Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.

Schizophrenia is a chronic mental disorder that often co-occurs with weight gain issues,which impacts medication adherence and symptom recovery in patients,and increases the risk of metabolic and cardiovascular diseases.However,the specific mechanism of weight gain in the patients with schizophrenia remains incompletely understood.Potential factors include increased appetite and abnormal glucose and lipid metabolism due to the effects of antipsychotic drugs on multiple neurotransmitter receptors,shared pathogenesis between schizophrenia and obesity,and unhealthy dietary preferences and lifestyles among the patients with schizophrenia.In recent years,the progress in non-pharmacological interventions in the treatment of weight gain in schizophrenia has been continuously updated,which mainly includes lifestyle interventions,bariatric surgery and neuromodulation technology.Lifestyle interventions include diet,exercises and cognition,and the effectiveness of comprehensive lifestyle intervention models and compliance of patients have become the mainstream of research.Bariatric surgery has a weight loss effect on obese patients with schizophrenia who meet the surgical indications,but the total number of reported cases is still small,and further exploration of perioperative symptom management is needed.In neuromodulation technologies,repeated transcranial magnetic stimulation(rTMS)appears to be promising in the treatment of weight gain in the patients with schizophrenia.The aim of this article is to provide more diversified clinical strategies for the treatment of weight gain in schizophrenia.

BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM_2.5) on AMD. METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM_2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM_2.5 on AMD. RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM_2.5 level during the study period was 63.1 ± 15.3 µg/m³. A significant positive association was detected between AMD and PM_2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM_2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM_2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM_2.5 and atmospheric pressure. CONCLUSIONS This study is among the first to characterize the coordinated effects of meteorological factors and PM_2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.
Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; China/epidemiology* ; Macular Degeneration/etiology* ; Meteorological Concepts

Objective:To investigate the expression of stanniocalcin-2 (STC-2) and cellular-mesenchymal epithelial transition factor (C-met) in tumor tissues of cervical cancer patients and their clinical significance.Methods:A total of 110 cervical cancer patients were selected in Foshan First People′s Hospital from January 2014 to December 2018. Patients′ cancer tissue samples and normal tissue samples were collected during modified radical resection to determine and compare the expression levels of STC-2 mRNA and C-met mRNA in the two tissues, and to analyze the correlation between the expression levels of STC-2, C-met and the clinicopathological characteristics of the patients as well as the multivariate analysis of tumor metastasis and recurrence in the patients. The correlation between the expression of STC-2 and C-met and the time of postoperative tumor metastasis and recurrence in cervical cancer patients were analyzed after 24 months of follow-up.Results:The expression levels of C-met mRNA and STC-2 mRNA in cancer tissues were higher than those in adjacent normal tissues: 4.51 ± 1.21 vs. 3.97 ± 1.14, 2.57 ± 0.21 vs. 2.12 ± 0.24, there were statistical differences ( t = 3.41, 14.80, P<0.05). The expression of STC-2 and C-met in cancer tissues had no significant difference with age, pathological type, federation international of gynecology and obstetrics (FIGO) stage and tumor size ( P>0.05), but had significant difference with tumor recurrence or metastasis ( P<0.05). The results of Logistic multivariate analysis showed that vascular emboli, lymph node metastasis, TNM stage, depth of tumor invasion, C-met expression and STC-2 expression were independent risk factors affecting the prognosis of cervical cancer patients ( P<0.05). The expression of STC-2 and C-met were negatively correlated with the time of tumor metastasis in patients with cervical cancer ( r = - 0.663, P<0.001; r = - 0.747, P<0.001). Conclusions:The expression levels of STC-2 and C-met in cancer tissues of cervical cancer patients are higher than those in adjacent normal tissues, and the expression levels of STC-2 and C-met are negatively correlated with the time of metastasis. The expression of C-met, the expression of STC-2, vascular emboli, lymph node metastasis, TNM stage, and the depth of tumor invasion are all independent risk factors affecting the prognosis of cervical cancer patients.

