Extracellular vesicles (EVs) have recently received much attention about the application of drug carriers due to their desirable properties such as nano-size, biocompatibility, and high stability. Herein, we demonstrate orange-derived extracellular vesicles (OEV) nanodrugs (DN@OEV) by modifying cRGD-targeted doxorubicin (DOX) nanoparticles (DN) onto the surface of OEV, enabling significantly enhancing tumor accumulation and penetration, thereby efficiently inhibiting the growth of ovarian cancer. The obtained DN@OEV enabled to inducement of greater transcytosis capability in ovarian cancer cells, which presented the average above 10-fold transcytosis effect compared with individual DN. It was found that DN@OEV could trigger receptor-mediated endocytosis to promote early endosome/recycling endosomes pathway for exocytosis and simultaneously reduce degradation in the early endosomes-late endosomes-lysosome pathway, thereby inducing the enhanced transcytosis. In particular, the zombie mouse model bearing orthotopic ovarian cancer further validated DN@OEV presented high accumulation and penetration in tumor tissue by the transcytosis process. Our study indicated the strategy in enhancing transcytosis has significant implications for improving the therapeutic efficacy of the drug delivery system.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

OBJECTIVE To provide reference for chronic disease management in grass-root institution . METHODS System structure design and audit class setting of the regional pretrial center in Changning district of Shanghai were introduced. The number of prescriptions/medical orders from the start of application to February 28，2022 were counted. The prescriptions/medical orders intercepted by the system ，prescriptions/medical orders intervened by physicians ，chronic disease types and drug use of regional multiple chronic diseases were counted and analyzed. RESULTS Compared with the data when the center was on line in September 2021，total qualified rate of prescriptions/medical orders （97.67％ vs. 86.42％）significantly increased ，the number of prescriptions/ medical orders intercepted by the system and intervened by physicians decreased by 55.39％ and 72.67％ in February 2022， respectively. The top five diseases were hypertension （26.52％），coronary heart disease （20.53％），sleep disorders （16.71％），diabetes（15.24％）and bone diseases （14.09％）. Among them ， there were many problematic prescriptions involving coronary heart disease ，sleep disorder and bone disease. CONCLUSIONS The incidence of chronic diseases among community residents remains high. In addition to common chronic diseases such as coronary heart disease ，hypertension and diabetes ，the incidence of sleep disorders and bone diseases is also increasing. With the help of the regional pretrial center ，the focus of chronic disease management can be adjusted timely ，drug supervision can be carried out in real time so as to improve the level of rational drug use in grass-root institution.

The clinical data of 5 patients with pneumonia type lung cancer from January 2017 to January 2020 were retrospectively analyzed.The results showed that the clinical symptoms of the 5 patients were cough and expectoration.The infection index was mildly abnormal, and the tumor marker index was increased.After anti infection treatment, the effect was not good.The diagnosis of pneumonia type lung cancer was confirmed by improving the fiberoptic bronchoscopy biopsy.Due to the lack of specificity of clinical manifestations, if the early diagnosis of pneumonia type lung cancer can not be confirmed, the chest imaging can be reviewed after anti infection treatment, and the pathological basis can be obtained by timely improvement of fiberoptic bronchoscopy, bronchoalveolar lavage and lung biopsy.

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.
Adrenal Cortex Hormones ; Adult ; Asian Continental Ancestry Group ; Asthma ; China ; Forced Expiratory Volume ; Humans ; Salmeterol Xinafoate ; Tiotropium Bromide

Objective To assess the feasibility of low concentration contrast medium (270 mgI/ml) and low radiation dose (100 kV) for enhanced CT scanning in infants and young children abdominal CT examination.Methods Ninety children with abdomen tumors or abdominal injuries who underwent contrast-enhanced CT examination were selected.The patients were divided into 3 groups (each n＝ 30):Group A with tube voltage of 120 kV for non-contrast enhanced and parenchymal phase scanning and iodixanol contrast-medium (320 mgI/ml);group B with tube voltage of 100 kV for non-contrast enhanced and parenchyrnal phase scanning and iodixanol contrast-medium (270 mgI/rnl);group C with tube voltage of 100 kV for non-contrast enhanced and parenchymal phase scanning and iodixanol contrast-medium (270 mgI/ml).The 4-point scale was used to evaluate the quality of parenchymal phase imaging.The standard difference (SD) of CT value in subcutaneous fat,SNR and CNR of liver parenchyma,splenic parenchyma,renal cortical,renal vein,and abdominal aorta were measured at parenchymal phase,and CT dose index of volume (CTDI,ol),dose length product (DLP) and effective dose (ED) were recorded.The data were statistically analyzed among 3 groups.Results There was no significant difference of SNR,CNR nor objective scores of liver parenchyma,splenic parenchyma,renal cortical,renal vein and abdominal aorta among 3 groups (all P＞0.05).The differences of CTDIvol,DLP and ED among 3 groups were statistically significant (all P＜0.01).The CTDIvol had no statistical difference between group B and group C (P ＝ 0.001,0.002),DLP (P ＝ 0.013,0.004) and ED (P ＝ 0.03,＜0.001) of group A had statistical difference with those of group B and C.Conclusion CNR of the abdominal image can be guaranteed using low concentration contrast medium (270 mgI/ml) combined with 100 kV tube voltage for CT scanning of infants and young children,therefore satisfying clinical diagnostic requirements.

