As an emerging drug delivery technology,microneedles can puncture the skin's stratum corneum to create micron-sized conduits,painlessly,minimally invasive,and efficiently deliver drugs into viable epidermis or dermis for local or systemic therapeutic effects.This paper reviews the current clinical trials of microneedles used in the treatment of various diseases,elaborates on the characteristics of various types of microneedles,and summarizes the latest research progress of microneedles used to treat skin tumors,including chemotherapy,photothermal and photodynamic therapy,immunotherapy,gene therapy,and combination therapy.This review provides ideas and directions for further research on microneedles in treating skin tumors.

Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.

OBJECTIVE：To optimize the f ormulation of docetaxel （DTX）-mPEG-PLGA-mPEG （PELGE）-nanoparticles （NPs），and to characterize it and evaluate its in vitro drug release and antitumor activity. METHODS ：PELGE were synthesized by ring-opening polymerization. DTX-PELGE-NPs were prepared by using emulsion solvent evaporation method. The content of DTX in DTX-PELGE-NPs was determined by HPLC. Box-Behnken design-response surface methodology was applied to optimize the formulation of the nanoparticles using the amount of DTX ，PELGE and poloxamer 188 as independent variable ，using entrapped efficiency as dependent variable. The particle size and Zeta-potential of DTX-PELGE-NPs were characterized by laser particle size analyzer and transmission electron microscope. The in vitro release of the DTX-PELGE-NPs was investigated by ultra-filtered centrifugation，using DTX injection as reference. In vitro cytotoxicity of the DTX-PELGE-NPs was investigated by MTT assay ， using DTX and PELGE-NPs without DTX as reference . RESULTS ：The optimal formulation included 2.80 mg DTX ，20.60 mg PELGE and 6％ poloxamer 188. The entrapped efficiency of optimized DTX-PELGE-NPs was （86.79±1.32）％；drug-loading amount was （10.21±0.78）％，and average particle size was （78.4±2.9）nm；polydispersity coeffici ent was （0.187±0.018）and Zeta potential was （－20.6±1.5）mV. Furthermore ，DTX- PELGE-NPs showed a regular spherical and uniform distribution under scanning electron microscopy. Compared with DTXinjection（accumulative release rate of 92.3％ at 4 h），DTX- PELGE-NPs had a significant sustained-release effect （accumu-lative release rate of 78.6％ at 36 h）. 0.1-50 μg/mL PELGE-NPs had no obvious cytotoxicity to human breast cancer cells MCF-7（P＞0.05）. 0.5-10 μg/mL DTX-PELGE-NPs could significantly inhibit the growth of human breast cancer cells MCF-7， and its inhibitory effect （except for DTX-PELGE-NPs 10 μg/mL group）was significantly stronger than that of DTX injection （P＜ 0.05）. CONCLUSIONS ：The optimized formulation is stable and feasible. The obtained DTX-PELGE-NPs not only have uniform particle size ，high encapsulation rate obvious slow-release effect ，but also have stronger anti-tumor effect in vitro than DTX injection.

Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.

Objective To investigate the overall incidence and risk of hypertension in the treatment of cancer patients who receive anlotinib and compare the differences between anlotinib and other VEGFR inhibitors. Methods Pubmed, Embase, Cochrane Library, ASCO, CNKI, Wangfang, VIP and CBM databases were searched. Eligible studies were phase II and III prospective clinical trials on cancer patients who received anlotinib and had the hypertension data available. Meta-analysis for the incidence and risk of anlotinib was performed by using R software (version 3.6.0). SPSS software (version 26.0) was used to compare the difference between anlotinib and other VEGFR inhibitors. Results A total of 1387 cancer patients from 13 clinical trials were included in the Meta-analysis. The overall incidences of all grade and high grade hypertension in cancer patients who received anlotinib were about 47.1% (95%CI: 37.7%−56.6%) and 10.6% (95%CI: 7.4%−14.2%). The use of anlotinib was associated with significantly increased risk of all grade (RR=5.58, 95%CI: 2.29−13.60, P<0.01) and high grade hypertension (RR=27.78, 95%CI: 3.56−216.86, P<0.01). In addition, the incidence of high grade hypertension associated with anlotinib was similar to axitinib (RR=0.79, 95%CI: 0.61−1.02, P=0.066) and cabozantinib (RR=0.87, 95%CI: 0.67−1.13, P=0.290). The incidences of rest of other VEGFR inhibitors were lower than that of anlotinib. Conclusions There is a high incidence and significant risk of developing hypertension in cancer patients receiving anlotinib. Adequate monitoring and timely treatment of hypertension is recommended.

Objective To review and analysis the clinical manifestations, occurrence rules, treatment and outcomes of adverse drug reactions caused by anlotinib in order to provide reference for safety and reasonable use of anlotinib in clinical practice. Methods The cases reports of anlotinib were searched in Web of Science, Pubmed, Wiley Online Library, CNKI, Wanfang and VIP. The basic patient information, adverse reaction time, characters, treatment, outcomes and involved systems or organs were collected and analyzed. Results A total of 20 cases were collected, 10 females and 10 males, with a median age of 63.5(36～76 years old). Adverse drug reactions mostly occurred within 2 months after the medication. 52 cases occurred in total, involving 9 systems/organs, of which blood and lymphatic system disorders (all were hypertension) were the most common (21.2%). Conclusion After the administration of anlotinib, the incidence rate of adverse reactions in the cardiovascular system is relatively high. The medication process should be closely monitored, and attention should be paid to monitoring the potential adverse reactions mentioned in the instructions.

