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ObjectiveThe relationship between gut microbiome and trimethylamine oxide (TMAO) has not been fully elucidated. We aimed to assess the causal effects of different gut microbes on TMAO using Mendelian randomization (MR).MethodsGut microbiome and TMAO datasets were acquired from genome-wide association studies and screened for single nucleotide polymorphisms according to the basic assumptions of MR. Inverse variance weighted was used as the main method in MR analysis to assess the causal relationship between the gut microbiome and TMAO. Finally, the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis were used to assess the horizontal pleiotropy, heterogeneity, and robustness of the results, respectively.ResultsMR analysis revealed that the species Bacteroides finegoldii (odds ratio [OR] 1.064, 95% confidence interval [CI] 1.003 to 1.128, p = 0.039), family Sutterellaceae (OR 1.188, 95% CI 1.003 to 1.407, p = 0.047), and phylum Pseudomonadota (OR 1.205, 95% CI 1.036 to 1.401, p = 0.016), as well as the species Bacteroides uniformis (OR 1.263, 95% CI 1.039 to 1.535, p = 0.019), were positively associated with increased genetic susceptibility to TMAO. In contrast, the species Bacteroides thetaiotaomicron (OR 0.813, 95% CI 0.696 to 0.950, p = 0.009) and Bilophila wadsworthia (OR 0.828, 95% CI 0.690 to 0.995, p = 0.044) were associated with reduced genetic susceptibility to TMAO. Additionally, the MR-Egger intercept indicated no horizontal pleiotropy (p ≥ 0.05), and Cochran's Q test and sensitivity analysis demonstrated that the results were not heterogeneous (p ≥ 0.05) and were robust.ConclusionOur findings revealed the role of the phylum Pseudomonadota, family Sutterellaceae, species Bacteroides finegoldii, and Bacteroides uniformis in increasing TMAO, as well as the species Bacteroides thetaiotaomicron and Bilophila wadsworthia in decreasing TMAO. This study provides new insights into the relationship between the gut microbiome and TMAO levels.

ObjectiveThis study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively.ResultsForward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn’s disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran’s Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results.ConclusionThis MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT.

BackgroundLinarine is a natural chemical component widely found in Buddleja officinalis Maxim., Chrysanthemum indicum L., Mentha canadensis L., and other medicinal plants. Modern pharmacological studies have shown that linarine with good anti-inflammatory and antioxidant activities can inhibit the proliferation and induce apoptosis of many kinds of tumor cells. Moreover, linarine showed protective effect on the liver, kidneys, and other organs.MethodsInflammation model of human corneal epithelial cell (HCEC) was constructed using NaCl induction, and cytotoxicity was detected by the CCK8 assay. The levels of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were measured using Enzyme-linked immunoassay (ELISA). Chronic painful stimulation (tail clamping) in combination with Benzalkonium Chloride Solution drops in a desiccator established a mouse model of dry eye disease (DED). The following parameters were recorded: body mass, anal temperature, tear secretion, tear film rupture time, and corneal fluorescein staining. The levels of inflammatory factors mitogen activated protein kinase (MAPK), nuclear factor kappa-B (NF-kB), c-Jun N-terminal kinase (JNK), IL-1β, Interleukin 18(IL-18), A2A, A3, P2X4, P2X7, P2Y1 were measured by using immunofluorescence (IF) staining.ResultsLinarine can inhibit the secreation of TNF-α, and IL-1β in HCECs. Linarine prolonged tear film rupture time, promoted tear secretion, repaired corneal damage, and reduced the levels of inflammatory factors of MAPK, NF-kB, JNK, IL-1β, IL-18, and modulated the levels of the purinergic receptor.ConclusionsLinarine is effective in treating dry eye in mice by inhibiting purinergic receptors-mediated inflammatory response.

ObjectiveThe relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves’ disease (GD).MethodsDatasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran’s Q test, and robustness was assessed via leave-one-out sensitivity analysis.ResultsMR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust.ConclusionsEvidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders.

