Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To investigate protective effect of Pinus massoniana needle extract (PMNE) against oxidative stress in human dermal papilla cells (HDPC) , and to explore its mechanisms. Methods:As research objects, some cultured HDPC were treated with H 2O 2 at different concentrations of 0 (control group) , 0.1, 0.2, 0.4, 0.8 and 1.0 mmol/L, in order to establish the optimal condition for in vitro oxidative stress in HDPC; some other HDPC were transfected with nuclear factor-erythroid 2-related factor 2 (Nrf2) specific small interfering RNAs (siRNA1, siRNA2, siRNA3) or a Nrf2-overexpressing plasmid (pCMV6-XL5-Nrf2) , the HDPC transfected with a scrambled-siRNA and an empty plasmid pCMV6-XL5 served as the control siRNA group and control plasmid group respectively, and HDPC subjected to conventional culture served as the blank group; after the above treatment, real-time fluorescence-based quantitative PCR and Western blot analysis were performed to determine Nrf2 mRNA and protein expression, respectively; cell viability and apoptosis were detected in the above transfected cells after the treatment with H 2O 2 at an optimal concentration. In the subsequent experiment, some HDPC were divided into several groups: control group subjected to conventional culture, dihydrotestosterone group treated with 0.03 μg/ml dihydrotestosterone, proanthocyanidin group treated with 0.03 μg/ml dihydrotestosterone and 6.00 μg/ml proanthocyanidin B2, PMNE groups treated with 0.03 μg/ml dihydrotestosterone and PMNE at different concentrations of 1, 5, 25 and 100 μg/ml; after the above treatment, cell viability and apoptosis were detected, relative fluorescence intensity of intracellular reactive oxygen species (ROS) , malondialdehyde (MDA) content, mRNA and protein expression of Nrf2, quinone oxidoreductase 1 (NQO1) , heme oxygenase 1 (HO-1) , Kelch-like ECH-related protein 1 (Keap1) , transforming growth factor (TGF) -β1, Sma- and Mad-related protein 2/3 (Smad2/3) , phosphorylated Smad2/3 (p-Smad2/3) were determined in HDPC. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference- t test for multiple comparisons. Results:The viability of HDPC ranged from 75% to 85% after the treatment with 0.4 mmol/L H 2O 2, which was selected as the optimal condition for in vitro oxidative stress in HDPC. Compared with the blank group and control siRNA group, the Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups showed significantly decreased Nrf2 mRNA and protein expression (all P < 0.05) , but significantly increased apoptosis rate (Nrf2-siRNA1, Nrf2-siRNA2, Nrf2-siRNA3 groups, blank group and control group: 12.50% ± 0.05%, 26.07% ± 0.05%, 58.44% ± 1.03%, 10.38% ± 0.64%, 13.05% ± 0.12%, respectively; all P < 0.05) . Nrf2 protein expression was the lowest in the Nrf2-siRNA2 group, so Nrf2-siRNA2 was selected as the optimal interfering fragment for subsequent experiments. Compared with the blank group and control plasmid group, the Nrf2 overexpression group showed significantly increased Nrf2 mRNA and protein expression (both P < 0.05) , but a significantly decreased apoptosis rate (all P < 0.05) . After the treatment with 0.4 mmol/L H 2O 2, the Nrf2 overexpression group showed a significantly decreased apoptosis rate, but significantly increased cell viability compared with the empty vector group ( t = 3.66, 40.40, respectively, both P < 0.001) ; the Nrf2-siRNA2 group showed a significantly increased apoptosis rate, but significantly decreased cell viability compared with the control group ( t = 13.13, 67.37, respectively, both P < 0.001) . In the PMNE treatment experiment, the proanthocyanidin group and PMNE groups showed significantly increased cell viability, but significantly decreased apoptosis rates compared with the dihydrotestosterone group (all P < 0.01) ; proanthocyanidin and PMNE at different concentrations could significantly inhibit dihydrotestosterone-induced overexpression of ROS and MDA in HDPC (all P < 0.01) ; the protein expression of Nrf2, NQO1 and HO-1 was significantly higher in the proanthocyanidin group, 5-, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) , while the protein expression of Keap1 and TGF-β1, and the Smad2/3 phosphorylation level were significantly lower in the proanthocyanidin group, 25- and 100-μg/ml PMNE groups than in the dihydrotestosterone group (all P < 0.05) . Conclusion:Nrf2 plays an important role in protecting against oxidative damage in HDPC, and PMNE may exert marked protective effect on HDPC by activating the Nrf2-antioxidant responsive element signaling pathway.