ObjectiveTo explore the formulation rules for the treatment of heart pain in the Medical Heart Enlightenment （《医学心悟》） from the perspective of the "Tangye Jingfa Tu"， thereby providing a way of thinking about the treatment of heart pain in traditional Chinese medicine （TCM） and the study of the Medical Heart Enlightenment. MethodThe "Tangye Jingfa Tu" contained in the Secrets for Auxiliary Cultivation Life： The Essential Method of Using Herbal Medicine for the Differential Treatment of the Five Zang Organs （《辅行诀五脏用药法要》） was used to analyze the nine prescriptions for heart pain in Volume Ⅲ of the Medical Heart Enlightenment by CHENG Guopeng in the Qing dynasty. A "table for analyzing the formulation of the nine prescriptions for heart pain" was developed. The analysis diagrams for decoction and meridian rules in nine prescriptions for heart pain were plotted and the compatible structure of the medicinal flavors was analyzed. ResultThe composition of Chenxiang Jiangqisan for the treatment of Qi-induced heart pain is "five pungent， four bitter， and two sweet drugs"， the composition of Shouniansan for the treatment of blood-induced heart pain is "five bitter， four pungent， three sweet， and one salty drugs"， the composition of Qingzhongtang for the treatment of heat-induced heart pain is "six bitter， three pungent， and two sweet drugs”， the composition of Jiangfutang with Cinnamomi Cortex for cold-induced heart pain is "three pungent and two sweet drugs"， the composition of Xiaobanxia modified with Fuling Tang for treating fluid retention-induced heart pain is "two pungent and two sweet drugs"， the composition of Baohetang for treating heart pain due to dietary stagnation is "five sweet， four pungent， four bitter， and one sour drugs"， the composition of Guipitang for the treatment of deficiency-induced heart pain is "eight sweet， four bitter， three pungent， and one sour drugs"， the combination of Huachongwan for the treatment of worm-induced heart pain is "seven bitter， six pungent， and four sweet drugs"， the composition of Shenzhusan， Congbaijiu， and Shengjiangtang for the treatment of resistance-induced heart pain is "eight pungent， four bitter， and two sweet drugs". ConclusionFrom the perspective of the "Tangye Jingfa Tu"， the Medical Heart Enlightenment is based on the compatibility principle of "pungent-bitter-sweet drugs" in the treatment of heart pain， with heart deficiency treated with salty drugs for tonifying， or bitter-sweet-salty drugs， and heart excess treated with bitter drugs for purging， or sweet-pungent-bitter drugs， mostly applying the transformation rules of five medicinal flavors， i.e.， "sweet-pungent-bitter drugs" and promoting the action of the pungent and sweet drugs acting on the spleen into the heart to relieve and purge the heart. In most cases， the treatment focuses on harmonizing the heart， liver， spleen， and kidneys， with an emphasis on the mother-child relationship and the application of the principles of the five elements generating and controlling each other. If the progression of the disease involves both the mother and child organs， the formulation should adhere to the compatibility rule of "the child organ makes the mother organ excess and the mother organ makes the child organ deficient".

OBJECTIVE To investigate the effect and mechanism of dihydroartemisinin(DHA)on lipo-polysaccharide(LPS)-induced acute lung injury(ALI)in mice using whole-genome sequencing.METHODS An ALI mouse model was established via intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide.The mice were divided into normal control group(n=10),model group(n=10)and model+DHA group(n=10).The mice in the model+DHA group were injected intraperitoneally with 20 mg·kg-1 DHA,while those in the normal control group and LPS group were injected intraperitoneally with solvent of DHA,saline containing 1%Tween 80 and 10%Macrogol 400.The mice were executed 24 h after drug administration.The wet and dry weight ratio(W/D)of lung tissue was calculated.Hematoxylin-eosin(HE)staining was used to observe histopathological damage in the lung.Classified counts of inflamma-tory cells in alveolar lavage fluid were performed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid.Real-time quantitative PCR(RT-qPCR)was used to detect mRNA levels of placenta-specific 8(Plac8),Toll-like receptor 7(TLR7),IL-1β,IL-6 and TNF-αin lung tissue.The whole gene transcriptome was sequenced by RNA transcriptome sequencing(RNA-seq)using the Illumina HiSeq high-throughput sequencing platform before the function and signal pathway of differentially expressed gene mRNA between the groups were enriched and analyzed using GO and KEGG enrichment analysis methods.RESULTS Compared with the model group,the lung W/D values of mice,the pathological damage,inflammatory cells in alveolar lavage fluid,expression levels of IL-1β,IL-6 and TNF-α in alveolar lavage fluid(P<0.01,P<0.01,P<0.01),and the mRNA expression levels of IL-1β,IL-6 and TNF-α were significantly reduced in lung tissues in the model+DHA group(P<0.01,P<0.05,P<0.05).Whole gene transcriptome sequencing revealed that immune-related Plac8 and TLR7 genes were significantly upregu-lated(P<0.01)in mouse lung tissue of the model group but significantly downregulated(P<0.05)in mouse lung tissue of the model+DHA group.The results of RT-qPCR of Plac8 and TLR7 verified the results of whole gene transcriptome sequencing.GO and KEGG analysis showed that Plac8 and TLR7 were mainly related to the regulation of cytokine production,T/B cell activation and signal transduction,chemo-kine signal transduction and NF-κB signal transduction.CONCLUSION DHA might reduce LPS-induced lung damage and ameliorate the inflammatory condition in lungs of ALI mice.The mechanism of action may be that DHA negatively regulates the signaling pathways involved in TLR7 and Plac8 by decreasing the expressions of TLR7 and Plac8 mRNA before regulating a series of immune responses such as secretion of inflammation-related cytokines and activation of immune cells,thereby reducing inflam-matory damage in lungs.

