There were many progressions of hepatocellular carcinoma (HCC) in the 2017 annual meeting of the American Society of Clinical Oncology (ASCO).(1) Sorafenib has been at the heart of treatment for advanced HCC,meanwhile,it has been confirmed to effectively prolong the life time of patients and improve the clinical efficacies combined with other therapies.A variety of molecular and clinical indicators also help screening out peoples.(2) New molecular targeted drugs have sprung up,and Lenvatinib (multiple receptor tyrosine kinases inhibitor) is expected to become the next first-line drug.The second-line Regorafenib has obtained supporting evidence from evidencebased medicine,and a combination therapy of Sorafenib and Regorafenib promises to be a new model of targeted therapy for HCC.However,the phase Ⅲ study (METIV-HCC) of which Tivatinib (ARQ 197) becomes the second-line drug for HCC has failed.(3) Immunization therapy remains a hotspot for HCC.The monoclonal antibodies of immunological checkpoint and adoptive immunotherapy have better safety and clinical efficacy.(4) Primary lesions resection of HCC and drug control of metastatic lesions are expected to be the therapy model for metastatic HCC.The liver transplantation for primary HCC will be further developed.(5) The combination and sequential application of multiple therapies will become an inevitable choice,and efficacy of stereotactic body radiation therapy is expected.The combination and sequential application of transcatheter arterial chemoembolization (TACE) and other therapies is still a main therapy for unresectable HCC.(6) The new predictors and models of prognosis have been popping up,nevertheless,its therapy effects should be further proven.

Objective To study the occurrence,risk factors,and direct economic losses caused by healthcare-asso-ciated infection(HAI)in hemodialysis patients in a hospital.Methods 840 patients who underwent hemodialysis in this hospital from April 2012 to September 2014 were selected,incidence of HAI,related factors,and economic los-ses due to HAI were investigated.Results Among 840 hemodialysis patients,89 patients developed 104 times of HAI,HAI density was 4.27‰ . Multivariate regression analysis showed that young age and old age,combined mul-tiple diseases,long duration of hemodialysis,two or more intubation sites,prolonged intubation,long length of hospital stay were all risk factors for HAI(OR= 1.123-2.325);Fees for bed,consultation,examination,treat-ment,nursing,medicine,and others in HAI group were all significantly higher than non-infected group(H= 49.6-1 038.9,all P<0.01 ),difference in medicine fees was most significant.Conclusion Risk factors for HAI are young age and old age,combined multiple diseases,long duration of hemodialysis,two or more intubation sites, prolonged intubation,and long length of hospital stay,the occurrence of HAI can increase the economic burden of hemodialysis patients.

OBJECTIVE To study the bactericidal efficacy of glutaraldehyde,and its stability and change in pH value.METHODS The carrier quantity bactericidal test,field mimic bactericidal test,stability test,pH value detection,periodical biological surveillance and follow-up investigation of hospital infection were used.RESULTS After using of 20 000 mg/L of neutral glutaraldehyde on Candida albicans(ATCC 10231),Pseudomonas aeruginosa(ATCC27853),Escherichia coli(ATCC 25922) and other 3 clinical isolates separately for 3,5,and 10 min,the average killing rate was 97.90%,99.83% and 100.00%;on the field mimic bactericidal test with MRSA contaminated gastroscope,the average killing rate was 87.84%,99.50%,and 100.00%,respectively.The concentration of disinfectant after storaging 14d on 54℃ was decreased,only loss 1.46%,the concentration loss of disinfectant on using endoscope 5,7,and 14d after disinfection was 2.64%,0.69% and 0.94%,respectively.The value of pH was decreased from 7.22 to 6.00,6.50,and 6.20.The qualification rate of 260 various endoscopes after surveillance was 100.00%.Their was one of hospital infection happened among 3 200 patients after endoscopy which were followed up.CONCLUSIONS The results show that,only under the following circumstances,namely the concentration of glutaraldehyde being no less than 20 000mg/L and the action time being no less than 10 min,timely alteration of glutaraldehyde,and regular biological and concentration monitoring could the disinfection of endoscope be qualified so that hospital infection can be prevented,and medical dispute may be put to an end.

