Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Cardiotoxicity is a critical issue in drug development that poses serious health risks, including potentially fatal arrhythmias. The human ether-à-go-go related gene (hERG) potassium channel, as one of the primary targets of cardiotoxicity, has garnered widespread attention. Traditional cardiotoxicity testing methods are expensive and time-consuming, making computational virtual screening a suitable alternative. In this study, we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds, with the aim of improving prediction accuracy and efficiency. We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms, including Gaussian naive Bayes (NB), random forest (RF), support vector machine (SVM), K-nearest neighbors (KNN), eXtreme gradient boosting (XGBoost), and Transformer models, to build predictive models. Our models demonstrated advanced predictive performance. The best machine learning model, XGBoost Morgan, achieved an accuracy (ACC) value of 0.84, and the deep learning model, Transformer_Morgan, achieved the best ACC value of 0.85, showing a high ability to distinguish between toxic and non-toxic compounds. On an external independent validation set, it achieved the best area under the curve (AUC) value of 0.93, surpassing ADMETlab3.0, Cardpred, and CardioDPi. In addition, we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods, such as voting and stacking, provided slight improvements in model stability. Furthermore, the SHapley Additive exPlanations (SHAP) explanations revealed the relationship between benzene rings, fluorine-containing groups, NH groups, oxygen in ether groups, and cardiotoxicity, highlighting the importance of these features. This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment. Using computational methods, this study facilitates a more efficient drug development process, reduces costs, and improves the safety of new drug candidates, ultimately benefiting medical and public health.

The development of deep learning systems in artificial intelligence (AI) has enabled advances in endoscopy, and AI-aided colonoscopy has recently been ushered into clinical practice as a clinical decision-support tool. This has enabled real-time AI-aided detection of polyps with a higher sensitivity than the average endoscopist, and evidence to support its use has been promising thus far. This review article provides a summary of currently published data relating to AI-aided colonoscopy, discusses current clinical applications, and introduces ongoing research directions. We also explore endoscopists’ perceptions and attitudes toward the use of this technology, and discuss factors influencing its uptake in clinical practice.

Robotic gastrectomy (RG) has always been a hot topic in the field of minimally invasive surgery for gastric cancer. More and more studies have confirmed that short- and long-term outcomes of RG are similar to those of laparoscopic gastrectomy. Robotic surgical systems have more advantages in specific regional lymph node dissection. More delicate operation can reduce intraoperative blood loss and the incidence of postoperative complications. Robotic surgical systems are also more ergonomically designed. However, there are also some problems such as high surgical cost, lack of tactile feedback and prolonged total operation time. In the future, robotic surgical system may be further developed in the direction of miniaturization, intelligence and modularity. At the same time, the robotic surgical system deeply integrated with artificial intelligence technology may realize the automation of some operation steps to some extent.
Humans ; Robotic Surgical Procedures/adverse effects* ; Stomach Neoplasms/pathology* ; Artificial Intelligence ; Treatment Outcome ; Lymph Node Excision/adverse effects* ; Gastrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Postoperative Complications/etiology* ; Retrospective Studies

OBJECTIVES: To explore the association between assisted reproductive technology (ART) and birth weight discordance in twins (BWDT). METHODS: A retrospective analysis was conducted on twin infants born between January 2011 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University, with complete basic birth data. The impact of ART on the occurrence of BWDT was identified by the multivariate logistic regression analysis. RESULTS: A total of 3 974 pairs of twins were included, with 1 431 conceived naturally and 2 543 through ART. Neonates in the ART group had higher birth weights than those in the naturally conceived group (P<0.001). The incidence of BWDT was lower in the ART group compared to the naturally conceived group (16.17% vs 21.09%, P<0.001). The multivariate logistic regression analysis, adjusting for confounding factors such as maternal age, parity, pre-pregnancy body mass index, gestational diabetes, hypothyroidism, gestational age, and chorionic properties, showed no significant difference in the risk of BWDT between the ART and naturally conceived groups (P>0.05). CONCLUSIONS ART is not associated with the risk of BWDT.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Birth Weight ; Pregnancy Outcome ; Infant, Premature ; Infant, Low Birth Weight ; Pregnancy, Multiple ; Premature Birth/epidemiology* ; Retrospective Studies ; Population Surveillance ; Reproductive Techniques, Assisted/adverse effects* ; Pregnancy Complications

