Objective: To investigate the association between nighttime sleep duration, physical activity and disability among the elderly, so as to provide the basis for reduce the risk of disability and promote healthy aging. Methods: Based on the 2020 database of China Health and Retirement Longitudinal Study (CHARLS), demographic information, lifestyle behaviors, chronic diseases and nighttime sleep duration were collected from people aged 60 years and older. Physical activity level was evaluated using the International Physical Activity Questionnaire-Short. Disability status was measured using the basic Activities of Daily Living (ADL) scale. Association between nighttime sleep duration, physical activity and disability among the elderly were analyzed using multivariable logistic regression model. Results: Totally 11 126 elderly participants were enrolled, with 5 423 males (48.74%) and 5 703 females (51.26%). The mean age was (69.92±7.08) years. Among them, 6 838 individuals (61.46%) had a nighttime sleep duration of <7 hours, and 2 247 individuals (20.20%) had a physical activity level of <600 MET-min/week. A total of 3 213 individuals were identified as having disability, with a detection rate of 28.88%. Multivariable logistic regression analysis showed that, after adjusting for age, gender, marital status, education level, residence, smoking, alcohol consumption, and multimorbidity of chronic diseases, compared with a nighttime sleep duration of 7-8 hours, those with <7 hours (OR=1.535, 95%CI: 1.386-1.700) and >8 hours (OR=1.186, 95%CI: 1.003-1.402) had an increased risk of disability by 53.5% and 18.6%, respectively. Compared with a physical activity level of ≥600 MET-min/week, those with <600 MET-min/week (OR=2.106, 95%CI: 1.901-2.335) had an increased risk of disability by 110.6%. Compared with those who had a nighttime sleep duration of 7-8 hours and a physical activity level of ≥600 MET-min/week, the elderly with a nighttime sleep duration of <7 hours and a physical activity level of <600 MET-min/week (OR=3.299, 95%CI: 2.831-3.843), a nighttime sleep duration of >8 hours and a physical activity level of <600 MET-min/week (OR=2.566, 95%CI: 1.954-3.369), a nighttime sleep duration of 7-8 hours and a physical activity level of <600 MET-min/week (OR=1.911, 95%CI: 1.564-2.334), and a nighttime sleep duration of <7 hours and a physical activity level of ≥600 MET-min/week (OR=1.503, 95%CI: 1.334-1.692) had an increased risk of disability by 229.9%, 156.6%, 91.1%, and 50.3%, respectively. Conclusion Short or long nighttime sleep duration and low physical activity levels can increase the risk of disability in the elderly.

