Genome-wide association and Mendelian randomisation analysis among 30,699 Chinese pregnant women identifies novel genetic and molecular risk factors for gestational diabetes and glycaemic traits.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is the most common disorder in pregnancy; however, its underlying causes remain obscure. This study aimed to investigate the genetic and molecular risk factors contributing to GDM and glycaemic traits. METHODS: We collected non-invasive prenatal test (NIPT) sequencing data along with four glycaemic and 55 biochemical measurements from 30,699 pregnant women during a 2 year period at Shenzhen Baoan Women's and Children's Hospital in China. Genome-wide association studies (GWAS) were conducted between genotypes derived from NIPTs and GDM diagnosis, baseline glycaemic levels and glycaemic levels after glucose challenges. In total, 3317 women were diagnosed with GDM, while 19,565 served as control participants. The results were replicated using two independent cohorts. Additionally, we performed one-sample Mendelian randomisation to explore potential causal associations between the 55 biochemical measurements and risk of GDM and glycaemic levels. RESULTS: We identified four genetic loci significantly associated with GDM susceptibility. Among these, MTNR1B exhibited the highest significance (rs10830963-G, OR [95% CI] 1.57 [1.45, 1.70], p=4.42×10-29), although its effect on type 2 diabetes was modest. Furthermore, we found 31 genetic loci, including 14 novel loci, that were significantly associated with the four glycaemic traits. The replication rates of these associations with GDM, fasting plasma glucose levels and 0 h, 1 h and 2 h OGTT glucose levels were 4 out of 4, 6 out of 9, 10 out of 11, 5 out of 7 and 4 out of 4, respectively. Mendelian randomisation analysis suggested that a genetically regulated higher lymphocytes percentage and lower white blood cell count, neutrophil percentage and absolute neutrophil count were associated with elevated glucose levels and an increased risk of GDM. CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic basis of GDM and glycaemic traits during pregnancy in an East Asian population and highlight the potential role of inflammatory pathways in the aetiology of GDM and variations in glycaemic levels. DATA AVAILABILITY: Summary statistics for GDM; fasting plasma glucose; 0 h, 1 h and 2h OGTT; and the 55 biomarkers are available in the GWAS Atlas (study accession no.: GVP000001, https://ngdc.cncb.ac.cn/gwas/browse/GVP000001) .

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Prevalence and risk factors for persistent symptoms after COVID-19: a systematic review and meta-analysis.

BACKGROUND: Long-term physical and mental persistent symptoms after COVID-19 represent a growing global public health concern. However, there remains a substantial knowledge gap regarding their prevalence and risk factors. OBJECTIVES: To estimate the prevalence and risk factors for persistent symptoms after COVID-19. METHODS OF DATA SYNTHESIS: We used a random-effects model to pool persistent symptom prevalence and risk ratios comparing COVID-19 patients with non-COVID-19 individuals. DATA SOURCES: Electronic databases were searched for studies published from December 2019 to January 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies that reported the prevalence and risk factors for persistent symptoms after COVID-19 were included. PARTICIPANTS: Patients who recovered from COVID-19. ASSESSMENT OF RISK OF BIAS: The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias in prevalence studies, whereas the risk of bias in cohort studies was evaluated with the Newcastle-Ottawa Scale. RESULTS: After screening 4359 studies, a total of 211 eligible studies were included, covering a population of 13 368 074 individuals. Fatigue, dyspnoea, post-traumatic stress disorder, anxiety, and depression were the most frequently reported persistent symptoms after COVID-19. Subgroup analyses revealed that individuals with more severe illness in the acute phase or from Europe exhibited a higher prevalence of certain symptoms, whereas children demonstrated a lower prevalence. Furthermore, COVID-19 patients had a significantly higher prevalence of most persistent symptoms compared with non-COVID-19 individuals. Factors frequently associated with a higher prevalence of persistent symptoms included female gender, advanced age, severe illness during the acute phase of COVID-19, multiple comorbidities, an extended duration of hospital stay, and a high body mass index. CONCLUSION: This meta-analysis provides a thorough review of the prevalence and risk factors for persistent symptoms following COVID-19. The findings underscore the importance of long-term monitoring and support for individuals recovering from COVID-19.

