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As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

OBJECTIVE To evaluat e the cost-effectiveness of Keluoxin capsule combi ned with chemical medicine in the treatment of diabetic kidney disease （DKD）from the perspective of the whole society. METHODS Six-state Markov model with 1 year cycle and 40 years time horizon was constructed by means of secondary literature review ，medical record analysis of sample hospital and clinical expert consultation. The cost-effectiveness of Keluoxin capsule combined with chemical medicine versus chemical medicine alone for DKD was evaluated by taking the quality-adjusted life year （QALY）as the output index ，setting the discount rate as 5％，and taking one time domestic gross domestic product （GDP）per capita in 2020 of China as the judgement threshold of incremental cost-effectiveness ratio （ICER）. RESULTS Within 40 years，Keluoxin capsule combined with chemical medicine group spent 8 644.09 yuan per capita more than chemical medicine alone group ，and gained more 0.143 QALYs；ICER was 60 460.25 yuan/QALY，which was less than one times GDP per capita of China in 2020（72 447 yuan）. The results of sensitivity analysis showed that the annual days of using Keluoxin capsule ，the health utility value of DKD at early stage had a great influence on the results of cost-effectiveness analysis. The results of probabilistic sensitivity analysis suggested that the basic analysis results of this study were robust. CONCLUSIONS At the current price level ，Keluoxin capsule combined with chemical medicine is more cost-effective to treat DKD than chemical medicine alone. The dosage of Keluoxin capsule and health utility value should be paid attention in specific decision- bjmu.edu.cn making scenarios.

Objective:To construct the nursing quality evaluation index system for the disabled elderly in medical-nursing combined institutions, so as to provide a basis for nursing managers to evaluate nursing quality of the disabled elderly in medical-nursing combined institutions.Methods:A total of 20 experts were selected by the convenient sampling method. From May 2020 to January 2021, the research team used literature analysis to construct the evaluation index framework of nursing quality for the disabled elderly in medical-nursing combined institutions and conducted two rounds of expert consultation among 20 experts through Delphi expert consultation method to determine the evaluation index system and weight of nursing quality for disabled elderly people in medical-nursing combined institutions.Results:The recovery rate of the two rounds of expert consultation questionnaire was 100.00% (20/20) , and the expert authority coefficient was 0.880. The Kendall's concordance coefficients of the first and second rounds were 0.138 and 0.128, respectively ( P<0.01) . Finally, the evaluation index system of nursing quality for the disabled elderly in medical-nursing combined institutions was constructed, including 3 first-level indicators, 8 second-level indicators and 43 third-level indicators. Conclusions:The nursing quality evaluation index system for the disabled elderly in medical-nursing combined institutions established in this study is scientific and reliable, which can provide a basis for nursing managers to quantitatively evaluate the nursing quality of the disabled elderly.

The outbreak of novel coronavirus pneumonia (NCP) has become the most severe public health issue at the moment, threatening people′s lives. Pediatricians in Shanghai have recently launched a discussion on the focused questions of NCP, including the incidence situation, epidemiological features, essentials of early screening, treatment and nosocomial infection prevention of children′s novel coronavirus infection (2019-nCoV), and further put forward the experts proposal upon the patterns of disease occurrence, development, diagnosis and control, for the reference of frontline pediatricians.