ObjectiveThis study aimed to explore the clinical efficacy and acupoint combinations of auricular pressure for treating type 2 diabetes.MethodsEight common databases were searched for publications related to auricular pressure in type 2 diabetes as of November 2023. A meta-analysis was performed to assess the efficacy and safety of auricular pressure therapy. Data mining was used to analyze the core acupoints for auricular pressure.ResultsMeta-analysis demonstrated that compared with the conventional treatment group, the combined auricular pressure and conventional treatment group had significantly reduced fasting blood glucose (mean difference [MD]: -0.93; 95% confidence interval [CI]: -1.17 to -0.68; p < 0.00001), 2-hour postprandial blood glucose (MD: -1.58; 95% CI: -2.04 to -1.12; p < 0.00001), glycated hemoglobin A1c (MD: -0.83; 95% CI: -1.19 to -0.48; p < 0.00001), total cholesterol (MD: -0.43; 95% CI: -0.72 to -0.14; p = 0.004), triglycerides (MD: -0.33; 95% CI: -0.64 to -0.03; p < 0.00001), systolic blood pressure (MD: -14.75; 95% CI: -24.46 to -5.05; p = 0.003), diastolic blood pressure (MD: -10.32; 95% CI: -20.14 to -0.50; p = 0.04), and body mass index (MD: -1.74; 95% CI: -2.61 to -0.87; p < 0.0001), while adverse events were comparable (RR: 0.84; 95% CI: 0.43 to 1.66; p = 0.61). Egger’s test revealed no publication bias (p = 0.715). Data mining identified AH6a, TF4, AT4, CO18, and CO10 as core acupoints for treating type 2 diabetes with auricular pressure.ConclusionAuricular pressure safely improves blood glucose and lipid levels, blood pressure, and body mass index in patients with type 2 diabetes. A regimen consisting of AH6a, TF4, AT4, CO18, and CO10 is expected to serve as a complementary treatment for type 2 diabetes.Systematic review registrationwww.crd.york.ac.uk/prospero/display_record.php?RecordID=524887, identifier CRD42024524887.

ObjectiveWhether the role of post-traumatic stress disorder (PTSD) on type 2 diabetes (T2D) is mediated by obesity or other mediating factors is controversial. This study was designed to assess the impact of PTSD on genetic susceptibility to T2D and mediating factors.MethodsThe datasets for PTSD, T2D, obesity, hypertension, hyperlipidemia, smoking status, and alcohol consumption were obtained from genome-wide association studies. Mendelian randomization (MR) was used to assess exposure-outcome causality, and inverse variance weighted was used as the primary tool for MR analysis. MR-Egger intercept, Cochran’s Q, and leave-one-out sensitivity analysis were employed to assess horizontal pleiotropy, heterogeneity, and robustness, respectively.ResultsThe MR analysis showed that PTSD was associated with increased genetic susceptibility to T2D (OR, 1.036; 95% CI, 1.008-1.064; p = 0.011), obesity (OR, 1.033; 95% CI, 1.016-1.050; p < 0.001), and hypertension (OR, 1.002; 95% CI, 1.000-1.003; p = 0.015), but not not with genetic susceptibility to hyperlipidemia, alcohol consumption, and smoking status (p ≥ 0.05). Mediated effect analysis showed that PTSD increased genetic susceptibility to T2D by increasing genetic susceptibility to obesity and hypertension, with obesity accounting for 9.51% and hypertension accounting for 2.09%. MR-Egger intercept showed no horizontal pleiotropy (p ≥ 0.05). Cochran’s Q showed no heterogeneity (p ≥ 0.05). Leave-one-out sensitivity analysis showed that the results were robust.ConclusionThis MR analysis suggests that PTSD increases the risk of T2D and that this effect is partially mediated by obesity and hypertension. Active prevention and treatment of PTSD can help reduce the risk of T2D.

ObjectiveThe relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) remains controversial. This study aimed to analyze the causal relationship between different types of DM and ASD by bidirectional Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and ASD were obtained from genome-wide association studies. Subsequently, inverse variance weighted, MR-Egger, and weighted median were used to test the exposure-outcome causality. Finally, MR-Egger’s intercept, Cochran’s Q, and leave-one-out method were used to assess horizontal pleiotropy, heterogeneity, and sensitivity of the results, respectively.ResultsThe positive analysis showed that T2DM was associated with an increased risk of ASD, whereas neither T1DM nor GDM was associated with the risk of ASD. The reverse analysis showed that ASD was associated with an increased risk of T2DM, while it was not associated with the risk of either T1DM or GDM. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05) for these results. Cochran’s Q showed no heterogeneity expect for the results of T1DM on the risk of ASD, and leave-one-out sensitivity analysis showed these results were robust.ConclusionThis MR analysis suggests that T2DM and ASD are reciprocal risk factors and that they may create an intergenerational risk cycling in female patients. Aggressive prevention and treatment of T2DM and ASD help to break the trap of this risk cycling. Additionally, this study does not support a causal relationship between T1DM and ASD, as well as GDM and ASD. And more studies are needed in the future to continue to explore the interactions and underlying mechanisms between different types of DM and ASD.

