Objective:To understand the utilization of clinical services provided through hospital-at-home to the elderly in Xuzhou City, and analyze patient satisfaction.Methods:The stratified cluster sampling method was used to select community elderly people aged 60 and above in Xuzhou city to conduct a face-to-face questionnaire survey.Descriptive analysis was used to examine the utilization and evaluation of home-based clinical services for the elderly.Multiple linear regression analysis was used to analyze associated factors for the satisfaction of the elderly in this care setting.Results:A total of 203 elderly people who had received this type of services were investigated.The overall satisfaction of the elderly in Xuzhou City with home-based clinical services was 79.3%(161/203), and the average satisfaction score of the comprehensive evaluation was(4.11±1.03)points.Age( β=-0.011), marital status( β=0.164), informed consent for service( β=0.162), doctors' bed-side services( β=0.146), service fee( β=0.346), and the home hospital bed assembling process( β=0.257)were the influencing factors for satisfaction with family hospital bed services, according to the patients involved in the comprehensive evaluation(all P<0.05). Conclusions:The utilization and evaluation with clinical services by elderly people in the hospital-at-home setting in downtown Xuzhou is relatively good, with relatively high satisfaction.Comprehensive measures should be taken in response to factors related to satisfaction to promote sustainable development of clinical services through hospital-at-home in China.

Objective　To explore the role of the allelic deletion and mutation of FHIT gene on the carcinogenesis and development of lung cancer. Methods　The allelic alterations of FHIT gene and microsatellites D3S1300, D3S1312,D3S1313 were detected in 35 cancer samples of NSCLC, their corresponding normal tissues, and 4 lung cancer cell lines, and 10 lung tissues of benign pulmonary lesions as control by PCR-SSCP and DNA sequence. Results　Loss of heterozygosity (LOH) affecting at least one locus of FHIT gene was observed in 22 out of 35 tumors, with a LOH rate of 62.86％. LOH of FHIT gene in squamous cell carcinoma (88.24％) was significantly higher than that in adenocarcinoma (38.89％) (P＜0.01). The LOH rate of FHIT gene in smoking patients (76.19％) was also significantly higher than that in non-smoking patients (42.86％)(P＜0.05).No significant relationship was found among the LOH of FHIT and cell differentiation, P-TNM stages, size of primary tumor, location of cancer and age of the patients (P＞0.05). LOH of FHIT was also detected in Lewis lung cancer and A549 cell lines. Mutation of microsatellite D3S1312 was observed in 4 lung cancer tissues. DNA sequence showed that CT mutation occurred in the 87 codon of microsatellite D3S1312. Conclusion　The alteration of FHIT gene is mainly allelic loss and the frequency of allelic mutation is rare. FHIT gene alterations preferentially occur in squamous cell carcinoma patients and smokers, and FHIT gene may be a candidate molecular target of carcinogenesis in tobacco smoker. Allelic deletion of FHIT gene might be an early molecular event in smoking-related lung cancer.

Objective:In order to develop an appropriate care service system and care security system for the elderly in urban communities, it is necessary to gain a comprehensive understanding of their needs and utilization of care services, as well as the cost of care and the factors that influence it.This will provide a theoretical basis for developing effective countermeasures.Methods:A stratified random cluster sampling method was utilized to conduct a questionnaire survey on individuals aged 60 and above in the Xuzhou urban community.The survey aimed to gain insight into the needs, utilization, and expenditure of care services for the elderly.To analyze the factors influencing care expenditure, a single factor χ2 test and Tobit regression model were employed. Results:In our survey of 1 623 elderly individuals, it was found that 32.4%(526 people)had been bedridden for more than one day in the past year and were unable to care for themselves.Of the elderly who are bedridden, 393 individuals(74.7%)have received care services from professional institutions, with a focus on medical care(312 people, 79.4%)and rehabilitation care(95 people, 24.2%).In terms of financial expenditures, 91.7% of respondents(1 489 people)reported spending zero yuan in the past year, while 6.0%(96 people)spent between 1 and 4 999 yuan.Only 1.0%(17 people)reported spending between 5 000 and 9 999 yuan, and 1.3%(21 people)spent 10 000 yuan or more.The findings from the univariate analysis revealed that various factors, including marriage, age, medical expenses, and life satisfaction had a significant impact on the care expenses of the elderly(all P<0.05).Furthermore, the Tobit regression model demonstrated that certain variables were particularly influential in determining care expenses.Specifically, elderly individuals with higher monthly income(Me=3.114), advanced age(Me=3.458), knowledge of care insurance(Me=7.647), disability(Me=10.998), no spouse(Me=14.387), and dementia(Me=20.473)had significantly higher care expenses. Conclusions:The survey conducted in Xuzhou suggests that the demand for care services is high, yet the utilization rate remains low, leading to a significant burden of care costs.To address these challenges, we must prioritize the care needs of disabled, mentally retarded, and advanced-age elderly individuals.We should also focus on enhancing medical and rehabilitation care services, improving the overall quality of elderly care, and promoting the development of a comprehensive elderly care service system and care security system that caters to the specific needs and financial constraints of the elderly population.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

OBJECTIVE To study of the dynamic evolution process of the themes of off-label drug use from a macroscopic perspective, perspective is needed to reveal the overall development vein of the field, and discover research hot spots and development trends of the field. METHODS A total of 3 876 literatures published in Web of Science from 2012 to 2022 on the topic of off-label drug use were used to obtain three visual maps of overlapping map, systematic evolution map and strategic map by using SciMAT analysis, and these maps of each period were analyzed. RESULTS Over the past ten years, there had been an increasing in the number of publications, themes, and keywords on the off-label drug use, with research themes from the former period having a large impact on the latter period, with complex evolutionary pathways and increasing evolutionary themes. Roughly, 14 evolutionary paths were formed in 4 research directions:adolescents and children, treatment, off label use, and drug RCT. CONCLUSION The content and scope of research in the field of off-label drug use will be diversified and developed, with greater focus on pediatric drug use, psychiatric drug use, COVID-19, and guidelines will be paid more attention.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn(2+) and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn(2+). The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.
Crystallography, X-Ray ; Protein Domains ; RNA Helicases ; chemistry ; RNA, Viral ; chemistry ; Viral Proteins ; chemistry ; Zika Virus ; enzymology

Selective occlusion of tumor vasculature has proven to be an effective strategy for cancer therapy. Among vascular coagulation agents, the extracellular domain of coagulation-inducing protein tissue factor, truncated tissue factor (tTF), is the most widely used. Since the truncated protein exhibits no coagulation activity and is rapidly cleared in the circulation, free tTF cannot be used for cancer treatment on its own but must be combined with other moieties. We here developed a novel, tumor-specific tTF delivery system through coupling tTF with the DNA aptamer, AS1411, which selectively binds to nucleolin receptors overexpressing on the surface of tumor vascular endothelial cells and is specifically cytotoxic to target cells. Systemic administration of the tTF-AS1411 conjugates into tumor-bearing animals induced intravascular thrombosis solely in tumors, thus reducing tumor blood supply and inducing tumor necrosis without apparent side effects. This conjugate represents a uniquely attractive candidate for the clinical translation of vessel occlusion agent for cancer therapy.