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Abstract Background Accumulating evidence has highlighted that lncRNA ABHD11-AS1 plays an essential role in tumorigenesis and is expected to become a new predictive biomarker and ideal target for cancer therapy, whereas some of their findings are conflicting due to the relatively small sample size of individual studies. Thus, this meta-analysis aimed to quantitatively ascertain the association of ABHD11-AS1 with diverse human malignancies. Methods Eight databases were comprehensively screened for relevant articles on January 1, 2024. The significance of ABHD11-AS1 in malignancies was determined by odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were applied to verify the reliability and robustness of the pooled results. Simultaneously, the GEPIA2021 and UCSC Xena databases were applied to further strengthen the results. Results Fourteen clinical studies comprising eight kinds of malignancies and 1215 malignancy cases were enrolled into this meta-analysis. The pooled results showed that increased ABHD11-AS1 expression was remarkably associated with lymph node metastasis (OR = 2.73, 95%CI [1.97, 3.77], I2 = 0%, p

Background To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs).Methods Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results.Results There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p

Background: People with amnestic mild cognitive impairment (aMCI) carry a substantial risk of developing dementia compared to non-amnestic MCI (naMCI). Several previous studies proved the remarkable effectiveness of acupuncture for MCI, but they didn't distinguish between aMCI and naMCI. We conducted this meta-analysis to systematically assess the evidence of the efficacy of acupuncture in this unique population with aMCI. Methods: We comprehensively searched nine databases on January 09, 2024, to identify relevant articles estimating the effects of acupuncture for aMCI, and then assessed the risk of bias of the included trials utilizing the RoB 2.0 tool which included the domain of randomization process, deviation from intended interventions, missing outcome data, measurement of the outcome, selection of the reported outcome, and overall bias. The results of this meta-analysis were exhibited with forest plots. Sensitivity analyses were conducted to determine the robustness of the pooled results, and publication bias was estimated by Egger's and Begg's tests. Besides, we also performed subgroup analysis to determine whether there was a difference in therapeutic effects between four weeks and eight weeks of treatment duration. The certainty of the evidence was graded using GRADEpro GDT. Results: A total of 15 randomized controlled trials (RCTs) involving 908 people with aMCI were included in this study. According to the meta-analysis, acupuncture treatment provided a remarkable improvement in cognitive function as assessed by Mini-Mental State Examination (MD = 1.09, 95 %CI [0.86, 1.31], p

Abstract In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.

ObjectiveThe aim of this study was to evaluate the therapeutic implications of acupuncture on improving ovarian function in women diagnosed with premature ovarian insufficiency (POI) through the implementation of randomized clinical trials (RCTs).MethodsA comprehensive search of eight databases was conducted to identify RCTs up until 5 October 2023. The outcomes included the levels of sex hormones, antral follicle count (AFC), Kupperman score, and total effective rate. The risk of bias (RoB) tool was utilized to evaluate the quality of the included studies. In order to guarantee the robustness and reliability of the findings, subgroup and sensitivity analyses were performed to investigate potential sources of heterogeneity.ResultsA total of 13 RCTs comprising 775 patients were included in the study. Acupuncture demonstrated significant efficacy in reducing follicle-stimulating hormone (FSH) [SMD = 0.83, 95% CI (0.27, 1.39), I2 = 92%, p = 0.004], enhancing estradiol levels (E2) [SMD = 0.50, 95% CI (0.07, 0.93), p = 0.02, I2 = 87%], and increasing anti-Müllerian hormone (AMH) [SMD = 0.24, 95% CI (0.05, 0.44), p = 0.01, I2 = 8%], as well as improving the overall effective rate [RR = 1.22, 95% CI (1.10, 1.35), p < 0.01, I2 = 14%]. Subgroup analysis revealed that compared with non-acupuncture therapy, the acupuncture with Chinese herbal medicine (CHM) and hormone replacement therapy (HRT) group exhibited a substantial reduction in FSH levels [SMD = 1.02, 95% CI (0.52, 1.51), I2 = 60%, p < 0.01]. Furthermore, the acupuncture with CHM group also exhibited a substantial reduction [SMD = 4.59, 95% CI (1.53, 7.65), I2 = 98%, p < 0.01]. However, only the acupuncture with CHM and HRT group demonstrated a significant increase in E2 levels [SMD = 0.55, 95% CI (0.23, 0.87), I2 = 12%, p < 0.01].ConclusionAcupuncture has demonstrated superiority over non-acupuncture in diminishing serum FSH levels and increasing serum E2, AMH, and the overall efficacy rate in women diagnosed with POI. These research findings suggest the necessity for broader-scale research with meticulous designs to fully demonstrate the efficacy and safety of acupuncture in the treatment of women with POI.Systematic review registrationhttps://www.crd.york.ac.uk, identifier CRD42023467751.

