Objective To investigate the assessing value of C-reactive protein to serum albumin ratio(CRP/Alb)and pan-im-mune-inflammation value(PIV)in the prognosis of advanced non-small cell lung cancer(NSCLC)before receiving first-line PD-1/PD-L1 inhibitors combined with chemotherapy.Methods The clinical data of 85 patients diagnosed with advanced NSCLC in the Affili-ated Hospital of Xuzhou Medical University from November 2018 to December 2021 who received first-line treatment with PD-1/PD-L1 inhibitors combined with chemotherapy regimens were retrospectively analyzed.The receiver operator characteristic curve(ROC curve)was used to determine the optimal cut-off value of CRP/Alb and PIV,and univariate and multivariate analysis were performed on the COX proportional risk regression model.Results In this study,a total of 85 patients were included,and the optimal cut-off value of CRP/Alb was 0.38,and the difference between the advanced NSCLC patients in the high and low CRP/Alb groups in the history of smok-ing and hypertension was statistically significant(P＜0.05);the optimal cut-off value of PIV was 666.77,and the difference in ECOG-PS scores between the advanced NSCLC patients in the high and low PIV groups was statistically significant(P＜0.05).The dis-ease control rate(DCR)and progression-free survival(PFS)of patients in the high CRP/Alb group and the high PIV group were lower than those in low CRP/Alb and low PIV groups,and the difference was statistically significant(P＜0.05).Univariate and multivariate COX regression analysis showed that high CRP/Alb and high PIV were predictors of poor prognosis of PFS in patients with advanced NSCLC in the first-line treatment of PD-1/PD-L1 inhibitors and chemotherapy regimens.Conclusion High CRP/Alb and high PIV are associated with poorer PFS in patients with advanced NSCLC,and may be potentially valuable prognostic factors for patients with ad-vanced NSCLC treated with first-line immunotherapy combined with chemotherapy.

Objective : To investigate the effect of exposure to low concentrations of benzene on miR-155 and miR-223 expression in peripheral blood lymphocytes among workers with benzene exposure. Methods : A hundred male employees at a risk of exposure to benzene (the exposed group) were randomly sampled from two small metal products manufacturing enterprises and one medium-sized chemical raw material and chemical products manufacturing enterprise in Ningbo City, Zhejiang Province, and 60 age-matched male employees without benzene exposure were randomly selected as the unexposed group. Age, body mass index ( BMI ), smoking status, alcohol consumption, disease history, medication history and routine blood testing results of subjects were collected using a questionnaire survey. The 8-hour time weighted average concentration ( CTWA ) of benzene was measured in the workplace using thermal desorption gas chromatography, and the urine 8-hydroxy-2' deoxyguanosine ( 8-OHdG ) levels were determined using high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). The miR-155 and miR-223 expression was quantified in peripheral blood lymphocytes using quantitative fluorescent reverse transcription-polymerase chain reaction assay, and the factors affecting miR-155 and miR-223 expression were identified using multivariable logistic regression analysis. Results : The subjects in the exposed group had a mean age of ( 31.17±7.30 ) years, and were exposed to low concentrations of benzene ( CTWA, 0.05 to 0.30 mg/m3 ) , while the subjects in the unexposed group had a mean age of ( 32.52±6.15 ) years. There were no significant differences between the exposed and unexposed groups in terms of age, BMI, proportion of smokers or proportion of alcohol consumers ( P>0.05 ). There was no significant difference in the median relative miR-155 expression between the exposed and unexposed groups ( 0.953 vs. 1.293, P>0.05 ), and lower median relative miR-223 expression was quantified in the exposed group than in the unexposed group ( 0.540 vs. 1.433, P<0.05 ). Multivariable logistic regression analysis revealed that down-regulation of miR-223 expression correlated with exposure to benzene ( OR=2.719, 95%CI: 1.308-5.651 ). Conclusion Down-regulation of miR-223 expression may be associated with exposure to low concentrations of benzene.

