Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.

Objective During the rapid expansion of postgraduate education,it is meeting more and more conflicts between enroll-ment scale and cultivation quality.The construction of a cultivation quality assurance system for postgraduates becomes an urgent task in the new situation.Methods The data was analyzed with SPSS 24.0,based on the anonymous review results of postgraduates'disserta-tions by a three-A stomatological hospital during 2022-2023.Results The results showed that the overall evaluation of anonymous dis-sertation opinions in 2022 was better than that in 2023,and the passing rate of anonymous dissertation evaluation of doctoral students was higher than that of master students.Irregular forms of composition,low research workload,and insufficient innovation were found in failed postgraduates'dissertations.Conclusion Strengthening the management of study style education and training process,and ex-ploring cultivating mode of overlapping subjects,are necessary to improve the construction of cultivation quality assurance system of postgraduates.

Objective:To analyze the change characteristics of creatinine level in the early stage of patients with diquat (DQ) poisoning, and to explore the early risk factors and the value of prognosis.Methods:A retrospective analysis was carried out on patients with DQ admitted to the the first affiliated hospital of Zhengzhou University from January 2020 to June 2022. The DQ patients were divided into death group and the survival group according to the 28 days survival status after posioning. The basic data and serum indexes and blood gas analysis of the patients on day 1 (D1), day 3 (D3) and day 5 (D5) were collected. The difference of clinical features between the two groups was analyzed, the variables were screened by multiple logistic regression analysis, and the predictive value of the variables was evaluated by drawing receiver operating characteristic curve (ROC curve).Results:A total of 88 patients were included, including 40 patients in the survival group and 48 patients in the death group. The toxic dose in death group was significantly higher than that in survival group [100(40.00, 120.00) mL vs. 50.00(20.00, 90.00) mL, P=0.003]. The higher the toxic dose, the higher the fatality rate. All 4 patients with oral doses greater than 200 mL died. Compared with the survival group, the levels of alanine aminotransferase (ALT) (D3, D5), creatinine (CR) (D3, D5), blood amylase (AMY) (D5) and oxygen partial pressure (PaO 2) (D5) in the death group were significantly higher than those in the survival group (all P<0.05). Multiple Logistic regression analysis showed that CR (D3) and AMY(D5) were independent risk factors for death after poisoning, and PaO 2(D5) was independent protective factor. ROC curve showed that the areas under ROC curve of CR (D3), AMY (D5) and PaO 2 (D5) were 0.814, 0.741 and 0.702, respectively. Conclusion:The higher the oral dose, the higher the death rate. After admission, CR(D3), AMY (D5) and PaO 2 (D5) were independent factors influencing the prognosis of DQ poisoning. In particular, CR (D3) is more effective in predicting death after poisoning.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Objective:To investigate the etiological characteristics and drug resistance patterns of multidrug-resistant organism (MDRO) infection in patients after cardiac surgery, so as to help clinicians rationally prescribe antimicrobials recommended by guidelines, increase the success rate of empirical antibacterial therapy and improve the prognosis of inpatients.Methods:Clinical data of 409 patients diagnosed with nosocomial infection (NI) after cardiac surgery from January 2018 to October 2021 were retrospectively collected. According to the results of culture, these cases were divided into two groups: MDR bacterial infection group (MDR, n=176) and non-MDR bacterial infection group (non-MDR, n=233). The etiological characteristics of MDRO infection and the patterns of drug resistance to commonly used clinical antibiotics were analyzed. Meanwhile, the etiological distribution, drug resistance and clinical outcome corresponding to different surgical types and clinical infection types were statistically analyzed. Results:A total of 306 strains of MDR bacteria were detected. Among the 176 patients, 97 (55.1%) were infected with more than one kind of MDRO and the mix infections were mainly caused by Klebsiella pneumoniae, Acinetobacter baumannii and/or Pseudomonas aeruginosa. Carbapenem-resistant (CR) bacteria accounted for 69.6% (213/306). Regardless of surgical type and clinical infection type, Acinetobacter baumannii (114/306, 37.3%) was the most common pathogenic bacteria, followed by Klebsiella pneumoniae (72/306, 23.5%) and Pseudomonas aeruginosa (55/306, 18.0%). Most of the clinical specimens were sputum specimens (528/601, 87.9%) and most of the isolated strains were carbapenem resistant, MDR and extensively drug-resistant (XDR). The positive rates of MDR bacteria were 53.7% and 53.1% in patients undergoing coronary artery bypass grafting (CABG) and aortic surgery, respectively, while the positive rates of pandrug-resistant bacteria were relatively low. In vitro drug sensitivity test results showed that MDR bacteria were highly resistant to levofloxacin (64.4%) and cefepime (61.4%), and then to ciprofloxacin (54.6%), ceftazidime (53.9%) and cotrimoxazole (52.4%). However, the resistance rates to polycolistin (5.5%) and amikacin (7.2%) were low. Compared with non-MDR bacteria, MDR bacteria were less susceptible to ceftazidime (χ 2=156.663, P<0.001), ceftriaxone (χ 2=27.844, P<0.001), cefepime (χ 2=210.181, P<0.001), imipenem (χ 2=173.242, P<0.001), levofloxacin (χ 2=201.521, P<0.001), ciprofloxacin (χ 2=180.187, P<0.001), amikacin (χ 2=16.661, P<0.001), gentamicin (χ 2=46.047, P<0.001), tobramycin (χ 2=106.546, P<0.001), piperacillin (χ 2=7.325, P=0.007), ampicillin/sulbactam (χ 2=5.415, P=0.020), piperacillin/tazobactam (χ 2=139.506, P<0.001), cefoperazone/sulbactam (χ 2=102.832, P<0.001), cotrimoxazole (χ 2=121.217, P<0.001), aztreonam (χ 2=6.977, P=0.008) and minocycline (χ 2=53.107, P<0.001). Although there was no significant difference in the detection rates of pathogenic bacteria between patients undergoing different types of surgery or having different types of infection, the mortality rate of NI after cardiac surgery, especially MDR bacterial infection, was as high as 30.0%. Moreover, the mortality rate was closely related to the types of clinical infection. The all-cause mortality of common pulmonary infection and bloodstream infection (BSI) was 10.0% to 20.0%, and once the patient′s condition was not under control and progressed to severe infection or even septic shock, the all-cause mortality would double. Conclusions:MDR bacterial infections would bring great challenges to patients after cardiac surgery, especially gram-negative bacteria (GNB) such as Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. More than half of the patients would have mixed infections caused by carbapenem resistant, XDR or even pandrug-resistant bacteria, resulting in limited choice of anti-infective drugs and poor prognosis in hospitalized patients.

