Objective To analysis the relationship between the lactate-to-albumin ratio(LAR)and the 28-day prognosis in patients with sepsis.Methods Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database,patients with sepsis aged≥18 years were selected.Patients were divided into survival and death groups according to their 28-day prognosis.The LAR was divided into quartiles:Q1(LAR<0.45),Q2(0.45≤LAR<0.70),Q3(0.70≤LAR<1.18),and Q4(LAR≥1.18);and into two groups based on the median LAR:low LAR group(LAR≤0.70)and high LAR group(LAR>0.70).Demographic characteristics,comorbidities,laboratory indicators,clinical treatments,and disease severity scores of patients were extracted.LAR was included as a continuous variable and a four-category variable in multiple Logistic regression models,with trend tests performed.Subgroup analyses were conducted based on gender,age,comorbidities,and sequential organ failure assessment(SOFA)score.Receiver operator characteristic curve(ROC curves)were plotted to analyze the predictive efficacy of lactate,albumin(Alb),LAR and SOFA score for the prognosis of sepsis patients.Kaplan-Meier survival curves were plotted to compare the difference of 28-day cumulative survival rates of sepsis patients in the high and low LAR groups.Results A total of 9 169 patients with sepsis were included,with 6 799 in the survival group and 2 370 in the death group.Compared with the survival group,the death group had older age[years:70.80(58.64,82.25)vs.65.07(53.56,76.92)],higher levels of potassium,creatinine,blood urea nitrogen(BUN),white blood cell count(WBC),lactate,LAR,SOFA score,simplified acute physiology scoreⅡ(SAPSⅡ),and higher proportions of chronic obstructive pulmonary disease(COPD),heart failure,use of vasopressors within 48 hours,and continuous renal replacement therapy(CRRT)[potassium(mmol/L):5.0(4.5,5.7)vs.4.8(4.4,5.4),creatinine(μmol/L):132.60(88.40,212.16)vs.97.24(70.72,159.12),BUN(mmol/L):11.42(7.14,18.56)vs.7.85(5.25,13.57),WBC(×109/L):13.1(8.7,19.1)vs.11.4(7.6,16.4),lactate(mmol/L):2.9(1.8,5.1)vs.2.0(1.4,3.1),LAR:1.03(0.63,1.88)vs.0.62(0.42,0.98),SOFA score:9(6,12)vs.6(4,8),SAPSⅡscore:52(42,64)vs.38(30,47),COPD:8.19%(194/2 370)vs.6.57%(447/6 799),heart failure:29.96%(710/2 370)vs.26.31%(1 789/6 799),use of vasopressors within 48 hours:62.19%(1 474/2 370)vs.37.56%(2 554/6 799),CRRT:19.45%(461/2 370)vs.9.56%(650/6 799),all P<0.05],while lower levels of body weight,chloride,calcium,hemoglobin(Hb),platelet count(PLT),Alb and lower proportions of hypertension were observed in the death group[body weight(kg):75.8(63.6,92.3)vs.78.7(66.5,95.0),chloride(mmol/L):104(98,109)vs.104(100,108),calcium(mmol/L):1.07(1.00,1.15)vs.1.09(1.03,1.15),Hb(g/L):103(87,120)vs.105(90,121),PLT(×109/L):173(104,246)vs.174(118,243),Alb(g/L):29(24,34)vs.33(28,37),hypertension:35.36%(838/2 370)vs.38.34%(2 607/6 799),all P<0.05].In the Logistic regression model adjusted for all confounding factors,the odds ratio(OR)and 95%confidence interval(95%CI)of LAR were 1.74(1.64-1.85),P<0.001;when LAR was treated as a four-category variable,the OR values of Q2,Q3,and Q4 increased progressively compared with Q1,being 1.49(1.22-1.82),2.27(1.88-2.75),and 5.05(4.20-6.08),respectively,P<0.001.Subgroup analyses showed that LAR was an independent risk factor for the 28-day prognosis of sepsis in different subgroups based on gender,age,comorbidities,and SOFA score(all P<0.001),with no interaction effects with the subgroup variables(all P>0.05).ROC curve analysis showed that the AUC of LAR predicted the 28-day prognosis of patients with sepsis was 0.688(0.675-0.700),higher than that of lactate[0.655(0.642-0.668)]and Alb[0.636(0.623-0.649)],both P<0.001,and not significantly lower than that of SOFA score[0.699(0.687-0.712),P=0.108].Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly higher in the low LAR group than in the high LAR group(Log-Rank test:χ2=533.24,P<0.001).Conclusion LAR is an independent risk factor for the 28-day prognosis of sepsis patients.Higher LAR is associated with adverse outcomes,and its predictive efficacy is superior to that of lactate and albumin.