Objective To compare the blood lipid levels of different brachial-ankle pulse wave velocity (baPWV) in young and middle-aged people with normal blood pressure and to explore the related factors affecting baPWV.Methods From January 2014 to December 2017,the clinical data of one thousand two hundred and sixty-eight middle-aged and young people with normal blood pressure who underwent physical examination in Dongying People's Hospital were retrospectively analyzed.Using baPWV＜ 1 400 cm/s as the standard of normal arterial stiffness,the patients were divided into normal arterial stiffness group (normal group,1 128 cases),abnormal arterial stiffness group (abnormal group,baPWV ≥ 1 400 cm/s,140 cases).The blood lipid indexes of the two groups were analyzed and compared.Logistic regression analysis was used for multivariate analysis and linear correlation analysis was used for linear correlation analysis.Pearson correlation analysis was used.Results Compared with the normal group,TC ((4.99 ± 1.10) mmol/L vs.(4.48 ± 1.03) mmoL/L,t =5.830),TG ((1.62 ± 0.27) mmol/L vs.(1.49 ± 0.23) mmol/L,t=5.102),LDL-C[(3.25±0.23) mmol/L vs.(3.11±0.16) mmol/L,t =4.712),Apo B((0.96 ±0.07) g/L vs.(0.87±0.08) g/L,t =4.297)in abnormal group all increased,and HDL-C((1.15±0.09) mmol/L vs.(1.27±0.07) mmol/L,t =4.712) decreased,and the differences were statistically significant (P＜0.05).Smoking,high FPG,high LDL-C,high Apo B,low HDL-C were the independent factors affecting baPWV abnormality (P＜ 0.05).TC,TG,LDL-C,Apo B and baPWV in abnormal group were positively correlated(P＜0.05),and HDL-C and baPWV were negatively correlated(P＜0.05).There was a linear regression relationship between LDL-C,Apo B and baPWV (P＜0.05).Conclusion The increase of LDL-C and Apo B are closely related to early arterial disease in the low-risk populations of normotensive young and middle-aged people,even the risk of blood lipid may already exist within the normal range.

Objective To investigate whether pyrrolidine dithiocarbamate (PDTC) can attenuate the acute radiation-induced heart damage (RIHD) by inhibiting the activation of NF-κB and its downstream signaling pathways in rat models. Methods Twenty-one male adult Sprague-Dawley (SD) rats were randomly divided into the blank control, irradiation and PDTC plus irradiation groups (n=7 for each group). In the irradiation and PDTC+ irradiation groups,the rats received 6 MV X-ray at a single fraction of 20.0 Gy. In the PDTC+ irradiation group, intraperitonal injection of PDTC was administered at a dose of 120 mg/kg body weight,30 minutes prior to radiation, once daily for 1-14 days. On the 14thday,pathological changes of myocardial tissue were observed. Masson's trichrome staining was performed to calculate the collagen volume fraction (CVF) of myocardial cells. The expression levels of NF-κB family members including p50, p65,HIF-1α,connective tissue growth factor (CTGF) and collagen type 1(COL-1) proteins and mRNA were quantitatively measured by Western blot and quantitative real-time PCR (qPCR). Statistical analysis was conducted by using t-test. Results HE staining demonstrated that compared with the irradiation group, the severity of myocardial edema was alleviated,the infiltration of inflammatory cells was mitigated and the quantity of fibroblasts was reduced in the PDTC+irradiation group. Masson's trichrome staining revealed that PDCT intervention could decrease the deposition of collagen fiber in the interstitial tissues. Semi-quantitative analysis demonstrated that the CVF value in the PDTC+irradiation group was (9.99± 0.32)%, significantly lower compared with (22.05±0.21)% in the irradiation group (P<0.05). Western blot and qRT-PCR demonstrated that the expression levels of p50,p65,and HIF-1αproteins and mRNA in the PDTC+ irradiation group were significantly down-regulated compared with those in the irradiation group (all P<0.05). Compared with the irradiation group,the expression levels of CTGF protein and mRNA tended to decline (all P>0.05),and the expression levels of COL-1 protein and mRNA were equally inclined to decrease (P<0.05 and P>0.05). Conclusion PDTC can alleviate the acute RIHD by suppressing the activation of NF-κB and its downstream HIF-1α transcription.

