Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Objective To investigate the effect of down-regulating adenosine deaminase acting on RNA-1(AD AR1)on the radiosensitivity of lung adenocarcinoma cells.Methods Lentiviral transfection was used to establish an ADAR1 knockdown cell line based on A549 cells.Then the cells were divided into negative control(shNC)and ADAR1 knockdown(shADAR1)groups,which were followed by a single-dose irradiation of 0 Gy and 6 Gy X-rays.Western blotting and RT-PCR were utilized to detect the expression of AD AR1 at protein and mRNA levels,respectively.CCK-8 assay,wound healing assay and Transwell migration assay were applied to measure cell proliferation and migration abilities.Meanwhile,clone formation assay was performed to detect the effect of down-regulating ADAR1 on the radiosensitivity of A549 cells.Flow cytometry and Western blotting were conducted to detect the expression levels of apoptosis and apoptosis-related proteins Bax and Bcl-2.Immunofluorescence assay and Western blotting were used to detect the expression level of γ-H2AX.Comet assay was performed to detect the level of cellular DNA damage.Twelve female nude mice(4～6 weeks old,weighing 16～18 g)were divided into shNC group,shADAR1 group,shNC+ionizing radiation(IR)group and shADAR1+IR group,with 3 mice in each group.The growth of tumor of different groups was observed with subcutaneous tumorigenesis assay.Results Western blotting and RT-qPCR showed that the protein and mRNA expression of ADAR1 were significantly reduced in A549 shADAR1 cells(P＜0.05).CCK-8 assay,wound healing assay and Transwell migration assay indicated that down-regulation of ADAR 1 inhibited the proliferation and migration abilities of A549 cells,and this inhibition trend became more obvious(P＜0.01)after IR.Cell clone formation assay showed that the clone formation rate of both groups was decreased,with the increase of radiation dose.But the number of formed clones was lower in the shADAR1 group than the shNC group.Flow cytometry and Western blotting displayed that down-regulation of AD AR1 increased the apoptotic rate and Bax expression in A549 cells(P＜0.01)and decreased Bcl-2 expression(P＜0.05),and the apoptotic rate and Bax protein level were further increased in A549 shADAR1 cells after IR(P＜0.01),and the Bcl-2 protein level was further decreased(P＜0.01).The number of γ-H2AX foci and protein level in A549 shADAR1 cells were significantly increased after IR(P＜0.05),and the results of comet assay showed that the DNA damage was more obvious in A549 shADAR1 cells after IR(P＜0.01).Subcutaneous tumorigenesis assay in nude mice showed that the growth of subcutaneous tumour of A549 shADAR1 cells was significantly inhibited after IR(P＜0.01).Conclusion Down-regulation of ADAR1 significantly inhibits the proliferation and migration of A549 cells after IR and promotes apoptosis and DNA damage,and thereby increases the radiosensitivity of lung adenocarcinoma cells.

Purpose: Oligometastatic non–small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis. Materials and Methods: We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity. Results: We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC.

Objective: To investigate the awareness of nutrition and health knowledge among adult residents in Hangzhou City, so as to provide insights into improving human nutrition and health. Methods: The permanent residents at ages of 18 to 64 years were sampled using a multi-stage stratified random sampling method from 13 counties (districts) of Hangzhou City from June to July, 2021. Participants' demographics and awareness of nutrition and health knowledge were collected using the Questionnaire on Nutrition and Health Knowledge among Chinese Adult Residents, and the awareness of nutrition and health knowledge was analyzed among participants with different demographic features. Results: A total of 5 106 questionnaires were allocated, and 4 920 valid questionnaires were recovered, with an effective recovery rate of 96.36%. The respondents included 2 575 men (52.34%) and 2 345 women (47.66%), and had a mean age of (39.89±12.85) years. The median score of nutrition and health knowledge was 67.50 (interquartile range, 16.50) points, and the awareness of nutrition and health knowledge was 24.49%, while the awareness of dietary recommendation, food characteristics, nutrition and disease, food choice and food safety was 15.89%, 16.77%, 54.17%, 26.36% and 60.69%, respectively. The awareness of nutrition and health knowledge was significantly lower among men than among women (21.01% vs. 28.32%, P<0.05), and among urban residents than among rural residents (22.94% vs. 27.34%, P<0.05). There were significant differences in the awareness of nutrition and health knowledge among residents in terms of age, occupation and educational level (P<0.05). Conclusions Age, gender, region, occupation and educational level may affect the awareness of nutrition and health knowledge among adult residents in Hangzhou City. Health education about nutrition and health knowledge requires to be reinforced with adaptations to characteristics of residents.