OBJECTIVE:To explore the potential correlation between clinical efficacy of pemetrexed in the treatment of ad-vanced breast cancer and TS mRNA expression. METHODS:Patients with advanced breast cancer were recruited in our study. Three cycles of pemetrexed was given to these patients,TS mRNA expression of their tumor tissues were detected. The relationship of ther-apeutic efficacies of different chemotherapy with TS mRNA expression were observed and compared during the study period. RE-SULTS:58 patients received pemetrexed chemotherapy and therapeutic efficacies of them were evaluated. One patient (1.7%) had complete response,19 patients(32.8%)had partial response,31 patients(53.4%)had stable response and 7 patients(12.1%)has progressive disease. Objective response rate was 34.5%,and disease control rate was 87.9%. TS mRNA expression level of 55 pa-tients with completed TS mRNA expression analysis varied from 0.04 to 5.11,with a median of 0.62. Mann-Whitney rank test showed that,responders had lower TS mRNA expression than nonsponders at all visits,there was statistical significance (P<0.05). Chi-square test showed that patients with low expression level of baseline(before chemotherapy)TS mRNA had significantly higher objective response rate(63.3%)than those with high expression(36.7%),there was statistical significance(P<0.05). CON-CLUSIONS:TS mRNA expression level is related to therapeutic efficacy of pemetrexed,which may be useful for predicting thera-peutic efficacy of pemetrexed therapy in patients with advanced breast cancer.

OBJECTIVE To know the disinfection efficacy of electrolyzed oxidizing water(EOW) and glutaraldehyde on clinical used gastroscope and enteroscope in our hospital and to analyze their stability and probable harm.METHODS The gastroscope and enteroscope before and after use on randomly selected outpatients and inpatients were examined on their contamination,and the efficacy of EOW was compared with that of glutaraldehyde.RESULTS After using EOW and glutaraldehyde to disinfect the gastroscope and enteroscope the former showed that its killing rate on commonly encountered pathogens for 1 min was 93.75-98.22%,for 3 min was 81.20-89.29%,and for 5 min was 100.00%;the latter showed that its killing rate for 3 min was 81.20-89.29%,for 5 min was 90.38-93.04%,and for 10 min was 99.92-99.96%.EOW was non-irritative to mucosa,and didn′t cause allergic reaction,but its stability was poor.The glutaraldehyle could bring some side effects,such as some allergy,and mucosa stimulation.CONCLUSIONS It only needs 3-5 min for EOW to kill polluted bacteria on gastroscope and enteroscope to attain the disinfection eligibility,but glutaraldehyde needs more than 10 min to get to the disinfection eligibility.The effect of EOW is strong,rapid,active and environment-safe,it is worthy of application,but it must be applied immediately as soon as possible after production.The use of glutaraldehyde must strengthen the measures of personal protection.

Objective:To elucidate the effect of hsa-microRNA-218(hsa-mir-218)on exogenous granulysin (GLS) expression in 293T cells.Methods:Total RNA was extracted from THP-1 cells induced by phorbol 12-myristate 13-acetatefor (PMA), and GLS gene was amplified by RT-PCR, and then cloned into pDsRed-Express-C1 to construct the GLS expression vector pDsRed-GLS.Then 293T cells were co-transfected with pDsRed-GLS and pGenesil-mir-218 (pGenesil-mir-control) and laser confocal microscopy was per-formed 36 h later to detect their co-expression .Total RNA and protein were extracted 48 h post transfection , and RT-PCR and Western blot were performed to detect the effect of hsa-mir-218 on exogenous GLS expression .Results:The GLS expression vector pDsRed-GLS was constructed successfully and laser confocal microscopy indicated that it was co -expressed with the interference vector .Compared with that of cells transfected with pGenesil-mir-control, Western blot showed a markedly decrease of GLS protein expression (50%) in the cells transfected with pGenesil-mir-218.However, GLS mRNA expression remained unchanged .Conclusion: hsa-mir-218 nega-tively regulates GLS expression at a post-transcriptional level , and this provides an experimental basis for future study of mechanism of GLS expression regulated by mir-218 .

Objective To evaluate the effect of artemether on the cell cycle and the radiosensitivity in human nasopharyngeal carcinoma cell line CNE-1.Methods Cell growth inhibition was assessed with MTT.The method of colony-forming was used to detect the radiation sensitivity.Cell cycle distribution was analyzed by using flow cytometry.The protein expressions of clyclin B1 and Weei were detected by using Western blot.Results The growth of CNE-1 cells was inhibited in a dose-dependent manner.The concentration of 20 μmol/L artemether had radiosensitive effect on CNE-1 cells at 24 h after administration,and SER was 1.481.When CNE-1 cell was irradiated,the G2/M cells increased (t =4.59,P ＜ 0.05).After exposure to combination of artemether and irradiation,the G2/M cells were decreased (t= 10.60,P ＜ 0.05).Western blot showed that artemether increased the level of cyclin B1 expression and inhibited the level of Weel expression.Conclusions The noncytotoxic concentration of artemether could enhance radiosensitization of CNE-1 cells.The radiosensitivity enhancement of artemether might depend on the exposure time.The effect is most obvious when radiation is delivered 24 h after expose to artemetherr.The radiosensitizing effect could be related to apoptosis.