Objective To examine the pathological changes in the myocardial tissues such as inflammatory response and fibrosis in a rat model of acute radiation-induced heart damage (RIHD),and to explore whether NF-κB and its downstream pathway are associated with acute radiation-induced myocardial fibrosis.Methods Fourteen nale adult Sprague-Dawley rats were randomly divided into control group and radiation group.Local heart irradiation was delivered to the precordial region of rats to establish an RIHD model in a single fraction with a dose of 20 Gy generated by a 6 MV linear accelerator.At 14 days after irradiation,the histopathological changes in myocardial and interstitial tissues were examined by HE staining;the distribution of collagen fibers was observed by Masson staining,and collagen volume fraction (CVF) was used as a semi-quantitative evaluation for myocardial collagen deposition,which was defined as the percentage of collagen area occupied in total area,and was compared using the independent-samples t test.The protein and mRNA expression levels of the NF-κB members p50 and p65 and the downstream pathway members hypoxia-inducible factor 1α(HIF-1o),connective tissue growth factor (CTGF),and type I (COL-1) were quantitatively analyzed by Western blot and qPCR,respectively.Results At 14 days after local heart irradiation,the radiation group showed significant myocardial edema and derangement,rupturc of some myocardial ceils,mild nuclear pyknosis,darkened nuclear staining,a small number of irregular nuclei,and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblast,as compared with the control group.The Masson staining showed that the collagen fibers in radiation group were widely distributed at the interstitial tissue and increased significantly compared with those in the control group;normal myocardial cells were in disordered array and had a tendency to be replaced by collagen fibers.The semi-quantitative analysis showed that radiation induced a significant increase in CVF (22.05％ vs.3.76％,P =0.003).Western blot and qPCR revealed that the protein and mRNA expression of p50,p65,HIF-1 α,CTGF,and COL-1 was significantly higher in the radiation group than in the control group (all P ＜ 0.05).Conclusions The pathological features of acute RIHD include significant myocardial edema and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblasts and collagen fibers.Radiation exposure can activate NF-κB and cause the upregulation of HIF-1α and CTGF at both protein and mRNA levels,which may play an important role in the progression of radiation-induced myocardial inflammation to fibrosis.

This paper was aimed to understand the clinical features of traditional Chinese medicine (TCM) through the analysis of relevant information among fracture patients treated by the Cervus and Cucumis Polypeptide Injection (CCPI).The study was conducted among fracture patients treated by CCPI in the hospital information systems (HIS) among 26 national triple-A hospitals from 2003 to 2014.The general information,TCM syndrome and solar term of morbidity were analyzed.The results showed that the number of patients from 45-64 years old were the most,accounting for 39.84％.Among them,the number of male patients from 18-44 years old was the most,accounting for 43.38％;the number of female patients from 45-64 year old was the most,accounting for 44.33％.The main TCM syndrome of admission and discharge was qi stagnation and blood stasis,which accounted for 60.53％ and 53.08％,respectively.Beginning of Summer (7th solar term) and Rain Water (2nd solar term) were solar terms with the most patients,which accounted for 5.26％ and 5.24％,respectively.It was concluded that the majority of fractures patients treated with CCPI were the elderly.The syndrome of qi stagnation and blood stasis was the most.The hospital admission of most patients was at the Beginning of Summer and Rain Water.It provided theoretical basis to pay attention on TCM syndrome differentiation in the treatment of clinical fractures.The treatment should be adapted to the characteristics of the disease itself,the change of solar terms,and dialectical medication.

Objective To simulate the possible systematic delivery errors introduced by monitor units ( MU) and multi-leaf collimator ( MLC) in radiotherapy plans for nasopharyngeal carcinoma ( NPC) , and to analyze the dosimetric sensitivity of static intensity-modulated radiotherapy ( IMRT ) and volumetric modulated arc therapy ( VMAT) with these errors. Methods Five IMRT plans were replanned using VMAT modality with the same physical parameters, and then MU errors of 125%, 250%, and 5. 00% were introduced into IMRT and VMAT plans. Meanwhile, to simulate leaf position errors during delivery, MLC position errors (025 mm, 050 mm, 100 mm, 150 mm, and 200 mm) were introduced by modifying the original plan documents. The types of MLC errors were as follows:( 1) the MLC banks moved in the same direction;( 2) the MLC banks moved in opposing directions ( expand or contract the MLC gaps ) . The differences in dosimetric sensitivity introduced by MU and MLC errors between IMRT and VMAT plans for NPC were calculated by linear regression analysis. Results With the increase in MU errors, the doses to target and organs at risk ( OARs) of IMRT and VMAT plans increased in a linear way, and met R2=0992-1000( P<005) . For MLC errors, the average dosimetric sensitivity for target and OARs of IMRT and VMAT were-026%/mm and-065%/mm in case of offset errors, 487%/mm and 868%/mm in case of expansion errors, and -604%/mm and -988%/mm in case of indentation errors. In addition, the dosimetric sensitivity with the three types of MLC errors was greater for VMAT plan than for IMRT plan. ConclusionsMU and MLC errors have a significant effect on the dose distribution of IMRT, and particularly VMAT, for NPC. It is important to execute routine quality assurance of MLC to ensure accurate radiotherapy.