Microneedles array based on micro electro-mechanical system (MEMS) technology is one of important applications in biomedicine and brings a new means in biomedicine field. The prospect for the development of microneedles technology in precision drug injection, clinical monitoring and biochemistry test is and save broad. This paper describes three important applications of MEMS microneedles array in biomedicine field: biomedicine microneedles electrode, transdermal delivery of drugs and fluid extraction, and then summarizes their application elements and recent development. It explains the characteristics of microneedles, which provide painless, effective and save biomedical method in accordance with human requirements. In addition, a series of the fabrication technology of microneedles array is discussed.
Drug Delivery Systems ; instrumentation ; Equipment Design ; Humans ; Microelectrodes ; Microinjections ; instrumentation ; Miniaturization ; Nanotechnology ; Needles

To reveal the anti-inflammation mechanism of koumine,we determined effects of different concentrations of koumine(100,200,400 mg/L) on the secretion of NO,IL-1β,IL-6 and TNF-a by nitrate reductase and ELISA as well as the mRNA of iNOS,IL-1β,IL-6 and TNF-α.Western blot was used to detect iNOS protein expression.The results showed that 100,200,400 mg/L of koumine can significantly inhibit the secretion of NO,IL-1β,IL-6 and TNF-α of RAW264.7 cell (P＜0.01).Koumine can dose-dependently down-regulate the mRNA of iNOS,IL-1β,IL-6 and TNF-α,meanwhile koumine can also significantly inhibit the protein expression of iNOS.The results indicated that koumine may play an anti-inflammation activity by mean of the reduction of NO and mediator of inflammation,down-regulating the mRNA expression of iNOS,IL-1β,IL-6 and TNF-a,decreasing protein expressions of iNOS.

OBJECTIVE: To evaluate the influence of fewer courses and prolonged intervals of chemotherapy on survival rate of advanced non small cell lung cancer (NSCLC) patients treated by sequential chemo-radiation therapy combined with traditional Chinese medicine (TCM). METHODS: From Jan. 2000 to Dec. 2001, 54 untreated advanced NSCLC patients (2 stage IIIa, 18 stage IIIb, 34 stage IV) were treated by sequential chemo-radiation therapy combined with TCM. The courses of chemotherapy were reduced and the intervals of chemotherapy were longer than that of the standard regimen. The efficacy and survival rate were documented and the prognostic factors were analyzed. RESULTS: Complete remission (CR) was observed in 1 case and partial remission (PR) in 20 cases. The overall objective response rate was 40.4%. Median survival was 15.3 months, 1-, 2- and 3-year survival rate were 53.7%, 28.9% and 9.6% respectively. The median survival of stage III and IV were 21.8 months and 12.5 months respectively. The 1-, 2-, and 3-year survival rates of stage III were 65.0%, 49.5%, 24.7% and that of stage IV were 47.0%, 23.3%, 0%, respectively. The quality of life was improved in most of the patients. Cox's proportional hazards regression showed that improved quality of life and treatment of TCM were the significant prognostic factors of overall survival. CONCLUSION: Chemotherapy and radiotherapy combined with TCM is beneficial to extending the interval of chemotherapy, improving the quality of life, and increasing the survival rate of advanced NSCLC patients.

Objective:To observe the effects of Etifoxine on proliferation and migration of RSC96 (Schwann cells of rat) and its potential molecular mechanisms.Methods:From March, 2020 to October, 2020, cultured RSC96 were treated with 20 μmol/L Etifoxine and saline respectively for 48 h. Cell proliferation was tested by EdU assay using Cell-Light EdU DNA Cell Proliferation Kit and the capability of migration was determined by wound healing assay and a transwell system. To investigate the effects of Etifoxine on CELSR2 protein expression, after treated with different concentrations of Etifoxine at 0-20 μmol/L for 48 hours, cells were subject to Western blot analysis to verify the expression of CELSR2 protein. To explore whether CELSR2 would be a potential target of Etifoxine, siRNA targeting CELSR2 and control siRNA groups were transfected into 20 μmol/L Etifoxine-treated RSC96 using Lipo3000. Again, the cell proliferation and migration of were investigated after 48 hours with the same procedures. The two-tailed Mann-Whitney U test was employed in statistical assessment.Results:EdU results showed a significant higher percentage of Edu-positive (proliferating) cells in the 20 μmol/L Etifoxine-treated group than the control group[(36.30±3.09)% vs (19.40±2.50)%, P<0.05]. Transwell migration assay demonstrated that the number of 20 μmol/L Etifoxine-treated RSC96 which migrated through the transwell membrane was higher than saline group, with significant statistical difference [(132.30±6.77) vs(65.33±7.37), P<0.05]. The percentage of reduction of wound area measured at 24 hours and 36 hours after the scratch also showed the similar results [(30.67±2.16)% vs (23.00±2.61)%; (86.00±2.19)% vs (49.67±2.81)%, respectively, P<0.05]. Besides, with increase of the concentration of etifoxine, the expression of CELSR2 showed an trend of increase in RSC96 ( P<0.05), but no significant statistical difference was found between 10 μmol/L and 20 μmol/L groups ( P>0.05). Interestingly, the rate of cell proliferation, the number of migrating cells and the percentage of wound area reduction of RSC96 in which were treated by Etifoxine and transfected with CELSR2 siRNA were significantly decreased compared with the control siRNA treatment ( P<0.05). Conclusion:Etifoxine could promote proliferation and migration of RSC96. Upregulation of CELSR2 protein expression in RSC96 is associated with the Etifoxine-induced enhancement of cell proliferation and migration.

