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.

Perioperative bleeding is closely related to the prognosis of patients, and massive blood loss can lead to serious adverse events. Tranexamic acid, a lysine derivative, exerts anti-fibrinolytic effects by competitively blocking lysine binding sites on plasminogen to achieve hemostasis. Perioperative use of tranexamic acid can effectively reduce the risk of bleeding and the need for blood transfusion, and reduce the risk of bleeding related complications and death. At present, the use of tranexamic acid for perioperative hemostasis is increasingly widespread, and it is gradually entering the consensus and guidelines in more surgical fields. In this paper, the mechanism of action, perioperative application and adverse reactions of tranexamic acid were reviewed, and the effectiveness and safety of tranexamic acid in different surgical types were discussed, so as to provide reference for the application and research of tranexamic acid in China.

Objective To explore the safety and mid-term efficacy of autologous hamstring tendon implantation in the treatment of severe anterior vaginal wall prolapse.Methods We performed a prospective single arm clinical study.From May 2021,pelvic organ prolapse(POP)patients with severe anterior vaginal wall prolapse as the main cause who had symptoms and required surgical treatment were included.The patient was fully informed and voluntarily selected autologous hamstring tendon implantation and high sacral ligament suspension.Postoperative follow-ups were carried out on the Pelvic Organ Prolapse Quantification(POP-Q),Pelvic Floor Distress Inventory-Short Form 20(PFDI-20),postoperative satisfaction score,and Patient Global Impression of Improvement(PGI-I).Function of the lower limb on the tendon removal side,as well as postoperative complications and re-operations were recorded.Results The operation time of tendon removal was(19.7±8.3)min,the operation time of pelvic floor was(122.1±37.8)min,the median intraoperative bleeding volume was 70 ml(range,50-400 ml),and there was no intraoperative co-morbidity or postoperative fever.A total of 12 cases were followed up for(26.4±2.5)months.The measured values of Aa,Ba,and C were 3(-1-3),5(2-10),and 4(-1-10)before operation and-3(-3-3),-3(-3-3),and-6(-6-3)at 24 months after operation,respectively,with significant difference(P＜0.05).The PFDI-20 scores of the 12 patients before surgery and at 24 months after surgery were 88.0 points(range,16.7-204.2 points)and 8.3 points(range,0-32.3 points),respectively,with significant difference(Z=-2.803,P=0.005).The PGI-I questionnaire showed 11 patients with significant improvement in postoperative symptoms and 1 patient with improvement.The satisfaction scores at 6 and 24 months after surgery were(4.8±0.4)points and(4.6±0.7)points,respectively.One patient experienced vaginal prolapse at 12 months after surgery,with a Ⅲ degree prolapse of the anterior wall and vaginal vault,the recurrence rate being 8.3％(1/12).Two patients had pulmonary embolism at 9 d and 2 weeks after surgery,with Clavien-Dindo Ⅱ and Ⅲ grades,and recovered after outpatient and hospitalization treatment.One patient was found fascia exposure at the vagina,and had improvement with medication treatment.All the patients had good wound healing at the tendon removal site,with normal muscle strength and lower limb activity.No re-operation was required due to recurrence or complications of tendon surgery.Conclusions Autologous hamstring tendon implantation is safe in the treatment of severe anterior vaginal wall prolapse with satisfactory mid-term efficacy.Before surgery,it is necessary to educate patients on lower limb exercise to prevent complications of venous thrombosis.