Objective:To explore the efficacy and safety of sivelestat, a neutrophil elastase (NE) inhibitor, in the treatment of acute lung injury (ALI) in the intensive care unit (ICU).Methods:A retrospective analysis was performed on 171 patients with ALI in the ICU of the First Affiliated Hospital of Zhengzhou University from June 2020 to June 2021, including 77 patients in the sivelestat group and 94 patients in the conventional treatment group. Acute physiology and chronic health evaluation (APACHE) Ⅱ score, Murray lung injury score, oxygenation index (PaO 2/FiO 2 ratio), inflammatory cytokines (IL-6, IL-10, TNF-α), ventilator-free days (VFD), the length of ICU stay, and the 28-day mortality were collected to assess the efficacy of sivelestat. At the same time, adverse reactions and laboratory test results within 30 days after the use of sivelestat were recorded to assess the safety. Results:Compared with conventional treatment, oxygenation index, Murray lung injury scores, IL-6, IL-10, and TNF-α were significantly improved after 7 days of sivelestat treatment. Compared with the conventional treatment group, the VFD was significantly longer ( P = 0.0119) and the length of ICU stay was significantly shorter ( P = 0.0269) in the sivelestat group. The mortality was 14.29% in the sivelestat group and 22.34% in the conventional treatment group and, with no statistically significant. In the meantime, sivelestat did not increase adverse reactions within 30 days after treatment. Conclusions:Sivelestat treatment is safe and more effective than conventional treatment for ALI patients in the ICU.

Clinical data of 93 patients with severe craniocerebral injury admitted in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Zhengzhou University from September 2016 to September 2018 were retrospectively analyzed. Forty six patients received 10% hypertonic salt solution 60 ml (hypertonic salt group) and 47 patients received 20% mannitol 125 ml (mannitol group) for relieving early postoperation cerebral edema. The changes of intracranial pressure, central venous pressure, heart rate, mean arterial pressure (MAP), urine volume and serum sodium level at 2, 4 and 6 h after dehydrating agents were compared between two groups. There were no significant differences in the intracranial pressure, central venous pressure, heart rate and urine volume between two groups at 2, 4 and 6 h after the first dehydration treatment (all P>0.05). The MAP values of the two groups were (88±11) and (80±10), (85±10) and (78±9), (79±12) and (73±13) mmHg (1 mmHg=0.133 kPa) at 2, 4 and 6 h after the first dehydration treatment; and the serum sodium levels were (145±5) and (136±4), (144±6) and (133±5), (140±5) and (135±4) mmol/L, respectively. There were significant differences between two groups (all P<0.05). It is suggested that hypertonic salt can reduce intracranial pressure and increase cerebral perfusion better than mannitol in severe craniocerebral injury.