OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Objective To find a more effective alternative therapy for antibiotic therapy and fecal microbiota transplantation in current primary treatment of clostridioides difficile infection (CDI) because of the high recurrence rate. Methods A series of 8-hydroxyquinoline derivatives were designed and synthesized based on 8-hydroxyquinoline scarffold. Results The activity test against C. difficile showed that most of the molecules exhibited good antibacterial activity against C. difficile, and compound 6f showed attractive anti-C. difficile activity. Conclusion A new type of 8-hydroxyquinoline derivatives with anti-clostridium difficile was found, which could be used as good lead compounds for further development.

Objective:To explore the protective effect and its mechanism of vitamin C on septic renal injury induced by lipopolysaccharide (LPS).Methods:Renal tubular epithelial cells HK-2 were induced with 10 mg/L LPS for 8 hours and 12 hours, respectively, and then 0.5 mmol/L and 1 mmol/L vitamin C were added, respectively. Cell viability was measured using cell proliferation and toxicity assay cell counting kit-8 (CCK-8) to determine suitable condition for subsequent experiments. HK-2 cells were divided into control group, LPS group and LPS+vitamin C group (LPS+VC group). The contents of necrosis factors phosphorylated mixed lineage kinase domain-like protein (p-MLKL) and phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) were measured by Western blotting. The contents of inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) in each group. Differences among the groups were compared.Results:CCK-8 showed that 1 mmol/L vitamin C improved the survival rate of HK-2 cells to 86% after 12 hours of LPS induction, so this condition was selected for subsequent experiments. After 12 hours LPS induction in HK-2 cells, the expressions of p-MLKL and p-RIPK3 were significantly higher than those of the control group, and the levels of IL-1β and TNF-α were also significantly higher than those of the control group [IL-1β (ng/L): 23.2±1.4 vs. 12.8±3.9, TNF-α (ng/L): 36.4±3.9 vs. 11.6±1.8, both P < 0.05], indicating the co-existence of cell necrosis and inflammation. Compared with LPS group, 1 mmol/L vitamin C significantly decreased the protein expression of p-MLKL and p-RIPK3, and also significantly decreased the levels of IL-1β and TNF-α [IL-1β (ng/L): 19.8±0.7 vs. 23.2±1.4, TNF-α (ng/L): 17.4±5.8 vs. 36.4±3.9, both P < 0.05]. Conclusion:Vitamin C can alleviate LPS-induced HK-2 cell damage, and reduce the expressions of necrotic factors and inflammatory factors.

In order to improve the management level of medicine list of medical institutions in China ，and help medical institutions build a medicine list of medical institutions with reasonable drug use structure ，standardized adjustment procedures ， convenient operation and application and scientific evaluation methods ，so as to meet the needs of clinical rational drug use to the greatest extent ，with the support of the Pharmaceutical Care Professional Committee of the Chinese Pharmaceutical Association ， China-Japan Friendship Hospital and the First Affiliated Hospital of University of Science and Technology of China （Anhui Provincial Hospital ）jointly initiate and complete Guideline for the Evaluation of Medicine List in Chinese Medical Institutions jointly with a number of medical institutions. In strict accordance with the methodological requirements of World Health Organization standard guidelines ，based on the Delphi method ，the guideline formulation working group has constructed the quality evaluation index system and quantitative scoring table of medicine list management in medical institutions from the 5 dimensions of organization and management ，structure，adjustment，application and e valuation of the list. It is used to help medical institutions evaluate the quality of their medicine list management ，so asto play a positive role in the fine management of medicine list in medical institutions.

Objective:To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors.Methods:The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (C min) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and C min was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUC 0-24 h) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUC 0-24 h/MIC was calculated. Results:285 patients with 529 records of C min were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the C min (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group ( P < 0.01). q6 h group and q8 h group showed higher C min than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both P < 0.05) and lower peak concentration (C max) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both P < 0.05). However, there was no significant difference in terms of percentage of PD target (AUC 0-24 h/MIC≥400) among the three groups (q12 h group, q8 h group, q6 h group were 38.1%, 41.3%, 45.5%, P > 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CLvancomycin) were the main influencing factors of vancomycin PD parameters such as C min and AUC 0-24 h/MIC ( r values of CCr were -0.391, -0.424, and rvalues of CLvancomycin were -0.673, -0.663, all P < 0.01), and were negatively correlated with age ( r values were -0.432 and -0.488, respectively, both P < 0.01). Conclusions:At the same daily dose, C min can be increased and C max can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUC 0-24 h/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CLvancomycin and age.