Objective:To analyze the data of critical care related literatures published in Web of Science core set by knowledge map visualizing technology, and summarize the research status and hotspots of critical care.Methods:The core set database of Web of Science from January 2011 to December 2020 was searched, the extracted information was standardized and analyzed by knowledge map visualizing technology.Results:A total of 783 articles in the field of critical care were included, and the number of literatures increased year by year, among which the number of articles published in the American Journal of Critical Care(305) was the most. The United States (437) was the country with the most published literatures, and Australia was the country with the highest centrality (centrality=0.67). The number and centrality of articles published from China were at the lower middle level. There was cooperation among countries, but not close cooperation. The cooperation among authors was in the state of small aggregation and large dispersion. Cluster analysis and keyword emergence analysis showed that many aspects in the field of intensive care had been the research hotspots, among which "post intensive care syndrome" and "children′s intensive care" were the research hotspots in recent years.Conclusions:The research field of intensive care is still in the rising stage of development, and post intensive care syndrome and children's intensive care are the latest hotspots in intensive care research.

Objective:To explore the clinical significance of prealbumin(PA) and γ-glutamyltranspeptidase (γ-GT) detection in evaluation of hyperbilirubinemia in neonates at different stages.Methods:From August 2017 to August 2018, 300 full-term delivery patients with neonatal hyperbilirubinemia were selected, including 210 early-stage neonates and 90 late-stage neonates.According to the severity of bilirubinemia, the patients were classified into mild group (50 cases), moderate group (150 cases), and severe group (100 cases). The blood levels of PA and γ-GT of each group were detected.Results:The levels of PA and γ-GT in late neonates were (95.81±4.58)mg/L, (44.97±5.21)IU/L, respectively, which were significantly higher than those in early neonates [(94.77±6.32)mg/L, (53.88±6.32)IU/L]( t=1.410, 11.767, P=0.160, 0.000). With the increase of bilirubin level, the blood PA level was gradually decreased( P<0.05). The blood γ-GT level of moderate and severe patients were significantly higher than that of mild ones ( t=2.222, 2.020, P=0.027, 0.046). The blood levels of γ-GT and PA had no statistically significant differences between moderate patients and severe patients ( t=0.712, 1.741; P=0.477, 0.083). The blood PA level of moderate and severe patients were significantly lower than that of mild patients ( t=2.357, 3.277, P=0.019, 0.001). The serum PA levels had no statistically significant difference between severe patients and moderate patients ( t=0.719, P=0.474); and the serum PA levels of severe and moderate patients were lower than that of mild patients ( t=3.234, 2.117, P=0.001, 0.043). The serum γ-GT levels among the three groups had no statistically significant differences (severe vs.moderate: t=0.297, P=0.767; severe vs.mild: t=0.269, P=0.788; moderate vs.mild: t=0.013, P=0.989). Conclusion:By detecting the levels of PA and γ-GT in neonatal hyperbilirubinemia in different periods, it can provide a reference for clinical judgment of the condition of the children, thus guiding clinical rational treatment.

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 （COVID-19） cases reported in Ningbo from January 22 to February 22, 2020, so as to provide guidance for the prevention and control of the COVID-19 epidemic. Methods: The confirmed cases of COVID-19 reported by Ningbo were selected from National Diseases Prevention and Control Information System to analyze the epidemiological characteristics by descriptive epidemiological method, including time, spatial and population distribution, clinical symptoms and exposure history. Results: A total of 157 confirmed cases of COVID-19 were reported and there was no death. The first confirmed case was reported on January 22. On the incidence curve, the peak was from January 22 to February 4, with a maximum of 15 cases in a single day. The incidence curve presented sustained human-to-human transmission. The number of the cases showed a declining trend from February 5. The confirmed cases were reported in all 10 counties（cities or districts）,among which 69（43.95%）cases were reported in Haishu District. The confirmed cases were mainly 30-69 years old,accounting for 78.34%;were mainly farmers,household workers and retired people,accounting for 59.87%;and were mainly clinically mild,accounting for 87.90%.There were 51 imported cases, accounting for 32.48%. The initial confirmed case was a local case. In the early stage of the epidemic, local cases and imported cases prevalent together,which was due to the outbreak caused by the large-scale buddhist activity on January 19.This event resulted in 67 confirmed cases and 15 asymptomatic cases. There totally reported 22 clusters with 138 （87.90%）confirmed cases. Conclusions In the early stage of the COVID-19 epidemic in Ningbo, the imported cases and local cases prevalent at the same time. Most of the cases were female, aged from 30 to 69 years, and their occupation were farmers, household workers and retired people. With comprehensive measures taken, the epidemic of COVID-19 in Ningbo have been under control.