Objective To analysis the relationship between the lactate-to-albumin ratio(LAR)and the 28-day prognosis in patients with sepsis.Methods Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database,patients with sepsis aged≥18 years were selected.Patients were divided into survival and death groups according to their 28-day prognosis.The LAR was divided into quartiles:Q1(LAR<0.45),Q2(0.45≤LAR<0.70),Q3(0.70≤LAR<1.18),and Q4(LAR≥1.18);and into two groups based on the median LAR:low LAR group(LAR≤0.70)and high LAR group(LAR>0.70).Demographic characteristics,comorbidities,laboratory indicators,clinical treatments,and disease severity scores of patients were extracted.LAR was included as a continuous variable and a four-category variable in multiple Logistic regression models,with trend tests performed.Subgroup analyses were conducted based on gender,age,comorbidities,and sequential organ failure assessment(SOFA)score.Receiver operator characteristic curve(ROC curves)were plotted to analyze the predictive efficacy of lactate,albumin(Alb),LAR and SOFA score for the prognosis of sepsis patients.Kaplan-Meier survival curves were plotted to compare the difference of 28-day cumulative survival rates of sepsis patients in the high and low LAR groups.Results A total of 9 169 patients with sepsis were included,with 6 799 in the survival group and 2 370 in the death group.Compared with the survival group,the death group had older age[years:70.80(58.64,82.25)vs.65.07(53.56,76.92)],higher levels of potassium,creatinine,blood urea nitrogen(BUN),white blood cell count(WBC),lactate,LAR,SOFA score,simplified acute physiology scoreⅡ(SAPSⅡ),and higher proportions of chronic obstructive pulmonary disease(COPD),heart failure,use of vasopressors within 48 hours,and continuous renal replacement therapy(CRRT)[potassium(mmol/L):5.0(4.5,5.7)vs.4.8(4.4,5.4),creatinine(μmol/L):132.60(88.40,212.16)vs.97.24(70.72,159.12),BUN(mmol/L):11.42(7.14,18.56)vs.7.85(5.25,13.57),WBC(×109/L):13.1(8.7,19.1)vs.11.4(7.6,16.4),lactate(mmol/L):2.9(1.8,5.1)vs.2.0(1.4,3.1),LAR:1.03(0.63,1.88)vs.0.62(0.42,0.98),SOFA score:9(6,12)vs.6(4,8),SAPSⅡscore:52(42,64)vs.38(30,47),COPD:8.19%(194/2 370)vs.6.57%(447/6 799),heart failure:29.96%(710/2 370)vs.26.31%(1 789/6 799),use of vasopressors within 48 hours:62.19%(1 474/2 370)vs.37.56%(2 554/6 799),CRRT:19.45%(461/2 370)vs.9.56%(650/6 799),all P<0.05],while lower levels of body weight,chloride,calcium,hemoglobin(Hb),platelet count(PLT),Alb and lower proportions of hypertension were observed in the death group[body weight(kg):75.8(63.6,92.3)vs.78.7(66.5,95.0),chloride(mmol/L):104(98,109)vs.104(100,108),calcium(mmol/L):1.07(1.00,1.15)vs.1.09(1.03,1.15),Hb(g/L):103(87,120)vs.105(90,121),PLT(×109/L):173(104,246)vs.174(118,243),Alb(g/L):29(24,34)vs.33(28,37),hypertension:35.36%(838/2 370)vs.38.34%(2 607/6 799),all P<0.05].In the Logistic regression model adjusted for all confounding factors,the odds ratio(OR)and 95%confidence interval(95%CI)of LAR were 1.74(1.64-1.85),P<0.001;when LAR was treated as a four-category variable,the OR values of Q2,Q3,and Q4 increased progressively compared with Q1,being 1.49(1.22-1.82),2.27(1.88-2.75),and 5.05(4.20-6.08),respectively,P<0.001.Subgroup analyses showed that LAR was an independent risk factor for the 28-day prognosis of sepsis in different subgroups based on gender,age,comorbidities,and SOFA score(all P<0.001),with no interaction effects with the subgroup variables(all P>0.05).ROC curve analysis showed that the AUC of LAR predicted the 28-day prognosis of patients with sepsis was 0.688(0.675-0.700),higher than that of lactate[0.655(0.642-0.668)]and Alb[0.636(0.623-0.649)],both P<0.001,and not significantly lower than that of SOFA score[0.699(0.687-0.712),P=0.108].Kaplan-Meier survival analysis showed that the 28-day cumulative survival rate was significantly higher in the low LAR group than in the high LAR group(Log-Rank test:χ2=533.24,P<0.001).Conclusion LAR is an independent risk factor for the 28-day prognosis of sepsis patients.Higher LAR is associated with adverse outcomes,and its predictive efficacy is superior to that of lactate and albumin.