Objective:To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity.Methods:Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg·kg -1·d -1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. Results:A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, μmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg·kg -1·d -1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (μmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (μmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. Conclusions:The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

Objective:To observe the changes of renal function in critically ill patients after using vancomycin and analyze the renal protective effect of reduced glutathione (GSH) on vancomycin nephrotoxicity.Methods:The clinical data of patients with severe infection who were administered with vancomycin or plus infusion of GSH admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019 were collected during the study period, and the patients were divided into only vancomycin group and vancomycin combined with GSH group. The gender, age, body weight, underlying diseases, clinical diagnosis, severity score, renal function before and after taking the medicine, average daily dose and treatment duration of vancomycin and GSH, length of ICU stay and clinical outcomes were recorded and analyzed.Results:A total of 217 patients were enrolled, with 127 patients in the only vancomycin group, and 90 in the combination with GSH group. There was no statistically significant difference between the two groups in terms of gender, body weight, duration of vancomycin treatment, history of chronic kidney disease, and ICU mortality. The main causes of 217 patients admitted to the ICU were lung infection, sepsis/septic shock, and severe acute pancreatitis (SAP) and so on. The majority of patients in only vancomycin group had lung infections (63.0%), while the main etiology in combination with GSH group was SAP (46.7%). Compared with the only vancomycin group, the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in the combination with GSH group significantly decreased [15.0 (10.5, 21.0) vs. 27.0 (20.0, 31.0), P < 0.01], but the quick sequential organ failure assessment (qSOFA) score was significantly higher [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], the basic renal function was poorer [serum creatinine (SCr, μmol/L): 102.0 (64.7, 178.0) vs. 56.0 (42.0, 71.0), blood urea nitrogen (BUN, mmol/L): 11.5 (6.7, 18.4) vs. 4.70 (3.5, 8.1), both P < 0.05], and the average daily dose of vancomycin was lower (mg·kg -1·d -1: 22.22±10.09 vs. 25.51±9.56, P < 0.05). The renal function of patients was getting worse significantly after vancomycin usage as compared with before [SCr (μmol/L): 68.0 (50.3, 103.4) vs. 56.0 (42.0, 71.0), BUN (mmol/L): 5.4 (3.6, 9.6) vs. 4.7 (3.5, 8.1), both P < 0.05]. However, the renal function indexes of the combination with GSH group were better than those before treatment [SCr (μmol/L): 81.0 (61.0, 129.0) vs. 102.0 (64.7, 178.0), P < 0.05; BUN (mmol/L): 8.4 (6.2, 17.8) vs. 11.5 (6.7, 18.4), P > 0.05], and the length of ICU stay was significantly shorter than that in the only vancomycin group [days: 29.0 (14.0, 54.2) vs. 37.0 (25.0, 55.0), P < 0.05]. Conclusions:The incidence of drug-induced renal injury caused by vancomycin is high. The GSH can significantly reduce their renal toxicity and shorten the length of hospital stay.