Motivating Inert Strontium Manganate with Iridium Dopants as Efficient Electrocatalysts for Oxygen Evolution in Acidic Electrolyte.

The search for high-performance and low-cost electrocatalysts in acid conditions still remains a challenging target. Herein, iridium (Ir) doped strontium manganate (named as Irx -SMO) is proposed as an efficient and durable low-iridium electrocatalyst for water oxidation in acidic media. The Ir0.1 -SMO with 75% less iridium in comparison to that of iridium dioxide (IrO2 ) exhibits excellent performance for oxygen evolution reaction (OER), which is even better than most of the iridium-based oxide electrocatalysts. The theoretical outcomes confirm the activation of the inert manganese sites in strontium manganate by the incorporation of iridium dopants. This work reveals the boosted effect of the iridium dopants on the OER activity of strontium manganate, providing a strategy to tune the activity of manganese-based perovskites in electrocatalysis.

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues.

OBJECTIVE: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. METHODS: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. RESULTS: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. CONCLUSION: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

Sorting Technology for Mesenchymal Stem Cells from a Single Tissue Source.

Mesenchymal stem cells (MSCs) are adult stem cells that can be obtained, enriched and proliferated in vitro. They owned enormous potential in fields like regenerative medicine, tissue engineering and immunomodulation. However, though isolated from the same origin, MSCs are still essentially heterogeneous cell populations with different phenotypes and functions. This heterogeneity of MSCs significantly affects their therapeutic efficacy and brings obstacles to scientific research. Thus, reliable sorting technology which can isolate or purify MSC subpopulations with various potential and differentiation pathways is urgently needed. This review summarized principles, application status and clinical implications for these sorting methods, aiming at improving the understanding of MSC heterogeneity as well as providing fresh perspectives for subsequent clinical applications.

An interval-valued carbon price forecasting method based on web search data and social media sentiment.

Accurate carbon price prediction is a crucial task for the carbon trading market. Previous studies have ignored the impact of online data and are limited to point predictions, which brings challenges to the accurate forecasting of carbon prices. To address those issues, this paper proposes an interval-valued carbon price forecasting method based on web search data and social media sentiment. First, we collect web search data and social media sentiment to improve prediction performance by synthesizing multiple types of data information. Second, we employ principal component analysis (PCA) to preprocess high-dimensional web search data, and utilize BosonNLP for quantifying social media information, thereby enhancing the predictability of the dataset. Subsequently, a variational mode decomposition (VMD) is applied to the carbon price and online data, followed by utilizing particle swarm optimization support vector regression (PSO-SVR) to predict each sub-modes and summing them up to obtain the ultimate forecasting outcome. Finally, using carbon prices in Guangdong and Hubei provinces as case studies, the experimental results demonstrate that web search data and social media sentiment significantly enhance the predictive accuracy of interval-valued carbon prices. Furthermore, the proposed VMD-PSO-SVR outperforms other comparative models in the accuracy and reliability of interval-valued forecasting.

Xanthogranulomatous inflammation involving the gallbladder, bile duct, and pancreas: a case report.

Xanthogranulomatous inflammation (XGI) is a rare, benign condition that can affect several organs, including the gallbladder, kidney, skin, gastrointestinal tract, lymph nodes, and soft tissues. It is often misdiagnosed as a malignancy. In this report, we present the case of a 79-year-old male who presented with persistent jaundice for 11 months. Computed tomography and magnetic resonance imaging revealed pancreatic head enlargement, gallbladder thickening, and common bile duct thickening, leading to a preoperative diagnosis of malignant neoplasm of the pancreatic head. During surgery, dense adhesions were found around the portal vein, suggestive of mass invasion. To relieve obstruction, choledochojejunostomy was performed. Postoperative pathological examination revealed xanthogranulomatous cholecystitis (XGCc), xanthogranulomatous cholangitis (XGCg), and xanthogranulomatous pancreatitis (XGP). XGI affecting the bile ducts and pancreas is extremely rare, and there are no reported cases of simultaneous involvement of the gallbladder, bile duct, and pancreas by XGI. This study provides valuable insight into the differential diagnosis of XGI by presenting the imaging features of XGI patients.

