OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Alzheimer's disease(AD),a common neurodegenerative disease,has been linked to periodontitis,espe-cially Porphyromonas gingivalis(P.gingivalis)infection.This review summarizes the potential mechanisms and path-ways through which P.gingivalis and its virulence factors are involved in AD pathogenesis,aiming to provide the scien-tific basis for the development of novel prevention and treatment strategies for AD.P.gingivalis can promote AD by ex-acerbating neuroinflammation,facilitating amyloid beta and Tau deposition,and disrupting the blood-brain barrier.Gin-gipains,secreted by P.gingivalis,serve as core effector molecules by increasing the blood-brain barrier permeability.The association between P.gingivalis and its effectors and AD pathology has been validated by metagenomic analysis and sample detection,indicating that P.gingivalis may be an environmental susceptibility factor or modifiable risk fac-tor for AD.However,the precise mechanisms by which P.gingivalis influences AD,and its interactions with other po-tential AD-related factors,remain unclear.Moreover,further research needs to be conducted on the therapeutic potential of P.gingvalis intervention in improving AD.

Objective To observe the changes in the subfoveal choroidal thickness(SFCT)of children and adoles-cents with different refractive states using optical coherence tomography angiography.Methods A total of 171 children and adolescents were followed.They were divided into the lower primary school group(6-8 years old),upper primary school group(9-11 years old),and junior high school group(12-14 years old)according to their age at the time of en-rollment.Dioptric examinations(including best corrected visual acuity,diopter,intraocular pressure,corneal curvature,axial length and SFCT)were performed,data collection was conducted twice in half a year(initial examination and review after half a year),and the eyeball parameters and changes in eyeball parameters after half a year among all groups were compared.Results The axial length and SFCT of subjects had significant differences among all groups(both P＜0.05).In children and adolescents,the axial length gradually lengthened and SFCT gradually thickened with age,while intraocular pressure and corneal curvature were not associated with age(both P＞0.05).In the initial examination and review after half a year,there was no significant difference in intraocular pressure,corneal curvature and SFCT of subjects with differ-ent refractive states in all groups(all P＞0.05),while the axial length of myopic subjects was greater than that of non-my-opic subjects in all groups(all P＜0.05).In the review after half a year,the SFCT of non-myopic subjects in the lower pri-mary school group and upper primary school group was significantly thickened(P＜0.001,P=0.003),while there was no significant difference in SFCT of myopic subjects in all groups compared with the value half a year ago(all P＞0.05).The axial length of all subjects showed a positive correlation with the SFCT in the initial examination and review after half a year(r=0.354,0.228,P＜0.05).Conclusion Myopia affects the increase in SFCT in children and adolescents.

Objective To evaluate the relationship between ceftazidime-avibactam(CAZ-AVI)blood concentrations and efficacy in critically ill patients and to investigate the factors influencing blood levels.Methods The CAZ-AVI trough concentrations(Cmin)were detected in 29 patients who received CAZ-AVI treatment for at least 48 hours.The clinical materials of the patients were collected together for retrospective analysis.Results The Cmin of ceftazidime(CAZ)and avibactam(AVI)were(50.95±5.17)and(7.52±0.96)mg·L-1 in the effective group and(31.16±7.03)and(5.37±1.32)mg·L-1 in the ineffective group,respectively.The Cmin of CAZ in the effective group was significantly higher than in the ineffective group(P<0.05),and there was no significant difference in AVI Cmin between the two groups(P>0.05).Spearman's correlation analysis showed that CAZ Cmin was positively correlated with clinical efficacy(P<0.05),and no correlation between AVI Cmin and clinical efficacy(P>0.05).The optimal CAZ Cmin threshold was 24.59 mg·L-1.Multiple linear regression analysis showed that age and creatinine clearance was significantly correlated with the Cmin of CAZ,and creatinine clearance was significantly correlated with AVI Cmin(P<0.05).Conclusions The Cmin of CAZ correlates with efficacy,and it may be more beneficial for clinical treatment to keep the concentration of CAZ-AVI always greater than the minimum inhibitory concentration during the dosing interval.The creatinine clearance should be fully considered when optimizing CAZ-AVI dosage in critically ill patients.

