Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Objective:To conduct simulated graduation skill assessment and annual skill assessment by self-designed objective structured clinical examination (OSCE) for standardized training of radiation oncology residents.Methods:The structured examination, standardized questions and standardized tasks of each disease were designed by teaching team of radiation oncology in the University of Hong Kong-Shenzhen Hospital. The implementation effect of the annual assessment and simulated completion assessment of standardized training for residents in radiation oncology from Class 2019 to 2021 was prospectively observed. The difference between scores by two independent examiners was analyzed by the paired t-test. The overall feedback of residents and examiners for the implementation were collected after the completion of OSCE. Results:A total of 18 residents participated in 67 sessions of 3-station skill assessments of different diseases, including 2 make-up tests. There was no difference in the score pairing and grade pairing tests between two examiners at 3 stations ( t=0.85, -0.68, -1.16; P=0.401, 0.499, 0.255). A total of 91.3% of the residents reported that the assessment well reflected their actual clinical competency. Conclusions:The current program of OSCE assessment for radiation oncology meets objectification, standardization and high efficiency, and achieves the goal of making trainers familiar with the graduation skill assessment and assessing comprehensive clinical competence. It is a reproducible and flexible structured assessment model.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

Background:Hepatitis B virus(HBV)is one of the most widespread viruses worldwide and a major cause of hepatitis,cirrhosis,and hepatocellular carcinoma.Previous studies have revealed the impacts of HBV infection on fertility.An increasing number of infertile couples with chronic hepatitis B(CHB)virus infection choose assisted reproductive technology(ART)to meet their fertility needs.Despite the high prevalence of HBV,the effects of HBV infection on assisted reproduction treatment remain limited and contradictory.Objective:The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes,vertical transmission,pregnancy complications,and viral activity during ART treatment.Methods:We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022.Results:HBV infection negatively affected fertility in both males and females.Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment.The impact of HBV infection on the pregnancy outcomes of ART is still controversial.Current evidence does not support that ART increases the risk of vertical transmission of HBV,while relevant studies are limited.With the development of ART,the risk of HBV reactivation(HBVr)is increasing,especially due to the wide application of immunosuppressive therapy.Conclusions:Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART.The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Objective To explore the clinical efficacy of fluoxetine hydrochloride capsules and escitalopram oxalate tablets in the treatment of first-episode depression disorder.Methods Eighty patients with first-episode depression disorder who were hospitalized in the 14th district of Integrated Traditional Chinese and Western Medicine of Xiamen Xianyue Hospital from February to November 2023 were selected,and divided into fluoxetine hydrochloride capsules group(n=40)and escitalopram oxalate tablets group(n=40)according to random number method;Conducted the Hamilton depression scale(HAMD)estimates before treatment and four weeks after treatment,to analyze and compare the clinical efficacy of two groups.Results After four weeks of treatment,the HAMD scores of all patients significantly decreased compared to before treatment in this group(P＜0.01);There was no statistically significant difference between two groups(P＞0.05).There was no statistically significant difference in the total effective rate between two groups(P＞0.05).Conclusion Escitalopram oxalate tablets and fluoxetine hydrochloride capsules were both effective in treatment of the first-episode depression disorder patients,and the total effective rates of them were similar.