People's Liberation Army 411 Hospital

Oocyte maturation defects are one of the common clinical phenotypes contributing to recurrent IVF/ICSI failures and female infertility. We aimed to identify novel pathogenic variants responsible for oocyte maturation defects. Whole-exome sequencing and in silico analysis were used to identify variants in disease-causing genes in a cohort of 442 female infertility patients with oocyte maturation defects. In vitro functional studies were performed to validate the destructive effects and pathogenicity of the novel variants. We identified five novel PABPC1L variants (c.280C > A (p.Arg94Ser), c.283A > T (p.Lys95*), c.611A > G (p.Glu204Gly), c.583G > T (p.Val195Leu), and c.691C > T (p.Arg231Trp)) in two independent infertile families. These variants followed an autosomal recessive inheritance pattern. Western blotting analysis confirmed that all the novel variants led to the downregulation of PABPC1L protein expression in HEK293T cells. Immunofluorescence results showed that the nonsense variant c.283A > T (p.Lys95*) altered the cytoplasmic localization of PABPC1L in HeLa cells. In addition, three-dimensional molecular modeling and cycloheximide chase assay indicated that all four missense variants impair the stability of the PABPC1L protein. Our findings expand the mutational spectrum of the pathogenic gene PABPC1L, further highlight its essential function in female reproduction, and provide new support for the genetic diagnosis of female infertility.

Acteoside, a phenylethanol glycoside, possesses various pharmacological properties. The aim of this study was to investigate the mechanism of its anti-obesity effects on high-fat diet (HFD)-induced obese mice, as well as to evaluate the anti-obesity effects of its two active metabolites, caffeic acid and hydroxytyrosol. Mice were randomly divided into six groups in the first part experiment and five groups in the second part experiment as follows: control diet group; control diet + acteoside at 150mg/kg/day group; HFD group; HFD + orlistat at 20mg/kg/day group; HFD + caffeic acid at 45mg/kg/day group; HFD + hydroxytyrosol at 40mg/kg/day group; HFD + acteoside at 75mg/kg/day group; and HFD + acteoside at 150mg/kg/day group. The results showed that acteoside exhibited more pronounced anti-obesity effects compared with its two active metabolites. Acteoside supplementation reduced body weight and white adipose tissue (WAT) weight and improved glucose tolerance and insulin sensitivity in obese mice, as well as partially reverse hepatic damage and fat accumulation. In addition, acteoside induced the production of brown adipose tissue (BAT) when compared with caffeic acid and hydroxytyrosol, as well as promote a thermogenesis program in BAT and activate AMPK and HSL signaling in both WAT and BAT. Furthermore, high-dose acteoside supplementation altered the gut microbiota by increasing the abundance of Akkermansia muciniphila in obese mice. In summary, our results indicate that long-term acteoside supplementation may partially reverse obesity by stimulating adipose thermogenesis, modulating lipid metabolism, and altering the gut microbiota.

Abstract Background Interleukin-23 inhibition is effective in treating ulcerative colitis. Picankibart is a monoclonal antibody that selectively targets the IL-23p19 subunit and has a longer half-life than guselkumab. We aimed to evaluate the efficacy and safety of picankibart as induction and maintenance therapy in patients with ulcerative colitis. Methods This phase 2, randomised, double-blind, placebo-controlled trial enrolled patients (18-75 years) with moderately to severely active ulcerative colitis. In the induction period, patients were randomly assigned (1:1:1) to receive picankibart 200 mg, picankiabrt 600 mg or placebo, administrated intravenously, at weeks 0, 4, and 8. At week 12, patients with picankibart achieving clinical response entered the maintenance period and were randomly assigned in a 1:1 ratio to receive picankibart 200 mg every 4 weeks or every 8 weeks, administrated subcutaneously. Patients with clinical response receiving placebo in the induction period continued the administration of placebo (every 4 weeks, subcutaneously) during the maintenance period. The primary endpoint was clinical remission at week 12. Secondary efficacy endpoints included clinical response, symptomatic remission, endoscopic remission, histologic-endoscopic mucosal remission, inflammatory bowel disease questionnaire, and 36-item short form healthy survey at week 12 and 52. Results A total of 150 patients were enrolled in the induction period. At week 12, a significantly greater proportion of patients receiving picankibart 200 mg or 600 mg intravenously achieved a clinical remission than in the placebo group (200 mg vs placebo: 20% vs. 2%, p = 0.0044; 600 mg vs. placebo: 14% vs. 2%, p = 0.0283). For all secondary endpoints excluding histologic-endoscopic mucosal remission, patients with picancibart 200 mg or 600 mg intravenously had a significantly greater proportion than with placebo. During the maintenance period, at week 52, proportions of patients achieving clinical remission were 46.9% in patients with picankibart 200 mg every 4 weeks, 48.5% in patients with picankibart 200 mg every 8 weeks, and 18.2% in patients with placebo, respectively. Most common adverse event in both induction and maintenance period was upper respiratory tract infection, and its incidence was higher in patients receiving picankibart than receiving placebo. No new safety signals were observed. Conclusion Picankibart was effective and safe as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. These findings support advancing to phase 3 clinical trials in this patient population. Conflict of interest: Chen, Baili: I have received research funding from Takeda (China). Zhuang, Kun: No conflict of interest Gao, Xiang: No conflict of interest Huang, Caibin: No conflict of interest Zheng, Changqing: no conflict o Liu, Wenjia: No conflict of interest Jiang, Qi: I have received research funding from Takeda (China). Yuan, Haipeng: No conflict of interest Qu, Bo: No conflict of interest Liu, Bingrong: No conflict of interest Lv, Xiaoping: No conflict of interest An, Ping: No conflict of interest Zhong, Lan: No conflict of interest Zhang, Yingjian: No conflict of interest Gao, Chunxian: No conflict of interest Tuo, Biguang: No conflict of interest Wang, Junping: No conflict of interest Pei, Zejun: No conflict of interest Gong, Lei: No conflict of interest Chen, Yan: No conflict of interest Zhang, Hongjie: No conflict of interest Li, Yanqing: No conflict of interest Huo, Xiaohui: No conflict of interest Deng, Tianwei: No conflict of interest Zhu, Haichao: No conflict of interest Du, Yiqi: No conflict of interest Tang, Wen: No conflict of interest Zhang, Xiaomei: No conflict of interest Li, Fangfang: No conflict of interest Tang, Tongyu: No conflict of interest Han, Yu: No conflict of interest Wang, Bangmao: No conflict of interest Wang, Xiaozhong: No conflict of interest Han, Wei: No conflict of interest Liu, Yulan: No conflict of interest Cai, Chenghang: The employee of Innovent Biologics Ye, Rouxuan: The employee of Innovent Biologics Chen, Mingxia: The employee of Innovent Biologics Qian, Lei: The employee of Innovent Biologics Chen, Minhu: I have received speaker honoraria from Takeda China, Xian Janssen, and AbbVie China, as well as research funding from Takeda (China).

