and meta-analysis.

This meta-analysis aimed to investigate whether hydroxychloroquine (HCQ) intervention could decrease the incidence of preeclampsia and other maternal and fetal outcomes among pregnant women with autoimmune disorders. PubMed, EMBASE, Web of Science, and the Cochrane databases were searched from inception until January 2022. Data on maternal or fetal outcomes of the control and hydroxychloroquine treatment groups were gathered and analyzed. Pooled odds ratio (OR) with 95% confidence intervals (CIs) were determined. Cochran's Q test, I2 statistics, leave-one-out analysis, Baujat plot analysis, GOSH plot analysis, and multivariable meta-regression were applied to assess between-study heterogeneity. The meta-analysis was performed using the Stata V.16.1 software. Baujat plot analysis and GOSH plot analysis were performed using the R V.4.0.0 software. Our study included 21 cohort studies and one case-control study with a total of 3948 pregnancies with immune disorders. HCQ treatment significantly reduced the incidence of preeclampsia (OR 0.45, 95% CI 0.33-0.63, p = 0.000, I2 3.68%). After outlier omission, HCQ treatment significantly reduced the incidence of premature delivery (OR 0.84, 95% CI 0.73-0.96, p = 0.01, I2 44.81%) in pregnant women with autoimmune disorders. In sub-group analysis, HCQ also significantly reduced the incidence of gestational hypertension (OR 0.42, 95% CI 0.26-0.68, p = 0.001, I2 49.33%) and preterm birth (OR 0.63, 95% CI 0.48-0.82, p = 0.001, I2 27.63%) in pregnant women with lupus. The heterogeneity of the findings mentioned above was low to moderate. There were no significant differences in the risk of other outcomes, including gestational diabetes, HELLP syndrome, thrombosis, spontaneous abortion, fetal loss, small for gestational age infant (SGA), low birth weight, stillbirth, APGAR score < 7, and congenital malformation. This meta-analysis indicated that HCQ treatment could significantly decrease the incidence of preeclampsia and premature delivery in pregnant women with autoimmune disorders. In addition, HCQ could reduce the risk of gestational hypertension in pregnant lupus patients.

Postoperative radiotherapy for supraglottic cancer on real-world data: can we reduce dose to lymph node levels?

PURPOSE: To evaluate prognosis for reducing postoperative radiotherapy (PORT) dose to lymph node levels of supraglottic cancer (SC) on real-world data. METHOD AND MATERIALS: Patients were derived from two cancer centers. In center 1, the involved nodal levels (high-risk levels, HRL) and the next level received a dose of 60.06 Gy/1.82 Gy per fraction, while the other uninvolved levels (low-risk levels, LRL) received 50.96 Gy/1.82 Gy per fraction. In center 2, all received 50 Gy/2 Gy per fraction. The rates of high-risk levels control (HRC), regional control (RC), overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. RESULT: Totally, 124 patients were included (62 in center 1, 62 in center 2). Most patients (106, 85.5%) had a stage T3/N + tumor. The median follow-up was 45 months (range 1-163 months). There were no significant differences in terms of OS (p = 0.126), RC (p = 0.514), PFS (p = 0.195) and DMFS (p = 0.834). Most regional recurrences (4, 80%) occurred within three years of treatment, and all occurred within the target volumes. No regional failure occurred in HRL in center 1, while three (3/4) failures occurred in center 2. Dose reduction prescription to HRL led to a lower HRC rate (100% vs. 90.6%, p = 0.009). While the rates of LRL control (98.4%) were equal between the two centers. CONCLUSION: Compared with a standard dose, the reduced dose to involved nodal levels showed inferior regional control for PORT, while uninvolved nodal levels showed equal outcomes. A dose of 50 Gy for HRL may be an unfavorable treatment option for SC.

Estimated optimal gestational weight gain for pregnant women with gestational diabetes mellitus: a prospective cohort study in China.