Objective:To investigate the incidence, risk factors, and outcomes of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs).Methods:A retrospective analysis was performed on the inpatients who received ICIs therapy in Beijing Shijitan Hospital, Capital Medical University from October 2015 to December 2020. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI, patients were divided into AKI group and non-AKI group, and the patients in the AKI group were further divided into ICIs related AKI (ICIs-AKI) and AKI due to other etiologies. The clinical characteristics of the patients were compared. Multivariate logistic regression was used to analyze the influencing factors of AKI, and sensitivity analysis was used to evaluate the influencing factors of ICIs-AKI.Results:A total of 279 cancer patients over 18 years old were included in this study, in which 175(62.7%) were males. There were 41 patients (14.70%) in AKI group, including 25 patients (8.96%) in ICIs-AKI group and 16 patients (5.73%) in AKI due to other etiologies group. Patients in the AKI group were characterized by higher proportions of hypertension, diuretics use and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, extrarenal immune-related adverse events (irAEs) and a lower plasma albumin level (all P<0.05). The patients in the ICIs-AKI group had higher proportions of new aseptic leukocyturia, blood eosinophil count>500/ml, combined extrarenal irAEs, glucocorticoid use and discontinued ICIs treatment (all P<0.05). Multivariate logistic regression results showed that hypertension ( OR=3.424, 95% CI 1.559-7.522, P=0.002), use of diuretics ( OR=4.620, 95% CI 2.111-10.112, P<0.001), baseline eGFR<60 ml·min -1·(1.73 m 2) -1 ( OR=3.668, 95% CI 1.336-10.070, P=0.012) and extrarenal irAEs ( OR=9.909, 95% CI 4.198-23.391, P<0.001) were associated with AKI in cancer patients receiving ICIs therapy. Sensitivity analysis indicated that the risk factors of ICIs-AKI included use of diuretics and baseline eGFR<60 ml·min -1·(1.73 m 2) -1, similar to the results of the above analysis, extrarenal irAEs ( OR=17.572, 95% CI 6.302-48.995, P<0.001) were also associated with ICIs-AKI independently. Conclusions:AKI is not uncommon in patients treated with ICIs. Concomitant hypertension, baseline eGFR<60 ml·min -1·(1.73 m 2) -1 and use of diuretics are independent risk factors for AKI in such patients. Patients should be alert to the risk of ICIs-AKI when appearing extrarenal irAEs. Distinguishing ICIs-AKI from AKI caused by other causes will present a frequent challenge to clinical practitioners.

Objective:To compare and analyze the clinical features of patients with severe coronavirus disease 2019 (sCOVID-19) and severe community acquired pneumonia (sCAP) who meet the diagnostic criteria for severe pneumonia of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS).Methods:A retrospective comparative analysis of the clinical records of 116 patients with sCOVID-19 admitted to the department of critical care medicine of Wuhan Third Hospital from January 1, 2020 to March 31, 2020 and 135 patients with sCAP admitted to the department of critical care medicine of Shanghai First People's Hospital from January 1, 2010 to December 31, 2017 was conducted. The basic information, diagnosis and comorbidities, laboratory data, etiology and imaging results, treatment, prognosis and outcome of the patients were collected. The differences in clinical data between sCOVID-19 and sCAP patients were compared, and the risk factors of death were analyzed.Results:The 28-day mortality of sCOVID-19 and sCAP patients were 50.9% (59/116) and 37.0% (50/135), respectively. The proportion of arterial partial pressure of oxygen/fraction of inspired oxygen (PaO 2/FiO 2)≤250 mmHg (1 mmHg ≈ 0.133 kPa) in sCOVID-19 patients was significantly higher than that of sCAP [62.1% (72/116) vs. 34.8% (47/135), P < 0.01]. The possible reason was that the proportion of multiple lung lobe infiltration in sCOVID-19 was significantly higher than that caused by sCAP [94.0% (109/116) vs. 40.0% (54/135), P < 0.01], but the proportion of sCOVID-19 patients requiring mechanical ventilation was significantly lower than that of sCAP [45.7% (53/116) vs. 60.0% (81/135), P < 0.05]. Further analysis of clinical indicators related to patient death found that for sCOVID-19 patients PaO 2/FiO 2, white blood cell count (WBC), neutrophils (NEU), neutrophil percentage (NEU%), neutrophil/lymphocyte ratio (NLR), total bilirubin (TBil), blood urea nitrogen (BUN), albumin (ALB), Ca 2+, prothrombin time (PT), D-dimer, C-reactive protein (CRP) and other indicators were significantly different between the death group and the survival group, in addition, the proportion of receiving mechanical ventilation, gamma globulin, steroid hormones and fluid resuscitation in death group were higher than survival group. Logistic regression analysis showed that the need for mechanical ventilation, NLR > 10, TBil > 10 μmol/L, lactate dehydrogenase (LDH) > 250 U/L were risk factors for death at 28 days. For sCAP patients, there were significant differences in age, BUN, ALB, blood glucose (GLU), Ca 2+ and D-dimer between the death group and the survival group, but there was no significant difference in treatment. Logistic regression analysis showed that BUN > 7.14 mmol/L and ALB < 30 g/L were risk factors for 28-day death of sCAP patients. Conclusions:The sCOVID-19 patients in this cohort have worse oxygen condition and symptoms than sCAP patients, which may be due to the high proportion of lesions involving the lungs. The indicators of the difference between the death group and the survival group were similar in sCOVID-19 and sCAP patients. It is suggested that the two diseases have similar effects on renal function, nutritional status and coagulation function. But there were still differences in risk factors affecting survival. It may be that sCOVID-19 has a greater impact on lung oxygenation function, inflammatory cascade response, and liver function, while sCAP has a greater impact on renal function and nutritional status.

