AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To evaluate the risks and benefits of endoscopic ligation and tissue adhesive injection for tortuous gastric varices.Methods:A total of 193 patients with esophagogastric varices, who underwent endoscopic variceal ligation or endoscopic tissue adhesive injection in Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University from June 2015 to June 2020, were included in the retrospective analysis. These cases were connected vessels (type Le and gf based on LDRf standard) of tortuous gastric varices (F1 in Hashizume standard). According to the treatment, the patients were divided into three groups: gastric fundus and esophageal ligation group (endoscopic ligation of gastric fundus and esophageal varices, 32 cases), tissue adhesive group (endoscopic tissue adhesive injection of gastric varices, endoscopic ligation of esophageal varices, 71 cases) and esophageal ligation group (endoscopic ligation of esophageal varices, 90 cases). The re-bleeding rate, the effectiveness rate, the significant effectiveness rate and complications of the three groups were compared.Results:The rates of re-bleeding in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 18.75% (6/32), 12.68% (9/71) and 3.33% (3/90), respectively.There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=6.110, P<0.016). The effectiveness rates of the three groups were all 100.00%. The significant effectiveness rates in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 37.50% (12/32), 25.35% (18/71) and 14.44% (13/90), respectively. There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=7.702, P<0.016). No pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis or perforation occurred in the three groups.The incidences of chest pain or abdominal pain in gastric fundus and esophageal ligation group, tissue adhesive group and esophageal ligation group were 18.75% (6/32), 11.27% (8/71) and 2.22% (2/90), respectively.There was significant difference only between gastric fundus and esophageal ligation group and esophageal ligation group ( χ2=10.524, P<0.016). There was no significant difference in the incidence of fever, nausea or vomiting among the three groups ( P>0.05). Conclusion:Simultaneous endoscopic ligation of gastric fundus and esophageal varices, and endoscopic tissue adhesive injection of gastric varices combined with endoscopic ligation of esophageal varices is of no benefit for patients with tortuous gastric varices, but endoscopic ligation of esophageal varices alone may yield more benefit.

Objective To summarize the clinical experience in the treatment of allogeneic lung transplantation with ABO-different donor. Methods Data of three cases of lung transplantation carried out in Tianjin First Central Hospital from August to September 2015 were retrospectively analysed. ABO blood groups were different but compatible in three donors who were with brain death, and their panel reactive antibody (PRA) and lymphocyte poison cross matching test were negative. The surgical approaches were left single-lung transplantation and sequential bilateral single-lung transplantation. After the surgery, measures for pneumonedema control, immuno suppression (mycophenolate mofetil + tacrolimus +glucocorticoids) and anti-infection (imipenem and cilastatin sodium+ micafungin sodium+ganciclovir) were carried out. Results The operation wsa completed successfully in all 3 patients, and the operative time was 5-6 hours. The cold ischemia time was less than 4 hours. The blood loss during the operation was 800-1000 mL. The trachea cannula extubation was pulled out within 24 h, thoracic drainage tube was pulled out within 72 h. All the patients were moved into general ward in 5-8 days. Patients discharged from hospital in 5 weeks after operation. Pneumonia infection occurred in 2 cases on the 6 th day after operation, and antibiotic treatment was upgraded and infection was cured after 3 weeks. All patients were followed up for 21-22 months, and 3 patients survived without serious complications such as graft rejection. Conclusion Comprehensive and effective surgical techniques, reasonable choice of donor lung and preservation method, active anti-infection strategy and triple immunosuppressive program can improve the survival rate after transplantation.

Objective To summarize the value of extracorporeal membrane oxygenation (ECMO) in right ventricular failure after heart transplantation. Methods Data of 31 cases with orthotopic heart transplantations from January 2016 to January 2018, in Tianjin First Central Hospital were retrospectively analyzed. Three patients received ECMO support because of right ventricular failure after operation.There were two males and one female in these three patients.Their ages were 52,38 and 67 years old.ECMO was performed in the heart transplantation(2 patients)and eight hours after the surgery. ECMO was established in these patients via femoral artery and femoral vein,V-A model.The mean blood flow was about 3.0 L/min.Continuous ventilator supports,low temperature sedation,anti-infection and nutrition support therapy were applied in the ECMO procedure.Results ECMO was weaned off successfully in all three patients.The time for ECMO was(144-177) h. All three patients were treated with continuous renal replacement therapy (CRRT). One patient had renal failure, the transition was given to regular dialysis after CRRT treatment, and the regular dialysis treatment after discharged from hospital.The ventilator time was(168.6±24.6)h in the three patients.The duration of staying in the intensive care unit was (31.8 ± 12.5) d. All three patients were discharged from the hospital successfully, and their cardiac function was normal. Conclusion ECMO can be used to treat right heart failure after heart transplantation,and the clinical effect is satisfactory.

