OBJECTIVE To discuss the antibiotic resistance situation of Pseudomonas aeruginosa and provide basis for therapy and control of the nosocomical infection. METHODS Fourteen strains of P.aeruginosa which derived from 60 and more years aged patients in intensive care unit(ICU) were analyzed by conventional chemistry test,PCR inspection,antimicrobial susceptibility test,plasmid pattern analysis and enterobacterial repetitive intergenic consensus(ERIC)-PCR polymorphism analysis. RESULTS Fourteen strains had the same chemistry traits,many strains appeared multi-antibiotic resistance,10 strains had a plasmid of 23kb or so without obvious association with(multi-antibiotic) resistance,14 strains were divided into three clusters by ERIC-PCR technique and their banding pattern cluster analysis,their similarity coefficients were from 0.62 to 0.86. CONCLUSIONS Nosocomial infection of P.aeruginosa which screened from aged patients in ICU has taken on sporadic state;ERIC-PCR fingerprinting technique genotyping method has high discrimination,and good reproducibility and give faster genotyping result with less hands-on time,which serves as nosocomial infection epidemiologic surveillances of P.aeruginosa.

To meet the demands of educating high-quality talents with broad basic medical knowledges background,strong operating skills and good innovative consciousness,we attempted to reform the conventional teaching models of clinical microbiology laboratory as following:①to optimize the teaching contents;②to enhance links between laboratory technologies and medicines;③to improve undergraduate students'examinations and evaluation systems.The teaching effect gets the recognition of students and peers.

OBJECTIVE:To evaluate the curative effect and safety of reduced glutathione for injection(Atomolan) on the Alcoholic Liver Disease(ALD).METHODS:This was a randomized,placebo controlled study,in which the reduced glutathione for injection(Gluthion) was used as control substance.A total of 261 ALD patients were randomly divided into 2 groups in 1:1 ratio(trial group,n=135;control group,n=126).The dosage,route and course of treatment in two groups were the same.Clinical data including biochemical parameters,symptoms and signs in two groups were monitored.RESULTS:The excellent effective rate,effect rate and total effective rate in the trial group were 58.5%,23.7% and 82.2%,respectively,those in the control group were 57.9%,22.2% and 80.2%,respectively,showing no significant difference between the 2 groups(P=0.90).CONC-LUSION:The study showed that the domestic glutathione for injection had a sound efficacy in improving clinical symptoms and recovery of liver biochemical parameters,showing equivalent efficacy to the control preparation good safety.

OBJECTIVEBy clarifying the natural history of chronic hepatitis B, to evaluate its long-term therapeutic outcome, antiviral drugs efficacy and economic significance.

METHODSA cohort of 183 (mean age of 31.75?.03 years, male/female ratio: 152:31) chronic hepatitis B patients with biopsy-proven and 247 cases of general population as control were followed up by retrospective cohort study. The follow-up time was 11.81?.08 years. This study was focused on long-term clinical outcome including the rate of liver cirrhosis, hepatocellular carcinoma and death, the long-term effect of antiviral drugs and prognostic factors.

RESULTSIn chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) hepatocellular carcinoma, and 20 (10.93%) died. The cumulative survival probabilities were 97.27%, 91.62%, and 84.47% in 5, 10, and 15 years, respectively. The cumulative probabilities of HCC were 0.00%, 3.19%, and 11.56% in 5, 10, and 15 years, respectively. In 247 control subjects, 6 (2.43%) died, none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in hepatitis B patients were markedly different (P<0.005) compared with controls. The overall mortality of hepatitis B patients was 4.50 folds of the general population. Cox multiple regression analysis showed that old age, severe histological injury, and the positive HBeAg were closely related to liver cirrhosis, while old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found.

CONCLUSIONSThe long-term outcome of hepatitis B is poor.