BackgroundThe benefits and risks of bifid triple viable preparations in patients with acute ischemic stroke (AIS) are still controversial. This study aimed to assess the efficacy and safety of bifid triple viable preparations in combination with enteral nutrition for the management of AIS.MethodsEight public databases including China National Knowledge Infrastructure, China Biology Medicine, VIP, WanFang, EBSCO, PubMed, Cochrane Library, and Web of Science were searched for relevant clinical literature, published through January 2024. These data were then used in the present meta-analysis.ResultsA total of 15 studies involving 1,544 patients were included in the meta-analysis. In terms of nutritional status, the results showed that compared with enteral nutrition alone, the bifid triple viable preparation combination group increased the levels of total protein (mean difference [MD], 5.53; 95%confidence interval [CI], 1.94–9.12; p = 0.003), albumin (MD, 4.01; 95%CI, 2.96–5.06; p

The molecular mechanisms driving the onset and metastasis of prostate cancer remain poorly understood. Actin, under the control of actin-binding proteins (ABPs), plays a crucial role in shaping the cellular cytoskeleton, which in turn supports the morphological alterations in normal cells, as well as the invasive spread of tumor cells. Previous research indicates that ABPs of various types serve distinct functions, and any disruptions in their activities could predispose individuals to prostate cancer. These ABPs are intricately implicated in the initiation and advancement of prostate cancer through a complex array of intracellular processes, such as severing, linking, nucleating, inducing branching, assembling, facilitating actin filament elongation, terminating elongation, and promoting actin molecule aggregation. As such, this review synthesizes existing literature on several ABPs linked to prostate cancer, including cofilin, filamin A, and fascin, with the aim of shedding light on the molecular mechanisms through which ABPs influence prostate cancer development and identifying potential therapeutic targets. Ultimately, this comprehensive examination seeks to contribute to the understanding and management of prostate diseases.

Cable-hole transmission is widely applied in cable-driven mechanisms to reduce the mechanical size. However, the driving tension is attenuated with the cable threading through the hole caused by uncertain factors such as local deformation, friction, and other effects, and errors in cable-hole transmission occur. To improve the transmission accuracy of cable-driven mechanisms, a tension distribution model considering the cable lateral extrusion is established. Then, an analytical tension ratio of the cable-hole transmission is derived based on the perturbation method and tension distribution model. Parameters of the tension ratio are identified using a particle swarm optimization algorithm. An adaptive tension control method considering the cable lateral extrusion is designed and compared with the method excluding the cable lateral extrusion in the cable-hole transmission. Finally, a cable-hole transmission experimental device was constructed to verify the tension ratio, parameter identification, and servo control method of the cable-hole transmission. The results show the motion control accuracy of the cable-driven mechanism can be significantly improved with the tension ratio considering the cable lateral extrusion. Compared to the case excluding the cable lateral extrusion, the errors in cable-hole transmission considering the lateral extrusion are reduced by an order of magnitude, and the tension vibration is significantly weakened.

The predominant characteristic of autoimmune gastritis (AIG) is corpus-dominant advanced atrophy, which is mostly observed in the middle to late stages. More reports are needed on the endoscopic features of the early stage. In this report, we present two cases of early-stage AIG in which endoscopic examinations showed no atrophy of the gastric mucosa but displayed a transition of collecting venules from a regular to an irregular arrangement. In addition, yellowish-white cobblestone-like elevations were observed in the fundic gland region. Histologically, the observed manifestations included pseudohypertrophy and protrusion of parietal cells into the lumen, possibly along with hyperplasia of G cells, lymphocytic infiltration and potentially pseudopyloric gland metaplasia. Serologically, the anti-parietal cell antibody returned positive results, whereas the anti-intrinsic factor antibody yielded negative results. In this study, we summarized some endoscopic features of two patients, aiming to provide clues for endoscopists to detect early-stage AIG.

ObjectiveThe effect of mental disorders (MD) on cardiovascular disease (CVD) remains controversial, and this study aims to analyze the causal relationship between eight MD and CVD by Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms of attention-deficit/hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), depression, obsessive-compulsive disorder (OCD), schizophrenia (SCZ), and CVD were obtained from UK Biobank and FinnGen. Exposure-outcome causality was tested using inverse variance weighted (IVW), MR-Egger, and weighted median. Horizontal pleiotropy and heterogeneity were assessed by MR-Egger intercept and Cochran's Q, respectively, while stability of results was assessed by leave-one-out sensitivity analysis.ResultsMR analysis showed that ANX (IVW [odds ratio (OR) 1.11, 95% confidence intervals (CI) 1.07–1.15, p 0.05). Intercept analysis showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity except for BD (p = 0.035). Sensitivity analysis suggested that these results were robust.ConclusionsANX, ASD, and depression are associated with an increased risk of CVD, whereas AN, ADHD, BD, OCD, and SCZ are not causally associated with CVD. Active prevention and treatment of ANX, ASD, and depression may help reduce the risk of CVD.