Objective : To investigate the effect of platelet particles on the extent of intestinal inflammation and in⁃ testinal mucosal permeability in mice with dextran sodium sulfate induced colitis. Methods : The experiment was divided into four groups : normal control group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of 0. 9% sodium chloride solution) , PMPs group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of PMPs) , DSS model group ( n = 10 , drinking DSS solution + intraperitoneal injection of 0. 9% sodium chloride solution) , and experimental group ( n = 15 , drinking DSS solution + intraperitoneal injection of PMPs) . Peripheral blood⁃derived PMPs suspension was collected from inflammatory bowel disease ( IBD) patients. A colitis model was constructed in mice by allowing them to freely drink a 5% DSS solution for 1 week , followed by continuous intraperitoneal injection of PMPs for 7 days. Disease activity index (DAI) scores was recorded daily and the severity of intestinal inflammation with histopathological scores (HI) was assessed by HE staining of colon samples at the end of the experiment. Myeloperoxidase (MPO) , neutrophil elastase (NE) , citrullinated histone H3 (citH3) , and free DNA levels were measured in colon homogenate , observe intestinal mucosal structure by transmission electron microscopy , and intestinal permeability was tested using fluorescein isothiocyanate⁃dextran (FITC⁃D) . Results: Compared with the normal control group , the colonic mucosa of mice in the PMPs group showed edema , severe destruction of epithelial structure , extensive aggregation of inflammatory cells , and increased overall HI score (P < 0. 01) ; the levels of inflammatory factors such as IL⁃1β and TNF⁃α in colonic tissue homogenates of mice in the PMPs group increased (P < 0. 05) , and the expression of NETs increased (P < 0. 05) ; the plasma FITC⁃D level of mice in the PMPs group significantly increased (P < 0. 05) , and the permeability of intestinal mucosa increased. Compared with the DSS group , the experimental group mice had higher plasma FITC⁃D levels ( P < 0. 05 ) and more electron microscopic colonic epithelial damage. Conclusion PMPs induces NETs formation in mice , promotes colonic inflammation in mice , increases intestinal mucosal permeability and aggravates intestinal inflammation in mice with DSS colitis.

Objective:To examine the association of blood uric acid (UA) and cognitive impairment (CI) among oldest-old adults in China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted during 2017-2018. Finally,1, 622 elderly aged 80 years and older with complete information on blood UA and cognitive function score were included in this study. Information on demographic characteristics, lifestyle, and health status were collected through questionnaire and physical examination. Venous blood samples of the participants were collected to test blood UA level. Cognitive impairment (CI) was assessed using the Chinese Mini-Mental State Examination (MMSE) according to personal educational level. Generalized Estimating Equations (GEE) model for binary data was used to analyze the association of blood UA and CI, and further compared the associations among different age and body mass index (BMI) groups.Results:Of the 1 622 oldest-old, the mean age was (92.2±8.1) years, 656 (40.4%) were male, the mean level of blood UA was (343.3±86.2) μmol/L, and 482 (29.7%) oldest-old had CI. Compared with the lowest quartile of UA, the risks of CI in the second, third and highest quartiles were gradually reduced, the corresponding ORs and 95% CI were 0.99 (0.71-1.33), 0.87 (0.68-0.94) and 0.69 (0.48-0.85), respectively; and the linear trend test was statistically significant ( P<0.001). Subgroup analysis showed that the effects of higher UA associated with lower risk of CI were stronger in younger oldest-old (aged 80-89 years) and thinner group (BMI<24) ( Pinteraction<0.05). Conclusions:Blood UA was negatively associated with the risk of having CI in the oldest-old among the nine longevity areas of China.

Objective:To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results:Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1 st quartile, the OR(95% CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion:Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above in 9 longevity areas in China.

Objective:To investigate the association of blood arsenic level with hyperuricemia among elderly aged 65 years and older.Methods:Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. 2 438 participants aged 65 years and older with complete information on blood arsenic and uric acid were included in this study. Information including demographics characteristic, life style and health status was collected by questionnaire and physical examination. Meanwhile, venous blood was collected to detect the levels of blood arsenic and uric acid. Subjects were stratified into three groups (low, middle and high) by tertiles of blood arsenic level. Logistic regression models were used to analyze the association of blood arsenic level with hyperuricemia.Results:The age of participants was (84.57±11.41) years, of which 1 172 (48.07%) were male and 1 525 (62.55%) were over 80 years old. The detection rate of hyperuricemia was 17.23% (420), and the detection rates of hyperuricemia were 11.77%, 19.25% and 20.62% among participants with low, middle and high blood arsenic, respectively ( P<0.001). After controlling confounding factors, compared with participants who had low blood arsenic, the ORs (95% CI) of hyperuricemia for the participants with middle and high blood arsenic were 1.57 (1.12-2.23) and 2.08 (1.46-2.99), respectively. Subgroups analysis showed that compared with female, the association between blood arsenic level and hyperuricemia was more obvious in males ( Pinteraction<0.05). Conclusion:Blood arsenic level is associated with the risk for hyperuricemia among the elderly aged 65 years and older in 9 longevity areas in China.