BACKGROUND:Ropivacaine and dexmedetomidine are two commonly used local anesthetic agents and adjuvants in elderly total hip arthroplasty. They provide sedation and analgesic effects during peripheral hip nerve blocks.OBJECTIVE:To explore the dose-effect relationship between dexmedetomidine and ropivacaine in continuous sedation during pericapsular nerve group block in elderly patients undergoing total hip arthroplasty.METHODS:A total of 120 elderly patients who received total hip arthroplasty in Dongguan Hospital,Guangzhou University of Chinese Medicine from January 2021 to January 2023 were selected as study subjects and randomly divided into two groups 1∶1 matching according to propensity matching method. The observation group (n=60) received pericapsular nerve group block by giving 20 mL mixture of ropivacaine and 1 μg/kg dexmedetomidine. The control group (n=60) received received pericapsular nerve group block by giving 20 mL of ropivacaine. The general data,perioperative indexes,postoperative analgesia,hemodynamic indexes,inflammatory factors,stress indexes,postoperative adverse reactions,length of hospital stay,and the occurrence of postoperative complications were compared and analyzed between the two groups. The median effective dose and 95％ effective dose concentrations of ropivacaine pericapsular nerve group block were calculated by the Probit method.RESULTS AND CONCLUSION:(1) The postoperative analgesia of the observation group was better than that of the control group,and the visual analog scale score at 6-hour dynamic,12-hour static,12-hour dynamic,24-hour static,24-hour dynamic,48-hour static,48-hour dynamic,as well as the time of first patient-controlled analgesia compression and the number of patient-controlled analgesia compression at 24 and 48 hours postoperatively were statistically different (P<0.05). (2) There were significant differences between the two groups in mean arterial pressure and heart rate at extubation and 12 hours after extubation (P<0.01). (3) The levels of interleukin-6,tumor necrosis factor-α,epinephrine,and noradrenaline in the observation group were significantly lower than those in the control group at 24 and 48 hours after surgery (P<0.01). (4) There was significant difference in the length of hospital stay between the two groups (P<0.01),and no difference was detected in the occurrence of postoperative complications (P>0.05). (5) The median effective dose and 95％ effective dose values of dexmedetomidine combined with ropivacaine were 0.164％ and 0.188％,respectively,while the median effective dose and 95％ effective dose values of ropivacaine alone were 0.194％ and 0.276％,respectively. (6) It is concluded that using dexmedetomidine combined with ropivacaine in pericapsular nerve group block can effectively alleviate postoperative analgesia in elderly patients with total hip arthroplasty,help maintain the hemodynamic stability of patients,reduce postoperative inflammation and stress response,and shorten the length of hospital stay. In addition,dexmedetomidine can reduce the dosage of ropivacaine under the condition of effective pericapsular nerve group block reaction.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

BACKGROUND:Ropivacaine and dexmedetomidine are two commonly used local anesthetic agents and adjuvants in elderly total hip arthroplasty. They provide sedation and analgesic effects during peripheral hip nerve blocks.OBJECTIVE:To explore the dose-effect relationship between dexmedetomidine and ropivacaine in continuous sedation during pericapsular nerve group block in elderly patients undergoing total hip arthroplasty.METHODS:A total of 120 elderly patients who received total hip arthroplasty in Dongguan Hospital,Guangzhou University of Chinese Medicine from January 2021 to January 2023 were selected as study subjects and randomly divided into two groups 1∶1 matching according to propensity matching method. The observation group (n=60) received pericapsular nerve group block by giving 20 mL mixture of ropivacaine and 1 μg/kg dexmedetomidine. The control group (n=60) received received pericapsular nerve group block by giving 20 mL of ropivacaine. The general data,perioperative indexes,postoperative analgesia,hemodynamic indexes,inflammatory factors,stress indexes,postoperative adverse reactions,length of hospital stay,and the occurrence of postoperative complications were compared and analyzed between the two groups. The median effective dose and 95％ effective dose concentrations of ropivacaine pericapsular nerve group block were calculated by the Probit method.RESULTS AND CONCLUSION:(1) The postoperative analgesia of the observation group was better than that of the control group,and the visual analog scale score at 6-hour dynamic,12-hour static,12-hour dynamic,24-hour static,24-hour dynamic,48-hour static,48-hour dynamic,as well as the time of first patient-controlled analgesia compression and the number of patient-controlled analgesia compression at 24 and 48 hours postoperatively were statistically different (P<0.05). (2) There were significant differences between the two groups in mean arterial pressure and heart rate at extubation and 12 hours after extubation (P<0.01). (3) The levels of interleukin-6,tumor necrosis factor-α,epinephrine,and noradrenaline in the observation group were significantly lower than those in the control group at 24 and 48 hours after surgery (P<0.01). (4) There was significant difference in the length of hospital stay between the two groups (P<0.01),and no difference was detected in the occurrence of postoperative complications (P>0.05). (5) The median effective dose and 95％ effective dose values of dexmedetomidine combined with ropivacaine were 0.164％ and 0.188％,respectively,while the median effective dose and 95％ effective dose values of ropivacaine alone were 0.194％ and 0.276％,respectively. (6) It is concluded that using dexmedetomidine combined with ropivacaine in pericapsular nerve group block can effectively alleviate postoperative analgesia in elderly patients with total hip arthroplasty,help maintain the hemodynamic stability of patients,reduce postoperative inflammation and stress response,and shorten the length of hospital stay. In addition,dexmedetomidine can reduce the dosage of ropivacaine under the condition of effective pericapsular nerve group block reaction.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