Abstract OBJECTIVE To analyze the characteristics of drug poisoning in children, and to explore the diverse pharmaceutical services that pharmacists can provide in the process of prevention and treatment. METHODS The 47 children diagnosed as drug poisoning in Ningbo Women and Children's Hospital from January 1, 2020 to June 30, 2023 were retrospectively enrolled. Combined with the actual situation of Ningbo Women and Children's Hospital, pharmaceutical services were discussed. RESULTS The majority of children with drug poisoning were adolescent girls. The main cause of poisoning was intentional drug ingestion for suicide, accounting for 33 cases(70.21%). Additionally, 12 cases(25.53%) were accidental ingestion by children and 2 cases(4.26%) of drug overdose were caused by parents misreading the dosage of drugs. The clinical symptoms included drowsiness and/or lethargy(28 cases), dizziness(16 cases), nausea and/or vomiting(14 cases), and abdominal pain(11 cases). The majority of toxic substances were psychiatric drugs, accounting for 39 cases(82.98%). After hospitalization, 40 patients(85.11%) were treated with gastric lavage, and 11 patients(23.40%) were treated with blood purification. Diuresis and catharsis were also applied to remove poison. In addition, specific drug antidotes were selected according to the type of poisons. Meanwhile, symptomatic and supportive therapies were used. Finally, all 47 patients improved or cured after hospitalization. CONCLUSION Based on the characteristics of drug poisoning in children, pharmacists can actively participate in prevention and treatment, in order to reduce the occurrence of drug poisoning and improve the prognosis of poisoned children. In terms of prevention, pharmacists should provide medication instructions and education when dispensing drugs, especially for psychotropic drugs and drugs with easily confused dosage. In the treatment, clinical pharmacists can provide comprehensive pharmaceutical care for poisoned children from various aspects such as drug detection and analysis, removal of toxics, selection of specific antidotes, and inquiry of drug dosage for children.

Objective:To analyze the detection rate of hyperuricemia (HUA) and the distribution of serum uric acid (SUA) levels by multiple correlation analysis in middle-aged and elderly population receiving health examination.Methods:In this cross-sectional study, the study object were 25 587 middle-aged and elderly people who receiving health examination in Nanfang Hospital from January to December in 2014. According to the latest diagnostic criteria, the population was divided into HUA and non-HUA groups. Furthermore, the subjects were divided into 4 groups with the level of SUA (Q 1: SUA<313 μmol/L, Q 2:313 μmol/L≤SUA<375 μmol/L, Q 3:375 μmol/L≤SUA<440 μmol/L, Q 4: SUA≥440 μmol/L). According to the data types, two independent sample t test, Mann-Whitney U test, Chi-square test and multiple correspondence analysis were used for statistical analysis. Results:The mean age of the study subjects was (54.78±8.80) years with 16 570 males (64.8%) and 9 017 females (35.2%). The overall detection rate of HUA was 31.5%, and it was higher in men (43.1%) than in women (10.1%). The body mass index(BMI), systolic blood pressure, diastolic blood pressure, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and fasting blood glucose (FBG) in the HUA group were all higher than those in the non-HUA group (all P<0.001); and high-density lipoprotein cholesterol (HDL-C) was lower than that in the non-HUA group( P<0.001). In multiple correspondence analysis, Cronbach′s α coefficients of the first dimension and the second dimension was 0.608 and 0.237, respectively. Further analysis was performed stratified by gender, it indicated that 45-<55 years old male and overweight were closely associated with the Q 3 group, fatty liver and hyperlipidemia were closely associated with Q 4 group; the 55-<65 years old female, hyperlipidemia, fatty liver and obesity were closely associated with the Q 3 group, while hyperglycemia and hypertension were closely associated with the Q 4 group. Conclusion:The detection rate of HUA in middle-aged and elderly population receiving health examination was high, and the detection rate of HUA in male was higher than that in female. SUA levels are higher in middle-aged and elderly men who have fatty liver and hyperlipidemia. While SUA levels are higher in middle-aged and elderly women who have hyperglycemia and hypertension.

