Objective To establish a method for rapid detection of tramadol in urine by liquid-liquid extraction（LLE）-surface-enhanced Raman spectroscopy （SERS）. Methods Tramadol was extracted from urine with chloroform∶isopropyl alcohol （9∶1） extractant and detected in urine samples by enhanced Raman spectroscopy （wavelength 785 nm）. Results The quantitative curve of tramadol was Y=204.35 X−465.62, r=0.9952, and the linear range was 1-100 μg/ml. The detection limit of tramadol by this method （S/N=3） was 0.53 μg/ml. The sensitivity of SERS was higher than that of conventional methods, and it had reasonable reproducibility. Conclusion This method is simple, efficient and economical, and can be used for qualitative and quantitative analysis of tramadol personalized medicine.

Objective To analyze the differences of free and esterified oxo-eicosatetraenoic acids (oxo-ETEs) in blood cells and plasma from arterial and venous blood in hemodialysis (HD) patients. Methods Arterial and venous blood samples from 12 patients with end-stage renal disease (ESRD) before and after HD treatment at Charité – Universitätsmedizin Berlin, Germany, from June to December 2020 were collected. The esterified and free oxo-ETEs derived from arachidonic acid in blood cells and plasma were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results Neither esterified nor free oxo-ETEs in blood cells displayed significant arteriovenous differences before and after HD. HD predominantly affected the metabolic levels of esterified and free oxo-ETEs in plasma. HD reduced the arteriovenous differences of esterified 12-oxo-ETE, free 15-oxo-ETE, and free 5-oxo-ETE in plasma, while raised the arteriovenous differences of esterified 15-oxo-ETE. Conclusions The oxo-ETEs in blood cells are relatively well-stabilized responding to HD treatment, whereas arteriovenous differences of free and esterified oxo-ETEs in plasma are present and active in response to HD treatment, potentially contributing to the cardiovascular disease.

Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

Objective To compare the effect of patient-controlled intravenous analgesia(PCIA)and superior inguinal liga-ment iliac fascia block combined with PCIA after hip replacement in the elderly.Methods Total of 82 elderly patients were treated with hip arthroplasty from June 2019 to June 2021 and randomly divided into observation group and control group.There were 42 patients in control group,including 18 males and 24 females,aged from 60 to 78 years old with an average of(70.43±3.67)years old,28 femoral neck fractures and 14 femoral head necrosis,who received PCIA.The study group consist-ed of 42 cases,including 20 males and 22 females,aged from 61 to 76 years old with an average of(69.68±3.74)years old,25 femoral neck fractures and 17 femoral head necrosis,who received superior inguinal ligament iliac fascia block combined with PCIA.Pain visual analogue scale(VAS)and Ramesay sedation scores at2h,6h,12h,24h and 48 h after operation were e-valuated.In addition,the follow-up results of the total consumption of sufentanil and the total number of PCIA compressions at 48 hours after operation,the first time of landing after surgery,the time of hospital stay,the incidence of adverse reactions,the satisfaction with analgesia of two groups were observed.Results All patients were followed up for 9 to 24 months with an aver-age of(13.85±2.67)months.There was no significant difference in operation time and intraoperative bleeding between two groups(P＞0.05).There was no difference in VAS between two groups at 2 hours after operation(P＞0.05),and the VAS of the study group at 6 h,12 h,24 h and 48 h after operation were lower than those of the control group(P＜0.05).The Ramesay seda-tion scores of the study group at 2 h,6 h and 12 h after operation were higher than those of the control group(P＜0.05),and there were no differences in Ramesay score between two groups at 24 h and 48 h after operation(P＞0.05).The consumption of sufentanil in the study group within 48 hours after operation was lower than that in the control group(P＜0.05),and PCIA com-pression times were lower than those in the control group(P＜0.05),and the time of first landing was earlier than that in the control group(P＜0.05).There was no significant difference in hospital stay,adverse reaction rate,complications between two groups(P＞0.05).The satisfaction of analgesia in the study group was higher than that in the control group(P＜0.05).Conclu-sion Superior iliac fascia block of inguinal ligament combined with PCIA has significant analgesic and sedative effects after hip arthroplasty in the elderly.It can reduce the amount of sufentanil used and the total number of PCIA compressions,which is conducive to the early activity of patients out of bed,improve the satisfaction of analgesia.

Objective To investigate the effects of saphenous nerve combined with posterior capsular block of knee joint on stress response,analgesic effect and joint function recovery of patients after total knee arthroplasty.Methods A total of 98 patients who received total knee arthroplasty in our hospital from January 2021 to January 2022 were selected and divided into the observation group(received saphenous nerve combined with posterior capsular block of knee joint)and the control group(received saphenous nerve block)by random number table,with 49 patients in each group.The visual analogue scale(VAS)score of resting and dynamic pain 6 hours,12 hours and 24 hours after surgery of patients in the two groups were compared.The range of knee joint motion before surgery,3 days,5 days and 7 days after surgery of patients in the two groups were compared.The stress indexes[cortisol(Cor),adrenocorticotropic hormone(ACTH)],and pain mediator indexs[calcitonin gene-related peptide(CGRP),beta-endorphins(β-EP),6-keto prostaglandin E1α(6-Keto-pGE1α),substance P(SP)]before surgery,4 hours,12 hours,24 hours,and 48 hours after surgery of patients in the two groups were compared.The occurrence of adverse reactions during treatment of patients in the two groups were recorded.Results There were statistically significant differences in the resting and dynamic VAS scores at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the range of knee joint motion at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the Cor and ACTH contents at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the contents of β-EP,SP,CGRP and 6-keto-PGE1α at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Saphenous nerve combined with posterior capsular block of knee joint for total knee arthroplasty can reduce patients' stress response,enhance postoperative analgesic effect,and improve the early motor function,with high safety.

