ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

OBJECTIVE To assess the cost-effectiveness of durvalumab combined with chemotherapy as a first-line treatment for advanced biliary tract cancer from the perspective of the Chinese healthcare system. METHODS Using data from the TOPAZ-1 clinical trial， a three-state Markov model comprising progression-free survival （PFS）， progressive disease （PD） and death was developed， with a cycle length of 21 days and a 10-year time horizon. Patients in the observation group received durvalumab in combination with gemcitabine and cisplatin， whereas those in the control group received placebo plus the same chemotherapy regimen. The evaluation indexes were quality-adjusted life year （QALY） and the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） threshold was set at three times the 2024 Chinese per capita gross domestic product （GDP） （287 247 yuan/QALY）. The sensitivity analyses， along with scenario analyses， were performed. RESULTS In the base-case analysis， the ICER of observation group compared to control group was 1 166 344.46 yuan/QALY， far exceeding the WTP threshold， indicating that the regimen was not cost-effective. One-way sensitivity analysis identified the PD state utility， discount rate， cost of durvalumab， and PFS state utility as the main drivers of ICER variation. Probabilistic sensitivity analysis showed that， at the above WTP threshold， the probability of the acceeptance of this regimen was 0， further supporting the robustness of the base-case findings. In the scenario analysis， inclusion of a patient assistance program reduced the ICER to 235 885.16 yuan/ QALY， below the above WTP threshold， suggesting cost-effectiveness under this assistance program. However， when applying a regional WTP threshold set at three times the per capita GDP （158 475 yuan/QALY） of Gansu Province （the province with the lowest GDP in China in 2024）， the ICER remained above the threshold， indicating that the regimen was not cost-effective at the regional level. CONCLUSIONS At current pricing， durvalumab plus chemotherapy as a first-line treatment for advanced biliary tract cancer is not cost-effective in China. Although the introduction of a patient assistance program can substantially reduce the ICER and achieve cost-effectiveness at a WTP threshold set at three times the 2024 per capita GDP of China， due to limited affordability in low-income areas， the program remains not cost-effective.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Aim To investigate the potential protein post-translational modifications of psychedelic-induced Head-twith response and underling mechanism. Methods Psychedelics LSD, DOM, or Psilocin was administered to rats by intraperitoneal injection to induce head-twitch response, then the most effective dosage was identified to create animal models of head-twitch behavior. Western blot was performed in detecting the protein phosphorylation, acetylation, and ubiquitination in prefrontal cortex of SD rats after 10 min or 30 min injection. Results LSD (0.025 mg • kg~, i. p.), DOM (3 mg•kg

Ketamine has been used clinically as an analgesic and anesthetic since 1970. Recently, it has been concerned due to its rapid and effective antidepressant effect. However, the psychiatric adverse reactions caused by ketamine such as addiction and hallucination limit its clinical application, yet the mechanism of the adverse reactions is still unclear. At present, it is generally believed that the pharmacological effects of ketamine are mainly mediated by N-methyl-D-aspartate acid (NMDA) receptors, but increasing numbers of research evidences suggest that the opioid receptor also play an important role in the pharmacological effects of ketamine. This review, based on the relevant literature published publicly in the past 20 years, summarizes the mechanisms of opioid receptors in the pharmacological effects of ketamine, such as anesthesia, analgesia, anti-depressant, anti-addiction and addiction, providing reference for revealing the mechanism of ketamine, and making beneficial exploration for solving the clinical side effects of ketamine.

Aim To investigate the effect of DNA methyltransferase 3A (DNMT3A) on the proliferation and migration of cardiac fibroblasts (CFs) in C57 mice under high glucose environment. Methods The hearts of C57 mice were taken from 1 to 3 days. After cutting and digesting, CFs were extracted by differential adherance centrifugattion and observed under microscope. After cell attachment, the cells were cultured under low glucose (5.5 mmol • L