ObjectiveThe role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR).MethodsDatasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran’s Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively.ResultsMR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031–1.254; p = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067–1.223; p < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032–1.210; p = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004–1.104; p = 0.035), CD28− CD8dim %T cell (OR, 1.097; 95% CI, 1.038–1.158; p < 0.001), CD127− CD8br AC (OR, 1.086; 95% CI, 1.006–1.171; p = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021–1.099; p = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041–1.158; p < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001–1.096; p = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012–1.131; p = 0.018), IgD+ CD38− %lymphocyte (OR, 1.103; 95% CI, 1.023–1.190; p = 0.011), CD62L− plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001–1.093; p = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003–1.153; p = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy (p ≥ 0.05). Cochran’s Q revealed no heterogeneity of results (p ≥ 0.05). Sensitivity analysis indicated that the results were robust.ConclusionThis MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD.

Objective:The role of esketamine in pediatric gastrointestinal endoscopy is still unclear. This study aims to evaluate the efficacy and safety of esketamine for pediatric gastrointestinal endoscopy.Methods:Clinical trials of esketamine for pediatric gastrointestinal endoscopy were searched in eight common databases, up to October 2023. These clinical trials were included in the meta-analysis and trial sequential analysis (TSA). The risk ratio (RR) and weighted mean difference (WMD) were used as the effect sizes for dichotomous variables and continuity variables, respectively. When the heterogeneity test showed I2 < 50%, the fixed effects model was used for the meta-analysis and TSA; Otherwise, the random effects model was used for them.Results:In terms of efficacy endpoints, the meta-analysis showed that compared with placebo or blank, esketamine significantly decreased recovery time by 2.34 min (WMD −2.34; 95% Confidence interval [CI] −3.65, −1.02; p = 0.0005) and propofol consumption by 0.70 mg/kg (WMD −0.70; 95% CI −0.98, −0.43; p < 0.00001), and increased mean heart rate by 4.77 beats/min (WMD 4.77; 95% CI 2.67, 6.87; p < 0.00001) and mean arterial pressure by 3.10 mmHg (WMD 3.10; 95% CI 1.52, 4.67; p = 0.0001), while induction time and mean blood oxygen remained comparable. TSA indicated conclusive evidence for these benefits. In terms of safety endpoints, the meta-analysis revealed that esketamine significantly reduced involuntary movements by 59% (RR 0.41; 95% CI 0.22, 0.76; p = 0.005) and choking by 51% (RR 0.49; 95% CI 0.26, 0.92; p = 0.03), while significantly increasing dizziness by 98% (RR 1.98; 95% CI 1.11, 3.56; p = 0.02) and there were no significant differences in total adverse events, respiratory depression, and vomiting. TSA demonstrated conclusive evidence for involuntary movements and dizziness. Low-dose analysis showed that esketamine at ≤0.3 mg/kg significantly reduced recovery time, propofol consumption and involuntary movements, and significantly increasing mean heart rate, with no increase in dizziness. The Begg’s test (p = 0.327) and the Egger’s test (p = 0.413) indicated no significant publication bias, yet the funnel plot suggested potential publication bias.Conclusion:Esketamine is an effective adjuvant anesthesia for children undergoing gastrointestinal endoscopy. However, the general dose of esketamine may increase the risk of dizziness, which can be avoided by administering a low dose (≤0.3 mg/kg).

ObjectiveThe impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran’s Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis.ResultsMR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962–0.989; p 0.05). Cochran’s Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust.ConclusionCHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.

ObjectiveThe specific benefit and selection of acupoints in acupuncture for diabetic kidney disease (DKD) remains controversial. This study aims to explore the specific benefits and acupoints selection of acupuncture for DKD through meta-analysis and data mining.MethodsClinical trials of acupuncture for DKD were searched in eight common databases. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore its acupoints selection.ResultsMeta-analysis displayed that compared with the conventional drug group, the combined acupuncture group significantly increased the clinical effective rate (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.20 to 1.51, P < 0.00001) and high-density lipoprotein cholesterol (mean difference [MD] 0.36, 95% CI 0.27 to 0.46, P < 0.00001), significantly reduced the urinary albumin (MD –0.39, 95% CI –0.42 to –0.36, P < 0.00001), urinary microalbumin (MD –32.63, 95% CI –42.47 to –22.79, P < 0.00001), urine β2-microglobulin (MD –0.45, 95% CI –0.66 to –0.24, P < 0.0001), serum creatinine (MD –15.36, 95% CI –21.69 to –9.03, P < 0.00001), glycated hemoglobin A1c (MD –0.69, 95% CI –1.18 to –0.19, P = 0.006), fasting blood glucose (MD –0.86, 95% CI –0.90 to –0.82, P < 0.00001), 2h postprandial plasma glucose (MD –0.87, 95% CI –0.92 to –0.82, P < 0.00001), total cholesterol (MD –1.23, 95% CI –2.05 to –0.40, P = 0.003), triglyceride (MD –0.69, 95% CI –1.23 to –0.15, P = 0.01), while adverse events were comparable. Data mining revealed that CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 were the core acupoints for DKD treated by acupuncture.ConclusionAcupuncture improved clinical symptoms, renal function indices such as uALB, umALB, uβ2-MG, and SCR, as well as blood glucose and blood lipid in patients with DKD, and has a favorable safety profile. CV12, SP8, SP10, ST36, SP6, BL20, BL23, and SP9 are the core acupoints for acupuncture in DKD, and this program is expected to become a supplementary treatment for DKD.