OBJECTIVES: We aimed to evaluate the inter-hospital variability of gestational weight gain (GWG) among women with gestational diabetes mellitus (GDM) in China and explore GDM-specific optimal GWG relative to the National Academy of Medicine (NAM) targets. METHODS: A prospective multicenter University Hospital Advanced Age Pregnant Cohort study was conducted from March 2017 to June 2021 at eight hospitals in China. The range of mean GWG across hospitals and the intraclass correlation coefficient (ICC) were used to evaluate the inter-hospital variability of GWG. For normal-weight and overweight women with GDM, potential optimal GWGs were derived by minimizing the joint risk of small and large for gestational age (SGA and LGA), and the incidences of adverse perinatal outcomes were compared between women who met the optimal GWGs and those who met the NAM targets. RESULTS: A total of 3,013 women with GDM and 9,115 women without GDM were included. The GWG variation among hospitals was larger in women with GDM (range: 10.0-14.1 kg, ICC = 7.1%) than in women without GDM (range: 13.0-14.5 kg, ICC = 0.7%). The estimated optimal GWGs for women with GDM were lower than the NAM targets, as 9.5-14.0 kg for normal-weight and 3.0-7.5 kg for overweight women. Women with GDM who met the optimal GWGs had lower incidences of LGA and macrosomia compared to those who met the NAM targets, with no significant increase in the incidences of SGA, preterm birth, etc. CONCLUSIONS: The marked variation of GWG among hospitals in women with GDM indicates the need to develop optimal GWGs for them. The potential optimal GWGs for women with GDM might be lower than the NAM targets, likely benefiting the perinatal outcomes.

Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis.

Background: To estimate the progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Methods: Systematic review and meta-analysis were conducted by searching Medline, Embase, and Cochrane between January 1, 2010 and December 31, 2021 for observational studies investigating progression to T2DM after GDM. Inclusion criteria were IADPSG-diagnosed GDM, studies with both GDM and controls, postpartum follow-up duration at least one year. Data were pooled by random effects meta-analysis models. Heterogeneity was assessed by I2 statistic. The pooled relative risk for incidence of T2DM and pre-diabetes between GDM participants and controls were estimated. Reasons for heterogeneity among studies were investigated by prespecified subgroup and meta-regression analysis. Publication bias was assessed by the Begg's and Egger's tests. Results: This meta-analysis of six studies assessed a total of 61932 individuals (21978 women with GDM and 39954 controls). Women with IADPSG-diagnosed GDM were 6.43 times (RR=6.43, 95% CI:3.45-11.96) more likely to develop T2DM in the future compared with controls. For GDM women, the cumulative incidence of T2DM was 12.1% (95% CI: 6.9%-17.3%), while the pooled cumulative incidence of T2DM was estimated to be 8% (95% CI: 5-11%) in studies with 1 to 5 years of follow-up and increased to 19% (95% CI: 3-34%) for studies with more than 5 years of follow-up. Women with IADPSG-diagnosed GDM had 3.69 times (RR=3.69, 95% CI:2.70-5.06) higher risk of developing pre-diabetes (including impaired fasting glucose and/or impaired glucose tolerance) than controls. Meta-regression analysis showed that the study effect size was not significantly associated with study design, race, length of follow-up, and maternal age (P>0.05). Overall, the studies had a relatively low risk of bias. Conclusions: Women with IADPSG-diagnosed GDM have higher risk of developing T2DM and pre-diabetes. The risk of T2DM in GDM women are higher with longer follow-up duration. Our results highlight the importance of promoting postpartum screening and keeping health lifestyle as well as pharmacological interventions to delay/prevent the onset of T2DM/pre-diabetes in GDM women. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier (CRD42022314776).

Risk Factors for Macrosomia in Multipara: A Multi-Center Retrospective Study.

