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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

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OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry （LC-MS/MS） method for the simultaneous determination of bepotastine and hydroxychloroquine concentrations in human breast milk and apply it in clinical practice. METHODS The milk samples （50 μL） were precipitated with 200 μL methanol containing the internal standard （100 ng/mL chloroquine）， and the supernatant was taken for analysis after vortexing and centrifugation. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of 0.1% formic acid-10 mmol/L ammonium acetate solution （phase A） and methanol （phase B） at gradient elution of 0.35 mL/min. The injection volume was 2 μL， and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 388.9→201.9 （bepotastine）， m/z 336.3→247.1 （hydroxychloroquine）， and m/z 320.2→247.2 （chloroquine）. The established LC-MS/MS method was researched in methodology and used to determine the drug concentrations in the breast milk of 1 case of lactating patient. RESULTS The linear range of bepotastine was 2-200 ng/mL（ r＝0.999）， and hydroxychloroquine was 50-1 000 ng/mL （r＝0.998）. The intra-assay and inter-assay precisions were both ≤15%， and the accuracy， extraction recovery， matrix effect， and stability all met the acceptance criteria for bioanalytical method validation. The concentration result of bepotastine and hydroxychloroquine in the breast milk of the lactating patient showed， after 2 h and 14 h， the concentrations of bepotastine in the breast milk of the patient were 34.95 ng/mL and 5.72 ng/mL； those of hydroxychloroquine were 211.92 ng/mL and 104.18 ng/mL， respectively. The relative infant doses were 1.83% and 0.56%， respectively. CONCLUSIONS The established method is simple， rapid， and sensitive. It is suitable for simultaneous determination of bepotastine and hydroxychloroquine concentrations in human milk and can provide reference for safe drug use during lactation.

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AimsCoronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy offers low in-hospital mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19. MethodsWe searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to October 1, 2021. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variation among studies. ResultsNineteen retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.54 (95% CI, 0.42-0.68), whereas the pooled OR adjusted with multivariable regression or propensity score matching was 0.72 (95% CI, 0.47-1.12). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.19 (95% CI, 0.10-0.36), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38-3.15). ConclusionsOur results suggest that there is a significant reduction of in-hospital mortality with metformin therapy in patients with type 2 diabetes mellitus hospitalized for COVID-19 in the unadjusted analysis, but this mortality benefit does not retain after adjustments for confounding bias.

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AimCoronavirus disease 2019 (COVID-19) is a new pandemic the entire world is facing since December of 2019. In this retrospective study, we aim to address whether metformin use offers a low mortality on patients with COVID-19 and pre-existing type 2 diabetes mellitus (T2DM). Materials and MethodsA cohort of 1356 hospitalized patients with COVID-19 and pre-existing T2DM was analyzed by multivariate regression. Covariates that potentially confound the association were further adjusted using propensity score matching or inverse probability of treatment weighting. A meta-analysis of the present study along with 5 published studies with metformin use prior to admission in patients with COVID-19 and T2DM was carried out. ResultsWe found that metformin therapy prior to admission in patients with COVID-19 and T2DM was significantly associated with less primary outcome events including in-hospital mortality and hospice care enrollment with an odds ratio (OR) of 0.25 (95% CI, 0.06-0.74) and less in-hospital length of stay, compared to non-metformin group. There were no statistical differences between the metformin group and non-metformin group for all three inflammatory markers (ferritin, CRP, and IL-6) on admission or peak levels during hospitalization. Furthermore, meta-analysis demonstrated that metformin use was significantly correlated with reduced mortality with an OR of 0.73 (95% CI, 0.65-0.82) in the fixed effect model and 0.58 (95% CI, 0.42-0.80) for the random effect model. ConclusionsOur results provide supporting evidence that metformin may confer increased survival in patients with COVID-19 and T2DM treated with Metformin prior to hospitalization.

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Objective To investigate the levels of 5-hydroxymethylcytosine (5-hmC) and teneleven-translocation proteins (TET1/2/3) in diagnosis and prognosis prediction of hepatocellular carcinoma (HCC).Methods The expression of 5-hmC in 130 cases of HCC tissues were detected by immunohistochemical staining.Kaplan-Meier test was used for survival analysis.TET family plays critical role in the conversion of 5-methylcytosine (5-mC) to 5-hmC.The TET levels were detected by using immunohistochemical staining and RT-PCR,the correlation between 5-hmC and TET was analyzed.Results The level of 5-hmC decreased in HCC tissues,as compared with non-tumor tissues,the expression of TET1 was downregulated in HCC.There was significant difference in the expression between low and high grades of HCC tissues (x2 =10.611,P =0.001).Kaplan-Meier survival analysis showed that there was significant difference between the 5-hmC expression level and the survival rate of HCC patients (x2 =4.412,P =0.036).Conclusions In HCC tissues the expression of 5-hmC was specifically downregulated.Low 5-hmC level is significantly correlated with poor differentiation of the tumor and worse overall survival.Decreased expression of TET1 is likely one of the mechanisms underlying 5-hmC loss in HCC.