ObjectiveThe effect of tea on gout and uric acid is still controversial. This study aims to analyze the effect of tea intake on genetic predisposition to gout, idiopathic gout, gout due to impairment of renal function as well as uric acid by Mendelian randomization (MR).MethodsForty independent single nucleotide polymorphisms (SNPs) associated with tea intake were selected from UK Biobank. SNPs for uric acid were obtained from BioBank Japan, SNPs for gout were obtained from UK Biobank, and SNPs for gout due to impairment of renal function and idiopathic gout were derived from FinnGen. The causal relationship of exposure-outcome was tested using inverse variance weighted, MR-Egger and weighted median. MR-Egger intercept was employed to assess horizontal pleiotropy, Cochran’s Q test was used to assess heterogeneity, and leave-one-out sensitivity analysis was utilized to analyze the stability of the results.ResultsThe results of MR analysis showed that tea intake was negatively associated with gout due to impairment of renal function (OR 0.997, 95% CI 0.994 to 0.999, P = 0.017), whereas there was no causal association with gout, idiopathic gout, and uric acid (P > 0.05), for which sensitivity analysis suggested that these results were robust.ConclusionsThere was a genetic predisposition effect of increased tea intake on the reduced risk of gout due to impairment of renal function, whereas there was no such effect on gout, idiopathic gout, and uric acid. Tea intake may become an important option in the dietary treatment of gout due to impairment of renal function.

ObjectiveThe influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD).MethodsData on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran’s Q test, and leave-one-out sensitivity analysis, respectively.ResultsThe results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q test showed no heterogeneity (p > 0.05). Sensitivity analysis suggested that these results were robust.ConclusionAn increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT.

ObjectiveThe efficacy of acupoint catgut embedding (ACE) for the treatment of pre-diabetes remains controversial. Therefore, this study investigated the clinical efficacy and acupoint selection in ACE for the treatment of pre-diabetes.MethodsEight common databases were searched for relevant literature on ACE for pre-diabetes. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore the protocol for acupoint selection.ResultsThe meta-analysis revealed that compared with conventional treatment alone, conventional treatment combined with ACE reduced the levels of glycated hemoglobin A1c [mean difference (MD) −0.45, 95% confidence interval (CI) −0.67 to −0.24%, p

ObjectiveMecobalamin is a commonly used drug in the treatment of diabetic peripheral neuropathy (DPN). This study aimed to systematically evaluate the efficacy and safety of acupoint injection of mecobalamin for DPN.MethodsRelevant clinical trials on acupoint injection of mecobalamin for DPN published before 31 January 2023 were searched in eight commonly used databases. After screening and confirming the included studies, meta-analysis and trial sequential analysis were performed.ResultsA total of 10 relevant studies were confirmed, and the total sample size was 927 cases. On the efficacy endpoints, meta-analysis showed that compared with other administration methods, acupoint injection of mecobalamin significantly increased the clinical effective rate by 27% [RR = 1.27, 95% CI = (1.19, 1.36), P < 0.00001], motor nerve conduction velocity (median nerve) by 5.93 m/s [MD = 5.93, 95% CI = (4.79, 7.07), P < 0.00001], motor nerve conduction velocity (common peroneal nerve) by 5.66 m/s [MD = 5.66, 95% CI = (2.89, 8.43), P < 0.0001], sensory nerve conduction velocity (median nerve) by 4.83 m/s [MD = 4.83, 95% CI = (3.75, 5.90), P < 0.00001], and sensory nerve conduction velocity (common peroneal nerve) by 3.60 m/s [MD = 3.60, 95% CI = (2.49, 4.71), P < 0.00001], and trial sequential analysis showed these benefits were conclusive. In terms of safety endpoints, meta-analysis indicated that the total adverse events for acupoint injection were comparable to other methods of administration, and trial sequential analysis suggested that the results needed to be validated by more studies. Subgroup analysis demonstrated that the benefits of acupoint injections of mecobalamin were not limited by the dose, duration of treatment, or number of acupoints reported in the included studies. Harbord's test showed no significant publication bias (P = 0.106).ConclusionThe efficacy of acupoint injection of mecobalamin for DPN was significantly better than other administrations, and its safety was comparable to other administrations. Therefore, acupoint injection may be the optimal method of mecobalamin for DPN.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=454120, identifier: CRD42023454120.