OBJECTIVE: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. RESULTS: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. CONCLUSIONS The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.
Antiviral Agents ; therapeutic use ; Betacoronavirus ; isolation & purification ; Cesarean Section ; Coronavirus Infections ; complications ; drug therapy ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Oxygen ; therapeutic use ; Pandemics ; Pneumonia, Viral ; complications ; drug therapy ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; pathology ; Pregnancy Outcome ; Retrospective Studies ; Treatment Outcome ; gamma-Globulins ; therapeutic use

Objective: To investigate the risk factors of pneumonia in maintenance hemodialysis (MHD) patients. Methods: The clinical data of patients undergoing dialysis longer than three months at the Hemodialysis Center of West China Hospital of Sichuan University from July 2013 to July 2018 were retrospectively analyzed. The patients were divided into pneumonia group and non-pneumonia group. Follow-up time started from admission to the beginning of hemodialysis. All patients were followed until the patient died, or withdrawn from hemodialysis, or transferred to another center, or until the study deadline (April 2019). Baseline clinical data were compared between the two groups, and the differences in clinical data between the pneumonia group and the baseline were also analyzed. Risk factors for pneumonia in hemodialysis patients was analyzed by binary logistic regression. Kaplan-Meier curve was used to compare the survival prognosis of the two groups, and the Log-rank method was used for significant test. A multivariate Cox proportional hazard model was used to analyze risk factors for MHD patients' death. Results: (1) A total of 311 patients were enrolled in the study, in which 178 (57.2%) of the patients were male, and 75(24.1%) of the patients had pneumonia. Compared with non-pneumonia group, the pneumonia group patients were older (P=0.002), had higher level of white blood cells (P=0.001) and lower level of serum creatinine (P=0.003), albumin (P=0.001), and serum magnesium (P=0.039). There were also statistically significant differences between the two groups in the proportion of females and underlying diseases (all P<0.05). (2) The time of pneumonia occurred from the initial time of dialysis was (10.69±9.82) months. Compared with baseline values, decreased hemoglobin and albumin level were found (both P<0.01). (3) Logistic regression analysis showed male patients had lower risk of pneumonia than female patients (OR=0.438, 95% CI 0.242-0.795, P=0.007). For every 1 g/L increase in albumin, the risk of pneumonia was reduced by 6.4% (OR=0.936, 95% CI 0.885-0.991, P=0.022). Kaplan-Meier survival curve analysis showed that the difference in 5-year cumulative survival rate between pneumonia group and non-pneumonia group was statistically significant (60.6% vs 84.4%, χ²=16.647, P<0.001). (4) Multivariate Cox regression analysis showed that long dialysis time (HR=0.870, 95% CI 0.832-0.909, P<0.001) and high serum albumin level (HR=0.898, 95%CI 0.845-0.955, P=0.001) were protective factors in patients with MHD. Pneumonia (HR=3.008, 95% CI 1.423-6.359, P=0.004) was an independent risk factor for death in MHD patients. Conclusions Hemoglobin and albumin level are reduced in MHD patients with pneumonia. Low albumin level is a risk factor for pneumonia in patients. MHD patients with pneumonia have a lower survival time than those without pneumonia.