Objective To evaluate the clinical efficacy and reliability of the minimally invasive treatment of patent ductus arteriosus (PDA) via the second intercostal incision on the left margin of sternum. Methods Clinical data of 31 infantile children undergoing ligation of PDA in Tianjin First Center Hospital from January 2014 to November 2017 were collected. All cases were performed operation through the second intercostal incision on the left margin of sternum. The operative process of this operation was summarized, and its clinical outcome was analyzed. Results The operation went smoothly,the length of the incision was(2.5±1.0)cm,the operation time was(1.5±0.2)h,the intraoperative bleeding was less than 5 mL,and the average length of hospital stay was(15.1±4.2)d.There were no complications such as death and massive hemorrhage in the perioperative period.The thoracic drainage tube was not needed after the operation.During the follow-up from 1 month to 4 years, catheter recanalization and aneurysm formation were undetected. Conclusion The treatment of PDA with the second intercostal incision on the left margin of sternum is safe and reliable.It has fewer complications and better long-term effect.

OBJECTIVETo determine whether early application of Duo positive airway pressure (DuoPAP), in comparison with nasal continuous positive airway pressure (NCPAP), can reduce the need for endotracheal intubation and mechanical ventilation and decrease the incidence of bronchopulmonary dysplasia (BPD) in preterm neonates with respiratory distress syndrome (RDS).

METHODSIn a single-center, randomized controlled trial, preterm neonates (gestational ages 30-35 weeks) with RDS were randomly assigned to receive DuoPAP (n=34) or NCPAP (n=33) within 6 hours of birth. If the two noninvasive ventilations were not effective, endotracheal intubation and mechanical ventilation were used, and pulmonary surfactant was administered as rescue therapy. The total invasive respiratory support rate and incidence of BPD within 24, 48 and 72 hours of birth were observed. The two groups were compared in terms of PaCO2, PaO2 and oxygenation index (OI) at 1, 12, 24, 48 and 72 hours after using the noninvasive respiratory support.

RESULTSThe total invasive respiratory support rates within 48 and 72 hours after birth were significantly lower in the DuoPAP group than in the NCPAP group (P<0.05). There was no difference in the incidence of BPD between the two groups (P>0.05). The OI in the DuoPAP group was significantly higher than in the NCPAP group at 1, 12, 24, 48 and 72 hours after noninlasive respiratory support (P<0.05). The DuoPAP group showed significantly lower PaCO2 than the NCPAP group at 1, 12, and 24 hours after noninvasive respiratory support (P<0.05). PaO2 was significantly higher in the DuoPAP group than in the NCPAP group at 1 and 12 hours after noninvasive respiratory support (P<0.05).

CONCLUSIONSCompared with NCPAP, early application of DuoPAP can decrease the need for endotracheal intubation and mechanical ventilation in preterm neonates with RDS, showing promise for broad use.

Bronchopulmonary Dysplasia ; epidemiology ; Continuous Positive Airway Pressure ; methods ; Female ; Humans ; Infant, Newborn ; Intermittent Positive-Pressure Ventilation ; methods ; Male ; Noninvasive Ventilation ; methods ; Respiratory Distress Syndrome, Newborn ; therapy

BACKGROUNDLeft main coronary artery (LMCA) stenosis has been recognized as a risk factor for early death among patients undergoing coronary artery bypass grafting (CABG). This study aimed to assess if LMCA lesions pose an additional risk of early or mid-term mortality and/or a major adverse cardiac and cerebrovascular event (MACCE) after off-pump coronary artery bypass grafting (OPCABG), compared with non-left main coronary artery stenosis (non-mainstem disease).

METHODSFrom January 1, 2009 to December 31, 2010, 4869 patients had a primary isolated OPCABG procedure at Beijing Anzhen Hospital. According to the pathology of LMCA lesions, they were retrospectively classified as a non-mainstem disease group (n = 3933) or a LMCA group (n = 936). Propensity scores were used to match the two groups, patients from the non-mainstem disease group (n = 831) were also randomly selected to match patients from the LMCA group (n = 831). Freedom from MACCE in the two groups was calculated using the Kaplan-Meier method.

RESULTSThe difference in the mortality and the rate of MACCE during the first 30 days between the non-mainstem disease group and the LMCA group did not reach statistical significance (P = 0.429, P = 0.127 respectively). With a mean follow-up of (12.8 ± 7.5) months and a cumulative follow-up of 1769.6 patient-years, the difference in the freedom from MACCEs between the two groups, calculated through Kaplan-Meier method, did not reach statistical significance (P = 0.831).

CONCLUSIONAnalysis of a high volume of OPCABG procedures proved that LMCA lesions do not pose additional early and mid-term risk to OPCABG. Therefore, a LMCA lesion is as safe as non-mainstem disease lesion during the OPCABG procedure.

Adult ; Aged ; Coronary Artery Bypass, Off-Pump ; adverse effects ; mortality ; statistics & numerical data ; Coronary Artery Disease ; surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Retrospective Studies