A two-stage interval-valued carbon price forecasting model based on bivariate empirical mode decomposition and error correction.

Economic development has brought about global greenhouse gas emissions and, thus, global climate change, a common challenge worldwide and urgently needs to be addressed. Accurate carbon price forecasting plays a pivotal role in providing a reasonable basis for carbon pricing and ensuring the healthy development of carbon markets. Therefore, this paper proposes a two-stage interval-valued carbon price combination forecasting model based on bivariate empirical mode decomposition (BEMD) and error correction. In Stage I, the raw carbon price and multiple influencing factors are decomposed into several interval sub-modes by BEMD. Then, we select artificial intelligence-based multiple neural network methods such as IMLP, LSTM, GRU, and CNN to conduct combination forecasting for interval sub-modes. In Stage II, the error generated in Stage I is calculated, and LSTM is used to predict the error; then, the error forecasting result is added to the first stage result to obtain the error-corrected forecasting result. Taking the carbon trading prices of Hubei, Guangdong, and the national carbon market, China, as the research object, the empirical analysis proves that the combination forecasting of interval sub-modes of Stage I outperforms the single forecasting method. In addition, the error correction technique in Stage II can further improve the forecasting accuracy and stability, which is an effective model for interval-valued carbon price forecasting. This study can help policymakers formulate regulatory policies to reduce carbon emissions and help investors avoid risks.

Detection of the communicating accessory bile duct in laparoscopic resection of residual gallbladder by the combination of the indocyanine green fluorescence cholangiography and the intraoperative cholangiography: A case report.

BACKGROUND: The partial cholecystectomy may be performed while in complicated laparoscopic cholecystectomy (LC). Biliary anomalies especially the accessory bile duct are established high risk of bile duct injury (BDI) in LC. Laparoscopic resection of residual gallbladder is a challenging procedure and extremely vulnerable to BDI. We report the execution of a laparoscopic resection of residual gallbladder with a communicating accessory bile duct using indocyanine green (ICG) fluorescence cholangiography and the intraoperative cholangiography (IOC). A case that has not been reported previously. PRESENTATION OF CASE: A 29-year-old female with history of laparoscopic partial cholecystectomy was admitted in our hospital. Magnetic resonance cholangiopancreatography (MRCP) revealed the residual gallbladder with an accessory bile duct. Considering the complexity of this patient, we performed a laparoscopic surgery using ICG fluorescence cholangiography. ICG was injected intravenously 1 h before the surgery, the residual gallbladder and the extrahepatic biliary structures including the accessory bile duct were imaged in green in fluorescence imaging that could be recognized clearly. IOC revealed that residual gallbladder communicated with intrahepatic bile duct through the accessory bile duct and drained into the common bile duct (CBD). The entire procedure was performed smoothly and successfully without bile duct injuries. DISCUSSION: Laparoscopic resection of residual gallbladder is a challenging procedure. Fluorescence cholangiography using ICG is regarded as a novel technique that could provide a real-time imaging intraoperative, which allowed to recognize and identify the residual gallbladder and the extrahepatic bile duct. IOC is also important in identifying a communicating accessory bile duct. Under the guidance of them, we completed this laparoscopic surgery. CONCLUSIONS: The combination of fluorescence cholangiography using ICG and IOC have profound significance in complicated LC.

Methodologies used in studies examining substance abuse, violence and HIV/AIDS (SAVA) constructs using a syndemic framework: a scoping review.