Objective:To investigate the nurses' attitude towards open visitation policy in intensive care unit (ICU) and its potential influence factors, and further to provide evidence for carrying out this policy in ICU.Methods:A self-designed, anonymous online questionnaire of "attitude of ICU nurses to open visiting system in ICU" was performed in 31 provinces, autonomous regions and municipalities in China from October to December 2019, using convenient sampling method approach. Only nurses working in ICU (including specialized ICU, but excluding the critical ward in general ward) and willing to participate in the survey were included. The survey included 35 items, including the general information of each participant, the attitude towards the implementation of the open visitation system in ICU and its potential influencing factors. Ordinal Logistic regression analysis was used to identify the significant influencing factors.Results:A total of 1 558 questionnaires were sent out and 1 546 effective questionnaires were retrieved, with a response rate of 99.2%. Overall, 32.2% of them agreed with the policy, 41.3% of them disagree with the policy and 26.5% of them were uncertain. The Ordinal Logistic regression analysis showed that the independent influencing factors of ICU nurses' attitude towards open visitation policy including the possibility of increasing healthcare-associated infection [disagree: β = 1.327, 95% confidence interval (95% CI) was 0.242 to 2.413, P = 0.017; uncertain: β = 0.697, 95% CI was 0.244 to 1.151, P = 0.003], the improvement of nurses' job satisfaction (disagree: β = -1.406, 95% CI was -1.750 to -1.062, P = 0.000; uncertain: β = -0.748, 95% CI was -1.030 to -0.466, P = 0.000), the information support for medical staffs from family members (disagree: β = -0.644, 95% CI was -1.048 to -0.240, P = 0.002; uncertain: β = -0.422, 95% CI was -0.721 to -0.124, P = 0.006), the feasibility that the family members can assist the nurses in the basic nursing for patients (uncertain: β = -0.465, 95% CI was -0.729 to -0.202, P = 0.001), reducing the time that a nurse spent on caring for the patients (uncertain: β = 0.349, 95% CI was 0.052 to 0.646, P = 0.021), improving early rehabilitation (disagree: β = -0.593, 95% CI was -1.166 to -0.019, P = 0.043), and getting psychological support for patients from family members (disagree: β = 1.293, 95% CI was 0.426 to 2.159, P = 0.003), family members' satisfaction (disagree: β = -0.981, 95% CI was -1.431 to -0.531, P = 0.000). Conclusion:ICU nurses in China have realized that open visitation policy has positive effect on patients' early rehabilitation, willing to live and satisfaction; meanwhile, this policy may need more improvement in many ways such as healthcare-associated infection control, disinfection and isolation, allocation of human resources and time spent treating and caring for patients.

