Objective:To screen the kinase genes related to radioresistance by high-throughput method and provide a theoretical basis for clinical treatment strategy of oral squamous cell carcinoma.Methods:The tongue squamous carcinoma cell line Cal-27 was infected with lentivirus shRNA kinase library that contains 4 675 different shRNAs regulating 709 human kinase genes. The uninfected cells were removed by puromycin screening. Then, the cells were irradiated with different doses (0, 10, 15 cGy) and continued to culture for 3 d to enrich the differences among groups. Afterwards, the cell genomic DNA was extracted and the complete shRNA sequences were obtained by PCR.Different tags were labeled in shRNAs of each group. An illumina platform was used for next generation sequencing to acquire the shRNA abundance, and then the differentiated expressed genes among different groups were identified.Results:A total of 5 kinase genes (PKLR, IPMK, AURKB, ITPKB and DLG2) were screened out from irradiated cells. Knockdown of PKLR and IPMK increased radiation resistance, while knockdown of AURKB, ITPKB and DLG2 increased radiation sensitivity, and the high expression of these genes would lead to radiotherapy tolerance.Conclusions:In this study, 3 genes relative to radioresistance of oral squamous cell carcinoma were identified by using shRNA lentivirus library combined with next generation sequencing, but the underlying mechanism requires further exploration.

Objective To study the nutritional risks in elderly patients with prostate cancer and explore its related factors.Methods 346 elderly patients with prostate cancer in Wuhan area from May 2013 to May 2014 were chosen as the objects in this study.Nutritional risk screening 2002 was used to evaluate nutritional risk.The sleep quality,anxiety,lower urinary tract symptoms,differentiation and other data of patients were collected.The influencing factors for nutritional risk in the patients were analyzed.Results The ratio of nutritional risk in elderly advanced prostate cancer patients was 35.3％ (122/346).The nutritional risk was increased with age (P＜0.05).The prostate cancer patients with nutritional risk had a higher international prostate symptom score (IPSS) (P＜ 0.05).Monovariate factor analysis showed that sleep quality,operation,pathology staging,radiotherapy,chemotherapy,lower urinary tract symptoms (LUTS) were the impact factors for nutritional status in elderly patients with prostate cancer (P＜0.05).Logistic regression analysis showed that age (OR=0.29),sleep quality (OR=0.25) were the protective factors for the nutritional status,while surgery (OR=12.67),pathological staging (OR=1.65),radiotherapy (OR=2.65),SPSS (OR=1.55),chemotherapy (OR=1.85) were the risk factors for nutritional status (P＜ 0.05).Conclusions The incidence of nutritional risk is high in elderly prostate cancer patients.Age,sleep quality are the protective factors,and operation,pathology staging,SPSS,chemotherapy,and radiotherapy are the risk factors for nutritional status.

Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.
Angiostrongylus cantonensis* ; Angiostrongylus* ; Animals ; Apoptosis* ; Behavior Rating Scale ; Caspase 3 ; Caspase 8 ; Central Nervous System ; Cerebral Cortex ; Diagnosis ; Eosinophils ; Gait ; Gene Expression ; Headache ; Hippocampus ; Humans ; Meningitis ; Meningoencephalitis ; Mice ; Neurons* ; Rats ; Receptors, Tumor Necrosis Factor, Type I ; Rodentia*

Objective: To explore the spatial distribution of low birth weight (LBW) and the potential environmental risk factors and provide the evidence for the prevention and intervention of LBW. Methods: Data were from a surveillance system for newly born population and adverse pregnancy outcome between 2007 and 2012 in Pingding county, Shanxi province. The data from 313 villages were analyzed. Spatial hierarchical Bayesian model was used to adjust the risk of LBW at village level, Moran’s I and Getis-Ord Gi* were used to analyze the difference in distribution of LBW risk area. Spatial negative binomial model was used to evaluate the association between the risk of LBW and chemical fertilizer application. Results: A total of 18 749 new births were recorded between 2007 and 2012, including 911 LBW cases, the total incidence of LBW was 4.86%. The result of the spatial hierarchical Bayesian model showed that high-risk area of LBW was in the southeast of Pingding and low-risk area was in the middle west of Pingding. The result of Moran’s I showed that there was a clustering pattern of LBW risk, and Getis-Ord Gi* found a high risk (hot spot) area in the south area. Moreover, the findings of association analysis showed that the risk of LBW increased with the increased chemical fertilizer application at village level. Conclusions There were area specific differences in the risk of LBW, and dose-response relationship between chemical fertilizer application and the risk of LBW. Our findings suggest that maternal exposure to chemical fertilizer during pregnancy might be a potential risk factor for LBW in rural area.