ObjectiveTo evaluate the potential benefits of hyperbaric oxygen intervention on people with Alzheimer’s disease (AD) based on the existing randomized controlled trials (RCTs).MethodsA systematic search was conducted in nine databases until November 17, 2023, for RCTs assessing the effect of hyperbaric oxygen intervention for AD. The primary outcomes included Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog), activities of daily living (ADL), and adverse events. All results were shown in forest plots, and sensitivity analysis was adopted to further verify the robustness of the pooled results.ResultsA total of 11 RCTs recruiting 847 participants were included in this meta-analysis. Based on the pooled evidence, hyperbaric oxygen could remarkably ameliorate MMSE [MD = 3.08, 95%CI (2.56, 3.61), p

BackgroundMAF transcription factor G antisense RNA 1 (MAFG-AS1), a novel long non-coding RNA discovered recently, was proved to be useful in predicting malignancy prognosis. Nevertheless, its association with cancer prognosis has been inconsistent. Therefore, this meta-analysis aimed to explore the clinicopathological and prognostic significance of MAFG-AS1 in diverse carcinomas.MethodsStudies focused on MAFG-AS1 expression as a prognostic role in cancers were thoroughly searched in six electronic databases. The value of MAFG-AS1 in malignancies was assessed by hazard ratios (HRs) or odds ratios (ORs). Additionally, the GEPIA database was utilized to further strengthen our conclusion.ResultsA total of 15 studies involving 1187 cases and nine types of cancers were recruited into this meta-analysis. High MAFG-AS1 expression was significantly related to advanced tumor stage (OR = 0.52, 95%CI [0.39, 0.69], P < 0.00001), earlier lymph node metastasis (OR = 3.62, 95%CI [2.19, 5.99], P < 0.00001), worse tumor differentiation (OR = 0.64, 95%CI [0.43, 0.95], P = 0.03), and poor overall survival (HR = 1.94, 95%CI [1.72, 2.19], P < 0.00001). No significant heterogeneity and publication bias was detected across studies. Meanwhile, MAFG-AS1 was significantly elevated in ten kinds of cancers based on the validation of the GEPIA database.ConclusionThe results of this meta-analysis indicated that high MAFG-AS1 expression is dramatically correlated with unfavorable prognosis in cancers. MAFG-AS1 may be served as a promising biomarker for malignancies.

ObjectiveTo evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence.MethodsAccording to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials.ResultsAdd up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p

Abstract Background Non-suicidal self-injury (NSSI) and suicide attempts (SAs) by adolescent patients with depression have become serious public health problems. There is still insufficient research evidence on the effects of NSSI and SAs on neurocognitive functioning in adolescents. Cognitive function alterations may be associated with SAs and self-injury. NSSI and SAs have different influencing factors. Methods Participants were recruited from outpatient clinics and included 142 adolescent patients with depression (12–18 years old). This cohort included the SAs group (n = 52), NSSI group (n = 65), and depression without SAs/NSSI control group (n = 25). All participants underwent a clinical interview and neuropsychological assessment for group comparisons, and post-hoc tests were performed. Finally, partial correlation analysis was used to explore factors related to changes in cognitive function. Results The SAs group performed significantly worse than the control group in executive function and working memory. The depression score was directly proportional to the executive function of the SAs group, whereas cognitive functioning in the NSSI group was associated with borderline traits and rumination. Conclusions These findings suggest that impairment of executive function and working memory may be a common pattern in adolescent depressed patients with SAs. However, borderline traits and rumination may be indicative of NSSI but not SAs.