Objective:To explore the correlation between IκB kinase-interacting protein(IKBIP)expression in tumor cells within cervical cancer tissues(TCCCT)and the clinical pathological characteristics and prognosis of patients,as well as its impact on the biological behaviors of cervical cancer(CC)cells HeLa and SiHa,and to elucidate its potential mechanism.Methods:GENT2 and Kaplan-Meier plotter databases were utilized to analyze the differential expression of IKBIP mRNA in CC and normal cervical tissues,as well as its correlation with the clinical prognosis of CC patients.The Hallmark reference gene set was chosen for pathway enrichment analysis using the Gene Set Enrichment Analysis(GSEA)software.Immunohistochemistry method was used to detect the IKBIP protein expression in TCCCT and epithelial cells in normal cervical tissue(ECNCT),and analyze the correlations between its expression level and clinicopathological characteristics and prognosis of CC patients.Furthermore,univariate and multivariate Cox regression analyses were performed to identify the risk factors impacting the prognosis of CC patients.The stably transfected cells of CC(HeLa cells and SiHa cells)with IKBIP knockdown were established for the experiment,which were divided into sh-NC group and sh-IKBIP group.The expression of IKBIP protein in various groups was assessed using Western blotting method.The cell proliferation activity and the percentage of 5-ethynyl-2'-deoxyuridine(EdU)positive cells were measured using cell counting kit-8(CCK-8)and EdU methods,while Transwell chamber assay was employed to determine the numbers of migration and invasion cells in various groups.Additionally,the expression levels of E-cadherin,N-cadherin,and Snail proteins in the cells in various groups were analyzed by Western blotting method.Results:The GENT2 database analysis revealed that the expression level of IKBIP mRNA in CC tissue was higher than that in normal cervical tissue(P＜0.001).The GSEA enrichment analysis identified the epithelial-mesenchymal transition(EMT)pathway as the top-ranked pathway in IKBIP high-expression group.The immunohistochemistry results indicated the positive expression rate of IKBIP protein in TCCCT was higher than that in ECNCT(50.5％vs 8.0％),and its over-expression was associated with FIGO stage(2018)and differentiation grade of tumor(P＜0.05).The univariate and multivariate Cox regression analyses suggested that lymph node metastasis(LNM)and high expression of IKBIP were the risk factors affecting the overall survival(OS)and progression-free survival(PFS)of CC patients(P＜0.05).The Western blotting method results showed that compared with sh-NC group,the expression level of IKBIP protein in the cells in sh-IKBIP group was decreased(P＜0.05).The CCK-8 and EdU assay results showed that compared with sh-NC group,the proliferation activity and the percentage of EdU positive cells in sh-IKBIP group were decreased(P＜0.05).The Transwell chamber assay results showed that compared with sh-NC group,the numbers of migration and invasion cells in sh-IKBIP group were significantly decreased(P＜0.05).Additionally,the Western blotting method results indicated that compared with sh-NC group,the expression level of E-cadherin protein in sh-IKBIP group in CC cells was increased(P＜0.05),while the expression levels of N-cadherin and Snail protein were decreased(P＜0.05).Conclusion:The expression of IKBIP protein is significantly up-regulated in HeLa and SiHa cells derived from CC,and it is closely correlated with poor prognosis in CC patients.Suppression of IKBIP protein expression can effectively inhibit the proliferation,invasion and migration capabilities as well as EMT process of CC cells.

AIM:To investigate the effect of protopanaxatriol(PPT)on the drug resistance of paclitaxel(PTX)-resistant human breast cancer MDA-MB-231 cells(MB231-PR cells).METHODS:The MB231-PR cells were constructed as cell models.They were treated with PPT,and incubated for a certain period of time according to the experi-mental settings.CellTiter-Glo was used to determine the viability of MB231-PR cells and MDA-MB-231 parental cells(MB231-PT cells).The change of sub-G1 phase was detected by flow cytometry.Western blot was used to evaluate the apoptosis-related proteins,such as cleaved caspase-3,cleaved poly(ADP-ribose)polymerase(PARP),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and survivin.The activity of nuclear factor-κB(NF-κB)was detected by lu-ciferase reporter assay and immunofluorescence assay.The mRNA expression levels of interleukin-6(IL-6),IL-8,chemo-kine CXC motif ligand 1(CXCL1),chemokine CC motif ligand 2(CCL2),CD44,NANOG,octamer-binding transcrip-tion factor 4(OCT4),sex-determining region Y-box 2(SOX2)and aldehyde dehydrogenase 1(ALDH1)were detected by qPCR.The protein levels of IL-6 and IL-8 were measured by ELISA.Tumor sphere formation assay was used to evaluate the characteristics of stem cells.RESULTS:(1)The viability of MB231-PR cells was suppressed by PPT treatment in a dose-dependent manner compared with MB231-PT cells(P<0.01).Besides,the viability of MB231-PR cells was de-creased after combined treatment with PPT and PTX(P<0.01),the accumulation of sub-G1 phase was induced(P<0.01),the ratio of Bax/Bcl-2 was elevated(P<0.01),and the protein levels of survivin,cleaved PARP and cleaved cas-pase-3 were increased(P<0.05).(2)After PPT treatment combined with PTX,the mRNA expression of inflammatory cy-tokines(IL-6,IL-8,CXCL1 and CCL2)and cancer stem cell-related markers(OCT4,SOX2,NANOG,ALDH1 and CD44)was reduced(P<0.05),and the protein levels of IL-6 and IL-8 were decreased(P<0.01).The activity of NF-κB in MB231-PR cells was suppressed(P<0.05),and the growth of tumor spheres from MB231-PR cells was damaged(P<0.05).(3)Immunofluorescence assay showed that PTX induced nuclear p-p65 expression,but this effect was attenuated by PPT.CONCLUSION:Combined treatment with PPT and PTX could attenuate PTX resistance of MB231-PR cells by inhibiting inflammatory cytokines and cancer stem cells.