Objective: This is the first study to explore the mechanism of colchicine in treating coronary artery disease using network pharmacology and molecular docking technology, aiming to predict the key targets and main approaches of colchicine in treating coronary artery disease. It is expected to provide new ideas for research on disease mechanism and drug development.Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Swiss Target Prediction and PharmMapper databases were used to obtain drug targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DrugBank and DisGeNET databases were utilized to gain disease targets. The intersection of the two was taken to access the intersection targets of colchicine for the treatment of coronary artery disease. The Sting database was employed to analyze the protein-protein interaction network. Gene Ontology (GO) functional enrichment analysis was performed using Webgestalt database. Reactom database was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was simulated using AutoDock 4.2.6 and PyMOL2.4 software.Results: A total of 70 intersecting targets of colchicine for the treatment of coronary artery disease were obtained, and there were interactions among 50 targets. GO functional enrichment analysis yielded 13 biological processes, 18 cellular components and 16 molecular functions. 549 signaling pathways were obtained by KEGG enrichment analysis. The molecular docking results of key targets were generally good.Conclusion: Colchicine may treat coronary artery disease through targets such as Cytochrome c (CYCS), Myeloperoxidase (MPO) and Histone deacetylase 1 (HDAC1). The mechanism of action may be related to the cellular response to chemical stimulus and p75NTR-mediated negative regulation of cell cycle by SC1, which is valuable for further research exploration. However, this research still needs to be verified by experiments. Future research will explore new drugs for treating coronary artery disease from these targets.

Atherosclerosis (AS) is the major form of cardiovascular disease and the leading cause of morbidity and mortality in countries around the world. Atherosclerosis combines the interactions of systemic risk factors, haemodynamic factors, and biological factors, in which biomechanical and biochemical cues strongly regulate the process of atherosclerosis. The development of atherosclerosis is directly related to hemodynamic disorders and is the most important parameter in the biomechanics of atherosclerosis. The complex blood flow in arteries forms rich WSS vectorial features, including the newly proposed WSS topological skeleton to identify and classify the WSS fixed points and manifolds in complex vascular geometries. The onset of plaque usually occurs in the low WSS area, and the plaque development alters the local WSS topography. low WSS promotes atherosclerosis, while high WSS prevents atherosclerosis. Upon further progression of plaques, high WSS is associated with the formation of vulnerable plaque phenotype. Different types of shear stress can lead to focal differences in plaque composition and to spatial variations in the susceptibility to plaque rupture, atherosclerosis progression and thrombus formation. WSS can potentially gain insight into the initial lesions of AS and the vulnerable phenotype that gradually develops over time. The characteristics of WSS are studied through computational fluid dynamics (CFD) modeling. With the continuous improvement of computer performance-cost ratio, WSS as one of the effective parameters for early diagnosis of atherosclerosis has become a reality and will be worth actively promoting in clinical practice. The research on the pathogenesis of atherosclerosis based on WSS is gradually an academic consensus. This article will comprehensively review the systemic risk factors, hemodynamics and biological factors involved in the formation of atherosclerosis, and combine the application of CFD in hemodynamics, focusing on the mechanism of WSS and the complex interactions between WSS and plaque biological factors. It is expected to lay a foundation for revealing the pathophysiological mechanisms related to abnormal WSS in the progression and transformation of human atherosclerotic plaques.

This paper reports a method for calculating the electromagnetic force acting on an aluminum honeycomb sandwich panel moving in a magnetic field. This research is motivated by the non-contact electromagnetic detumbling technology for space non-cooperative targets. Past modeling of the electromagnetic forces and torques generally assumes that the target is homogeneous. However, aluminum honeycomb sandwich panels are extensively used in spacecraft structures to reduce weight without sacrificing structural strength and stiffness, which are so inhomogeneous and complicated that it is difficult to obtain the induced electromagnetic force even by numerical methods. An equivalent conductivity tensor of an aluminum honeycomb sandwich panel is proposed, which allows the aluminum honeycomb sandwich panel to be treated as a homogeneous structure when calculating the induced electromagnetic forces. The advantage of the equivalent conductivity tensor in the calculation of induced electromagnetic forces is verified by finite element simulations. The proposed method makes it possible to evaluate the electromagnetic force of a large aluminum honeycomb sandwich structure moving in a magnetic field.