ObjectiveTo appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF).MethodsRelevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook.ResultsOf the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05).ConclusionFor infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future.Systematic review registrationhttps://www.crd.york.ac.uk PROSPERO (CRD42023421739)

Abstract Background Increasing evidence has demonstrated that high TTN‐AS1 expression is highly related to poor prognosis in diverse human cancers. However, the findings concerning the prognostic value of TTN‐AS1 were inconsistent, as these conclusions were usually drawn with relatively small sample sizes. Hence, this meta‐analysis proposes to investigate the prognostic significance of TTN‐AS1 in multiple malignancies systematically. Methods Web of Science, Springer, Embase, PubMed, Cochrane Library, and Scopus databases were comprehensively searched to retrieve studies related to the TTN‐AS1 expression with the prognosis of malignancies. The significance of the TTN‐AS1 in cancers was estimated by hazard ratios (HRs) or odds ratios (ORs). Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) analysis tool was used to strengthen our results further. Results Twenty studies involving 17 different cancers and 1330 patients were recruited into this meta‐analysis. The research revealed that high TTN‐AS1 expression was remarkably associated with unfavorable overall survival (OS) (HR = 2.07, 95%CI [1.78, 2.41], p

ObjectiveTo evaluate the clinical efficacy of acupuncture for the treatment of diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs).MethodsNine databases from their inception to December 6th, 2022, were comprehensively searched to retrieve RCTs related to the clinical efficacy of acupuncture for the treatment of DOR. The outcomes of interest were sex hormones level and antral follicle count (AFC). Risk of Bias (RoB) was adopted to assess the quality of the included trials.ResultsA total of 13 RCTs involving 787 patients were included in this meta-analysis. The review of available evidence revealed acupuncture produced a significant efficacy in decreasing follicle-stimulating hormone (FSH) levels (SMD = -1.07, 95%CI [-1.79, -0.36], p = 0.003), FSH/LH ratio (MD = -0.31, 95%CI [-0.54, -0.09], p = 0.006) and increasing anti-Müllerian hormone (AMH) levels (SMD = 0.25, 95%CI [-0.00, 0.49], p = 0.05), along with AFC (MD = 1.87, 95%CI [0.96, 2.79], p < 0.0001) compared to controls. Compared with electro-acupuncture treatment, manual acupuncture was superior in reducing FSH levels, FSH/LH ratio, and increasing AMH levels and AFC (p < 0.05). A notable association was also seen when acupuncture was combined with traditional Chinese medicine therapy for improving FSH levels, FSH/LH ratio, and AFC (p < 0.05). Besides, a high dose of acupuncture (≥10 acupoints) was more conducive to ameliorating FSH levels, FSH/LH ratio, and AFC (p < 0.05) than a low dose of acupuncture (

Background: With the increasing number of new cancer cases and mortality rates, cancer has become a serious global health problem, but there are no ideal cancer biomarkers for effective diagnosis. Currently, mounting evidence demonstrates that lncRNAs play a fundamental role in cancer progression. BBOX1 anti-sense RNA 1 (BBOX1-AS1) is a recently clarified lncRNA and has been identified as dysregulated in various carcinomas, and it contributes to poor survival in cancer patients.Methods: We thoroughly searched six databases for eligible articles published as of 27, April 2023. The association of BBOX1-AS1 expression levels with prognostic and clinicopathological parameters was assessed by odds ratios (OR) and hazard ratios with 95% CIs. Additionally, we further validated our results utilizing the GEPIA online database.Results: Eight studies comprising 602 patients were included in this analysis. High BBOX1-AS1 expression indicated poor overall survival (OS) (hazard ratios = 2.30, 95% Cl [1.99, 2.67], p < 0.00001) when compared with low BBOX1-AS1 expression. Furthermore, BBOX1-AS1 expression was positively correlated with lymph node metastasis (OR = 3.00, 95% CI [1.71–5.28], p = 0.0001) and advanced tumor stage (OR = 3.74, 95% CI [2.63–5.32], p < 0.00001) for cancer patients. Moreover, BBOX1-AS1 was remarkably upregulated in 12 malignancies, and the elevated BBOX1-AS1 expression predicted poorer OS and worse disease-free survival (DFS) confirmed through the GEPIA online gene analysis tool.Conclusion: The findings highlight that BBOX1-AS1 was significantly associated with detrimental overall survival, disease-free survival, lymph node metastasis and tumor stage; thus, it could act as a novel promising biomarker to predict the clinicopathological characteristics and prognosis for various cancers.

BackgroundTo determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment.MethodsNine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg’s and Egger’s tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively.ResultsA total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], p = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], p = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], p = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], p < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], p = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], p < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], p < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed.ConclusionsBased on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR.Systematic review registrationwww.crd.york.ac.uk, identifier CRD42023430202.