OBJECTIVE：To study the effects of gentiopicroside on the apo ptosis o f human pancreatic cancer cells PANC- 1，and to explore its mechanism from the perspective of IL- 6/JAK2/STAT3 signaling pathway. METHODS ：Using PANC- 1 cells as model ， the proliferation inhibition rate of cells was tested by MTT assay after treated with 0（negative contro ），2，4，8，16，32，64，128 mg/L gentiopicroside for 72 h and IC 50 were calculated. The cells were divided into negative control group ，gemcitabine group （positive control，4 mg/L）and gentiopicroside low-concentration ，medium-concentration and high-concentration groups （15，30，60 mg/L）. After cultured for 1，3，5，7 d，Trypan blue exclusion staining was used to count the survival cell ，and the growth of cells was investigated. After cultured for 72 h，colony formation assay was used to observe colony formation rate of cells ；the apoptotic rate of cells was detected by Hoechst 33258 staining；the mRNA and protein expressions of IL- 6，JAK2，STAT3 in cells were detected by RT-PCR and Western blotting assay. RESULTS ：4-28 mg/L gentiopicroside could inhibit the proliferation of cells （P＜0.05 or P＜ 0.01），in concentration dependent trend ；IC50 was 9.54 mg/L. Compared with negative control group ，survival cell count （cultured from 3，5，7 d），mRNA and protein expressions of IL- 6，JAK2 and STAT 3 in cells were decreased significantly in gemcitabine group ， gentiopicroside medium-concentration and high-concentration groups （P＜0.05 or P＜0.01），while the apoptotic rate was increased significantly （P＜0.01）. The colony formation rate of cellswere decreased significantly in gemcitabine group and gentiopicroside high-concentration group （P＜0.01）. mail：hb.gz@163.com Compared with gemcitabine group ，there was no statistical significance in above indexes of gentiopicroside high- 6716008。 concentration group （P＞0.05）. CONC LUSIONS：30，60 mg/L gentiopicroside could inhibit the proliferation and induce apoptosis of PANC- 1 cells，and 60 mg/L gentiopicroside is similar to gemcitabine in the effects. Its mechanism may be related to inhibiting the activation of IL- 6/JAK2/STAT3 signaling pathway.

Objective:To investigate the value of programmed death-1（PD-1） expression on the T lymphocytes for the prognosis of septic patients.Methods:From September 2017 to May 2019, septic patients were included in Department of Intensive Care Unit at 6 hospitals. The PD-1 expression on T cells were measured by flow cytometry. Logistic regression was conducted to analyze independent risk factors related to death within 28 days，and receiver operating characteristic curve(ROC) was conducted to evaluate the prognostic value of PD-1 expression on T cells in septic patients.Results:A total of 64 septic patients were enrolled to this study，including 32 survivors and 32 deaths. The PD-1 expression on T cells in the death group was significantly higher than that in the surviving group ( P<0.05). Correlation analysis showed that the percentages of PD-1 +/CD3 +T cells and PD-1 +/CD8 +T cells were positively correlated with procalciton in ( r=0.313, P =0.015； r=0.375, P=0.003), logistic regression analysis showed that the percentages of PD-1 +/CD3 +，PD-1 +/CD4 +，PD-1 +/CD8 +T cells were independent risk factors for the death of sepsis patients. The percentage of PD-1 +/CD3 +T cell was 3.63%, with AUC 0.842, sensitivity to predict the mortality 96.43% and specificity 59.38%, ( P<0.000 1). The percentage of PD-1 +/CD4 +T cell was 4.65%, with AUC 0.847, sensitivity 96.43%, specificity 62.50%，( P<0.000 1). The percentage of PD-1 +/CD8 +T cell was 3.91%, with AUC 0.771, sensitivity 64.29%, specificity 81.25%，( P=0.000 3). Conclusions:The T cell PD-1 expression is an independent risk factor to predict the 28-day mortality in septic patients. Combining the proportions of PD-1 +/CD3 +, PD-1 +/CD4 +and PD-1 +/CD8 +T cells may further enhance the predictive value for death.