OBJECTIVEWe studied the licorice provenance rule under the manual simulative water stress conditions, discussed geographical variation pattern and the ecology mechanism and laid the theoretical basis for the licorice seed regionalization and the seed allocation.

METHODOn the spot we investigated and collected seed materials. Setting up water potential gradient by PEG, we observed the seed germination characteristic through the experiment of indoor germination.

RESULTThe sensitivity of various provenance seed germinative energy show quite remarkable difference for water potential reducing. Along with geographic longitude increasing, the seed germinates variation sensitivity increasing gradually to the water stress. The results of climatic factors' correlation analysis indicated that provenance seed germinate energy to the water stress is sensitive, in which the annual average temperature is low and annual precipitation is abundant. But it is insensitive in which the annual precipitation is little, the annual average temperature, average temperature in July and the annual average ground temperature is high.

CONCLUSIONUnder the water stress condition the licorice provenance seed germination characteristic exists remarkable geographical variation. Geographical variation is the result of natural selection.

OBJECTIVETo minimize of the radiation dose of cardiovascular CT angiography (CTA) imaging while preserving the image quality.

METHODSTo reduce the radiation dose in CTA imaging, the normal-dose scan induced non-local means (ndiNLM) algorithm was adapted for low-mAs scanned CTA image restoration by using the previous scanned high-quality image.

RESULTSQualitative and quantitative evaluations were carried out on both simulated phantom and clinical CTA scans in terms of accuracy and resolution properties. Compared to the original NLM algorithm, the ndiNLM method could achieve noticeable gains in terms of noise-induced artifacts suppression and enhanced structure preservation.

CONCLUSIONThe ndiNLM algorithm is a potential useful technique to reduce the radiation dose in CTA imaging.

OBJECTIVE:With the popularity of simulated barefoot running,minimalist shoes have become a new way of foot exercise.As an important muscle group of the foot,the maintenance of foot muscle morphology is important for the execution of foot functions.In this paper,by combing the literature about the effect of minimalist shoes on foot muscle morphology in recent years,we systematically evaluate the effect of minimalist shoes on foot muscle morphology compared with traditional running shoes. METHODS:The relevant articles published from 2012 to 2022 were searched in Chinese and English databases(PubMed,Web of Science,ProQuest,CNKI and WanFang databases)with"minimal shoes,minimal footwear,minimalist shoes,minimalist footwear,foot muscle,feet muscle"as Chinese and English keywords,respectively.Meta-analysis,sensitivity tests were performed on the included literature using Review Manager 5.4.1 and Stata 14 software,the Egger method was used to test for publication bias in the literature,and Meta-regression was used to identify the subgroups with heterogeneity. RESULTS:Compared with traditional running shoes,minimalist shoes increased muscle circumference of the abductor hallucis[standardized mean difference=2.034,95%confidence interval(1.192,2.877),Z=4.73,P＜0.001].And the results were not reversed after clipping and patching,with a more robust combined effect size(P＜0.05).For the toe short flexors,the total combined effect size did not show a difference between traditional running shoes and minimalist shoes[standardized mean difference=0.470,95%confidence interval(-0.45,1.39),Z=1.00,P=0.318]. CONCLUSION:Compared with traditional running shoes,minimalist shoes intervention can effectively improve muscle circumference of the abductor hallucis,but the promoting effect on the flexor digitorum brevis muscle is not obvious.Running in minimalist shoes has positive implications for the maintenance of the medial longitudinal arch,but it is necessary to enrich the research content of minimalist shoes on different foot muscles and different populations in order to further explore the mechanisms by which minimalist shoe interventions promote foot function.

