Objective:To evaluate the effect of gender on dose-effect relationship of remimazolam combined with alfentanil in painless gastroscopy.Methods:Subjects who planned to undergo elective painless gastroscopy,aged 18-60 years old,body mass index 19-24 kg/m2,American Society of Anesthesiologists physical status Ⅰ or Ⅱ,were enrolled.They were divided into male group and female group.The first subject in both groups received afentanil 5 μg/kg and remimazolam 0.2 mg/kg,and was implanted into a gastroscope 2 minutes later.Positive reactions were defined as body movement,coughing,swallowing and frowning during gastroscopy placement and examination.Remimazolam 0.05 mg/kg was used as a dose gradient by using modified Dixon's up-and-down method.The dose of the next subject was adjusted according to whether the subject had a positive reaction.If there was a positive reaction,the dose of the next subject was increased by one level of gradient,otherwise,the dose was decreased by one level of gradient,and so on.The process was terminated at the seventh intersection point of positive-negative reaction.And 50% effective dose(ED50),95% effective dose(ED95)and 95% confidence interval(CI)of remimazolam for inhibiting gastroscopic implantation reaction was calculated by Probit method.Results:A total of 46 subjects were included,with 23 subjects in each group.There was no significant difference in general data between the two groups.The ED50 of afentanil combined with remimazolam was 0.193 mg/kg(95% CI:0.145-0.286),and the ED95 was 0.293 mg/kg(95% CI:0.237-0.903)in male group.The ED50 of afentanil combined with remimazolam was 0.215 mg/kg(95% CI:0.155-0.293),and the ED95 was 0.316 mg/kg(95% CI:0.261-0.968)in female group.The ED50 and ED95(P＜0.05).Conclusion:When combined with 5 μg/kg of afentanil,remimazolam is more effective in inhibiting responses to gastroscopy inserting in male subjects than in female subjects.

BACKGROUND:It is of great significance to find new diagnostic markers of the disease and molecular targets for the treatment of the disease and the alleviation of organ injury.Ferroptosis is a newly discovered form of cell death.Overactivation of ferroptosis in animal models of sepsis is associated with the activation of inflammatory response and the injury of the liver,heart,kidney and other important organs,but the relationship between ferroptosis and bloodstream infection is not very clear. OBJECTIVE:To study the changes and biological significance of ferroptosis in a mouse model of blood stream infection induced by different bacteria. METHODS:Blood stream infection models induced by gram negative bacteria Escherichia coli,Klebsiella pneumoniae and gram positive bacteria Staphylococcus aureus and Enterococcus faecalis were established in SPF-grade ICR male mice,with 42 mice in each group.The mRNA expression levels of ferroptosis marker genes transferrin receptor 1 and glutathione peroxidase 4 in the liver,myocardium and kidney were detected at 0.5,1,3,6,12,24 and 48 hours after modeling.Another 18 SPF-grade ICR male mice were selected and randomly divided into dimethyl sulfoxide(DMSO)control group,DMSO+Klebsiella pneumoniae group,and Ferrostatin-1+Klebsiella pneumoniae group,with 6 mice in each group.In the latter two groups,animal models of Klebsiella pneumoniae bloodstream infection were established by tail vein injection of Klebsiella pneumoniae suspension,and 5 mg/kg Ferrostatin-1 and an equal dose of DMSO were given intraperitoneally 1 hour prior to the modeling of bloodstream infection,respectively.Serum levels of alanine aminotransferase,aspartate aminotransferase,blood creatinine,blood urea nitrogen,phosphocreatine kinase isoenzyme,lactate dehydrogenase,and mRNA expression levels of ferroptosis marker genes in various tissues were assayed at 6 hours after modeling. RESULTS AND CONCLUSION:After bloodstream infection modeling,the mRNA expression levels of transferrin receptor 1 in the liver,myocardium and kidney of bloodstream infection mice with different bacteria increased first and then decreased;and the mRNA expression level of glutathione peroxidase 4 decreased first,then increased,and reached the peak at 6 hours after modeling.The changes in transferrin receptor 1 and glutathione peroxidase 4 mRNA levels in bloodstream infection mice induced by gram-negative bacteria were more significant than those in blood stream infection mice induced by gram-positive bacteria,especially in bloodstream infection mice induced by Klebsiella pneumoniae.At 6 hours after bloodstream infection induced by Klebsiella pneumoniae,the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,lactate dehydrogenase in mice were significantly increased.Before modeling,Ferrostatin-1 intervention significantly reduced the levels of alanine aminotransferase,aspartate aminotransferase,serum creatinine,blood urea nitrogen,creatine phosphate kinase isoenzyme,and lactate dehydrogenase.All these findings indicate that the activation of ferroptosis in bloodstream infection mice induced by different bacteria is obvious,and the activation of ferroptosis in bloodstream infection mice induced by gram-negative bacteria is more obvious.Inhibition of iron death significantly attenuates liver,myocardial,and kidney injury in the mouse model of bloodstream infection induced by Klebsiella pneumoniae.

