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.

Objective:To analyze the efficacy and safety of FOLFOX-hepatic arterial infusion chemotherapy (HAIC) combined with targeted immunotherapy for initial unresectable hepatocellular carcinoma.Methods:A retrospective analysis was conducted on the data of initial unresectable hepatocellular carcinoma patients who visited Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2022 to June 2023. A total of 51 patients were enrolled, including 47 males and 4 females, with the age of (56.1±10.7) years. All 51 patients received HAIC combined with immune targeted therapy. After each HAIC combined with immune targeted therapy, the efficacy was evaluated according to the modified response evaluation cirteria in solid tumor (mRECIST). Objective response rate and disease control rate were calculuted. The conversion surgery rate and adverse events during treatment were recorded. Follow up patients' disease progression and survival status, and meanwhile analyze prognosis.Results:According to mRECIST assessment, the number of patients with complete remission, partial remission, disease stability, and disease progression were 4 (7.8%), 27 (52.9%), 14 (27.4%), and 6 (11.8%), respectively. The disease remission rate was 60.8%(31/51), and the disease control rate was 88.2%(45/51). After HAIC combined with immune targeted therapy, 13 patients underwent liver cancer resection, with a surgical conversion rate of 25.5%(13/51). The median progression free survival of 51 patients was 14.2 months, and the median overall survival has not yet been reached. The progression free survival rates of 51 patients at 6 and 12 months were 90.2% and 64.7%, respectively, and the cumulative survival rates at 6 and 12 months were 100% and 86.3%, respectively. During the treatment period, all patients experienced various degrees of adverse reactions, 38(75.5%) patients were grade 1-2 adverse accidents, which could be relieved and controlled after corresponding treatment.Conclusion:FOLFOX-HAIC combined with targeted immunotherapy provides an effective and safe treatment option for unresectable hepatocellular carcinoma, offering surgical resection opportunities for unresectable hepatocellular carcinoma patients.

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.

Liver is a unique organ with polyploidy.About 20 to 50 percent of hepatocytes in adult human are polyploid cells,which contain more than two sets of chromosomes.Hepatocytes polyploidization is triggered by the changes in insulin signal during weaning,and regulated by various cell cycle regulator genes to ensure the polyploid cells proportion,ploidy and zonation.The regulation of polyploid hepatocytes is crucial for liver's metabolic and regenerative function,and protecting liver from tumorigenesis.However,in chronic virus hepatitis and nonalcoholic fatty liver disease,the pathological hepatocytes polyploidization can be found in disease progression because of cell cycle checkpoint inhibition and oxidative stress.Distinguishing physiological and pathological hepatocyte polyploidization will be helpful for the understanding the relationship between chronic liver disease and tumorigenesis.

Objective    To evaluate the early and mid-term safety of transcatheter aortic valve replacement via transfemoral (TF), transapical (TAp) and transsubclavian (TSc) approaches by meta-analysis. Methods    We systematically searched the clinical comparative trials published from inception to June 2019 from PubMed, Web of Science, EMbase and The Cochrane Library, to evaluate the safety of transcatheter aortic valve replacement through TF, TAp or TSc approaches. The information of all-cause mortality at 30 days, 1 year, 2 years and the incidence of common complications at 30 days after operation (including pacemaker-dependent block, major vascular complications, severe bleeding events, acute renal injury and stroke) were exacted, and a meta-analysis was conducted by RevMan 5.3 software. Results    This study included 11 literatures, with a total of 7 833 patients, among whom 5 348 patients were treated by TF TAVR, 1 796 patients by TAp TAVR and 689 patients by TSc TAVR. The results of the meta-analysis were as follows: (1)  at 30 days after operation, the mortality of TF and TSc approaches were lower than that of the TAp approach (TF vs. TAp:OR=0.57, 95%CI 0.39-0.84, P=0.004; TSc vs. TAp: OR=4.12, 95%CI 1.93-8.79, P=0.000 3). There was no statistical difference between the TF and TSc approaches (TF vs. TSc: OR=0.98, 95%CI 0.38-2.51, P=0.97); at 1 year, there was no statistical difference in mortality among the three approaches (P>0.05); at 2 years, there was no statistical difference between TSc and TF or TAp approaches (TF vs. TSc: OR=1.21, 95%CI 0.95-1.54, P=0.13; TSc vs. TAp: OR=1.02, 95%CI 0.76-1.36, P=0.91). (2) The incidence of acute kidney injury after TF approach was lower than that of the TAp approach (OR=0.30, 95%CI 0.22-0.41, P<0.000 01). (3) There was no statistical difference in major vascular complications between TSc and TF or TAp approaches (TF vs. TSc: OR=0.75, 95%CI 0.38-1.49, P=0.41; TSc vs. TAp: OR=1.37, 95%CI 0.56-3.32, P=0.49). (4) There was no statistical difference in severe bleeding events between TF and TSc (OR=0.97, 95%CI 0.53-1.76, P=0.92). (5) There was no statistical difference in the incidence of postoperative stroke, pacemaker dependent block among the three approaches (P>0.05). Conclusion    TAp and TSc approaches are safe and effective. They are not only an alternative to TF approach, but also the first choice in some patients with poor condition of iliofemoral artery.