Objective:To detect serum levels of vitamin A (Vit A), vitamin D(Vit D)25-hydroxy vitamin D[25-(OH)D] and vitamin E(Vit E) in children aged 0-6 years in Tibetan Plateau of Garzi Prefecture, thus providing references for physical examinations and prevention of 4 key diseases (rickets, malnutrition anemia, pneumonia and diarrhea) in children in plateau areas by relevant government departments.Methods:A total of 2 122 children who participated in physical examination in 12 townships of Xiangcheng County and 14 townships of Daocheng County, Garzi Tibetan Autonomous Prefecture, Sichuan Province from April 2017 to April 2019 with 0-6 years old were recruited for surveying physical measurements and collection of venous blood.Serum Vit A and Vit E levels were detected by high performance liquid chromatography.Serum levels of 25-(OH)D were detected by high performance liquid chromatography tandem mass spectrometry.The relationship between Vit A, Vit E and 25-(OH)D levels with the gender, age, seasonal change and altitude was analyzed.Results:The serum Vit A level, subclinical Vit A deficiency rate and marginal vitamin A deficiency rate were(1.05±0.27) μmol/L, 8.15%(173/2 122 cases) and 45.99%(976/2 122 cases), respectively in 2 122 children with 0-6 years old.There were significant differences in the serum Vit A level, the subclinical Vit A deficiency rate and the marginal vitamin A deficiency rate in children with different ages, seasons and altitudes (all P<0.05). The serum level of 25-(OH)D and 25-(OH)D deficiency rate insufficient rate were (24.65±6.45) ng/L, 6.03%(128/2 122 cases) and 16.59%(352/2 122 cases), respectively.There were significant differences in the serum level of 25-(OH)D, 25-(OH)D deficiency rate and 25-(OH)D insufficient rate in children with different ages and seasons (all P<0.05). The mean serum Vit E level, Vit E deficiency rate and Vit E insufficient rate were (7.81±1.74) mg/L, 2.78%(59/2 122 cases) and 29.59%(628/2 122 cases), respectively.There were significant differences in serum Vit E level, Vit E deficiency rate and Vit E insufficient rate in children with different ages and seasons (all P<0.05). The mean serum levels of Vit A and Vit D remained the lowest before the age of 1 year, and their deficiencies at this age were the most significant.The mean serum level of Vit E remained the lowest in >1-2 years old, and its deficiency and insufficient at this age were the most significant.Vit A, D and E levels were significantly affected by seasonal changes, which were significantly higher in the summer than in the spring, autumn and winter.In addition, Vit A and 25-(OH)D were significantly affected by the altitude, which were the lowest above 4 km altitude. Conclusions:The overall serum levels of Vit A, 25-(OH) D and E in children with 0-6 years old in Tibetan Plateau areas of Ganzi Prefecture are lower than those in plain areas.Vit A, 25-(OH) D and Vit E levels significantly differed in the age, season and altitude, which are related to the lack of local resources, insufficient maternal nutrition during pregnancy and insufficient intake after birth, as well as temperature and light caused by changes in local seasons and altitude.Therefore, it is necessary to make reasonable supplements during pregnancy to prevent vitamin deficiency.

Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16 and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor-g in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.
Animals ; Cells, Cultured ; Cellular Senescence ; drug effects ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diabetic Nephropathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; metabolism ; Glucose ; Kidney Tubules, Proximal ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL

Based on the big data of Electronic Medical Records (EMR),information retrieval and the deep learning method,an auxiliary diagnosis Question Answering (QA) system is designed.The paper introduces the design of general framework,EMR database,value network and policy-based network of the system,provides the system operation process.This system can not only help patients to examine their conditions independently,but also provide reference for doctors when they make the diagnosis and treatment schemes.