Objective:To describe the basic characteristics of clusters of coronavirus diseases 2019 (COVID-19) cases in Ningbo, Zhejiang province, and evaluate the generation time (Tg) and basic reproduction number ( R0) of COVID-19. Methods:The basic information and onset times of the clusters of COVID-19 cases in Ningbo were investigated, the inter-generational interval of the cases were fitted by using gamma distribution, and the R0 was calculated based on the SEIR model. Results:In the 15 clusters of COVID-19 cases, a total of 52 confirmed cases, 5 cases of nucleic acid-positive asymptomatic cases. The cases occurred from January 23 to February 4, the cases were mainly women. The incubation period was (6.11±3.38) days, and the median was 5 days. The Tg was (6.93±3.70) days. There were no significant differences in Tg between age group<60 years and age group 60 years and above, and between men and women ( P=0.551). According to the Tg calculated in this paper, the R0 of COVID-19 in Ningbo was 3.06 (95 %CI: 2.64- 3.51); according to the reported case transmission interval of 7.5 days in the literature, the R0 was 3.32 (95 %CI: 2.51-9.38). Conclusion:There is no age and gender specific differences in the Tg of clusters of COVID-19 cases in Ningbo, and COVID-19 has high infectivity and spreading power in early phase.

Spinal cord injury often leads to permanent disability or death,which can cause heavy burden to the family and society.Currently,there is no cure for spinal cord injury,the main purpose of the treatment is to preserve the residual function of the spinal cord to the greatest extent.In this review,the recent advances of the therapy of spinal cord injury will be elaborated in two aspects,including the neuroprotection and the neuranagenesis,and the past treatment strategies will be reassessed,in order to strengthen the understanding of the treatment of spinal cord injury,so as to provide a reference for the formulation of more effective clinical therapy.

Parkinson′s disease(PD)is a neurodegenerative disease,there is no effective means of curative treatment.The purpose of treatment is to control the clinical symptoms of patients and delay the development of the disease.The clinical treatment is based on levodopa-based drug treatment as a gold standard, but long-term drug treatment will reduce the efficacy of treatment,and movement fluctuations,dysmotility and other complications would occur at the same time.In recent years,brain deep electrical stimulation,stem cell transplantation,gene therapy and other surgical treatment have been gradually applied in the clinical practice,the technology become more and more mature.In this paper,based on the recent literature,the study of PD surgical treatment of the status quo and progress were reviewed.