Anesthesia is indispensable for surgere, but a growing number of studies have confirmed its togic effects on the developing nervous sestem, and has attract increasing attentions from the scientific communite. In this review, we briefle introduce the preclinical and clinical studies on the neurotogic effects of anesthetic drugs on the developing brain, and summare the mechanisms from the aspects of molecular mechanisms (Ca

Objective: To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery. Methods: Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers. Results: (1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers. Conclusions SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Objective: To evaluate treatment experience for mesh infection after inguinal hernia repair. Methods: 392 cases underwent surgery for mesh infection after inguinal hernia repair in Beijing Chaoyang Hospital from Jan 2007 to Jun 2018. For mesh infection after open inguinal hernia repair, infected mesh and tissue were removed by open operation, while laparoscopic operation was adopted for mesh infection after laparoscopic inguinal hernia repair. Time of infection, type of bacteria, and hernia recurrence were evaluated. Results: 369 cases suffered mesh infection after open inguinal hernia repair and 23 cases were after laparoscopic inguinal hernia repair. 61 cases suffered mesh infection within 3 months, 258 cases were from 3 months to 1 year and 73 cases were after one year. During follow up of 6 to 36 months after operation, 29 cases suffered hernia recurrence in 24 to 34 months after removal of mesh. Bacterial culture were positive in 193 cases, including 126 cases of staphylococcus aureus, 18 cases of escherichia coli and 15 cases of pseudomonas aeruginosa. Conclusion Individualized treatment policy based on original mesh placement is safe and effective for mesh infection after inguinal hemiorrhaphy.

Objective To explore the value of primary and Advanced levels of laparoscopic simulating training in different seniority of gynecologic residents.Methods 77 residents in their first to forth training-year were divided into two groups:1-2 year resident and 3-4 year resident,trained with different levels of simulating training plans respectively and then assessed in the Department of Obstetrics and Gynecology in Peking University Third Hospital.Results The qualified rate of primary and advanced simulation training was 85.7％ and 57.1％ respectively.The qualified rate of primary training (80.4％ vs.100.0％,P=0.028) and advanced training (12.5％ vs.57.14％,P=0.000) were significantly different between 1-2 year residents and 3-4 year residents.The operative skills improved significantly in all the residents.In the 1-2 year residents,the scores of the primary training increased more obviously,while in the 3-4 year residents,the scores of the advanced training increased significantly.Conclusion It might be more effective for residents with different seniority to receive different levels of simulating training accordingly,so as to improve their laparoscopic operative skills more effectively.

Objective: To evaluate the effectiveness of different laboratory methods for the supplementary diagnosis of pulmonary tuberculosis（PTB）and provide reference data for the early diagnosis of PTB. Methods: A total of 298 suspected PTB patients, who were diagnosed and treated in the outpatient department of Shanghai Tongren Hospital from January 2016 to December 2018, were divided into 3 groups: active PTB (138 cases)，inactive PTB (43 cases) and non-PTB (117 cases) group. Sputum acid-fast staining, MGIT liquid culture system and Xpert MTB/RIF test were performed to detect the sputum specimens. The sensitivity and specificity were compared by Chi-square test. Results: The three methods showed certain significance for distinguishing active PTB, inactive PTB combined with non-PTB (χ 2 values were 89.08, 138.94 and 137.12 respectively, all P＜0.01). There was no significant difference for the positive rate of the three methods between inactive PTB and non-PTB. The sensitivities of acid-fast staining, MGIT liquid culture, Xpert MTB/RIF test and the combination of three methods in the diagnosis of active PTB were 45.7% (63/138), 63.8% (88/138), 65.4% (87/133) and 78.2% (104/133) respectively. The sensitivities of MGIT culture and Xpert MTB/RIF test were significantly higher than that of acid-fast staining (χ 2 was 35.79 and 11.26 respectively，all P＜0.01). There was no significant difference for the sensitivities between MGIT liquid culture and Xpert MTB/RIF test（χ 2 was 29.87, P＞0.05) . The sensitivity of combined detection was higher than that of single detection（χ 2 was 30.84, 64.62, 70.14, respectively, all P＜0.01）. The diagnostic specificities of the three methods and their combination were 99.1%（116/117), 98.3%（115/116）, 99.1%（113/114) and 97.3%（110/113）respectively. There was no significant difference for the specificities of the three methods. Conclusion High sensitivities of MGIT liquid culture and Xpert MTB/RIF test were shown in PTB diagnosis. Combined detection of the three methods may improve the sensitivity of detection.