The epidemiological and spatiotemporal distribution characteristics of human leptospirosis in Zhejiang Province from 2018 to 2022 were analyzed,to provide a scientific basis for formulating leptospirosis prevention and control strategies.Data on leptospirosis were collected from the China Information System for Disease Control and Prevention,and analyzed with descriptive epidemiological methods.ArcMap 10.8 software was used for spatial autocorrelation analysis and visual display of the results.SaTScan 10.1.2 software was used for spatiotemporal scanning,to analyze and describe the spatiotemporal aggrega-tion characteristics of leptospirosis.A total of 255 human cases of leptospirosis were reported in Zhejiang Province from 2018 to 2022,including one death;the average annual incidence was 0.084 3/100 000,and the average annual mortality was 0.000 3/100 000.The highest incidence of leptospirosis in Zhejiang occurred from August to October.Most cases were in middle-aged and older people 45-86 years of age(221 cases,86.67％).The number of cases was highest among people 65-69 years of age(57 cases).The male to female ratio was 4.67∶1.The main occupation was farming(190 cases,74.51％).The cumulative number of cases in Wenzhou and Lishui in 3 years(201 cases)accounted for 78.82％of the total cases.The global spatial auto-correlation analysis from 2018 to 2022 showed that the incidence of leptospirosis in the province presented a positive spatial au-tocorrelation.Local spatial autocorrelation analysis indicated that the"high-high"gathering areas were concentrated primarily in Wenzhou,Lishui,and Taizhou in the mountainous and hilly areas of southern Zhejiang Province.Spatiotemporal scanning anal-ysis revealed three clusters with high incidence in southern Zhejiang Province.The incidence of leptospirosis in Zhejiang Prov-ince showed clear regional clustering and seasonality,and the high incidence area was mainly in the mountainous and hilly areas of southern Zhejiang Province.The cases occurred mainly in middle-aged and older male farmers.Health education among rural resi-dents should be strengthened to prevent potential epidemic risks.

This study adopted the policy text analysis method,review the historical background of the enactment,aimed to comparatively analyze the international pharmaceutical trade policies of the BRICS countries.The main objectives of the BRICS countries'international pharmaceutical trade policies included ensuring stable and accessible drug supply,expanding exports of domestic products and creating a favorable political environment.For these purposes,Brazil,Russia,and South Africa all ensure drug supply through substantial imports.However,they have also taken measures such as compulsory patent licensing and promoting localization of production by foreign companies to reduce import dependence.India,on the other hand,protects its domestic industry by resisting drug imports to ensure drug supply while simultaneously promoting the export of pharmaceutical products.China continually optimizes approval and data monitoring procedures to align with international standards,creating a favorable trade environment and expanding exports.China should further refine its international pharmaceutical trade policies while ensuring the autonomy of domestic drug research and supply,fostering stronger collaboration within BRICS nations and promoting global access to public healthcare products.

Objective:To investigate the effects of modified electroconvulsive therapy(MECT)in combina-tion with medication and medication alone on relapse and cognitive functioning in patients with major depressive disorder(MDD).Methods:Totally 324 patients meeting the diagnostic criteria ofthe DSM-5 for MDD were select-ed and divided into combined MECT group(n=117)and non-combined MECT group(n=207).At baseline and 5 years of follow-up,both groups completed the General Information Questionnaire,Montreal Cognitive Assessment(MoCA),and Hamilton Depression Scale(HAMD)to analyze associations between cognitive functioning and mul-tiple variables.Results:At baseline,there were no significant differences between the two groups on general infor-mation,MoCA,and HAMD scores(Ps＞0.05).After 5 years of follow-up,the relapse rate was lower in the com-bined MECT group than in the un-combined MECT group[(37.6％vs.72.0％),P＜0.001].MECT was a protec-tive factor against recurrence of MDD[RR(95％CI)=0.52(0.40-0.66)],and the MoCA scores were lower in the combined MECT group than in the un-combined MECT group[(20.9±3.5)vs.(23.6±4.2),β=-1.93,P＜0.001].Conclusion:Combined MECT is a protective factor against MDD recurrence.Its effects on the cognitive functioning of MDD patients may have long-term effects.

Objectives To explore factors associated with false positive treadmill exercise testing(TET)in patients with hypertensive responses to exercise.Methods Between November 2019 and October 2022,154 patients with positive TET and hypertensive response to exercise were selected from the de-partment of cardiac rehabilitation of Jiangsu Province Official Hospital,and divided into a false posi-tive group of 72 and a true positive group of 82.Then,demographic and TET-related parameters were compared between the two groups.Results There was a significant difference between the two groups in gender(P<0.05).Compared with the male,the female were more likely to get false-positive results.Moreover,the systolic blood pressure(SBP)at the time of ST segment depression in the false positive group was 203.87±8.70 mmHg,significantly different from the true positive group of 187.25±16.66 mmHg(P<0.05).According to logistic regression analysis,only the SBP at the time of ST seg-ment depression and gender were significantly correlated with TET false positives(P<0.05).The cut-off value of SBP at the time of ST segment depression was 188 mmHg,with a sensitivity of 1,a specific-ity of 0.625,and an area under the curve of 0.813.Conclusions In patients with hypertensive re-sponse to exercise,SBP at the time of ST segment depression can be considered as a predictor of false positive TET.When its value is no less than 188 mmHg,TET-positive conclusions should be drawn with caution,especially for female patients.

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.