Adolescent ; Adult ; Aging ; physiology ; Carcinoma, Hepatocellular ; epidemiology ; etiology ; Cohort Studies ; Female ; Follow-Up Studies ; Hepatitis B e Antigens ; physiology ; Hepatitis B, Chronic ; complications ; epidemiology ; mortality ; Humans ; Liver Cirrhosis ; epidemiology ; etiology ; Liver Failure ; physiopathology ; Liver Neoplasms ; epidemiology ; etiology ; Male ; Middle Aged ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Sex ; Survival Rate

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Objective:To explore eye movement characteristics in newly diagnosed, drug-naive Parkinson′s disease (PD) patients and their correlation with motor and non-motor symptoms.Methods:Seventy-five newly diagnosed, drug-naive PD patients and 46 healthy controls (HCs) were included in this cross-sectional study. Patients were recruited from the Department of Neurology, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from November 2017 to December 2021, while HCs were recruited from the local community during the same period. For PD patients, motor severity was measured with the modified Hoehn and Yahr stage, Movement Disorder Society Unified Parkinson′s Disease Rating Scale part Ⅲ and the Freezing of Gait questionnaire. Non-motor symptoms were evaluated by serial scales such as Non-Motor Symptoms Questionnaire, 16-item odor identification test from Sniffin Sticks, 17-item Hamilton Rating Scale for Depression, Chinese version of Mini-Mental State Examination, Montreal Cognitive Assessment Basic and REM Behavior Disorder Screening Questionnaire. All subjects underwent oculomotor test including pro-saccade task and smooth pursuit eye movement (SPEM) task in the horizontal direction via videonystagmography. Visually guided saccade latency, saccadic accuracy and gain in SPEM at three frequencies (0.1, 0.2, 0.4 Hz) of the horizontal axis were compared between the 2 groups. The association between key oculomotor parameters and clinical phenotypes was explored in PD patients. The receiver operating characteristic (ROC) analyses of eye movement parameters as independent factors were also performed for detecting PD from HCs, then combining the saccadic latency, saccadic accuracy and the most significant SPEM gain (0.4 Hz) as the model to distinguish PD from HCs.Results:Relative to HCs, newly diagnosed, drug-naive PD patients showed prolonged saccadic latency [(210.4±41.3) ms vs (191.3±18.9) ms, t=-3.445, P=0.001] and decreased saccadic accuracy (88.4%±6.8% vs 92.2%±6.1%, t=3.064, P=0.003). SPEM gain in PD was uniformly reduced at each frequency(0.1 Hz: 0.68±0.15 vs 0.74±0.14, t=2.261, P=0.026; 0.2 Hz: 0.72±0.16 vs 0.79±0.16, t=2.704, P=0.008; 0.4 Hz: 0.67±0.19 vs 0.78±0.19, t=2.937, P=0.004). The ROC analyses of saccade latency, saccadic accuracy and gain in SPEM at 0.1, 0.2, 0.4 Hz as independent factors for detecting PD from HCs showed that the area under the curve (AUC) of each parameter was lower than 0.7: the AUC of saccade latency was 0.641 ( P=0.010), the AUC of saccadic accuracy was 0.681 ( P=0.001), the AUC of gain in SPEM at 0.1 Hz was 0.616 ( P=0.032), at 0.2 Hz was 0.652 ( P=0.005), at 0.4 Hz was 0.660 ( P=0.003). Combining the saccadic latency, saccadic accuracy and the most significant SPEM gain (0.4 Hz) revealed that the model could significantly distinguish PD from HCs with an 80.4% sensitivity and a 73.3% specificity (AUC=0.780, P<0.001). Prolonged saccadic latency was correlated with long disease duration ( β=0.334, 95% CI 0.014-0.654, P=0.041), whereas decreased SPEM gain was associated with severe motor symptoms in newly diagnosed drug-naive PD patients (0.1 Hz: β=-0.004, 95% CI -0.008--0.001, P=0.036; 0.4 Hz: β=-0.006, 95% CI -0.011--0.001, P=0.012). Conclusions:Ocular movements are impaired in newly diagnosed, drug-naive PD patients. These changes could be indicators for disease progression in PD.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

OBJECTIVES: To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity. METHODS: C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice. RESULTS: In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice. CONCLUSIONS Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.
Male ; Humans ; Animals ; Mice ; Reactive Oxygen Species/metabolism* ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Mice, Inbred C57BL ; Apoptosis ; Poly(ADP-ribose) Polymerases/metabolism*