Objective To understand the internal circuit contamination of ventilator in mechanical ventilation patients, to evaluate the effect of ventilator internal circuit disinfection and the impact on the incidence of ventilator-associated pneumonia (VAP). Methods A total of 39 patients with mechanical ventilation admitted to intensive care unit (ICU) of Hangzhou Geriatric Hospital from January 2017 to June 2018 were enrolled. Routine mechanical ventilation treatments for patients included pipeline replacement, aseptic operation, prevention of infection, etc. After 2 weeks of mechanical ventilation, the internal circuit of the ventilator was disinfected using the internal circuit sterilizer of the ventilator. Microorganism sampling and detection at 3 cm to the exhalation port of the internal circuit of the ventilator was performed before and after disinfection. The number of colonies was < 5 cfu/cm2 and no pathogenic bacteria could be detected. During the observation period, if the patient was complicated by VAP for anti-infective treatment, the ventilator with internal loop disinfection was replaced after infection control, and was incorporated again into the group for observation. The number of microbial colonies in the internal circuit of the ventilator before and after disinfection, the microbiological test pass rate and the incidences of VAP during the 2 weeks were observed. Results All 39 patients were included in the analysis, with 23 male and 16 female; with age of 65-97 years old, average (78.7±7.6) years old. Before the disinfection, 9 604 strains were detected in the internal circuit of the ventilator, including 8 687 strains of Gram-negative bacilli (90.4%), 902 strains of Gram-positive cocci (9.4%), and 15 strains of fungi (0.2%), which were detected in the lower respiratory tract of the patients. The strain concordance rate was 41%. The qualified rate of microbial detection in the internal circuit of the ventilator was 5.1%; 13 cases (33.3%) of VAP occurred during 2 weeks of mechanical ventilation. After disinfection, 785 strains of pathogens were detected in the internal circuit of the ventilator, and the number of colonies was significantly reduced compared with that before disinfection [cfu/cm2: 0 (0, 20) vs. 150 (15, 500), P < 0.01], of which 688 strains of Gram-negative bacilli (87.7%), 92 strains of Gram-positive cocci (11.7%) and 5 strains of fungi (0.6%) were found; the qualified rate of microbial detection in the internal circuit of ventilator reached 71.8%, which was significantly higher than that before disinfection (P < 0.01); 2 weeks after mechanical ventilation the incidence of VAP decreased slightly during the period [20.5% (8/39) vs. 33.3% (13/39)], but there was no significant difference (P > 0.05). Conclusions The internal circuit of the ventilator can be used to detect the pathogen and the sputum culture of the patients on mechanical ventilation with a high consistency. The disinfection of the pathogen could significantly reduce the air pollution of the ventilator and reduce the occurrence of VAP in the patients.

OBJECTIVETo screen for KIT gene mutations in two Han Chinese pedigrees affected with Piebaldism.

METHODSClinical data of the pedigrees was collected. Genomic DNA was extracted from blood samples collected from the pedigrees and 120 unrelated healthy controls. All coding exons of the KIT gene were subjected to PCR amplification and direct sequencing.

RESULTSTwo missense mutations, c.1861G>A(p.Ala621Thr) and c.1872G>A(p.Met624Ile), were identified respectively in the two pedigrees. Neither mutation was found among healthy members from the respective pedigree and the 120 unrelated healthy controls. c.1872G>A is a novel mutation.

CONCLUSIONMutations of the KIT gene may affect the structure and function of the transmembrane receptor KIT, which lead to the disease.

OBJECTIVETo detect mutations of the NF1 gene in two sporadic cases with neurofibromatosis type 1 (NF1) and explore their molecular mechanisms.

METHODSClinical data of the two patients was collected. Genomic DNA was extracted from peripheral blood samples. Specific primers were designed to exclude pseudogenes. PCR was performed to amplify all coding exons of the NF1 gene. PCR products were directly sequenced.

RESULTSTwo novel mutations of the NF1 gene (c.1019-1020delCT in exon 9 and c.7189G to A in exon 48) were respectively identified in the two patients but not among their unaffected parents or 100 healthy controls.

CONCLUSIONMutations of the NF1 gene may have predisposed to the NF1 in the two patients.