Objective To investigate the relationship between genetic variants in the Toll-like receptor (TLR) pathway genes and susceptibility of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC).Methods The data of whole genome association studies of the high-risk population of GC and ESCC in China were analyzed by adaptive rank-truncated product (ARTP) method in pathway and gene level.The associations between single nucleotide polymorphism (SNP) and susceptibility of GC and ESCC were analyzed with additive model of unconditional Logistic regressions.PLINK 1.07 and SPSS 19.0 software were performed for statistical analyses,and ARTP package in R3.0.2 was used for pathway and gene level analysis.Results In gene-level analyses,eight genes were found to be associated with susceptibility of GC (P ＜0.05) and six genes were associated with susceptibility of ESCC (P ＜ 0.05).In single SNP-level analyses,21 SNPs were statistically correlated with susceptibility of GC (P ＜ 0.01),and 11 SNPs were statistically correlated with susceptibility of ESCC (P ＜0.01).Conclusions Some genetic variants in TLR pathway are associated with risk of GC and ESCC.The potential molecular mechanisms need further investigation.

Objective Inhaled corticosteroids combined with long β2-adrenoceptor agonist are widely used in treatment of chronic obstructive pulmonary disease,but mechanisms remain unclear.Methods Macrophage cells differentiated from THP-1 cell line were stimulated with dexamethasone and/or formoterol with or without lipopolysaccharide (LPS).TLR4 mRNA and protein were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting.Results A dose-dependent up regulation in TLR4 mRNA and protein expression in the presence of LPS was found.Treatment with dexamethasone (10-10 ～ 10-6mol/L) resulted in a dose-dependent reduction in TLR4 mRNA and protein.Stimulation with formeterol (10-7 mol/L and 10-6 mol/L) caused up regulation of TLR4.Formoterol (10-6mol/L)partially reversed the inhibitory effect of dexamethasone (10-6 mol/L) on TLR4 expression in the presence of LPS.Conclusions Modulation of TLR4 in macrophages by dexamethasone and/or formoterol may be one of the mechanisms for combination and have important implications for the treatment of airway inflammation in response to gram-negative bacteria.

Objective To study the effects of cardiac and pulmonary response in pailents with chronic obstructive pulmonary disease(COPD) on their exercise capacity.Methods Thirty four patients with COPD(including 8 patients in stage Ⅰ,15 patients in stage Ⅱ,10 patents in stage Ⅲ and 1 patent in stage Ⅳ and 24 healthy controls performed incremental exercise testing.Oxygen uptake(VO_2) and carbon dioxide output(VCO_2)were measured breath-by-breath.Arterial blood samples were drawn both at rest and peak exercise.Results The VO_2 at peak exercise was significantly lower in COPD group than in control group(15.81±3.65ml/min/kg vs 18.96±6.10ml/min/kg,P=0.042).The respiration reserve was lower in COPD patients compared to controls.The rBorg dyspnea score at the peak exercise for COPD patents was 4.24±2.01,significantly higher than that for controls(1.754±1.50).Oxygen pulse and heart rate reserve had not statistically difference between COPD group and control group.Significant increase of PO_2 and PCO_2 were found during exercise,which were 26.374±15.40 vs 10.26±22.65 mmHg and 42.33±3.65 vs 40.29±4.46 mmHg respectively compared to at rest.Conclusion Abnormal pulmonary response to exercise might be the main cause inducing exercise intolerance in patents with COPD.

Objective To study clinical features, diagnosis and treatment of allergic bronchopulmonary aspergillosis (ABPA) . Methods Clinical data and auxiliary examinations of eight patients with ABPA were analyzed, as well as relevant literatures were reviewed. Results All patients had symptom of cough, expectoration, out of breath and wheezing tale, seven of them with history of asthma, and all of them had increased peripheral blood eosinophil (EOS) count, serum levels of total immunoglobulin E (IgE) and lgE specific for Aspergillus fumigatus and showed positive prick test specific for Aspergillas fumigatus. Six of them showed infiltration shadows and six of them showed bronchiectasis in their chest CT images. Lung function test indicated obstructive ventilation dysfunction or mixed ventilation dysfunction with reversible airflow obstruction after administration of bronchodilator. Conclusions Diagnosis for ABPA should be made by integration of clinical features, increased blood eosinophil count and serum level of IgE, and result of prick test specific for Aspergillus fumigatus. Corticosteroid is a mainstay therapy for ABPA, ancillary with anti-fungi therapy. Patients with ABPA should be followed-up to prevent its recurrence.