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Objective@#To observe the histopathological features of different opportunistic infections and tumors of the intestinal mucosa in AIDS patients, and to explore the correlation between different lesions and CD4+ T lymphocyte levels.@*Methods@#Colonic mucosal biopsy specimens of 263 patients with clinically diagnosed AIDS and abdominal pain, diarrhea, blood in the stool and other gastrointestinal symptoms were collected from Beijing Ditan Hospital from 2010 to 2018. There were 232 males and 31 females, with age range 10-81 (mean 40±13) years. HE staining, histochemical special staining, immunohistochemical staining, and in-situ hybridization were used to detect the expression of different opportunistic infection pathogens, tumors and CD4+ T lymphocytes. Peripheral blood was also taken for CD4+ T lymphocytes, CD8+ T lymphocytes, HIV viral load and routine indicators.@*Results@#The cohort included 263 intestinal mucosal biopsy specimens. There were 175 cases (66.5%) of non-specific inflammation, and pathogens were detected in 41 cases (15.6%), including 20 cases(7.6%) of cytomegalovirus (CMV) infection, 12 cases (4.6%) of mycobacterial infection, eight cases (3.0%) of amoeba infestation, and one case (0.3%) of talaromycesmarneffei infection; there were also 41 (15.6%) neoplastic lesions including 25 cases (9.5%) of intraepithelial neoplasia, 10 cases (3.8%) of adenocarcinoma and squamous cell carcinoma, six cases (2.3%) of lymphoma; and six cases (2.3%) of ulcerative colitis. The peripheral blood CD4+T lymphocyte levels of patients with CMV, mycobacteria and talaromycesmarneffei were less than 200/μL; the peripheral blood CD4+ T lymphocyte level (P<0.01) and intestinal mucosa CD4+T lymphocytes (P<0.01) were all significantly lower than those in patients with non-specific inflammation. The peripheral red blood cells and hemoglobin levels of patients with CMV and mycobacterial infection (P<0.01), adenocarcinoma and squamous cell carcinoma (P<0.05) were significantly lower than those of non-specific inflammation patients.@*Conclusions@#Pathologic examination of intestinal mucosa can identify specific infections and neoplastic lesions in AIDS patients; the most common lesions are non-specific inflammation, and CMV infection is the most common opportunistic infections; CMV, mycobacteria and talaromycesmarneffei infections are associated with decreased levels of CD4+ T lymphocytes in peripheral blood and intestinal mucosa; entamoeba histolytica infestation and non-HIV-related neoplastic lesions such as intraepithelial neoplasia, adenocarcinoma and squamous cell carcinoma are not associated with changes in AIDS immune function.

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Objective To investigate the expression of liver kinase B1 (LKB1) and phosphatase and tensin homology deleted on chromosome ten (PTEN) in hepatocellular carcinoma (HCC) and their relationship with pathological characteristics and prognosis of HCC.Methods hnmunohistochemistry was used to detect expression of LKB1 and PTEN in 115 HCC cases.The relationship between clinicopathologic factors and the expressions was analyzed.Results The positive expression rate of LKB1 and PTEN was 10.4％ (12/115) and 28.7％ (33/115) respectively.The coexpression ratio of LKB1 and PTEN was 5.2％ (6/115).LKB1 and PTEN double deletion rate was 66.1％,with the latter most often found in those ≥ 50 years of age group (x2 =7.968,P =0.001),middle low differentiation HCC group (x2 =11.297,P =0.025) and vascular tumor thrombus group (x2 =6.797,P =0.011).The 5 year survival rates of LKB1 and PTEN protein coexpression and double deletion patients were 100％ and 36.5％ (x2 =10.969,P =0.004),respectively.Multivariate COX regression analysis showed that vascular tumor thrombus,PTEN deletion and LKB1/PTEN double deletion were independent risk factors for the prognosis of HCC.Condusions Double deletion of LKB1/PTEN protein is one of the independent factors that affect the survival time of HCC patients.

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Objective To investigate the effects of Puerarin on glucose and lipid metabolism and gastric motility in early period type 2 diabetic (T2DM) rats.Methods Rat model of T2DM was established by high fat-sugar diet fed and low-dose streptozotocin-treated. SD rats were divided randomly into normal control group (NC), normal+Puerarin group (NP), diabetes control group (DC) and diabetes+Puerarin group (DP). NP and DP rats were given Puerarin 400 mg/(kg?d) once per day for 5 weeks, NC and DC rats were given PBS. Half time of gastric emptying and emptying rate were evaluated by SPECT. The serum level of FBG, GSP, FFA, TC, TG and INS were measured by kit.Results Compared with NC group, DC rats had higher FBG, FFA, TC, GSP, TG and emptying rate, but INS and half time of gastric emptying decreased significantly (P<0.05,P<0.01). Compared with DC group, TG, GSP, FFA and emptying rate of DP rats were reduced (P<0.05), but had more half time of gastric emptying (P<0.05). The results of multivariate stepwise regression analysis showed that FBG related to half time of gastric emptying.Conclusion Type 2 diabetic rats have faster gastric motility, higher blood glucose and lipid. Puerarin might improve the disorders of GSP, TG, FFA and gastric emptying in diabetic rats.