Objective:To investigate the relationship between triglyceride glucos (TyG), C-reaction protein/albumin (CRP/Alb), 25-hydroxy vitamin D[25(OH)D] and the prognosis of patients with continous ambulatory peritoneal dialysis (CAPD).Methods:A total of 220 CAPD patients in the Affiliated Hospital of Jining Medical University from January 2017 to March 2020 were prospectively selected and divided into death group and survival group according to the 6-month prognosis. The peritoneal urea clearance index (Kt/V urea), TyG, CRP/Alb, 25(OH)D were compared between the two groups. Logistic regression was used to analyze the prognostic factors of CAPD patients. The predictive value of TyG, CRP/Alb and 25(OH)D on the prognosis of CAPD patients was analyzed by receiver operating characteristic (ROC) curve. Results:After 3 months and 6 months of dialysis, the peritoneal Kt/V urea in the death group [(1.21±0.18)ml/(s·1.73 m 2), (1.02±0.14)ml/(s·1.73 m 2)] was significantly lower than that in the survival group [(1.57±0.40)ml/(s·1.73 m 2), (1.49±0.42)ml/(s·1.73 m 2)] (all P<0.05). After 3 months and 6 months of dialysis, the TyG [(8.79±0.86), (9.24±1.03)] and CRP/Alb [(4.98±0.94)×10 -4, (5.14±1.39)×10 -4] in the death group were higher than those in the survival group [(8.03±0.60), (7.26±0.93), (3.57±1.19)×10 -4, (3.07±0.88)×10 -4], while the 25(OH)D [(19.14±2.29)ng/ml, (17.79±3.17)ng/ml] was lower than that of survival group [(22.67±3.03)ng/ml, (24.31±2.51)ng/ml] (all P<0.05). TyG and CRP/Alb at 3 months and 6 months of dialysis were negatively correlated with Kt/V urea, while the 25(OH)D was positively correlated with Kt/V urea (all P<0.05). Logistic regression analysis showed that Kt/Vurea, TyG, CRP/Alb and 25(OH)D were associated with prognosis in the two groups after 3 and 6 months of dialysis (all P<0.05). The AUC of TyG, CRP/Alb and 25(OH)D at 6 months of dialysis combined to predict the prognosis of CAPD patients was the highest, which was 0.911. Conclusions:TyG, CRP/Alb and 25(OH)D are associated with all-cause mortality in CAPD patients. High TyG and CRP/Alb and low 25(OH)D suggest a higher risk of all-cause mortality. Combined detection of all indicators can effectively predict the prognosis of CAPD, which is convenient for early clinical intervention.

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

ObjectiveTo describe the characteristics of treatment outcomes of multidrug-resistant tuberculosis （MDR-TB） patients enrolled in second-line treatment in Shanghai from 2017 to 2018， and to analyze the influencing factors of treatment outcomes. MethodsTotally 182 MDR-TB patients were analyzed by using data collected from the China tuberculosis management information system， the hospital's electronic medical record information system， whole genome sequencing results and a questionnaire survey， and logistic regression analysis was used to analyze the factors affecting the success of treatment. ResultsIn 182 MDR-TB patients， the success rate of treatment was 65.4%， the loss to follow-up rate was 8.2%， the mortality rate was 4.9%， the unassessable rate was 13.7%， and the drug withdrawal rate was 7.7%. The factors affecting the success of treatment in MDR-TB patients included age （35‒ years old， OR=5.28， 95%CI： 1.58‒17.59， P=0.007； 55‒ years old， OR=16.30， 95%CI： 4.36‒60.92， P<0.001） and compliance to medication （OR=0.55， 95%CI： 0.42‒0.72， P<0.001）. ConclusionThe treatment success rate of MDR-TB patients in Shanghai from 2017 to 2018 is significantly higher than the average level in China. Older patients and patients with less compliant are at higher risk of adverse treatment outcomes.

OBJECTIVETo investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML).

METHODSA total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (=386) and moderate to severe WML group (=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML.

RESULTSUnivariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups ( < 0.05), but ApoB levels were similar between them ( > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% : 3.622-36.229, < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% : 0.018-0.262, < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML ( < 0.001).

CONCLUSIONSAn increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.

The prevalence rate of nonalcoholic fatty liver disease （NAFLD） reaches up to 30% around the world， and the disease has a serious impact on human health and constitutes a public health burden. Due to difficulties in the diagnosis and monitoring of NAFLD， it is important to identify potential drug targets and biomarkers， and multi-omics techniques hold great promise in the search for early diagnostic markers， therapeutic targets， and outcome and prognostic assessment of NAFLD. This article reviews the research advances in multi-omics techniques in the field of NAFLD in recent years， in order to provide a richer theoretical basis and new strategies for the prevention and treatment of NAFLD.