Objective To investigate the prognostic factors of transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (HCC).Methods A retrospective analysis was performed on 326 HCC patients treated with TACE.Kaplan-Meier method was used to calculate the 1-year,2-year and 3-year cumulative survival rates.Log-rank test and Cox proportional hazards model were used to analyze univariate and multivariate prognostic factors,respectively.Results The 1-year,2-year and 3-year cumulative survival rate of HCC patient was 73.90％,40.20％and 22.20％,respectively.The median survival time was 21 months.Univariate analysis showed that the alpha-fetoprotein (AFP),gamma-glutamyl transpeptidase (GGT),tumor size,tumor number,Child-Pugh grade,Barcelona clinic liver cancer (BCLC) stage,portal vein thrombosis,arteriovenous fistula and distant metastasis were factors affecting the prognosis of HCC patient (all P＜0.05).Multivariate COX regression analysis showed that AFP,GGT,tumor size,tumor number,BCLC stage,arteriovenous fistula were the independent prognostic factors of HCC patients (all P＜0.05).Conclusion AFP,GGT,tumor size,tumor number,BCLC stage and arteriovenous fistula are independent prognostic factors of HCC patients treated with TACE.

Objective To analyze the clinical characteristics and follow-up data of catheter ablation of recurrent atrial tachycardias (ATs) after Mini-Maze surgery,and to explore prognostic factors for recurrence.Methods 59 patients in Guangdong General Hospital with ATs post Mini-Maze and concomitant open-heart surgery from April.2010 to June.2015 were included.According to high density precise mapping,activation mapping,voltage mapping and entrainment mapping,they underwent electrophysiological study and ablation which was guided by three-dimensional mapping system.All patients were followed up regularly.We explored the prognostic factors for recurrence by the Cox regression analysis.Results There were 88 types of ATs being mappedwith mean (1.49 ± 0.75) types of ATs identified per case.Most ATs were macro-reentry ATs(67/88,76.1％)and focal ATs (20/88,22.7％),respectively.56 patients (94.9％) achieved immediate ablation success.In a mean follow-up of (30.8 ± 17.7) months,recurrences were observed in 12 patients after the first time catheter ablation.Recurrent time was 3.5 (1.3,12.0) months and the overall ablation success rate was 74.6％ (44/59).6 patients received second ablation and the achievement of freedom from arrhythmias reached 79.7％ (47/59).Multivariate analysis showed that the LA diameter was the independent predictor for recurrence (HR 1.108,95％ CI 1.002 to 1.226,P =0.045).Conclusion Catheter ablation of ATs post Mini-Maze with concomitant surgery is save and feasible.LA diameter is the independent predictor for recurrence.

OBJECTIVETo analyze the correlation between the genotype and phenotype of 18q deletion syndrome with chromosome microarray analysis (CMA).

METHODSEight cases with 18q deletion syndrome were selected, including two affected fetuses and six children patients. DNA was extracted and hybridized with Affymetrix CytoScan TM 750K arrays following the manufacturer's standard protocol. The data was analyzed with a special software package.

RESULTSCMA analysis identified pathogenic copy number variations (CNVs) on 18q in all cases, which ranged from 6.612 Mb to 22.973 Mb. NFATC1, GALR1, MBP, SALL3 and TSHZ1 are likely to be causative genes for congenital heart disease, psychological, growth retardation, and cleft palate.

CONCLUSIONCMA can precisely locate the breakpoints of 18q and facilitate definition of the genotype-phenotype correlations, which is useful for prognosis.

Child, Preschool ; Chromosome Deletion ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Infant ; Male ; Microarray Analysis

Objective To summarize the clinical features and vascular lesions in patients who suffered from cerebellar infarction with vertebral artery hypoplasia(VAH). Methods Retrospective analysis was used in the research. The selected patients suffered from cerebellar infarction with VAH or stenosis (stenosis rate≥50%). Seventy-one patients with cerebellar infarction were enrolled. There were 34 patients in VAH group and 37 patients in vertebral artery stenosis group. The age, sex, risk factors, clinical manifestations and characteristics of vascular examination were compared. Results The age, sex, risk factors between two groups had no significant differences (P>0.05). The scores of National Institutes of Health Stroke Scale (NIHSS) between two groups had no significant difference (P>0.05). The proportion of early neurological deterioration in VAH group (41.2%, 14/34) was higher than that in vertebral artery stenosis group (18.9%, 7/37), χ2=4.21, P<0.05. There were more patients with anterior circulation artery stenosis in the VAH group (35.3%, 12/34), compared with that in artery stenosis group (13.5%, 5/37),χ2=4.62, P<0.05. Except the ipsilateral vertebral artery, other arteries stenosis in VAH group (44.1%, 15/34) was significantly higher than that in vertebral artery stenosis group (13.5%, 5/37),χ2=8.20, P<0.05. Conclusions Cerebellar infarction with vertebral artery hypoplasia is more likely to have multiple cerebral arterial stenosis (stenosis rate ≥50%). The patients who suffered from cerebellar infarction with vertebral artery hypoplasia might be prone to early neurological deterioration.