Objective To research the antiviral activity of artesunate (ART) in vitro fighting against both standard laboratory strains and ganciclovir(GCV)-resistance strains of human cytomegalovims(HCMV) and to explore whether fractionation dosage method can obviously enhance the antiviral effect of ART.Methods 1.Cytotoxicity assay to ART was performed by the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetry.The 0％ toxic concentration (TC0) were determined,and median cytotoxic concentration (TC50) was calculated with Probit regression method.2.Antiviral activity assays of ART against HCMV:human embryonic lung fibroblast cells (HELs) were infected with standard laboratory strains and GCV-resistance strains of HCMV,respectively,after which virus was removed and overlays of dulbecco's modified eagle medium(MEM) containing different antiviral drugs were added to the wells.All cells were cultured continuously at 37 ℃ in a 50 mL/L CO2 humidified atmosphere for 7-10 days and the cytopathic effect (CPE) was observed under a microscope.When the degree of CPE was clear (+ + +-+ + + +),the values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The cell survival rate (CSR)and drug inhibitory rate (IR) for HCMV were calculated.By Probit regression method,the median inhibitory concentration (IC50) of 2 drugs was calculated respectively.3.To explore whether fractionation dosage method could obviously enhance the antiviral effect of ART against HCMV,the experiment was divided into 3 groups and compared with GCV group,respectively:Group 1:ART antiviral compounds were added to cell layers by one dosage.Group 2:Total drug dosage was divided into 3 parts,and each part was added to cell layers once a day for 3 days.Group 3:Total antiviral compounds were divided into 6 and delivery 2 times a day.The values of absorbency at 490 nm of all cell wells were measured by MTT colorimetry.The CSR and viral inhibitory rates were calculated.All data were statistically analyzed by One-Way ANOVA analyzing using SPSS 18.0 statistical software.P value of ＜0.05 was considered to indicate statistical significance.Results 1.Cytotoxicity assay showed that cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.TC0 and TC50 value of ART were 62.5 μmol/L and 171.7 μmol/L.2.In concentration of 5 μmol/L,15 μmol/L and 30 μmol/L,ART and GCV could obviously inhibit growth of HCMV AD169 strains.There was no significant difference between them.The value of GCV IC50 was 3.49μmol/L,and the value of ART IC50 was 2.17 μmol/L.Treatment index (TI) of ART was 28.8,and GCV was 716.3.ART could still obviously inhibit growth of HCMV resistant strains,but GCV couldn't.Differences between them were statistically significant.The value of GCV IC50 to HCMV resistant strains was 44.4 μmol/L,and the value of ART IC50 was 2.5 μmol/L.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.Difference was statistically significant(P ＜ 0.01).GCV delivered as the same method had little different changes in virus suppression ratio(P ＞ 0.05).Conclusions 1.Cytotoxicity was not found in the relevant range of ART concentrations under 62.5 μmol/L.2.ART could obviously inhibit growth of HCMV resistant strains and standard laboratory strains.3.Fractionation dosage method (2 times a day) of ART could improve the inhibition rate of virus significantly compared to that used once a day and single dose method.4.Because the action mode of ART is different from other anti-HCMV drugs,and ART has a high biological activity and fewer side effects,it is expected to become a kind of new antiviral drugs for HCMV infections.

OBJECTIVETo monitor human cytomegalovirus (HCMV) drug resistance in recipients of hematopoietic stem cell transplantation by phenotypic and genotypic methods.

METHODSHCMV clinical isolates was isolated from the urine of hematopoietic stem cell transplantation recipients treated with GCV. Tissue cell infection median dose (TCID50) of the isolates was calculated using Reed-Muench method, and their drug susceptibility was determined by plaque reduction assay. We amplified the UL97 DNA fragment of the virus by nested PCR followed by automated DNA sequencing.

RESULTSHCMV clinical strain isolated from the urine samples of the recipients using a human fibroblast cell line showed a TCID50 value of 10(-4.618)/0.1 ml and a 50% inhibitory concentration (IC50) to GCV of 5.847 µmol/L, suggesting its sensitivity to GCV. Alignment with the AD169 DNA reference sequence identified 4 point mutations of the virus at 1509 (T-C), 1575 (C-T), 1794 (T-C), and 1815 (C-G), and only the last mutation resulted in one amino acid mutation to D605E. No gene mutation was found in relation to GCV resistance.

CONCLUSIONSPhenotypic and genotypic assays were established to examine antiviral drug resistance of HCMV in recipients of hematopoietic stem cell transplantation. We did not find any drug resistance of the clinical HCMV isolate.

Antiviral Agents ; pharmacology ; Cell Line ; Cytomegalovirus ; drug effects ; genetics ; isolation & purification ; Drug Resistance, Viral ; genetics ; Ganciclovir ; pharmacology ; Genes, Viral ; Genotype ; Hematopoietic Stem Cell Transplantation ; Humans ; Mutation ; Phosphotransferases (Alcohol Group Acceptor) ; genetics