The syndemic theoretical framework has been used in health disparities research to explain several co-occurring epidemics, particularly in populations facing disparate health conditions. A prominent example of this is seen in Singer's Substance Abuse, Violence and HIV/AIDS (SAVA) syndemic theory. However, even though numerous studies support some of the theoretical underpinnings of the SAVA syndemic, the empirical applications of the theory remain methodologically underdeveloped. The current review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review (PRISMA-ScR), to present the state of the science of methodologies examining SAVA constructs using the syndemic framework. Seven bibliographic databases were searched with no language or date restrictions. Studies were synthesized by author, year of publication, study location, total sample size, study population, SAVA outcomes, analytic method of SAVA measurement, intervention type, level of influence, disease interaction and concentration, main findings of the study, and possible future areas of research. Our search yielded a total of 967 articles, and 123 were included in the review. Methodologic and statistical innovation is needed to elevate the impact of syndemic theory for elucidating the synergistic effects of determinants leading to health disparities.

Detection of the intraoperative bile leakage in laparoscopic cholecystectomy using indocyanine green fluorescence imaging: A case report.

Herein, we report two cases of successful application of indocyanine green (ICG) fluorescence imaging for detecting intraoperative bile leakage during laparoscopic cholecystectomy (LC). Bile leakage was detected rapidly and accurately using fluorescence guidance. Based on our findings, we recommend using ICG fluorescence imaging during LC because it is effective and feasible for detecting intraoperative bile leakage.

Molecular identification of a flavone synthase I/flavanone 3ß-hydroxylase bifunctional enzyme from fern species Psilotum nudum.

The enzyme flavone synthase Is (FNS Is) converts flavanones to flavones, whereas flavanone 3ß-hydroxylases (F3Hs) catalyze the formation of dihydroflavonols, a precursor of flavonols and anthocyanins. Canonical F3Hs have been characterized in seed plants, which are evolutionarily related to liverwort FNS Is. However, as important evolutionary lineages between liverworts and seed plants, ferns FNS Is and F3Hs have not been identified. In the present study, we characterized a bifunctional enzyme PnFNS I/F3H from the fern Psilotum nudum. We found that PnFNS I/F3H catalyzed the conversion of naringenin to apigenin and dihydrokaempferol. In addition, it catalyzed five different flavanones to generate the corresponding flavones. Site-directed mutagenesis results indicated that the P228-Y228 mutant protein displayed the FNS I/F2H activity (catalyzing naringenin to generate apigenin and 2-hydroxynaringenin), thus having similar functions as liverwort FNS I/F2H. Moreover, the overexpression of PnFNS I/F3H in Arabidopsis tt6 and dmr6 mutants increased the content of flavones and flavonols in plants, further indicating that PnFNS I/F3H showed FNS I and F3H activities in planta. This is the first study to characterize a bifunctional enzyme FNS I/F3H in ferns. The functional transition from FNS I/F3H to FNS I/F2H will be helpful in further elucidating the relationship between angiosperm F3Hs and liverwort FNS Is.

Monotropein Improves Dexamethasone-Induced Muscle Atrophy via the AKT/mTOR/FOXO3a Signaling Pathways.

The present study aimed to investigate the effects of monotropein (MON) on improving dexamethasone (DEX)-induced muscle atrophy in mice and C2C12 mouse skeletal muscle cells. The body weights, grip strengths, and muscle weights of mice were assessed. The histological change in the gastrocnemius tissues was also observed through H&E staining. The expression of myosin heavy chain (MyHC), muscle ring finger 1 (MuRF1), and muscle atrophy F-box (Atrogin1) and the phosphorylation of AKT, mTOR, and FOXO3a in the muscle tissues of mice and C2C12 myotubes were analyzed using Western blotting. MON improved muscle atrophy in mice and C2C12 myotubes by regulating catabolic states via the AKT/mTOR/FOXO3a signaling pathways, and enhanced muscle function by the increases of muscle mass and strength in mice. This suggests that MON could be used for the prevention and treatment of muscle atrophy in patients.

Partial hepatectomy vs. transcatheter arterial chemoembolization for multiple hepatocellular carcinomas of BCLC-B stage: A meta-analysis of high-quality studies.