ObjectiveTo evaluate the efficacy and safety of dorzagliatin in the treatment of type 2 diabetes mellitus (T2DM) by using meta-analysis and trial sequential analysis (TSA).MethodSearch for clinical trials of dorzagliatin for T2DM in eight databases, with a time limit of build to July 2022. The included studies that met the requirements were carried out for meta-analysis and TSA.ResultsIn terms of efficacy endpoints, meta-analysis showed that dorzagliatin decreased glycated hemoglobin A1c(HbA1c) [mean difference (MD) −0.65%, 95% confidence interval (CI) −0.76 ~ −0.54, P < 0.00001], fasting plasma glucose (FPG) (MD −9.22 mg/dL, 95% CI −9.99 ~ −8.44, P < 0.00001), 2 h postprandial glucose (2h-PPG) (MD −48.70 mg/dL, 95% CI −55.45 ~ −41.96, P < 0.00001), homeostasis model assessment 2 of insulin resistance (HOMA2-IR) (MD −0.07, 95% CI −0.14 ~ −0.01, P = 0.03) and increased homeostasis model assessment 2 of ß-cells function (HOMA2-β) (MD 2.69, 95% CI 1.06 ~ 4.31, P = 0.001) compared with placebo. And TSA revealed that the benefits observed for the current information set were conclusive, except for HOMA2-IR. In comparison with placebo, dorzagliatin increased triglyceride(TG) (MD 0.43 mmol/L, 95% CI 0.30 ~ 0.56, P < 0.00001), total cholesterol (TC) (MD 0.13 mmol/L, 95% CI 0.05 ~ 0.21, P = 0.001), body weight (MD 0.38 kg, 95% CI 0.12–0.63, P = 0.004) and body mass index (BMI) (MD 0.14 kg/m2, 95% CI 0.05–0.24, P = 0.003), while low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were comparable. And TSA demonstrated that TG, TC, body weight, and BMI were conclusive. In terms of safety endpoints, dorzagliatin increased total adverse events (AEs) [risk ratio (RR) 1.56, 95% CI 1.06 ~ 2.30, P = 0.03], while serious AEs, hyperlipidemia, and hypoglycaemia were all comparable. And TSA indicated that the results need to be confirmed by additional studies. Harbord regression showed no publication bias.ConclusionDorzagliatin was effective in lowering glycemia, reducing insulin resistance and improving islet ß-cells function without affecting blood pressure, LDL-C, and HDL-C. Although dorzagliatin caused a mild increase in TG and TC, it did not increase the incidence of hyperlipidemia, and the small increases in body weight and BMI were not clinically significant enough. In terms of safety, the total AEs caused by dorzagliatin may be a cumulative effect of single AEs, with no drug-related adverse event being reported at a higher incidence than placebo alone. Dorzagliatin's serious AEs, hyperlipidemia, and hypoglycemia are comparable to that of placebo, and dorzagliatin has a good safety profile.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371802 identifier: CRD42022371802.

ObjectiveThe purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA).MethodsClinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables.ResultsCompared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD −0.24, 95%CI −0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD −5.82, 95%CI −8.35~-3.28, P < 0.00001) and weight (MD −2.47, 95%CI −2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD −0.37, 95%CI −0.44~-0.29, P < 0.00001), FSG (MD −8.52, 95%CI −11.07~-5.98, P < 0.00001) and weight (MD −4.63, 95%CI −5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD −0.12, 95%CI −0.19~-0.05, P = 0.001), FSG (MD −2.73, 95%CI −5.29~-0.17, P = 0.04) and weight (MD −2.18, 95%CI −2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of “TZP 15 mg vs. TZP 10 mg”. In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of “TZP 15 mg vs. TZP 5 mg” were conclusive.ConclusionsTZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested.Systematic review registrationUnique Identifier: CRD42022341966.

Complex space missions require more space robotic extravehicular operations required to crawl on spacecraft surfaces with discontinuous features at the graspable point, greatly increasing the difficulty of space robot motion manipulation. Therefore, this paper proposes an autonomous planning method for space dobby robots based on dynamic potential fields. This method can realize the autonomous crawling of space dobby robots in discontinuous environments while considering the task objectives and the self-collision problem of robotic arms when crawling. In this method, a hybrid event–time trigger with event triggering as the main trigger is proposed by combining the working characteristics of space dobby robots and improving the gait timing trigger; the dynamic potential field function is designed to adjust the space robot robotic arm grasping point adaptively according to the space robot state. Simulation results verify the effectiveness of the proposed autonomous planning method.

With the development of nuclear industry, spent nuclear fuel (SNF) generated from nuclear power plants arouses people’s attention as a result of its high radioactivity, and how to guarantee the reliable operation of nuclear facilities and the staff’s safety occupies a crucial position. To avoid the lethal irradiation, a lot of functional neutron shielding composites have been developed to transform fast neutrons into thermal neutrons which can be absorbed with high macroscopic cross-sectional elements. Irradiation characteristics of nuclear industry have promoted the advancement of neutron shielding materials. Here, we review the latest neutron shielding materials for the storage of spent nuclear fuel containing additives such as boron carbide (B4C), boron nitride (BN), boric acid (H3BO3), and colemanite. Different types of neutron shielding materials, including metal matrix alloys, polymer composites, high density concrete, heavy metals, paraffin, and other neutron shielding composites with high macroscopic cross-sectional elements, arediscussed. The elemental composition, density, and thermal and mechanical properties of neutron shielding materials are also summarized and compared.