BackgroundRecent studies have highlighted mobile phone addiction (MPA) as a potential risk of suicidal ideation. However, the mechanisms underlying that association require attention.ObjectiveThis investigation aims to examine whether the relationship between MPA and suicidal ideation would be mediated by depression, and buffered by online social support (OSS) in university students.MethodsA convenient sample of 1,042 Chinese university students completed the measures of mobile phone addiction, depression, suicidal ideation, OSS in classroom settings. Moderated mediation analyses were performed to test the roles of depression and OSS in the association between MPA and suicidal ideation.ResultsMPA was positively associated with suicidal ideation through depression (indirect effect =. 23, 95% CI: 0.18, 0.28, p < 0.001); OSS moderated the association between depression and suicidal ideation (B = − 0.09, 95% CI: −0.13, −0.04, p

For the problem that it is difficult to separate the lubricating oil from the natural gas in the devices of offshore oil and gas platform, the performance measurement devices of gas-liquid coalescence filter elements were established in the laboratory and the offshore platform, and comparative tests were carried out for the filter elements from different manufacturers at home and abroad. The results indicate that the filtration performance of various filter elements is affected by the particle size distribution of droplets. Therefore, blocking effect of small droplet and prevention of secondary droplet release should be considered in the filter element design. In addition, the test results of the laboratory and the offshore platform are in good agreement, and under the high pressure conditions, more liquid can be captured by the domestic filter D, which could replace the in-service filter element to meet the requirements for lubrication oil separation and recovery.

Few studies have explored the trajectories of Chinese early adolescent depressive symptoms or comprehensively considered the factors of family and peers. The present study aimed to identify the trajectories of depressive symptoms in early adolescence using a school-based sample assessed in three waves. The study also examined whether family and peer factors were significant predictors. A total of 586 Chinese primary and middle school students participated in the survey. A growth mixture model was used to find the trajectories of depressive symptoms, and multinominal logistic regression was used to identify the predictors. Three trajectories were identified, including a stable-low class, an increasing class, and a high-decreasing class. Results indicated that gender, parental psychological aggression and neglect, parental psychological control, traditional bullying/cyberbullying victimization, and friendship quality were significant predictors. However, witnessing intimate partner violence, parental behavior control, and traditional bullying/cyberbullying perpetration could not significantly predict the trajectories. The findings of this study can provide an empirical basis for teachers and clinical interveners to determine different development trajectories of depressive symptoms and carry out prevention and intervention.

Background: Promoting cholesterol reverse transport (RCT) has been proven to be a promising hyperlipidemia therapy since it is more effective for the treatment of atherosclerosis (AS) caused by hyperlipidemia. Liver X receptor (LXR) agonists can accelerate RCT, but most of them trigger undesirable liver steatosis due to the activation of liver LXRα.Aim: We aim to figure out whether isochlorogenic acid C (ICAC) facilitates RCT without causing hepatic steatosis.Methods:In vitro study, we established foam macrophages and macrophages with loaded NBD-cholesterol models to investigate the competence of RCT promoting ICAC. RT-qPCR and Western blot were used to verify ICAC’s regulation of RCT and NF-κB inflammatory pathways. In this in vivo study, male 6-week-old C57BL/6 mice were fed a high-fat diet (HFD) to investigate ICAC’s anti-hyperlipidemic effect and its functions in regulating RCT. The anti-hyperlipidemic effect of ICAC was evaluated by blood and liver lipid levels, liver hematoxylin, oil red o staining, and liver coefficient. Finally, mRNA levels of genes involved in RCT and inflammation pathways in the liver and intestine were detected by RT-qPCR.Results: ICAC prevented macrophages from foaming by up-regulating the LXRα mediated RCT pathway and down-regulating expression of the cholesterol absorption genes LDLR and CD36, as well as suppressing iNOS, COX2, and IL-1β inflammatory factors. In HFD-fed mice, ICAC significantly lowered the lipid level both in the serum and the liver. Mechanistic studies showed that ICAC strengthened the RCT pathway in the liver and intestine but didn’t affect liver LXRα. Furthermore, ICAC impeded both adipogenesis and the inflammatory response in the liver.Conclusion: ICAC accelerated RCT without affecting liver LXRα, thus resulting in a lipid-lowering effect without increasing liver adipogenesis. Our results indicated that ICAC could be a new RCT promoter for hyperlipidemia treatment without causing liver steatosis.

Glucagon-like peptide-1 receptor (GLP-1R) plays an important role in glucose homeostasis and treatment of type 2 diabetes. Here authors report the peptide-free crystal structure of human GLP-1R in an inactive state which reveals a unique closed conformation of the extracellular domain.