Background and purpose:The young breast cancer patients were treated with goserelin without individualized regimen, and lack of available clinical marker. The aim of this study was to investigate the role of anti-Müllerian hormone (AMH) in evaluation of individualized treatment of ovarian function suppression in the young breast cancer patients.Methods:Forty-one young patients with estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer from May 2012 to Jan. 2014 were randomly divided into 2 groups to undergo radical resection of breast cancer. According to postoperative treatment, one group was treated with goserelin + chemotherapy (n=20), and the other group received chemotherapy alone (n=21). Thirty female patients in the same age group were selected as normal control group. The time of menopause and menstrual recovery after the goserelin + chemotherapy or chemotherapy alone were observed in 2 groups. In early follicular phase (day 3-5) of the cycle preceding the operation and 3, 6 courses after the goserelin + chemotherapy treatment or chemotherapy treatment, serum levels of AMH, FSH and E2 were measured in 2 groups. Accordingly, serum levels of AMH, FSH and E2 were evaluated as well in normal control group.Results:There were no signiifcant differences in preoperative general conditions and preoperative serum FSH and E2 levels among the 3 groups (P>0.05). Compared with normal control group, the preoperative serum AMH levels of young breast cancer patients were decreased signiifcantly (P=0.04). The menopause time and menstrual recovery time in 2 chemotherapy groups were signiifcantly shorter than that in normal control group (P=0.00). Compared with normal control group and preoperative measurement, the differences in serum FSH and E2 levels were not statistically significant in goserelin + chemotherapy group or chemotherapy alone group (P<0.05). The serum AMH levels measured at different time points of the goserelin + chemotherapy group and chemotherapy alone group were decreased signiifcantly (P<0.05). Compared with the chemotherapy group, the serum AMH levels of the goserelin + chemotherapy group after 6 courses were signiifcantly decreased, and then signiifcantly increased 6 months after menstrual recovery (P<0.05).Conclusion:This study demonstrated that the serum AMH levels were obviously decreased after the ovarian function suppression treatment and increased after the menstrual recovery compared with evaluation of other ovarian reserve index. The serum AMH level could suggest ovarian reserve damage even after ovarian function has recovered to the noticeable level. Thus, AMH could be used clinically to evaluate the ovarian reserve of breast cancer patients as a potential marker for the individualized ovarian function suppression treatment in young breast cancer patients.

Objective:To investigate the distribution of four polyphyllins in different parts of paris polyphylla by means of compa-ring the contents of relative constituents in paridis rhizome and fibril to provide reference for comprehensive exploitation and utilization of paris polyphylla. Methods:Paris polyphylla samples were collected from Wudang mountain area and Shennongjia forest area. The contents of main secondary metabolites including polyphillinⅠ,Ⅱ,Ⅵ andⅦin paridis rhizome and fibril were evaluated by HPLC. Results:The four polyphyllins contents had obvious differences in different parts of polyphylla. The total content of four polyphillins in fibril was significantly higher than that in rhizome. Diosgenin compositions had no significant difference in the two parts, and the con-tents of pennogenin compositions in fibril showed significantly higher than those in rhizome. Conclusion:As for the main chemical com-positions contained in polyphylla, there is chemistry equality between fibril and rhizome, thus both of them can be used for medicine. However, as for the contents of four steroidal saponins, the distribution of secondary metabolites has obvious difference between fibril and rhizome, and the result may be caused by steroidal saponins transferred to rhizome for storage after the synthesis in fibril.

OBJECTIVETo investigate the anti-cancer effect of low-molecular-weight heparin (LMWH) combined with doxorubicin and explore the mechanism.

METHODSHepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were evaluated for cell viability with MTT assay and for changes in their migration ability using wound healing assay and Transwell migration assay. The changes in cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting, and ELISA was used to determine heparanase (HPA) concentration in the cell culture medium.

RESULTSHepG2 cells exhibited suppressed proliferation in response to LMWH and doxorubicin treatments. The combined treatment caused a significantly higher inhibition rate of cell migration than LMWH and doxorubicin alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA in the cells.

CONCLUSIONSLMWH can enhance the inhibitory effect of doxorubicin on the migration of HepG2 cells, the mechanism of which may involve the down-regulation of MMP-9, MMP-2 and HPA expressions.

Cell Movement ; drug effects ; Cell Survival ; Down-Regulation ; Doxorubicin ; pharmacology ; Glucuronidase ; chemistry ; Hep G2 Cells ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; RNA, Messenger ; Real-Time Polymerase Chain Reaction