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<p><b>OBJECTIVE</b>To evaluate the effect of antiviral therapy on the quality of life (QOL) of patients with chronic hepatitis C (CHC) and cirrhosis during the 5-year period following splenectomy to treat hypersplenism.</p><p><b>METHODS</b>Data of patients with CHC and cirrhosis who had undergone treatment for hypersplenism were retrospectively selected from the hospital database of medical records. The patients were first grouped according to the hypersplenism treatment: splenectomy (group A, 28 cases) and conservative/non-operative (group B, 30 cases). Sub-grouping was carried out according to the CHC treatment: interferon-alpha-2a and ribavirin (15 cases in the A1 group, and 19 cases in the B1 group) and non-antiviral (13 cases in the A2 group, and 11 cases in the B2 group). To determine the intergroup differences in QOL during the 5-year period following the hypersplenism treatment, the QOL was assessed by chronic liver disease questionnaire (CLDQ), listing of specific symptoms (SS), and the World Health Organization QOL scale (WHOQOL-BREF).</p><p><b>RESULTS</b>Between-group statistical comparison of the subjective feeling, physiological status, mental state, and social life relationship of the patients showed no significant differences among the patients who received splenectomy compared to those who received the conservative treatment. However, the QOL of splenectomy-treated patients who received non-antiviral CHC treatment was worse than that of the patients who were given conservative treatment for the hypersplenism and antiviral therapy for the CHC. The patients who received splenectomy and antiviral therapy had better QOL than the other patient group(3.69 +/- 0.75 vs 2.15 +/- 0.98, P = 0.0003).</p><p><b>CONCLUSION</b>Splenectomy followed by antiviral therapy may improve the QOL of patients with CHC-related cirrhosis and hypersplenism.</p>

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Objective To summarize the characteristics of nosocomial infections in the patients treated in intensive care unit (ICU).Methods The incidence of nosocomial infections was monitored in ICU from March 2012 to August 2012.The incidence rate of infection was adjusted with Average Severity of Illness Score (ASIS)score and analyzed in relation to three invasive pro-cedures.Pathogen distribution of nosocomial infections in ICU was also analyzed.Results Nosocomial infection was identified in 357 of the 3 700 ICU patients (9.65%).The overall daily infection rate was 30.34‰,specifically,49.10‰ for ventilator asso-ciated pneumonia (VAP),13.86‰ for catheter-related bloodstream infections (CRBSI),and 1.09‰ for catheter-associated urinary tract infections (CAUTI).Of the 688 bacterial isolates,gram negative bacteria accounted for 82.70%.The top three bacterial species were Acinetobacter baumanii ,Pseudomonas aeruginosa ,and Klebsiella pneumoniae .Conclusions ICU is the focus for surveillance of nosocomial infections.Objective investigation is critical for nosocomial infection surveillance.

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Objective To explore the expression of Tiaml in clear cell renal cell carcinoma and analyze its correlations to pathology of disease and prognosis.Methods The expressions of Tiam1 protein in 107 specimens of human clear cell renal cell carcinoma and 20 specimens of normal renal tissues were detected by immunohistochemical staining and its clinical significance was then analyzed.Results The expression of Tiam1 protein was higher in renal cancers than in the adjacent normal tissues ( P ＜ 0.01 ).Tiam1 protein expression rates were 47.6％ and 72.7％ in Ⅰ - Ⅱ and Ⅲ - Ⅳ tumors,while 49.3％ and 76.5％ in T1 - T2 and T3 - T4 tumors,respectively ( P ＜ 0.01 ).Expression of Tiam1 protein was higher in lymph node positive renal carcinoma tissues than in lymph node negative renal carcinoma tissues ( 71.7％ versus 47.5％,P ＜ 0.05 ).The expression of Tiam1 in carcinoma tissues showed a positive relationship with tumor vascular invasion (81.3％ versus 48.0％,P ＜ 0.01 ).In patients followed-up 5 - 8 years,Kaplan-meier analysis and the log-rank test showed that the 5-year survival was significantly different between the group of lower and higher Tiaml expression groups ( 84.4％ versus 46.8％,P ＜ 0.05 ).Conclusions The expression of Tiaml protein was higher in human primary renal carcinoma than in normal renal tissues.The positive rate of Tiam1 protein expression was related to classification,TNM stage,lymph node metastasis and vascular invasion.The detection of the expression of Tiaml protein may be helpful in the diagnosis and prognosis of renal carcinoma.

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Objective To evaluate the effects of applying XF-9801 type of anesthetics waste gas absorber, an activated carbon filter,to removing nitrogen oxides (NOx) and fluoride. Methods Thirty patients, undergoing general anesthesia with enflurane or isoflurane/nitrous oxide, were enrolled in this study.The gas samples were taken at the waste gas outlet of anesthetic machine,to identify the concentrations of nitrogen oxides and fluoride before and after the application of anesthetics waste gas absorber. Results Compared with those before the absorber application, nitrogen oxides and fluroide concentrations in anesthetic waste gas decreased significantly following the absorber application (P