Relaxin/insulin-like family peptide receptor 3 (RXFP3) belongs to class A G protein-coupled receptor family. RXFP3 and its endogenous ligand relaxin-3 are mainly expressed in the brain with important roles in the regulation of appetite, energy metabolism, endocrine homeostasis and emotional processing. It is therefore implicated as a potential target for treatment of various central nervous system diseases. Since selective agonists of RXFP3 are restricted to relaxin-3 and its analogs, we conducted a high-throughput screening campaign against 32,021 synthetic and natural product-derived compounds using a cyclic adenosine monophosphate (cAMP) measurement-based method. Only one compound, WNN0109-C011, was identified following primary screening, secondary screening and dose-response studies. Although displayed agonistic effect in cells overexpressing the human RXFP3, it also showed cross-reactivity with the human RXFP4. This hit compound may provide not only a chemical probe to investigate the function of RXFP3/4, but also a novel scaffold for the development of RXFP3/4 agonists.

Objective: The aim of this study was to evaluate the therapeutic implications of acupuncture on improving ovarian function in women diagnosed with premature ovarian insufficiency (POI) through the implementation of randomized clinical trials (RCTs). Methods: A comprehensive search of eight databases was conducted to identify RCTs up until 5 October 2023. The outcomes included the levels of sex hormones, antral follicle count (AFC), Kupperman score, and total effective rate. The risk of bias (RoB) tool was utilized to evaluate the quality of the included studies. In order to guarantee the robustness and reliability of the findings, subgroup and sensitivity analyses were performed to investigate potential sources of heterogeneity. Results: A total of 13 RCTs comprising 775 patients were included in the study. Acupuncture demonstrated significant efficacy in reducing follicle-stimulating hormone (FSH) [SMD = 0.83, 95% CI (0.27, 1.39), I2 = 92%, p = 0.004], enhancing estradiol levels (E2) [SMD = 0.50, 95% CI (0.07, 0.93), p = 0.02, I2 = 87%], and increasing anti-Müllerian hormone (AMH) [SMD = 0.24, 95% CI (0.05, 0.44), p = 0.01, I2 = 8%], as well as improving the overall effective rate [RR = 1.22, 95% CI (1.10, 1.35), p < 0.01, I2 = 14%]. Subgroup analysis revealed that compared with non-acupuncture therapy, the acupuncture with Chinese herbal medicine (CHM) and hormone replacement therapy (HRT) group exhibited a substantial reduction in FSH levels [SMD = 1.02, 95% CI (0.52, 1.51), I2 = 60%, p < 0.01]. Furthermore, the acupuncture with CHM group also exhibited a substantial reduction [SMD = 4.59, 95% CI (1.53, 7.65), I2 = 98%, p < 0.01]. However, only the acupuncture with CHM and HRT group demonstrated a significant increase in E2 levels [SMD = 0.55, 95% CI (0.23, 0.87), I2 = 12%, p < 0.01]. Conclusion: Acupuncture has demonstrated superiority over non-acupuncture in diminishing serum FSH levels and increasing serum E2, AMH, and the overall efficacy rate in women diagnosed with POI. These research findings suggest the necessity for broader-scale research with meticulous designs to fully demonstrate the efficacy and safety of acupuncture in the treatment of women with POI. [ABSTRACT FROM AUTHOR]

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic a-cell, thereby establishing a liver-a-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and a-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acidmetabolism. It was found that GcgrV369M+/+ mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of a-cell proliferation and hyperglucagonemia. [ABSTRACT FROM AUTHOR]

Glucagon is a peptide hormone secreted by islet a cells. It plays crucial roles in glucose homeostasis and metabolism by activating its cognate glucagon receptor (GCGR). A naturally occurring deleterious mutation V368M in the human GCGR leads to reduced ligand binding and down-regulation of glucagon signaling. To examine the association between this mutation and metabolic disorders, a knock-in mouse model bearing homozygous V369M substitution (equivalent to human V368M) in GCGR was made using CRISPRCas9 technology. These GcgrV369M+/+ mice displayed lower fasting blood glucose levels with improved glucose tolerance compared with wild-type controls. They also exhibited hyperglucagonemia, pancreas enlargement and a cell hyperplasia with a lean phenotype. Additionally, V369M mutation resulted in a reduction in adiposity with normal body weight and food intake. Our findings suggest a key role of V369M/V368M mutation in GCGR-mediated glucose homeostasis and pancreatic functions, thereby pointing to a possible interplay between GCGR defect and metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of indocyanine green(ICG) fluorescence imaging to indicate blood supply of sigmoid-rectal anastomosis in laparoscopic anterior resection of rectal cancer. Methods Here a retrospective cohort study including 175 consecutive patients with rectal cancer scheduled for laparoscopic surgery in Department of Gastrointestinal Surgery of Renji Hospital between January 2019 and December 2022 was analysed. These patients were classified into two groups, according to using ICG or not within surgery: the ICG group (n=65) and the control group (n=110). Operation situations and complications were compared between the two groups. Results The operation time of ICG group was longer than that of control group [(151.6±4.8) min vs (139.5±3.7) min, P=0.04], and the preventive ileostomy rate was lower than that of control group (12.3% vs 34.6%, P=0.01), while the other operation data (intraoperative blood loss, number of lymph node dissection), were similar between the two groups (P>0.05). The rate of anastomotic leakage in ICG group were lower than that in control group (4.6% vs 14.6%, P=0.04), and there was no significant differences in wound infection, urinary retention and intestinal obstruction between the two groups (P>0.05). Conclusions The ICG displays that the blood supply in laparoscopic anterior resection of rectal cancer can reduce the incidence of anastomotic leakage, which improves the surgical safety and the quality of postoperative life.