Objective:To explore the clinical and genetic characteristics of asparagine synthase deficiency.Methods:Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed.Results:All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor.Conclusions:Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

Objective:To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body(AVB)in the surgical procedure of anterior cervical corpectomy and fusion(ACCF).Methods:Following the proposal of IDEAL(idea,development,exploration,assessment,and long-term follow-up)framework,we designed and conducted this single-armed,retrospective cohort study.The patients with cervical spondylotic myelopathy were recruited,and these patients exclusively received the surgical procedure of single-level ACCF in our single center.After the process of corpectomy,the size was tailored using different trials and the most suitable stand-alone AVB was then implanted.This AVB was manufactured by the fashion of 3D-printing.Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies,to stabilize the AVB.The participants were regularly followed-up after the operation.Their clinical data were thoroughly reviewed.We assessed the neurological status according to Japanese Orthopedic Association(JOA)scale.We determined the fusion based on imaging examination six months after the operation.The recorded clinical data were analyzed using specific software and they presented in suitable styles.Paired t test was employed in comparison analysis.Results:In total,there were eleven patients being recruited eventually.The patients were all followed up over six months after the operation.The mean age of the cohort was(57.2±10.2)years.The mean operation time was(76.1±23.1)min and the median bleeding volume was 150(100,200)mL.The postoperative course was uneventful for all the cases.Dysphagia,emergent hematoma,and deterioration of neurological func-tion did not occur.Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up,which were significantly different(P＜0.001).The mean recovery rate of neurological func-tion was 85.9％.By comparing the imaging examinations postoperatively and six months after the opera-tion,we found that the average subsidence length was(1.2±1.1)mm,and that there was only one ca-ses(9.1％)of the severe subsidence(＞3 mm).We observed significant improvement of cervical lor-dosis after the operation(P=0.013).All the cases obtained solid fusion.Conclusion:3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study.The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.

Drug therapy is a common method to cure diseases and relieve symptoms.The value of patient-reported outcome(PRO)in evaluating the effect of drug therapy has been increasingly paid attention.The PRO scale is a standardized questionnaire,which can scientifically evaluate the experiences and subjective effects of drug use from a patient-centered perspective,and help patients and clinicians make more reasonable medication decisions.By reviewing and sorting out relevant global literature,this paper found that the content of the PRO scales relevant to drug therapy focused on five fields:"medication satisfaction""medication adherence""drug treatment burden""medication-related quality of life"and"adverse drug reactions".This paper described the basic information,measurement characteristics and application of common scales in recent years respectively,and summarized and analyzed the problems and enlightenment of scale development,aiming to provide theoretical reference for the selection,application and development of PRO scales.

Objective:To improve the determination method of sodium alginate pharmaceutical excipient in the USP for the analysis of sodium alginate content in the Chinese market.Methods:High and low viscosity sodium alginate samples were subject to acid-water and acid-isopropanol precipitation methods,respectively,followed by acid-base neutralization capacity analysis to calculate the sodium alginate content in the sample.Results:The line-ar relations were good between sample weight and the volume of sodium hydroxide titrant consumed in the range of 0.5-1.5g(R2=1.000 0,0.999 9).For two precipitation methods,the average recovery rates were 104.2％with RSD value of 0.3％(n=6)and 101.9％with RSD value of 0.2％(n=6),respectively.Conclusion:The improved method has good specificity,accuracy and precision,which is convenient and low cost that can be performed in the assay of sodium alginate pharmaceutical excipient.