OBJECTIVE:To provide reference for pharmacists to participate in the management of chronic disease. METHODS:A total of 259 patients with chronic airway disease [included asthma and chronic obstructive pulmonary disease (COPD)] met the inclusion criteria were selected from our hospital and 5 community health care centers of medical consortium. These patients received medication safety assessment management,which was led by clinical pharmacists of our hospital with the participation of community pharmacists,including medication safety comprehensive evaluation and risk classification management, follow-up and medication guidance, integrated prescriptions checking, establishment of shared database. 1 years after the implementation,the effectiveness were evaluated by score the relatived indicators in related groups. RESULTS:After a year of the management mode practice,compared with before intervention,the patients'safety medication cognitive ability score in high-risk and low-risk group increased from(4.49±1.26)and(7.31±1.01)to(5.40±1.56)and(7.44±0.91);medication adherence score increased from(4.96±1.21)and(7.08±1.24)to(6.66±1.08)and(7.38±0.98);ACT score from asthma patients increased from (16.15±2.58)and(21.15±1.03)to(16.80±2.57)and(21.64±1.55);CAT score from COPD patients decreased from(25.51± 4.07) and (14.90 ± 3.95) to (24.20 ± 3.96) and (13.80 ± 4.08);the rate of irrational prescription effective identification and intervention by pharmacists increased from 3.6％ and 1.4％ to 9.4％ and 7.6％,respectively. All the differences above were statistically significant (P<0.05). CONCLUSIONS:The participation of pharmacists in long-term medication safety assessment management for chronic airway disease patients can improve patients'safety medication cognitive ability,medication adherence, disease control and the pharmacists'ability of irrational drug use identification and intervention.

Objective:To explore the new management mode of long-term medication safety assessment for chronic obstructive pul-monary disease (COPD) with the participation of pharmacist team in medical treatment alliance to provide reference for pharmacists participating in the management of chronic diseases under the new situation of new medical reform. Methods:Totally 126 patients with COPD meeting the inclusion criteria in our hospital and medical treatment alliance were selected. The patients received medication management including drug safety comprehensive evaluation,classification management,follow-up with medication guidance,integrat-ed prescriptions checking and shared database building etc with the participation of our clinical pharmacists to guide the community pharmacists in coordination with physicians. Results:After one-year management mode practice,the cognitive ability of safe medica-tion and compliance of the patients significantly increased(P<0.01) with significant improvement of control situation of COPD(CAT score) (P<0.05 or P<0.01), and the capacity of effective identification and irrational prescription intervention significantly in-creased (P<0.01). Conclusion:The management mode of long-term medication safety assessment for COPD patients with the partic-ipation of pharmacist team in medical treatment alliance has significant effects on COPD patients' safe medication and drug efficacy, which can improve the professional service of pharmacist team.

Objective: To evaluate the expression of cytokeratin (CK)7, CK8/18, CK19 and p40 in esophageal squamous cell carcinoma (ESCC) and its significances. Methods: One hundred and ninety cases of surgically resected ESCCs and 154 normal esophageal tissues as control were collected at the First Affiliated Hospital of Zhengzhou University in 2012.Of the 190 ESCC cases including 116 male and 74 female, aged 28-82 (60.3±8.6) years, 88 cases <60 years old and 102 cases ≥60 years old. Tissue sections were immunostained for CK7, CK8/18, CK19 and p40, and the expression was evaluated and correlated with the clinicopathologic findings and outcome. Results: CK19 and p40 were expressed in 190 cases of ESCCs; with 147 cases (77.4%) and 151 cases (79.5%) showing high p40 and CK19 expression, respectively; while 43 cases (22.6%) and 39 cases (20.5%) showed low p40 and CK19 expression, respectively. The low expression groups showed more lymph node metastases and higher pTNM stages compared to the high expression groups. The high CK19 expression group showed better prognosis than the low expression group (P<0.01); p40 expression was not correlated with prognosis(P>0.05). In contrast, CK7 and CK8/18 expression was only seen in 29 cases (15.3%) and 59 cases (31.1%) of ESCCs, respectively, and their expression correlated significantly with the degree of tumor differentiation and lymph node metastasis (P<0.05). The prognosis in the CK7 negative group was better than that in the CK7 positive group. Similar results were found in CK8/18 expression. Multivariate analysis revealed that pTNM stages, low CK19 expression and CK8/18 expression were independent prognostic factors. Conclusions Low p40 expression and the expression of CK7 and CK8/18 cannot exclude poorly-differentiated ESCCs.CK7 and CK8/18 expression and low CK19 and p40 expression in the ESCCs are associated with lymph node metastasis and poor prognosis. Decreased expression of CK19 and positive expression of CK8/18 in ESCCs are independent prognostic markers.