Objective: To obtain experience and generate suggestions for reducing average hospital stays, optimizing perioperative management of patients with gastric cancer and improving utilization of medical resources by analyzing the factors influencing super-long hospital stays in patients undergoing radical gastrectomy in the age of enhanced recovery after surgery (ERAS). Methods: This was a case-control study. Inclusion criteria: (1) pathologically diagnosed gastric adenocarcinoma; (2) radical surgery for gastric cancer; and (3) complete clinicopathologic data. Exclusion criteria: (1) history of upper abdominal surgery; (2) presence of distant metastasis of gastric cancer or other ongoing neoplastic diseases; (3) concurrent chemoradiotherapy; and (4) preoperative gastric cancer-related complications such as obstruction or perforation. The study cohort comprised 285 eligible patients with hospital stays of ≥30 days (super-long hospital stay group). Using propensity score matching in a 1:1 ratio, age, sex, medical insurance, pTNM stage, and extent of surgical resection as matching factors, 285 patients with hospital stays of < 30 days during the same period were selected as the control group (non-long hospital stay group). The primary endpoint was relationship between pre-, intra-, and post-operative characteristics and super-long hospital stays. Clavien-Dindo grade was used to classify complications. Results: Univariate analysis showed that number of comorbidities, number of preoperative consultations, preoperative consultation, inter-departmental transference, operation time, open surgery, blood loss, intensive care unit time, presence of surgical or non-surgical complications, Clavien-Dindo grade of postoperative complications, and reoperation were associated with super-long hospital stays (all P<0.05). Inter-departmental transference (OR=4.876, 95% CI: 1.500-16.731, P<0.001), preoperative consultation time ≥ 3 d (OR=1.758, 95%CI: 1.036-2.733, P=0.034), postoperative surgery-related complications (OR = 6.618, 95%CI: 2.141-20.459, P=0.01), and higher grade of complications (Clavien-Dindo Grade I: OR = 7.176, 95%CI: 1.785-28.884, P<0.001; Clavien-Dindo Grade II: OR = 18.984, 95%CI: 6.286-57.312, P<0.001; Clavien-Dindo Grade III-IV: OR=7.546, 95%CI:1.495-37.952, P=0.014) were independent risk factors for super-long hospital stays. Conclusion: Optimizing preoperative management, enhancing perioperative management, and surgical quality control can reduce the risk of prolonging average hospital stay.
Humans ; Case-Control Studies ; Retrospective Studies ; Length of Stay ; Stomach Neoplasms/pathology* ; Enhanced Recovery After Surgery ; Gastrectomy/adverse effects* ; Postoperative Complications/etiology*

Alanine Transaminase ; Animals ; Carbon Tetrachloride ; Gastrointestinal Microbiome ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Quinazolines

OBJECTIVE：To establish the f ingerprint of Qinlian runfei decoction，determine the contents of 11 components， and conduct cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）. METHODS ：HPLC method was used. The determination was performed on ZORBAX Eclipse Plus C 18 column with mobile phase consisted of acetonitrile- 0.05％ phosphoric acid solution （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 260 nm， and column temperature was 30 ℃. The sample size was 10 μL. Using wogonoside as reference，HPLC fingerprints of 10 batches of Qinlian runfei decoction were drawn and the similarity evaluation was conducted with Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition），the common peaks were also confirmed ；the contents of 11 components in Qinlian runfei decoction were determined by the same method. SPSS 21.0 software was used for clus ter analysis ，and SIMCA 14.0 software was used for OPLS-DA to screen marker components affecting quality. RESULTS ：There were 21 common peaks in 10 batches of Qinlian runfei decoction ，and the similarity with control fingerprint was greater than 0.98. A total of 11 common peaks were identified ， which were rutin ， forsythiaside A ， forsythiaside B ， iris， irigenin， baicalin， forsythiaside， wogonoside， baicalein， irisflorentin and wogonin. The line ar ranges of 11 components were 9.960 0-49.800 0，1.974 0-9.870 0，0.672 0-3.360 0，0.960 0-4.800 0，0.549 0- 2.745 0，5.040 0-25.200 0，1.374 0-6.870 0，0.615 0-3.075 0，0.759 9-3.795 0，0.162 0-0.810 0，0.042 0-0.210 0 μg（all r＞ 0.999）； RSDs of precision ， stability （48 h） and repeatability tests were less than 2％ ； the average recoveries were 95.81％-100.29％ with RSDs of 0.43％-1.73％（n＝6）；the contents were 8.924 4-12.820 8，0.352 2-0.868 7，0.435 6-0.711 2， 0.389 8-1.309 0，0.335 8-0.530 1，1.680 5-4.542 3，0.701 8-1.584 2，2.240 2-5.442 5，2.351 0-5.558 9，0.106 0-0.182 2，0.076 8- 0.128 9 mg/g，respectively. The results of cluster analysis showed that when class spacing was 10，it could be divided into two groups，S1-S3 and S 4-S10；when the class spacing was 5，the second class could be divided into two categories ，S6，S7，S9 were clustered into one category ，and S 4，S5，S8，S10 were clustered into one category. The results of OPLS-DA analysis showed that S6，S7 and S 9 were at the top of the figure ，S4，S5，S8 and S 10 were at the lower left side of the figure ，and S 1-S3 were at the lower right side of the figure ，which was consistent with the cluster analysis results ；VIP values of baicalin ，iris，forsythiaside A ， baicalein and wogonoside were all greater than 1. CONCLUSIONS ：Established fingerprint and content determination methods have high precision and good stability. Combined with multivariate statistical analysis ，it can be used for the quality control of Qinlian runfei decoction. Five components as baicalin are the marker components affecting the quality of Qinlian runfei decoction.

