Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P＜0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P＜0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

Tafamidis is a selective stabilizer for transthyretin （TTR）， used for the treatment of transthyretin amyloidosis with cardiomyopathy （ATTR-CM） and transthyretin amyloidosis with polyneuropathy （ATTR-PN）. This article provides a review of the basic information and clinical studies on the efficacy and safety of tafamidis. It is found that tafamidis slows down or prevents the progression of TTR amyloidosis by inhibiting the dissociation of TTR tetramers. Multiple clinical studies have shown that tafamidis has good efficacy and safety， significantly reducing all-cause mortality and cardiovascular-related hospitalization rates in patients with amyloidosis， and delaying disease progression. Although tafamidis treatment may have certain limitations， it is still a key drug for the treatment of TTR amyloidosis， and the first drug approved for the treatment of ATTR-CM.

ObjectiveTo analyze the trends in life expectancy and cause-eliminated life expectancy of the registered residents in Qingpu District, Shanghai from 2002 to 2021, and to identify the major diseases causing life expectancy loss in the area, so as to provide a theoretical basis for strengthening disease prevention and interventions and optimizing health resources allocation. MethodsUsing the International Classification of Diseases (ICD)-10 classification of death causes, average life expectancy and cause-eliminated life expectancy were calculated with the abbreviated life table and the cause-eliminated life expectancy table. A trend forecast of life expectancy from 2022 to 2029 was made. ResultsFrom 2002 to 2021, the life expectancy of Qingpu District residents showed an increasing trend, with an average annual growth of 0.32 years (AAPC=0.39%, P<0.001). Among the seven major causes of death, the cause-eliminated expected life expectancy for circulatory system diseases showed the most significant upward trend (AAPC=0.53%, P<0.001), rising from the third leading cause of death in 2002 to the first in 2021. The life expectancy loss rate due to circulatory system diseases increased from 3.79% to 7.97%. Respiratory system diseases showed the largest decline, decreasing from the first leading cause of death in 2002 to the fourth in 2021, with the life expectancy loss rate decreasing from 6.83% to 0.99%. ConclusionLife expectancy of the registered residents in Qingpu District has reached a leading level in China. Future efforts should focus on effectively increasing the life expectancy of male residents, strengthening the comprehensive prevention and treatment of chronic diseases such as cerebrovascular diseases, diabetes, and malignant tumors, and improving health promotion policies for residents to achieve a steady long-term increase in regional life expectancy.

After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.