The increased incidence of macrosomia has caused an enormous burden after the transition from the almost 40-year one-child policy to the universal two-child policy in 2015 and further to the three-child policy in 2021 in China. However, studies on risk factors of macrosomia in multipara under the new fertility policy in China are limited. We aim to explore the incidence and risk factors for macrosomia in multipara to provide the scientific basis for preventing macrosomia in multipara. A multi-center retrospective study was conducted among 6200 women who had two consecutive deliveries in the same hospital and their second newborn was delivered from January to October 2018 at one of 18 hospitals in 12 provinces in China. Macrosomia was defined as birth weight ≥ 4000 g. Logistic regression models were performed to analyze risk factors for macrosomia in multipara. The incidence of macrosomia in multipara was 7.6% (470/6200) and the recurrence rate of macrosomia in multipara was 27.2% (121/445). After adjusting for potential confounders, a higher prepregnancy BMI, higher gestational weight gain, history of macrosomia, a longer gestation in the subsequent pregnancy were independent risk factors of macrosomia in multipara (p < 0.05). Healthcare education and preconception consultation should be conducted for multipara patients with a history of macrosomia to promote maintaining optimal prepregnancy BMI and avoid excessive gestational weight gain to prevent macrosomia.

Soil Microbes Drive the Flourishing Growth of Plants From Leucocalocybe mongolica Fairy Ring.

Fairy ring is a natural phenomenon in which fungal fruiting bodies occur as a ring on a spot. This ring is produced due to spore ejection by Basidiomycetous fungi and forms a lush growing plant belt. However, the drivers for such formations and the potential plant growth-promoting rhizobacteria in fairy ring soils remain unknown. Fairy rings formed by Leucocalocybe mongolica were selected in this study. Soil characteristics and microbial (bacteria and fungi) community structures between beneath and outside the fairy rings were compared through high-throughput sequencing. Beneficial bacterial resources were excavated using dependent culturable methods. Soil electrical conductivity and available potassium were higher in the soil beneath the ring than outside it. These parameters were positively correlated with the dominant microbial community, but microbial diversity was lower. In the soil beneath the fairy ring, Bacteroidetes and Basidiomycota were more abundant, whereas Verrucomicrobia was less prevalent. Bacillus pumilus (strain BG-5) was isolated from the soil beneath the ring. Strain BG-5 can solubilize phosphorus and produce indole-3-acetic acid, NH4 +, and siderophores. Furthermore, strain BG-5 enhanced salt tolerance and promoted the growth of Arabidopsis thaliana, wheat (Triticum aestivum), and cotton (Gossypium hirsutum) seedlings. This study indicated the presence of abundant beneficial microbes driving the flourishing growth of plants in the fairy ring soil and provided bio-resources for agricultural growth-promoting agents.

Gestational Diabetes Mellitus as an Effect Modifier of the Association of Gestational Weight Gain with Perinatal Outcomes: A Prospective Cohort Study in China.

The association of gestational weight gain (GWG) with perinatal outcomes seems to differ between women with and without gestational diabetes mellitus (GDM). Whether GDM is an effect-modifier of the association has not been verified. This study aimed to assess the modifying effect of GDM on the association of GWG with perinatal outcomes. Data on 12,128 pregnant women (3013 with GDM and 9115 without GDM) were extracted from a prospective, multicenter, cohort study in China. The associations of total and trimester-specific GWG rates (GWGR) with perinatal outcomes, including small size for gestational age, large size for gestational age (LGA), preterm birth, cesarean delivery, and gestational hypertension disorders, were assessed. The modifying effect of GDM on the association was assessed on both multiplicative and additive scales, as estimated by mixed-effects logistic regression. As a result, total GWGR was associated with all of the perinatal outcomes. GDM modified the association of total GWGR with LGA and cesarean delivery on both scales (all p < 0.05) but did not modify the association with other outcomes. The modifying effect was observed in the third trimester but not in the first or the second trimester. Therefore, maternal GWG is associated with perinatal outcomes, and GDM modifies the association with LGA and cesarean delivery in the third trimester.