Purpose: To investigate the hypoglycemic and hepatoprotective effects of Angelica dahurica polysaccharide (ADP). Methods: The contents of neutral sugar, total glyoxylate and total protein, molecular mass and monosaccharide composition of ADP were determined by the phenol-sulfuric acid method, the sulfuric acid-carbazole method, the Coomassie brilliant blue method, high performance gel permeation chromatography (HPGPC) and high performance liquid chromatography (HPLC), respectively. Type 2 diabetes mellitus (T2DM) was induced in rats by high-fat and high-sucrose diet feeding combined with injection of streptozotocin (STZ). Five groups of rats were set up: blank control, model, low-dose ADP (200 mg/kg mb), high-dose ADP (400 mg/kg mb), and positive control (200 mg/kg mb metformin). The rats in the blank control and model groups were gavaged with distilled water. After four weeks of administration, body mass, fasting blood sugar (FBG), oral glucose tolerance test (OGTT), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR) and glycogen levels were measured, hematoxylin-eosin (HE) staining was used to observe hepatic histopathological changes, and commercial kits were used to determine lipid metabolism, oxidative stress and liver function indexes. Results: ADP had the following composition: (83.26 ± 0.67)% neutral sugar, (8.32 ± 1.25)% glyoxylate, and (0.64 ± 0.07)% protein, and its molecular mass was 10.28 × 103 Da. Monosaccharide composition analysis showed that ADP consisted of rhamnose, arabinose, galactose, glucose, mannose, glucuronide acid and galacturonic acid with a molar ratio of 0.09:0.45:0.43:1.00:0.05:0.53:0.08. ADP significantly increased body mass, blood glucose, FINS and glycogen levels of T2DM rats (P < 0.01), significantly decreased FBG and HOMA-IR (P < 0.01), improved liver histopathology, and significantly improved lipid metabolism, oxidative stress and liver function indexes (P < 0.01). Conclusion: ADP has hypoglycemic and hepatoprotective effects, probably through regulating abnormal lipid metabolism and oxidative stress.

Unimolecular dual agonists of the glucagon (GCG) receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) are a new class of drugs that are potentially superior to GLP-1R–specific agonists for the management of metabolic disease. The dual-agonist, peptide 15 (P15), is a glutamic acid 16 analog of GCG with GLP-1 peptide substitutions between amino acids 17 and 24 that has potency equivalent to those of the cognate peptide agonists at the GCGR and GLP-1R. Here, we have used cryo-EM to solve the structure of an active P15-GCGR-Gs complex and compared this structure to our recently published structure of the GCGR-Gs complex bound to GCG. This comparison revealed that P15 has a reduced interaction with the first extracellular loop (ECL1) and the top of transmembrane segment 1 (TM1) such that there is increased mobility of the GCGR extracellular domain and at the C terminus of the peptide compared with the GCG-bound receptor. We also observed a distinct conformation of ECL3 and could infer increased mobility of the far N-terminal His-1 residue in the P15-bound structure. These regions of conformational variance in the two peptide-bound GCGR structures were also regions that were distinct between GCGR structures and previously published peptide-bound structures of the GLP-1R, suggesting that greater conformational dynamics may contribute to the increased efficacy of P15 in activation of the GLP-1R compared with GCG. The variable domains in this receptor have previously been implicated in biased agonism at the GLP-1R and could result in altered signaling of P15 at the GCGR compared with GCG [ABSTRACT FROM AUTHOR]