Remote sensing images usually reveal various objects with complex structures and different locations within vast ground area backgrounds. That leads to a major challenge for conventional generative models in handling remote sensing objects with correct shapes and clear textures. Integrating additional object-level controls can be a potential solution to improve generation quality, yet previous approaches inject the object-related conditions by specifying their locations, causing a limitation in object layout in generated results. To enable high object fidelity, high layout diversity and object customizable generation for remote sensing images, we propose a remote sensing image generation via object text decoupling, namely OTD-GAN. OTD-GAN takes advantage of the inherent text-to-image generation procedure and adaptively integrates the decoupled textual representations of visual objects into the global captions, thus achieving object-level controls without layout restrictions. Specifically, we design an object text decoupling module to predict a semantically consistent textual representation for each object. By decoupling the textual representation into a class invariant part and an object specific part, the converted representation is able to catch general semantic for similar objects as well as differentiated details for individual objects. After that, we use an object text semantic enhancement module to fuse the obtained object text representations with the global captions to enrich the object-related semantic within the textual modality. As a result, the generator will benefit from the object conditions and reinforce the generation quality while remaining flexibility to create diverse layouts. Extensive experiments on remote sensing image-caption datasets including NWPU-Captions and RSICD demonstrate that our method achieves leading performance compared to existing state-of-the-art approaches.

Ovarian stimulation (OS) is a critical component of assisted reproduction techniques (ART), in which gonadotropins are administered to induce follicular development and maturation to improve the chances of conception. It has been reported that ovarian response to OS can be affected by certain genetic factors. This study explores the relationship among SNVs of AMHR2 (c.-482A > G/rs2002555 and c.1749C > T/rs2071558), basal FSH and estradiol levels, gonadotropin dosage, and ovarian response to identify predictive indicators. Oocytes were retrieved from 684 infertile Chinese women treated with ART. All patients were divided into three groups: low (< 6 oocytes), normal (6-14 oocytes), high response (> 14 oocytes). Genotyping of c.-482A > G and c.1749C > T were detected on the Sequenom iPlexMassARRAY platform. Transcriptional function of c.-482A > G variant in AMHR2 promoter was validated by Luciferase Reporter Assay in 293T cells. Our results indicated that both c.-482A > G and c.1749C > T SNVs were associated with basal FSH levels (p = 0.047 and 0.023, respectively). Genotype and allele distribution frequencies of AMHR2 c.-482A > G were significantly different among the three ovarian response groups (p = 0.007 and 0.009, respectively). AMHR2 c.-482A > G was associated with the number of total oocytes retrieved (p = 0.011). FSH was associated with the ovarian response (p < 0.001). Validation by Luciferase Assay indicated AMHR2 c.-482A > G mutation in the promoter region affect the promoter activity. AMHR2 c.-482A > G SNVs may be involved in the mechanism of the ovarian response to OS. AMHR2 c.-482A > G SNVs can interact with basal FSH levels, and jointly serve as predictor of the ovarian response to OS.

To investigate the effects of paravertebral block (PVB) on postoperative pancreatic fistula (POPF) and major complications in adult pancreatic surgery. All data of patients who underwent pancreatic surgery at Changhai hospital between January 2017 and June 2021 were retrieved. According to whether they received PVB or not, the patients were divided into the PVB and non-PVB groups. POPF-related factors were balanced by covariate balancing propensity score (CBPS) based inverse probability weighting. After that, the POPF and postoperative major complications between the two groups were compared. Another propensity score matching, multivariate logistic regression and instrumental variable regression were employed for sensitivity analysis. Results of sensitivity analysis were expressed as relative risk (RR) or odd ratio (OR) and 95% confidence interval (CI). A total of 3360 patients were included in the study, with 374 patients in PVB group and 2986 patients in non-PVB group. After CBPS, there was no significant difference in incidence (5.7% VS 6.2%, P = 0.785) between the groups (PVB VS non-PVB). Postoperative nasogastric tube retention time (2d VS 3d, P < 0.001), and length of hospital stay (11d VS 12d, P = 0.031) were significantly reduced in the PVB group. delayed gastric emptying (DGE) (RR 0.476; 95% CI 0.262–0.863; P = 0.014) and postpancreatectomy hemorrhage (PPH) (RR 0.426; 95% CI 0.287–0.630; P < 0.001) were reduced more than 50% in PVB group. PVB did not increase the risk of POPF, but reduced DGE and PPH by more than 50%, and improved postoperative recovery after pancreatectomy.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-22372-w.