Objective To explore the status quo and potential profile of self-management in elderly patients with venous leg ulcers,analyse the differences and influencing factors in different profiles,and provide references for clinical nursing.Methods Convenient sampling method was used to select patients who were followed up in the department of vascular surgery and vascular department of 3 tertiary A hospitals in Shanghai from October 2022 to May 2023 as the study subjects.General data questionnaire,Chronic Wound Patient Self-management Behavior Questionnaire,Health Literacy Management Scale,Brief Illness Perception Questionnaire,Social Support Rating Scale,Chronic Disease Self-Efficacy Scale and Geriatric Depression Scale-15 were used for investigation.Mplus 8.3 was used for potential profile analysis,and SPSS 25.0 was used for univariate analysis and multiple Logistic regression analysis.Results A total of 316 valid questionnaires were collected,and the patients were divided into 3 potential profiles according to their self-management level:low management-inefficient wound response,middle management-highly effective compliance and high management-efficient wound response,accounting for 25.63％,46.84％and 27.53％respectively.Multiple Logistic regression analysis showed that duration of illness,depression,health literacy,self-efficacy and illness perception were factors influencing the potential profile of self-management in elderly patients with venous leg ulcers.Conclusion The self-management level of elderly patients with venous leg ulcers is at a medium level and has obvious classification characteristics.Clinical nurses can take targeted nursing measures according to different characteristics of patients to improve their self-management ability.

Objective:To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid (BP) .Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients, who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg (except for the initial dose being 600 mg). Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios ( ORs) were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios ( HRs) were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results:A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration ( M [ Q1, Q3]) was 4.0 (2.0, 17.0) months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients (53.9%) were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 (15.0, 30.0) mg/d. At week 2 after the start of treatment, 63 patients (60.6%) achieved disease control, and 37 (35.6%) achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 (98.2%) achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 (10.0, 17.5) mg/d. Disease control was achieved in 92 of 104 patients (88.5%) within 16 weeks, with the time to disease control being 14.0 (13.0, 26.0) days and the time to pruritus relief being 12.0 (3.0, 14.0) days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 (compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05). Multivariate Cox regression analysis showed that compared with severe BP patients, mild ( HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014) and moderate BP patients ( HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031) were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief ( P = 0.006), and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients (10.6%), including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion (with a high likelihood of idiopathic pericarditis), 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion:Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.

Objective To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers(DFU),to develop a predictive model,and to conduct internal validation of the model.Methods The clinical data of DFU patients admitted to West China Hospital,Sichuan University between January 2012 and December 2022 were retrospectively collected.The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3.Hospital stays longer than 75th percentile were defined as prolonged length-of-stay.A thorough analysis of the risk factors was conducted using the training cohort,which enabled the development of an accurate risk prediction model.To ensure robustness,the model was internally validated using the validation cohort.Results A total of 967 inpatients with DFU were included,among whom 245 patients were identified as having an extended length-of-stay.The training cohort consisted of 622 patients,while the validation cohort comprised 291 patients.Multivariate logistic regression analysis revealed that smoking history(odds ratio[OR]=1.67,95%confidence interval[CI],1.13 to 2.48,P=0.010),Wagner grade 3 or higher(OR=7.13,95%CI,3.68 to 13.83,P＜0.001),midfoot ulcers(OR=1.99,95%CI,1.07 to 3.72,P=0.030),posterior foot ulcers(OR=3.68,95%CI,1.83 to 7.41,P＜0.001),multisite ulcers(OR=2.91,95%CI,1.80 to 4.69,P＜0.001),wound size≥3 cm2(OR=2.00,95%CI,1.28-3.11,P=0.002),and white blood cell count(OR=1.11,95%CI,1.05 to 1.18,P＜0.001)were associated with an increased risk of prolonged length of stay.Additionally,a nomogram was constructed based on the identified risk factors.The areas under the receiver operating characteristic(ROC)curves for both the training cohort and the validation cohort were 0.782(95%CI,0.745 to 0.820)and 0.756(95%CI,0.694 to 0.818),respectively,indicating robust predictive performance.Furthermore,the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts.Conclusion Smoking history,Wagner grade≥3,midfoot ulcers,posterior foot ulcers,multisite ulcers,ulcer area≥3 cm2,and elevated white blood cell count are identified as independent predictors of prolonged hospitalization.Therefore,it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.