The glutenites in the Permian Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin possess great potential for oil and gas exploration. However, uncertainties in the reservoir characteristics and formation mechanisms of these glutenites seriously restrict their effective exploration. The study provides a compre- hensive analysis on the characteristics, main controlling factors, and development models of glutenite reservoirs of the Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin using microscopic thin sections, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results show that: (1) Two types of interstitial materials are observed in the glutenites of the Upper Wuerhe Formation, where the spaces between gravels are primarily interstitially filled with coarser sandy components, and the cementation mainly occurs between these sandy components. (2) The glutenites generally exhibit low porosity, with minimal pore development within gravels, while the pores in sandy interstitial materials are more developed. The reservoir space is mainly composed of intercrystalline and secondary dissolution pores. (3) Diagenetic processes related to reservoir formation mainly occur within the coarse sandy interstitial materials between gravels, mainly involving aluminosilicate dissolution, which results in abundant dissolution pores. (4) In high-energy sedimentary microfacies, such as estuary bars and underwater distributary channels, reservoirs are more favorably developed, where the reservoir space is mainly associated with feldspar dissolution. Fractures and unconformities are the main channels for acidic fluid migration. (5) During the eodiagenesis, acidic fluids, mainly atmospheric water, infiltrated along unconformities, with more significant dissolution near the Beisantai arch. During the middle diagenetic period, dissolution was mainly attributed to organic acid. (6) Three types of reservoirs are developed in the glutenites: atmospheric acid dissolution reservoirs, organic acid dissolution reservoirs, and dual-source acid superimposed dissolution reservoirs. The distribution of these reservoir types determines the exploration strategies for oil and gas reservoirs of glutenites of the Upper Wuerhe Formation in the Fukang Sag of the Junggar Basin. Glutenites in the slope and sag areas and zones of superimposed fault development are the key objectives for oil and gas exploration of glutenite reservoirs of the Upper Wuerhe Formation in Fukang Sag.

As an important research topic in recent years, semantic segmentation has been widely applied to image understanding problems in various fields. With the successful application of deep learning methods in machine vision, the superior performance has been transferred to agricultural image processing by combining them with traditional methods. Semantic segmentation methods have revolutionized the development of agricultural automation and are commonly used for crop cover and type analysis, pest and disease identification, etc. We first give a review of the recent advances in traditional and deep learning methods for semantic segmentation of agricultural images according to different segmentation principles. Then we introduce the traditional methods that can effectively utilize the original image information and the powerful performance of deep learning-based methods. Finally, we outline their applications in agricultural image segmentation. In our literature, we identify the challenges in agricultural image segmentation and summarize the innovative developments that address these challenges. The robustness of the existing segmentation methods for processing complex images still needs to be improved urgently, and their generalization abilities are also insufficient. In particular, the limited number of labeled samples is a roadblock to new developed deep learning methods for their training and evaluation. To this, segmentation methods that augment the dataset or incorporate multimodal information enable deep learning methods to further improve the segmentation capabilities. This review provides a reference for the application of image semantic segmentation in the field of agricultural informatization.

[Introduction] Under the backdrop of "carbon peak and neutrality", coastal provinces and cities in China are gradually developing clean energy towards the ocean. The development of offshore wind farm has begun to take shape and achieved equal price of connection to power grid, and pilot projects for offshore floating photovoltaic (FPV) systems are emerging. The comprehensive development of a variety of marine resources, the intensive use of sea resources in the energy sector, and the creation of an integrated marine energy system are of great significance for coastal provinces to achieve high-quality carbon neutrality. [Method] The article summarized the current development and pilot projects of offshore FPV technology both inside and outside of China, analyzed the advantages and challenges of various offshore FPV technologies, predicted the future market size of offshore FPV in China, explored the integration development mode of offshore FPV and other offshore infrastructure, and provided the integration scenarios and economic analysis based on case studies. [Result] The offshore FPV technology is currently at the pilot stage with broad market in the future. The main technical challenge is the viability of floating structure under harsh marine environmental conditions, and the unit cost of the existing pilot projects is relatively high, however, it has enormous potential of combination with other marine facilities. [Conclusion] The integration of offshore FPV and other offshore facilities such as offshore wind power can effectively improve the utilization efficiency of energy facilities and reduce the cost of construction and operation. The complementary use of marine scenery also effectively solves the stability and security problems of a single energy supply.