Objective: To explore the relationship between dietary behavior, dietary frequency and central precocious puberty (CPP) among children in Wuhan, so as to provide a scientific basis for elucidating the possible and related dietary factors leading to precocious puberty. Methods: From February to December 2023, 100 children with CPP and 100 healthy children were collected in Wuhan Children s Hospital for a case control study. Questionnaires and interviews were used to collect demographic information, child lifestyle, as well as dietary behavior and dietary frequency in the past six months. Conditional Logistic regression model was used to analyze the relationship of children s dietary behavior and dietary frequency with CPP. Results: No associations were found between three dietary behavior, including emotional eating, restrictive eating, and external eating, with CPP at baseline ( P >0.05). In the association analysis of dietary frequency and CPP, the risk of CPP was higher in those who consumed red meat >5 times/week ( OR =1.93, 95% CI =1.01-3.68), carbonated beverages ≥4 times/month ( OR =2.70, 95% CI =1.03-7.08), fruit juices ≥4 times/month ( OR =2.31, 95% CI =1.02-5.25), and nutritional supplementation ( OR =2.77, 95% CI =1.47- 5.22 ), whereas the risk of CPP was lower in those who consumed nuts ≥4 times/month ( OR =0.21, 95% CI =0.08-0.57) ( P < 0.05 ). Conclusion Consumption of higher amounts of red meat, high frequency of carbonated and juice based sugary drinks, and nutrient supplementation may be contributing factors to the development of CPP, whereas regular consumption of nuts is less likely to be associated with the development of CPP.

Objective:To analyze the clinical characteristics and risk factors of impaired liver and renal function in hospitalized patients with gout.Methods:A total of 494 hospitalized patients with confirmed gout were selected and divided into four groups according to liver and renal function, control(Con), impaired liver function (ILF), impaired renal function (IRF), and both function impaired (ILRF) group. Multivariate logistic regression was used to analyze the risk factors related with impaired liver and renal function.Results:Compared to Con group, ILF group were younger with shorter gout duration, higher body mass index, waist circumference, homeostasis model assessment for insulin resistance (HOMA-IR), serum uric acid, low density lipoprotein-cholesterol (LDL-C), total cholesterol, triglycerides, C reactive protein, higher prevalence of dyslipidemia, obesity, fatty liver, and monosodium urate crystal (MSU) deposition (all P<0.05). IRF group were older and with higher serum uric acid, serum creatinine, C reactive protein, and hypertension, MSU deposition prevalence, with lower prevalence of fatty liver (all P<0.05). Compared to ILF group, IRF group were older, with longer gout duration, lower level of body mass index, waist circumference, HOMA-IR, LDL-C, total cholesterol, triglycerides, lower prevalence of obesity, fatty liver, and higher prevalence of hypertension and type 2 diabetes (all P<0.05). The univariate logistic regression analysis showed that age( OR=0.941, 95% CI 0.906-0.977, P<0.001), serum uric acid ( OR=1.002, 95% CI 1.000-1.005, P=0.043), HOMA-IR ( OR=1.147, 95% CI 1.024-1.285, P=0.018), and MSU deposition ( OR=1.959, 95% CI 1.154-3.326, P=0.013) were the independent risk factors of impaired liver function, while the independent risk factors of impaired renal function were age ( OR=1.104, 95% CI 1.048-1.162, P<0.001), serum uric acid ( OR=1.007, 95% CI 1.004-1.010, P<0.001), and MSU deposition ( OR=2.393, 95% CI 1.191-4.805, P=0.014). Conclusions:Serum uric acid and MSU deposition are the common independent risk factors for impaired liver and renal function in patients with gout. Younger patients with insulin resistance are susceptible to impaired liver function, older patients with hypertension and diabetes are susceptible to impaired renal function.

Immune checkpoint inhibitors can enhance the anti-tumor effect of T cells by blocking the negative regulatory signal of T cells, and meanwhile, they may also cause the imbalance of immune tolerance or normal immune hyperfunction, thus leading to immune hepatitis. This article mainly reviews the therapeutic mechanism of immune checkpoint inhibitors, their mechanism in causing the adverse reaction of liver injury, related risk factors, and incidence rate and summarizes the treatment methods for liver injury caused by immune checkpoint inhibitors. It is believed that while promoting anti-tumor immunity, immune checkpoint inhibitors may cause non-homogeneous immune-related liver injury due to the specificity of non-tumor tissue targets, and the main purpose of treatment is to restore immune homeostasis. Therefore, the management of patients using immune checkpoint inhibitors often requires a balance between treatment window, toxicity, and treatment of specific injury, as well as multidisciplinary collaboration.