Objective To evaluate protective effects of dexmedetomidine combined with lung-protective ventilation on lungs in patients undergoing thoracic surgery.Methods Eighty patients with normal pulmonary function,aged 40-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with body mass index of 20-25 kg/m2,scheduled for elective right lobectomy for lung cancer performed via a thoracoscope,were divided into 4 groups (n =20 each) using a random number table:conventional ventilation group (group C),dexmedetomidine combined with conventional ventilation group (group DC),lung-protective ventilation group (group P) and dexmedetomidine combined with lung-protective ventilation group (group DP).In DC and DP groups,dexmedetomidine was intravenously infused as a loading dose of 0.5 μg/kg (over 10 min) starting from 10 min before anesthesia induction,followed by an infusion of 0.6 μg · kg 1 · h-1 until the end of surgery.In C and DC groups,the tidal volume was set at 9 ml/kg,positive end-expiratory pressure 0 cmH2O,fraction of inspired oxygen 100％,respiratory rate 10-12 breaths/min,inspiratory/expiratory ratio 1 ∶ 2,and end-tidal pressure of carbon dioxide was maintained at 35-45 mmHg during both two-lung ventilation (TLV) and one-lung ventilation (OLV).In P and DP groups,the tidal volume was set at 6 ml/kg,positive end-expiratory pressure 5 cmH2O,fraction of inspired oxygen 70％,respiratory rate 14-16 breaths/min,i nspiratory/expiratory ratio 1 ∶ 2,and end-tidal pressure of carbon dioxide was maintained at 35-45 mmHg during TLV and OLV.Airway peak pressure (Ppe~),airway plateau pressure (Pp~t),dynamic lung compliance and airway resistance (Raw) were monitored and recorded immediately before OLV (T1),at 30 min,1 h and 2 h of OLV (T2-4) and at 15 min after restoration of TLV (T5).Arterial blood samples were collected at 10 min before induction of anesthesia (T0) and T1-5 for blood gas analysis,and oxygenation index was calculated.At T0,T1,T3,T4 and 2 and 24 h after surgery (T6,7),blood samples were taken from the right internal jugular vein for determination of the concentrations of serum tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) by enzyme-linked immunosorbent assay.Results Compared with group C,Raw was significantly decreased at T2-4 in group DC,Ppeak,Pplat and Raw were significantly decreased at T2-4 in P and DP groups,oxygenation index was significantly increased at T5 in DC and P groups,oxygenation index was significantly inereased at T2-5 in group DP,the concentrations of serum TNF-α and IL-6 were significantly decreased at T3,4 and T6,7 in P,DC and DP groups,and the concentrations of serum HMGB1 were significantly decreased at T6,7 in DC and DP groups (P＜0.05).Compared with group DC,Ppeak,Pplat and Raw were significantly decreased at T2-4,oxygenation index was increased at T3-5,and the concentrations of serum TNF-α and IL-6 were decreased at T3,4 and T6,7 in group DP (P＜0.05).Compared with group P,Raw was signifieantly decreased at T2-4,oxygenation index was increased at T2-5,and the concentrations of serum TNF-α and IL-6 were decreased at T3,4 and T6,7,and the concentrations of serum HMGB1 were decreased at T6,7 in group DP (P＜0.05).There was no significant difference in dynamic lung compliance at each time point among the four groups (P＞0.05).Conclusion The combination of dexmedetomidine and lung-proteetive ventilation provides protective effects on lungs and exterts better efficacy than either alone,and the mechanism may be related to inhibiting systemic inflammatory responses of patients undergoing thoracic surgery.

Objective Using an adenoviral vector , the wild-type PTEN gene was transduced into activated hepatic stellate cell (HSC) in vitro and the phosphorylation status of Akt were investigated. Methods The wild type PTEN gene was transduced into activated HSC in vitro mediated by adenoviral vector. The expressions of PTEN and total Akt in HSC were measured by Western blot and Real-time fluorescent quantitation PCR. And the expressions of phosphorylated Akt (Thr308) in HSC was determined by Western blot. Results The data showed that exogenous wild type PTEN gene was successfully transduced and expressed in activated HSC in vitro. The over-expression of wild type PTEN resulted in the significant down-regulated expression of phosphorylated Akt (Thr308) in activated HSC (P < 0.01). But no significant defferences were found in the expression of total Akt in activated HSC at both transcriptional and translational levels(P>0.50). Conclusions The overexpression of wild-type PTEN can negatively regulate PI3K/Akt signaling transduction by inhibiting the phosphorylation of Akt in activated HSC in vitro.

Objective To evaluate the efficiency of dexmedetomidine combined with flurbipro-fen axetil preventing agitation and reducing extubation reaction after general anesthesia. Methods Eighty patients,ASA Ⅰ or Ⅱ,scheduled for selective oral and maxillofacial surgery were randomly divided into four groups,20 patients in each group.30 mins before end of the operation, patients intravenously received flurbiprofen axetil 50 mg (group F),dexmedetomidine 0.5 μg/kg (group D),dexmedetomidine 0.25 μg/kg plus flurbiprofen axetil 50 mg (group DF),normal saline (group C),respectively.MAP,HR were recorded before extubation (T0 ),extubation (T1 ),5 mins after extubation (T2 ).The recovery time,extubation time,Riker sedation-agitation score(RSAS)be-fore extubation and Ramsay sedation score 5 min after extubation were observed.Results Compared with T0 ,MAP,HR at T1 ,T2 in group C and group F were significantly increased (P <0.05 or P <0.01),MAP,HR at T1 ,T2 in group D and group DF were significantly lower than those in group C (P <0.01 ).The recovery time,extubation time in group D were significantly longer than those in group C,group F and group DF(P <0.05).Ramsay scores in group D was significantly higher than other groups(P <0.05).The incidence of agitation in group D and group DF were significantly lower than those in group C(P <0.05 or P <0.01).Conclusion Dexmedetomidine 0.25 μg/kg plus flurbi-profen axetil 50 mg can effectively prevent agitation and reduce extubation cardiovascular reaction dur-ing recovery period,without the disadvantage of prolonging the recovery and extubation time.