Objective:To evaluate the effect of thymosin alpha 1 on the prognosis of patients with coronavirus disease 2019 (COVID-19).Methods:A retrospective cohort study was performed to collect clinical data of 95 patients treated by Shanghai Aid Medical Team in Wuhan Third Hospital during January 31, 2020 and March 4, 2020, who were confirmed COVID-19. They were divided into two groups according to whether they were treated with thymosin alpha 1 after admission. The 28-day mortality (primary outcome), and 28-ventilator-free-day, lymphocyte count (LYM) level, C-reactive protein (CRP) level (secondary outcomes) were compared between two groups. Survival analysis was performed using the Kaplan-Meier curve. The effect of thymosin alpha 1 on 28-day survival was evaluated with Cox regression model.Results:Among the 95 patients, there were 31 cases in thymosin group and 64 cases in non-thymosin group; 29 patients died 28 days after admission, including 11 cases (35.5%) in thymosin group and 18 cases (28.1%) in non-thymosin group. Kaplan-Meier survival curve showed that thymosin alpha 1 could improve the 28-day survival of patients with COVID-19, but the univariate Cox model analysis showed that the difference was not statistically significant [hazard ratio ( HR) = 0.48, 95% confidence interval (95% CI) was 0.20-1.14, P = 0.098]; multivariate Cox model analysis showed that thymosin alpha 1 was the factor to improve the 28-day mortality ( HR = 0.15, 95% CI was 0.04-0.55, P = 0.004), old age ( HR = 1.10, 95% CI was 1.05-1.15, P < 0.001), accompanied by chronic renal dysfunction ( HR = 42.35, 95% CI was 2.77-648.64, P = 0.007), decrease of LYM at admission ( HR = 0.15, 95% CI was 0.04-0.60, P = 0.007) and the use of methylprednisolone ( HR = 4.59, 95% CI was 1.26-16.67, P = 0.021) were also risk factors for the increase of 28-day mortality. The use of immunoglobulin and antiviral drugs abidol and ganciclovir did not affect the 28-day mortality. After adjustment for age, gender, LYM and other factors, weighted multivariate Cox analysis model showed thymosin alpha 1 could significantly improve the 28-day survival of COVID-19 patients ( HR = 0.45, 95% CI was 0.25-0.84, P = 0.012). In terms of secondary outcomes, no statistical difference (all P > 0.05) was found between two groups in days without ventilator at 28 days after admission (days: 17.97±13.56 vs. 20.09±12.67) and the increase of LYM at 7 days after admission [×10 9/L: -0.07 (-0.23, 0.43) vs. 0.12 (-0.54, 0.41)]. But the decrease of CRP at 7 days after admission in thymosin alpha group was significantly greater than that in non-thymosin group [mg/L: 39.99 (8.44, 82.22) vs. 0.53 (-7.78, 22.93), P < 0.05]. Conclusion:Thymosin alpha 1 may improve 28-day mortality and inflammation state in COVID-19 patients.