Objective To evaluate the risk factors for intraoperative hemodynamic instability (HI) in patients with adrenal incident pheochromocytoma.Methods Perioperative clinical parameters of patients undergoing surgery for adrenal incident pheochromocytoma at the First Hospital of Peking University from January 2001 to July 2018 were analyzed.There were 39 males and 41 females,with mean age of 45.1 years (13-76 years old).The median tumor length was 5.1 cm (1.5-14.0 cm),with 25 cases (31.3％) on the left side,55 cases (68.8％) on the right side.There were 37 cases combined with coronary heart disease or diabetes or BMI≥24 kg/m2.Patients were divided into hemodynamic instability (HI group) and hemodynamic stability group (HS group) by whether intraoperative hemodynamic instability occurred.The differences of demographic characteristics and clinical parameters between the two groups were compared.Logistic regression analysis was done for seeking the risk factors for hemodynamic instability during surgery.Results There were 54 cases (67.5％) in the HS group and 26 cases (32.5％) in the HI group.Univariate analysis showed that there was no significant difference in age [(44.06 ± 13.58) years old vs.(47.35 ± 16.11) years old],combined with coronary heart disease or diabetes or BMI≥24 kg/m2 [50.0％(27/54) vs.38.5％ (10/26)],tumor long diameter [median 5.0 cm(1.5-14.0 cm) vs.6.0cm(1.5-13.5 cm)],tumor location [left:29.6％ (16/54) vs.34.6％ (9/26)],preoperative catecholamine test positive [44.4％ (20/45) vs.50.0％ (10/20)],open surgery [27.8％ (15/54) vs.34.6％ (9/26)]and preoperative non-alpha blockers[13.0％ (7/54) vs.30.8％ (8/26)] between HS group and HI group (P ＞ 0.05).Further logistic regression analysis was used to analyze the risk factors of intraoperative hemodynamic instability.Multivariate analysis found that patients who preoperative non-alpha blockers before surgery were independent risk factor for HI (OR =4.574,95 ％ CI 1.273-16.432,P =0.020).Conclusions Preoperative non-alpha blocker in patients with adrenal incidental pheochromocytoma could be independent risk factor for intraoperative hemodynamic instability.Therefore,it is recommended that patients with adrenal incidental tumors,especially those who fail to rule out pheochromocytoma,take preoperative alpha blockers.

Objective To investigate the early diagnosis value of MR by detecting spinal inflammatory lesions in ankylosing spon-dylitis (AS).Methods Forty patients were involved in this study,including 20 cases with short inflammatory back pain (IBP)histo-ry (duration ≤18 months)and 20 cases with long IBP history (duration ≥24 months).MR images were analyzed retrospectively. Results Patients with a short history of IBP had 7 lesions in vertebral bodies (anterior/posterior spondylitis and spondylodiscitis) and 33 lesions in posterior spinal structures (arthritis of costovertebral joints,costotransversal joints,zygapophyseal joints and en-thesitis of spinal ligaments).Patients with a long history of IBP had 27 lesions in vertebral bodies and 24 lesions in posterior spinal structures.Patients with a short history of IBP had significantly more lesions in posterior spinal structures than in vertebral bodies with 82.5% (33/40)vs 1 7.5% (7/40),respectively (P <0.01).In contrast,patients with a long history of IBP had significantly more inflammation in vertebral bodies with 79.4% (27/34)vs 20.6% (7/34),respectively (P <0.01).Conclusion Inflammatory spinal lesions in patients with a short history of IBP are seen more often in the posterior structures.Early detection of inflammatory spinal lesions by MRI is useful for early diagnosis of AS.

OBJECTIVETo investigate the effect of oral administration of Zaocys type II collagen (ZCII) on the percentages of Treg/Th17 cells in mesenteric lymph node lymphocytes (MLNLs) in mice with collagen-induced arthritis (CIA).