Objective:To construct a prediction model for difficult tracheal intubation in the patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).Methods:A total of 324 patients with OSAHS undergoing surgery with general anesthesia, admitted to our hospital from June 2019 to June 2021, were included in model group, and 175 patients with OSAHS undergoing surgery with general anesthesia, admitted from July 2021 to July 2022, were selected and served as validation group. The patients in model group were divided into occurrence group and non-occurrence group according to whether difficult tracheal intubation occurred. Logistic regression was used to construct the prediction model, and R4.2.1 software was used to draw the risk nomogram and calibration curve. The predictive accuracy of the model was evaluated by the area under the receiver operating characteristic curve.Results:Body mass index (BMI), sagittal minimum cross-sectional area, horizontal minimum cross-sectional area and mandibular distance were risk factors for difficult tracheal intubation in OSAHS patients ( P<0.05). A prediction model was developed using the above factors: Logit P=33.726+ 1.411×BMI score-0.014×sagittal airway minimum cross-sectional area-0.013×airway horizontal minimum cross-sectional area-0.312× mandibular distance. The area under the receiver operating characteristic curve was 0.846, Youden index 0.585, sensitivity 0.831, specificity 0.755, and the accuracy 0.889 (Hosmer-Lemeshow test χ2=9.24, P=0.322) in model group. The area under the external validation curve was 0.802, Youden index 0.545, sensitivity 0.636, specificity 0.908, and the accuracy 0.893 (Hosmer-Lemeshow test χ2=10.24, P=0.287) in validation group. Conclusions:The prediction model based on BMI, sagittal minimum cross-sectional area of airway, horizontal minimum cross-sectional area of airway and mandibular distance has a high value in predicting the risk of difficult tracheal intubation in patients with OSAHS.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Objective The prevalence of obesity is constantly increasing. Multiple metabolic complications are related to obesity, including type 2 diabetes mellitus and non-alcholic fatty liver disease(NAFLD). Our study aimed to investigate the prevalence of obesity comorbidities and its association with BMI. Methods 765 individuals who visited the multidisciplinary clinic for obesity in Peking University First Hospital from 2015, Jun. to 2018, Sept. were enrolled in this study. The height, body weight, waist circumference, hip circumference were measured during the first visit. Body adipose percentage and basal metabolic rate were recorded. Questionnaires for daily food intake, comorbidity, and lifestyle were recorded. Fasting insulin, C peptide, glucose, HbA1C , uric acid, liver enzymes and lipid profile were measured. Statistical analysis was performed using SPSS 16. 0, and P<0. 05 was considered as statistical significant. Results Daily energy intake was higher in obesity group [ obese vs non-obese, (2136.6±739.4vs1905.7±468.4)kcal/d,P=0.046].Hypertension,NAFLDandgoutriskincreasedsignificantly in obesity group (obese vs non-obese, 36.0％vs 24.5％, P=0.02;76.5％ vs 60.6％, P<0.01;6.9％ vs 1.8％, P=0.04, respectively) . Family history of obesity and diabetes increased in obesity group ( obese vs non-obese, 64.5％vs 53.6％, P=0.03;47.4％vs 37.3％, P=0.048). Fasting insulin and C-peptide levels were higher in obesity group [obese vs non-obese, (24.8 ± 15.3 vs 13.6 ± 9.5)μIU/ml, P<0.01;(3.72 ± 1.40 vs 2.70 ± 1.16)μIU/ml, P<0.01). Liver enzymes increased significantly in obesity group [obese vs non-obese, (47.2±45.4 vs 23.3±21.4)U/L, P<0.01; ( 30. 4 ± 24. 0 vs 19. 9 ± 8. 5 ) U/L, P=0. 001 ] . Conclusions Obesity population had higher risk of hypertension, NAFLD and gout. Fasting insulin, C-peptide, liver enzymes, and UA also increased significantly in these patients. It is critically important to those obese individuals for regular screening of NAFLD and diabetes mellitus.