Background and purpose:New treatment methods should be explored for non-small cell lung cancer (NSCLC) patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). This study compared the curative effect of pemetrexed with geiftinib or pemetrexed alone in advanced NSCLC with acquired resistance to EGFR-TKI.Methods:This study included 62 NSCLC patients with advanced EGFRgene mutation and acquired resistance to EGFR-TKI. Among those, 32 patients were treated with pemetrexed and geiftinib, and 30 patients treated with geiftinib alone. The differences in outcomes between the two strategies were assessed.Results:Objective response rate (ORR) was 46.9% for those treated with pemetrexed and geiftinib and 20%for those treated with pemetrexed alone(χ2=4.933,P<0.05). There was no signiifcant differences between the two groups on disease control rate (DCR) (P>0.05). The median progression-free survival (PFS) was 8.0 months on pemetrexed and gefitinib group and 6.3 months on pemetrexed alone (χ2=8.063,P<0.05). There was no significant differences between the two groups on overall survival (OS) (P>0.05). Higher occurrence of leukocytopenia and rash was observed in the pemetrexed and geiftinib group than in the pemetrexed group (P<0.05). There was no signiifcant differences be-tween the two groups on grade 3-4 toxicities (P>0.05).Conclusion:This study was to demonstrate that continuation of EGFR-TKI with pemetrexed in patients with acquired resistance improves outcomes compared with pemetrexed alone. An improved response rate and PFS were observed in this study. A larger prospective clinical trial is needed to further evaluate this promising strategy.

OBJECTIVE:To explore the clinical utilization of carbapenems in a hospital,analyze and evaluate its medication rationality. METHODS:All the 508 medical records of inpatients treated with carbapenems from Jul. 2012 to Jun. 2015 were retro-spectively investigated,the utilization and pathogenic examination of carbapenems were evaluated;by setting the carbapenems eval-uating standard,the medication rationality of carbapenems was evaluated and inappropriate cases were classified and analyzed statis-tically. RESULTS:The drug utilization indexed (DUI) of Imipenem and cilastatin sodium for injection and Meropenem for injec-tion were 0.80 and 1.32,respectively;the total rate of microbial inspection was 95.9%;according to the drug sensitive test result, the rate of drug selection was 62.8%;there were 54 cases(10.6%)of irrational use records,in which,irrational dosage(42.6%) and improper drug selection (31.4%) were the major problems. CONCLUSIONS:There are some inappropriate medication prob-lems in carbapenems utilization in the hospital. Developing the carbapenems utilization evaluation is helpful to discover typical medi-cation problems,which can provide reference for intervention and continuous improvement of rational drug use.

Objective To explore the clinical manifestations,antimicrobial therapy,and risk factors of mortality in patients with Acinetobacter baumannii bloodstream infection.Methods Clinical data of 153 patients with Acinetobacter baumannii bloodstream infection hospitalized in First Affiliated Hospital of Zhejiang University from January 2013 to September 2014 were analyzed retrospectively.According to the 28-day survival after diagnosis,the patients were divided into death group (n =76) and survival group (n =77).Data related to demographic and clinical characteristics,underlying diseases,treatment,invasive procedures,bacterial resistance to antibiotics,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ)scores at onset,and antimicrobial therapy were collected.The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis.Results This study included 153 patients with Acinetobacter baumannii bloodstream infection.The 28-day mortality was 49.7％.The independent risk factors of mortality were APACHE Ⅱ score ≥22 at onset (OR =15.7,95％ CI 5.1-48.1,P ＜ 0.001),septic shock (OR =6.3,95 ％ CI 1.9-21.3,P =0.003),and administration of steroids (OR =3.6,95％ CI 1.0-12.3,P =0.043).Compared with subjects treated with non-cefoperazone-sulbactam-based regimen,those treated with cefoperazone-sulbactam for multidrug-resistant Acinetobacter baumannii (MDR-AB) had significantly lower mortality on day7,day14 and day28 (8.9％ vs 59.2％,31.1％ vs 65.8％,44.4％ vs 72.4％ respectively).Conclusions The patients with Acinetobacter baumannii bloodstream infection have high mortality within one month.Administration of steroids and septic shock are associated with poor prognosis.APACHE Ⅱ score ≥ 22 at onset predicts adverse outcome.Cefoperazone-sulbactam-based antimicrobial therapy improves patients' survival.