METHODSCIA was induced in male C57BL/6 mice by immunization with chicken type II collagen. Three weeks later, ZCII, purified by pepsin digestion, was orally administered in the mice for 7 consecutive days (daily dose of 10, 20, or 40 µg/kg). The severity of arthritis in each limb was evaluated using a macroscopic scoring system, and histopathological changes of the joint were observed microscopically with HE staining. The percentages of Treg and Th17 cells in MLNLs was detected by flow cytometry, and the levels of transforming growth factor-β (TGF-β) and interleukin-17 (IL-17) in the supernatant of MLNLs were measured by enzyme-linked immunosorbent assay.

RESULTSCompared with normal control mice, the mice with CIA had significantly higher scores for arthritis and histopathological changes, with also significantly increased percentages of Treg and Th17 cells in MLNLs and elevated levels of TGF-β and IL-17 in MLNL supernatant (P<0.05). In ZCII peptide-treated mice, the scores for arthritis and histopathological changes were significantly lower than those in CIA model group (P<0.05), and Treg cell percentage in MLNLs was up-regulated while Th17 cell percentage lowered; the level of TGF-β was increased but IL-17 was decreased significantly (P<0.05).

CONCLUSIONOral administration of ZCII improves CIA in mice by regulating the percentages of Treg/Th17 cells and the cytokine levels in MLNLs, suggesting the value of ZCII as a promising candidate agent for treatment of rheumatoid arthritis.

Animals ; Arthritis, Experimental ; immunology ; Arthritis, Rheumatoid ; Collagen Type II ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Interleukin-17 ; metabolism ; Lymph Nodes ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology ; Transforming Growth Factor beta ; metabolism

Objective To investigate the effect of oral administration of Zaocys type II collagen (ZCII) on the percentages of Treg/Th17 cells in mesenteric lymph node lymphocytes (MLNLs) in mice with collagen-induced arthritis (CIA). Methods CIA was induced in male C57BL/6 mice by immunization with chicken type II collagen. Three weeks later, ZCII, purified by pepsin digestion, was orally administered in the mice for 7 consecutive days (daily dose of 10, 20, or 40 μg/kg). The severity of arthritis in each limb was evaluated using a macroscopic scoring system, and histopathological changes of the joint were observed microscopically with HE staining. The percentages of Treg and Th17 cells in MLNLs was detected by flow cytometry, and the levels of transforming growth factor-β(TGF-β) and interleukin-17 (IL-17) in the supernatant of MLNLs were measured by enzyme-linked immunosorbent assay. Results Compared with normal control mice, the mice with CIA had significantly higher scores for arthritis and histopathological changes, with also significantly increased percentages of Treg and Th17 cells in MLNLs and elevated levels of TGF-β and IL-17 in MLNL supernatant (P<0.05). In ZCII peptide-treated mice, the scores for arthritis and histopathological changes were significantly lower than those in CIA model group (P<0.05), and Treg cell percentage in MLNLs was up-regulated while Th17 cell percentage lowered;the level of TGF-βwas increased but IL-17 was decreased significantly (P<0.05). Conclusion Oral administration of ZCII improves CIA in mice by regulating the percentages of Treg/Th17 cells and the cytokine levels in MLNLs, suggesting the value of ZCII as a promising candidate agent for treatment of rheumatoid arthritis.

Objective To evaluate the positions and forms of temporomandibular joints(TMJ) with different vertical skeletal patterns in Class Ⅱ division 1 patients.Methods Cone-beam CT scans of 117 Class Ⅱ division 1 adolescent patients (including 30 patients with high angle,58 with average angle and 29 with low angle) were selected and reconstructed using Mimics 10.0 software.Fourteen measurements related to the positions and forms of condyle,forms of fossa and joint spaces were performed.Results Compared with high and average angle patients,the condyles in low angle patients located more posteriorly and inferiorly [the vertical distances between condyle and S was (20.67 ± 1.99) mm and the antero-posterior distances between condyle and S was (9.15± 1.61) mm].The joint fossae were deeper[the fosse depths was (7.83 ± 1.06) mm].The angles of posterior joint node bevels were bigger[the inclinations were (28.91 ±3.94)°].The condyles were shorter,thicker,tipped more anteriorly and positioned more posteriorly[the proportions of post-positioned condyles of low angle,average angle and high angle patients were 26％,4％,0％ respectively].Conclusions Class Ⅱ division 1 adolescents with different vertical skeletal patterns had different forms of fossae,and different positions and forms of condyles.