Objective:To summarize and analyze the current application status of oral mucosal graft (OMG) technique in the repair of ureteral strictures in China, and clarify the feasibility, safety and effectiveness of this technique.Methods:The 175 patients who underwent repair of ureteral stricture using oral mucosal patches from June 2015 to February 2022 were etrospectively analyzed in 14 medical centers in China, including 49 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 32 cases in Affiliated Seventh Medical Center of PLA General Hospital, 3 cases in The Second Hospital of Anhui Medical University, 6 cases in The First Affiliated Hospital of Zhengzhou University, 56 cases in Peking University First Hospital, 3 cases in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 cases in Shanghai Sixth People' s Hospital, 4 cases in General Hospital of Estern Theater Command, 4 cases in Lanzhou University Second Hospital, 2 cases in Guizhou Province People 's Hospital, 2 cases in Peking University People' s Hospital, 5 cases in Jinzhou First People's Hospital, 5 cases in The First Affiliated Hospital of Wannan Medical College, 1 case in Shandong Provincial Hospital. In this study, 127 patients (72.6%) used lingual mucosal patches, 32(18.3%) labial mucosa, and 16(9.1%) buccal mucosa. The surgical approach for OMG ureteral reconstruction was mainly minimally invasive, with robot-assisted laparoscopy in 84 patients (48.0%), traditional laparoscopic surgery in 87 patients (49.7%), and open surgery in only 4 patients (2.3%). There were 133 males and 42 females with an average age of (35.0±17.2) years. The mean body mass index (BMI) and stenosis length were (23.1±4.1) kg/m 2 and (4.7±1.8) cm, respectively. The stricture was located in the left ureter in 116 patients, right ureter in 58 case and bilateral ureter in 1 case. The most common causes of ureteral stricture were endoscopic surgery in 88(50.3%)patients, congenital stricture in 55(31.4%)patients, failed ureteroplasty in 29(16.6%)patients, history of extracorporeal shock wave lithotripsy in 13(7.4%)patients, radiotherapy history in 3(1.7%)patients and other causes in 6(3.4%)patients. Strictures were mainly located in the upper ureter, accounting for 61.7% (108/175 cases), followed by 36.0% (63/175) at the ureteropelvic junction and 2.3%(4/175)in the middle ureter. According to the surgical methods, the patients were divided into robot-assisted laparoscopic surgery group ( n=84), traditional laparoscopic surgery group ( n=87)and open surgery group ( n=4). Subgroup analysis of patients in robot-assisted laparoscopic and traditional laparoscopic surgery groups was performed. There were no significant difference in preoperative data between the two groups except for age (32.0±18.3) years vs.(37.0±15.9)years, P=0.040], BMI[(22.5±4.3)kg/m 2 vs. (23.7±3.6)kg/m 2, P=0.028], and etiology of stenosis [endoscopic injury, 34(40.5%) vs. 53(60.9%), P=0.012]. Preoperative hydronephrosis and stricture length were assessed by CTU and ureterography. Ureterography 7-9 weeks after surgery showed patency of the reconstructed segment, or no recurrence of hydronephrosis was judged as success. Evaluate the operation method, operation time, success rate, length of OMG in repairing ureteral stricture between laparoscopic and robot-assisted groups. Results:The overall success rate of oral mucosal graft repair surgery reached 97.7%(171/175). The success rate of ureteral reconstruction in the two groups were 96.4%(81/84)and 98.9%(86/87), respectively ( P=0.351), and the difference was not statistically significant. There was no significant difference for operation time, intraoperative blood loss, and mean oral mucosal length between the robotic and laparoscopic groups[(244.7±85.8) min and (222.7±83.5)min ( P=0.116), (58.9±38.6) ml and (68.4±45.5) ml ( P=0.217), (5.0±2.0) cm and (4.6±1.5) cm ( P=0.350)], respectively.Postoperative complications were reported in 23 (13.1%) patients, such as fever, urinary leakage, lymphatic leakage, infection, but only 2 (1.4%) cases patients had complications of Clavien-Dindo score ≥ Ⅲ. The two patients developed urinary stricture after surgery with failed conservative treatment, and no urinary stricture occurred following endoscopic treatment.The short-term (three months after surgery)incidence of complications in the site where the oral mucosa was taken, such as difficulty in opening mouth, pain, and swelling, was 12.0% (21/175), and there was no significant difference for oral complications between patients harvesting different length of mucosal graft. Conclusions:Ureteroplasty with oral mucosal graft is a safe, feasible and reliable technique for ureteral reconstruction. At present, minimally invasive technology is the main surgical approach for ureteroplasty, and there is no significant difference in operation time and success rate between robotic surgery and laparoscopic surgery.

Enhanced recovery after surgery(ERAS)is not only an evidence-based set of perioperative interventions, but also a highly innovative multidisciplinary collaboration model and organizational system. The authors reviewed the research status of the organizational structure and service process of ERAS at home and abroad, elaborated the establishment mode and management operation system of ERAS-multidisciplinary team(ERAS-MDT), discussed the communication mechanism between the teams to strengthen the communication and cooperation of ERAS-MDT, and emphasized the reasonable allocation of human resources of ERAS-MDT to reduce the workload of members. At the same time, the authors reviewed the standardized clinical pathway to facilitate the connection of all aspects during the perioperative period, and through the quality control and quality improvement measures of ERAS mode, the authors hope to further standardize the ERAS service process and escort the efficient operation of ERAS.