Objective To explore the mediating effect of health-promoting lifestyle on the relationship between health literacy and stigma among middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). Methods A stratified random sampling method was used to select 415 patients with T2DM from three general hospitals in Weifang to conduct a questionnaire survey using the Disease Stigma Assessment Scale for Type 2 Diabetes Mellitus (DSAS-2), the Health Literacy Scale, and the Type 2 Diabetes Health Promotion Scale (T2DHPS). Results Sickness stigma was negatively correlated with health literacy (r=-0.547, P<0.01) and negatively correlated with health promotion (r=-0.505, P<0.01), while health promotion was positively correlated with health literacy (r=0.398, P<0.01). Health-promoting lifestyle mediated the association between health literacy and stigma (β=0.0383, P<0.01), with the mediating effect accounting for 16.00% of the total effect. Conclusion Health literacy can influence the stigma of patients with type 2 diabetes mellitus through health promotion lifestyle, suggesting that the stigma of patients with diabetes can be improved through health promotion lifestyle intervention.

Objective:To investigate the correlation between cytokeratin 19 fragment(CYFRA21-1), modified ultrasound B-line and connective tissue disease associated with interstitial lung disease (CTD-ILD).Methods:The data of 112 patients with CTD hospitalized in the Department of Rheumatology and Immunology of the Second Hospital of Fujian Medical University from September 2019 to December 2021 were retrospectively collected. Sixty patients in the CTD-ILD group and 52 patients in the connective tissue disease without interstitial lung disease (CTD-noILD) group were included. The t-test and χ2 test were used to compare the demographic characteristics and tumor-associated antigens of the two groups of patients. Modified ultrasound score and HRCT Warrick score were evaluated by Pearson correlation analysis. In addition, the relationship between CYFRA21-1, modified ultrasound score and Warrick score were evaluated, and the diagnostic efficacy of CYFRA21-1 and modified ultrasound of CTD-ILD was evaluated and analyzed by binary logistic regression analysis. Results:Patients in the CTD-ILD group had higher CYFRA21-1 concentrations than the CTD-no-ILD group[5.74(4.25, 9.79) ng/ml vs. 2.79(2.21, 3.23) ng/ml, Z=45.94, P<0.001], patients in the CTD-ILD group had higher modified ultrasound scores than the CTD-no-ILD group [44.5(36.5, 60.0) vs. 5.0 (3.2, 6.8), P<0.001]. Modified ultrasound score was positively correlated with Warrick score ( r=0.93, P<0.001) and CYRFA21-1 was positively correlated with modified ultrasound score ( r=0.39, P=0.042). The sensitivity of CYFRA21-1 in determining CTD-ILD was 81.7% and the specificity was 92.3% [ AUC (95% CI)=0.88(0.81, 0.95), P<0.001], the sensitivity of modified ultrasound B-line to determine CTD-ILD was 96.4% and the specificity was 92.9% [ AUC (95% CI)=0.99 (0.97, 1.00), P<0.001]. History of smoking[ OR(95% CI)=9.26(1.11, 77.12), P=0.040] and elevated CYFRA21-1 concentration[ OR(95% CI)=19.40(4.89, 76.95), P<0.001] were risk factors for CTD-ILD. Conclusion:CYFRA21-1 is expected to be a serum marker indicating concomitant ILD in patients with CTD. Modified ultrasound B-line to determine concomitant ILD in CTD patients has good diagnostic utility and can reflect the severity of pulmonary fibrosis in CTD-ILD patients.

Objective:To evaluate the predictive value of mechanical power (MP) on the risk of in-hospital mortality in critical ill patients in emergency department.Methods:A total of 105 critical ill patients with invasive mechanical ventilation in the Department of Emergency of Second Affiliated Hospital of Guangzhou Medical University between December 1, 2017 and October 31, 2020 were retrospectively analyzed. Based on the clinical prognosis, the patients were divided into the in-hospital survival group (80 patients) and the in-hospital death group (25 patients). The clinical data and ventilator parameters were recorded, and the MP of the two groups was calculated in order to assess the predictive efficacy of MP on in-hospital death.Results:Compared to the in-hospital death group, the oxygenation index PaO 2/FiO 2 was significantly higher (271 mmHg vs. 217 mmHg, P=0.020) and blood lactate (1.59 mmol/L vs. 2.56 mmol/L, P<0.001) and procalcitonin (0.31 ng/mL vs. 3.55 ng/mL, P=0.028), minute ventilation (7.03 L/min vs.8.32 mmol/L, P=0.013), MP (14.37 J/min vs. 16.12 J/min, P=0.041), SOFA score (5 vs. 8, P=0.001) and APACHE II score (16 vs. 22, P=0.041) were significantly lower in the in-hospital survival group. Multivariate Logistic regression analysis showed that PaO 2/FiO 2( OR=1.015, P=0.044), MP ( OR=1.813, P=0.039) and SOFA score( OR=2.651, P=0.010) were independent risk factors for predicting hospital mortality in patients with mechanical ventilation. The areas under the ROC curves (AUC) were 0.62, 0.63 and 0.75, respectively. Moreover, the MP combined with SOFA score for predicting in-hospital death was significantly higher than that of MP alone (0.77 vs. 0.63, P<0.05). Conclusions:MP is associated with in-hospital death in patients with invasive mechanical ventilation in emergency department. MP combined with SOFA score can enhance its predictive efficacy

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.