Objective: To evaluate the safety and feasibility of treating de novo coronary lesions with paclitaxel-eluting balloon. Methods: This is a retrospective study, which enrolled 76 patients with 80 de novo coronary lesions treated with paclitaxel-eluting balloons(<30% residual stenosis and there was no blood flow limited dissection after pretreatment) from April 2015 to November 2016 in Guangdong general hospital. The data of basic characteristics,procedures,devices and follow-up information were retrieved and analyzed. The primary endpoint was the composite of cardiac death, recurrent myocardial infarction and target lesion revascularization. Results: (1)The age was (63.3±10.3) years. There were 68.4%(52/76) acute coronary syndrome patients, prevalence of type 2 diabetes was 36.8%(28/76), and 64.5%(49/76)patients with at least one high bleeding risk. (2)The lesion length was (17.4±7.6)mm, and the stenosis was (88.1±8.2)%.The reference vessel diameter≥2.75 mm accounted for 51.2% (41/80), and bifurcation stenosis accounted for 67.5%(54/80). (3)53.7%(43/80) lesions were pretreated with scoring balloon to optimize plaque modification. The paclitaxel-eluting balloon length and diameter were (22.3±5.5)mm and (2.74±0.52)mm.The residual stenosis was (12.3±10.3)%. Procedural success was 88.8%(71/80).Bail-out stenting rate was 5.0%(4/80). (4)The median follow-up duration was 12(6, 25) months. Primary endpoint occurred in 3 cases (3.9%), including 2 cardiac deaths(1 patient died of recurrent myocardial infarction, and 1 patient died of acute heart failure induced by severe mitral insufficiency), and one patient receivedtarget lesion revascularization. Conclusion In case of no more than 30% residual stenosis and no blood flow limited dissection after lesion pretreatment,it is safe and feasible to treat de novo coronary lesionsusing paclitaxel-eluting balloon.

OBJECTIVETo study the difference in pathologic diagnostic accuracy among different histologic subtypes of osteosarcoma and different methods of preoperative biopsy, and the influence of diagnostic accuracy on prognosis of osteosarcoma.

METHODSThe preoperative biopsies, complete clinical, radiological and pathological data of 347 pathologically confirmed osteosarcomas were evaluated. According to the Pathological Diagnostic and Technical Specifications, the accuracy of preoperative biopsies was divided into 6 grades. 1: definite diagnosis, 2: basically definite diagnosis, 3: significant diagnosis, 4: descriptive diagnosis, 5:inadequate sampling, 6:misdiagnosis. 1 to 3 were defined as successful diagnosis,while 4 to 6 were defined as unsuccessful diagnosis.

RESULTSOf the 347 biopsies, 252 were CT-guided needle biopsies by the radiologists, and 95 were core-needle biopsies by orthopedic surgeons without CT-guidance. The latter showed a higher overall biopsy success rate (97.9%) in all osteosarcomas. Biopsies by surgeons showed a higher biopsy success rate (95.4%) in conventional osteosarcoma, but lower success rate in telangiectatic (55.6%) and low-grade central osteosarcomas (63.7%). The accuracy of pathologic diagnosis of preoperative biopsy was related to patients' age, serum AKP level, imaging diagnosis, method of biopsy and the subtype of osteosarcoma. Comparing the groups with successful and unsuccessful diagnosis, there were significant differences in recurrence rate and mortality after operation (P<0.01).

CONCLUSIONSThe accuracy of pathologic diagnosis of preoperative biopsy are related to recurrence rate and mortality after operation. Biopsy by orthopedic surgeons without CT-guidance is reliable and safe, followed by primary diagnosis at frozen section and final diagnosis by routine pathologic sections for osteosarcomas located in the long bones of the extremities. Close integration of the preoperative pathologic diagnosis with clinical and radiological data will improve the accuracy of diagnosis.

Objective To study the difference in pathologic diagnostic accuracy among different histologic subtypes of osteosarcoma and different methods of preoperative biopsy, and the influence of diagnostic accuracy on prognosis of osteosarcoma.Methods The preoperative biopsies, complete clinical, radiological and pathological data of 347 pathologically confirmed osteosarcomas were evaluated.According to the Pathological Diagnostic and Technical Specifications, the accuracy of preoperative biopsies was divided into 6 grades.1:definite diagnosis, 2:basically definite diagnosis, 3:significant diagnosis, 4:descriptive diagnosis, 5:inadequate sampling, 6:misdiagnosis.1 to 3 were defined as successful diagnosis,while 4 to 6 were defined as unsuccessful diagnosis.Results Of the 347 biopsies, 252 were CT-guided needle biopsies by the radiologists, and 95 were core-needle biopsies by orthopedic surgeons without CT-guidance.The latter showed a higher overall biopsy success rate (97.9%) in all osteosarcomas.Biopsies by surgeons showed a higher biopsy success rate (95.4%) in conventional osteosarcoma, but lower success rate in telangiectatic ( 55.6%) and low-grade central osteosarcomas ( 63.7%) . The accuracy of pathologic diagnosis of preoperative biopsy was related to patients′age, serum AKP level, imaging diagnosis, method of biopsy and the subtype of osteosarcoma.Comparing the groups with successful and unsuccessful diagnosis, there were significant differences in recurrence rate and mortality after operation ( P <0.01 ) .Conclusions The accuracy of pathologic diagnosis of preoperative biopsy are related to recurrence rate and mortality after operation.Biopsy by orthopedic surgeons without CT-guidance is reliable and safe, followed by primary diagnosis at frozen section and final diagnosis by routine pathologic sections for osteosarcomas located in the long bones of the extremities.Close integration of the preoperative pathologic diagnosis with clinical and radiological data will improve the accuracy of diagnosis.