Objective:To investigate the effects of berberine on Sprague Dawley (SD) rat retinal Müller cells cultured by high concentration glucose.Methods:The cultured SD rat retinal Müller cells were divided into normal-glucose group, high-glucose group, high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group, and the cells were cultured in 5 mmol/L glucose, 25 mmol/L glucose, 25 mmol/L glucose+ 10 μmol/L berberine, and 25 mmol/L glucose+ 25 μmol/L berberine, respectively.After 72 hours cultured, cell apoptosis rate was detected by flow cytometry; the expressions levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA); the L-glutamate-L-aspartate transporter (GLAST) and the related protein expression levels were detected by real-time fluorescence quantitative PCR; the expressions levels of GLAST, protein phosphatase magnesium-dependent 1A (PPM1A), nuclear factor-κB (NF-κB) and cleaved caspase-3 in the cytoplasm, and the expression level of NF-κB protein in the nucleus were detected by Western blot.Results:The cell apoptosis rate was (1.37±0.21)%, (17.67±1.17)%, (10.60±0.17)% and (5.57±0.35)% in the normal-glucose group, high-glucose group, high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group, respectively, and the overall comparative difference was statistically significant ( F=375.97, P<0.01). The cell apoptosis rates in the high-glucose group was increased in comparison with those in the normal-glucose group ( P<0.01). The cell apoptosis rates in the high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group were significantly reduced in comparison with that in the high-glucose group (both at P<0.01). And the cell apoptosis rate in the high-glucose+ 25 μmol/L berberine group was lower than that in the high-glucose+ 10 μmol/L berberine group ( P<0.01). ELISA results revealed that the overall comparative differences of the concentrations of TNF-α, IL-8 and COX-2 among the four groups were statistically significant ( F=28.36, 35.88, 41.59; all at P<0.01). The concentrations of TNF-α, IL-8 and COX-2 in the high-glucose group were significantly higher than those in the normal-glucose group ( P<0.01). Compared with the high-glucose group, the concentrations of TNF-α and COX-2 were significantly decreased in the high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group (both at P<0.05). The concentrations of TNF-α and IL-8 in the high-glucose+ 25 μmol/L berberine group were lower than those in the high-glucose+ 10 μmol/L berberine group (both at P<0.05). Real-time fluorescence quantitative PCR showed that the relative expression levels of GLAST mRNA in Müller cells among the four groups were statistically significant ( F=268.60, P<0.01). Compared with the normal-glucose group, the relative expression level of GLAST mRNA was significantly decreased in the high-glucose group ( P<0.01). In the high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group, the relative expression level of GLAST mRNA was significantly elevated compared with the high-glucose group (both at P<0.05). Western blot analysis results showed that the overall comparative differences of the GLAST, PPM1A, cleaved caspase-3, NF-κB in cytoplasm and NF-κB in nucleus among the four groups were statistically significant ( F=135.20, 156.98, 80.96, 128.07, 47.36; all at P<0.01). The relative expression levels of GLAST, PPM1A and NF-κB protein in cytoplasm in the high-glucose group were significantly lower than those in the normal-glucose group, high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group (all at P<0.05). The relative expression levels of cleaved caspase-3 and NF-κB protein in nucleus in the high-glucose group were significantly higher than those in the normal-glucose group, high-glucose+ 10 μmol/L berberine group and high-glucose+ 25 μmol/L berberine group (all at P<0.05). Conclusions:High-concentration glucose can induce cell apoptosis and inflammatory response of SD rats retinal Müller cells in vitro.However, berberine can inhibit cell apoptosis and inflammatory response induced by high-concentration glucose via suppressing NF-κB translocation and transcription activity, and thereby inhibiting the expression of inflammatory cytokines.

Objective To compare the therapeutic effects of orthotopic injection and tail vein injection of human amniotic mesenchymal stem cells(hAMSCs)on histological restoration and neurological functions of rats with spinal cord injury. Methods Transected spinal cord injury model in rats was established by transplanting DAPI prelabelled hAMSCs one week after injury.BBB scores were used to evaluate the hindlimb movement of rats. The histological patterns.and morphology of medullary sheath of spinal cord were observed. Results BBB scores in the orthotopic injection group and tail vein injection group were increased gradually from one to six week after hAM-SCs transplantation and reached 6.5 ± 0.5 and 7.12 ± 1.61 respectively 6 weeks after cell transplantation,higher than that of the control group(both P < 0.01). However,there was no statistical significance between the two groups.Histological results indicated that the repair of injured tissue in the orthotopic injection group and tail vein injection group were both better than that in the control group,and there were more vesica and loosened layers forming in the injured spinal cord of rats in the PBS control group as compared with the orthotopic and tail vein transplantation group. Conclusion hAMSCs transplantation through tail vein injection could promote histological restoration and neurological regeneration of rats with spinal cord injury,which has the similar therapeutic effects with hAMSCs orthotopic transplantation.