OBJECTIVETo analyze the clinical and genetic features of 9 ethnic Han Chinese patients with disseminated superfacial actinic porokeratosis (DSAP).

METHODSGenomic DNA was extracted from peripheral blood samples collected from the patients. PCR and direct sequencing were carried out for five patients from a family, 4 sporadic cases, and 120 healthy controls to identify potential mutations of four genes (MVK, MVD, PMVK, FDPS) involved in the mevalonate pathway as well as SLC17A9, SSH1, and SART3 genes. Pathogenecity of suspected mutations were assessed with SIFT, and Polyphen-2 scores.

RESULTSA c.746T>C mutation was identified in the family and two sporadic cases, while a c.875A>G mutation was identified in another sporadic case. No mutation was identified in the remainder genes among all patients. Scoring has suggested that the c.746T>C and c.875A>G mutations of the MVD gene are probably pathogenic.

CONCLUSIONc.746 T>C and c.875A>G of the MVD gene are most common mutations. Skin rashes of the patients have a strong connection with the sunlight, albeit a significant difference among patients was discovered.

Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Male ; Middle Aged ; Mutation ; genetics ; Pedigree ; Porokeratosis ; genetics

Objective To assess the therapeutic effect of plum-blossom needle tapping combined with topical imiquimod immunotherapy on cutaneous squamous cell carcinoma (SCC) in SKH-1 mice,and to explore the immunological mechanism.Methods A total of 40 SKH-1 mice with ultraviolet light-induced cutaneous SCC were randomly and equally divided into 4 groups:control group receiving no treatment,plum-blossom needle group receiving plum-blossom needle tapping on all the tumors once a day,imiquimod group topically treated with imiquimod 5％ cream at a dose of 1.2 g/kg once a day,combination group firstly treated with plum-blossom needle tapping on all the tumors,and after the stop of bleeding topically treated with imiquimod 5％ cream at the same dose as the imiquimod group once a day.All the mice were treated for 30 days.Morphological changes of tumors in all groups were photographed and recorded every day.The tumor size was measured once every three days,and changes of total tumor volume and survival rate of the mice were compared among the 4 groups.At the end of treatment,tunor tissues were resected,and histopathological changes were compared among the 4 groups.Real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to measure the mRNA expression of interferon-α (IFN-α),IFN-β,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-o) and IL-12 in tumor tissues.Results In the combination group,tumors on the back of mice grew slowly,and some even regressed.However,tumors grew fast in the control group,plum-blossom needle group and imiquimod group,and grew more slowly in the plum-blossom needle group and imiquimod group than in the control group.Before the treatment,there was no significant difference in the total tumor volume among the 4 groups (F =0.90,P ＞ 0.05).After 24-day treatment,the total tumor volume significantly differed among the 4 groups (F =5.16,P ＜ 0.05).The LSD-t test showed that the total tumor volume significantly decreased in the combination group compared with the control group (P ＜ 0.01),but no significant difference was observed among the other groups (P ＞ 0.05).Log-rank test revealed that survival curves significantly differed among the 4 groups (x2 =8.32,P ＜ 0.05).The survival rate was significantly higher in the combination group than in the control group (x2 =4.62,P =0.03),but did not differ between the plum-blossom needle group or imiquimod group and the control group or combination group (all P ＞ 0.05).Histopathological examination showed atypical cells arranged closely,a large number of tumor cells and some keratin pearls in the control group and plumblossom needle group,few dead tumor cells in the imiquimod group,and plenty of dead tumor cells,mild nuclear atypia and increased keratinization in the combination group.qRT-PCR revealed that the relative mRNA expression levels of IFN-α,IFN-β,IL-12,IL-1β and TNF-α were significantly higher in the combination group than those in the control group,plum-blossom needle group and imiquimod group (P ＜ 0.05).The imiquimod group showed significantly higher mRNA expression of IL-1β than the control group (P ＜ 0.01),but no significant differences were observed among the other groups (P ＞ 0.05).Conclusion Plum-blossom needle tapping can effectively enhance the anti-SCC activity and immunological effects of imiquimod in SKH-1 mice.