BACKGROUND/AIM: The Barcelona Clinic Liver Cancer (BCLC) recommends that transcatheter arterial chemoembolization (TACE) are indicated in patients with multiple hepatocellular carcinomas (HCCs) of BCLC-B stage. However, partial hepatectomy (PH) has increasely performed in these patients. The purpose of this meta-analyses is to illustrate the comparative survival benefits of PH and TACE for patients with multiple HCCs of BCLC-B stage. METHOD: Electronic databases were systematically searched for eligible studies that compared PH and TACE performed in patients with multiple HCCs of BCLC-B stage. Studies that met the inclusion criteria were reviewed systematically. The reported data were aggregated statistically using the RevMan5.3 software. Primary endpoint was overall survival (OS), and secondary endpoint were the 1-, 3-, and 5-year survival rates, postoperative 30-day mortality and postoperative complications. RESULTS: A total of seven high-quality studies (one randomized controlled trial [RCT], six propensity-score matching (PSM) nonrandomized comparative trials [non-RCTs] that met the inclusion criteria, which comprised of 2487 patients (1245 PH and 1242 TACE) in the meta-analysis. When compared with the TACE group, the PH group had a significantly higher OS (HR, 1.65; 95% CI, 1.48-1.84; P = 0.26; I2 = 22%) and 1-, 3-, 5-year survival rates (OR, 1.96; 95% CI, 1.59-2.41; P = 0.0005; I2 = 75%; P < 0.00001; OR, 2.92; 95% CI, 1.94-4.42; P = 0.0001; I2 = 78%; P < 0.00001; OR, 2.60; 95% CI, 2.17-3.11; P = 0.13; I2 = 44%; P < 0.00001; respectively). Survival benefits persisted across sensitivity and subgroup analyses; High heterogeneity remained after sensitivity and subgroup analyses for 3-year survival rates. CONCLUSION: PH can provide more survival benefit for patients with multiple HCCs of BCLC-B stage compared with TACE.

A Modified Minimally Invasive Approach for the Treatment of Mandibular Condylar Fracture.

ABSTRACT: In this study, we introduced a small "V" shaped incision around the ear lobe modified from fact-lift approach to treat the mandibular condylar neck and subcondylar fractures to further minimize and hide the postsurgical scars. A total of 15 cases with mandibular condylar fractures from low levels of condylar neck to high levels of subcondylar region were treated by this approach. An incision was designed from the posterior rim of the tragus down to the anterior skin wrinkle to the ear lobe, surrounding it, continually up and backward for a little distance, forming a "V"-like shape. After cutting and elevation of the skin flap, the remaining steps were the same as those in trans-parotid mini-invasive approaches. The surgical scars introduced in this study were more hidden than those in other mini-invasive approaches and all patients were satisfied with their aesthetic appearances. We suggested that the modified "V" shaped mini-invasive approach has an advantage in achieving aesthetic results and could be an alternative incision in treating some types of mandibular condylar and subcondylar fractures.

Primary tuberculous granuloma in the falciform ligament of liver.

Isolated tuberculous granuloma in the falciform ligament of the liver has never been reported. Here, we report a case of tuberculous granuloma in the falciform ligament of the liver of a 45-year-old woman who complained only of persistent right upper abdominal pain. On abdominal contrast-enhanced CT and MRI, it is difficult to distinguish benign from malignant masses. Imaging on 18 F-FDG PET/CT showed high uptake of 18 F-FDG in the lesion, which was thus considered more likely to be malignant. However, postoperative pathological examination showed granulomatous inflammation with caseous necrosis, which was diagnosed as tuberculosis.

Detection of the common bile duct in difficult bile duct exploration using indocyanine green fluorescence imaging: A case report.

We describe two cases using indocyanine green (ICG) fluorescence imaging for visualization of the common bile duct (CBD) in patients with difficult Bile duct exploration (BDE) due to extensive dense adhesions around the hepatoduodenal ligament. The CBD was rapidly detected under fluorescence guidance without excessive dissection of extensive dense adhesions. It is illustrated that the use of ICG fluorescence imaging is effective and feasible for detecting the CBD and thus we highly recommend this method during difficult BDE.