Goat Warble Fly Infestation (GWFI) is also known as subcutaneous myiasis caused by Przhevalskiana silenus (Diptera: Oestridae). It is widely distributed in tropical and sub-tropical areas of the world. In goats, WFI is usually detected through conventional procedure which underestimated the infestation. The current study was designed to determine the serodiagonsis of GWFI (through IDEXX Hypodermosis serum antibody test) and also aimed to investigate its seroepizootiological profile in Pothwar region, Pakistan from 2013-14. The results showed that average seropositivity (ELISA kit) of GWFI was 18.5% whereas, it was 11% by using conventional procedure (Palpation method) depicting a significant difference (p<0.05). Higher seropositivity (30.8%) was observed in Jhelum district as compared to e Attock district (6%). The L1 larvae were found in September, while nodules start appearing in October to December and last until the end of February. The month wise peaks of optical density (OD) was higher in December which gradually decrease along with the end of winter season. The prevalence of GWFI revealed no significant difference among three host breeds (Jattal, Beetal and Tedy). According to the results, high infestation rate (28%) was observed in young animals of age group < 1 year as compared to old animals (> 2 years). Topographically, hilly areas (33%) provide favourable climatic conditions for the propagating of larval stages. Sex difference showed no significant difference. The seroprevalence varied significantly with respect to age, month, districts and topographical location. The current study proved that serologic diagnosis (commercial ELISA kit) as more sensitive and accurate for timely diagnosis of GWFI than traditional method. The information on the epizootiology of P. silenus in goats of Pothwar region would help in devising effective control strategies.

OBJECTIVE：To compare the an ti-hepatocarcinoma effects of curcumin （CUR）and its derivative hydrazincurcumin （HZC），and to explore the mechanism. METHODS ：MTT assay was used to detect the effects of CUR or HZC （2.5，5，10，20， 40，80 μmol/L）on the proliferation of HepG 2 cells. Flow cytometry was used to detect the effects of CUR or HZC （10，20，40 μmol/L）on cell cycle distribution and apoptosis of HepG 2 cells. Western blotting assay was used to detect the effects of CUR or HZC（10，20，40 μmol/L）on the expression of apoptosis-related protein in HepG 2 cells. The male SD rats were randomly divided into normal control group （n＝10），CUR control group （n＝10），HZC control group （n＝10），model group （n＝30），CUR protection group （n＝30）and HZC protection group （n＝30）. CUR control group and HZC control group were given CUR 85917439。E-mail：zhaoji-an-88@163.com or HZC （80 mg/kg） intraperitoneally. Model group ，CUR protection group and HZC protection group were given diethylnitrosamine （50 mg/kg）intraperitoneally to establish hepatocarcinoma model ；at the same time ，2 protection groups were given CUR or HZC （80 mg/kg）intraperitoneally，twice a day，for consecutive 12 weeks. During medication ，the change of body weight and death of rats were recorded. Twenty four weeks later，liver index of rats was calculated and appearance was observed ；the number of cancer nodules was counted ；HE staining was used to observe the pathological changes of liver tissue and calculate the nuclear division index of hepatocarcinoma ；the proliferating cell nuclear antigen （PCNA）index was detected by immunohistochemistry. RESULTS ：CUR and HZC could increase the inhibitory rate of HepG 2 cells（P＜0.05），and increased the percentage at G 0/G1 phase and apoptotic rate of HepG 2 cells（P＜ 0.05）. CUR and HZC could significantly decrease the protein expression of p-JAK 2，p-STAT3，Bcl-2 and Bcl-xl ，while increased the protein expression of Bax ，Cyt-c，Caspase-9，Caspase-3 and PAPR （P＜0.05）. Above effects of HZC were significantly better than those of CUR （P＜0.05）. The results of animal experiment showed that there was no death ，no liver canceration and no pathological changes in liver appearance and tissue section of the three control groups ；there was no statistical significance in body weight and its increased weight ，liver index ，nuclear division index of carcinoma or PCNA index （P＞0.05）. Compared with model group， survival rate of rats were increased significantly in CUR protection group and HZC protection group ， while hepatocarcinoma incidence and the number of cancer nodules were decreased significantly （P＜0.05）；body weight and its increased weight were increased significantly ，while liver index ，nuclear division index of carcinoma and PCNA index were decreased significantly （P＜0.05）. There were some pathological changes in liver appearance and tissue section ；cancerous lesions with focal necrosis or cancerous lesions with patchy necrosis were observed. There was no statistical significance in the improvement of above indexes in 2 protection groups （P＞0.05）. CONCLUSIONS ：HZC could inhibit the proliferation and induce apoptosis of HepG 2 cells by inhibiting JAK 2/STAT3 signaling pathway and regulating the activation of mitochondrial endogenous pathway，which shows stronger anti-hepatocarcinoma effect in vitro than CUR. On the other hand ，there was no significant difference in the improvement of liver caner indexes in hepatic cancer model rats between HZC and CUR.