ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

Objective To investigate the role and regulatory mechanism of stress-inducing protein 1(SESN1)in liver gluconeogenesis of fasting mice.Methods RT-qPCR was used to detect mRNA expression of SESN1 in liver tissues of C57BL/6J mice and primary mouse hepatocytes treated with forskolin(Fsk)and dexamethasone(Dex).HepG2 cells were transfected with plasmids and the effects of SESN1 overexpression on mRNA expression of gluconeogenesis related genes PGC-1α,PEPCK and G6Pase was detected by RT-qPCR.The effect of SESN1 on the promoter activity of PGC-1α in HepG2 cells was studied using a dual luciferase reporter system.The effect of SESN1 on PGC-1α deacetylation was detected by overexpression of SESN1 and inhibition of SIRT1 expression.By knocking down SIRT1 expression,we detected whether it mediated the changes in mRNA levels of SESN1 in-duced gluconeogenesis related genes.Results The mRNA expression of SESN1 was significantly increased in liver tissues of starved C57BL/6J mice and in primary hepatocytes treated with Fsk and Dex(P<0.001).Over-expression of SESN1 in HepG2 cells promoted mRNA expression of PGC-1α,PEPCK and G6Pase(P<0.001)and promoter activity of PGC-1α(P<0.001).Over-expression of SESN1 decreased the acetylation level of PGC-1α in primary hepatocytes.Sirt family inhibitors NAM and shRNA adenovirus interfered with SIRT1 expression respective-ly,and antagonized the deacetylation effect of SESN1 on PGC-1α.The expression of PGC-1α,PEPCK and G6Pase induced by SIRT1 was also significantly impaired(P<0.000 1).Conclusions SESN1 regulates liver gluconeogene-sis in mice with a SIRT1-dependent mechanism.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Patient-based real-time QC (PBRTQC) uses patient-derived data to assess assay performance. PBRTQC algorithms have advanced in parallel with developments in computer science and the increased availability of more powerful computers. The uptake of Artificial Intelligence in PBRTQC has been rapid, with many stated advantages over conventional approaches. However, until this review, there has been no critical comparison of these. The PBRTQC algorithms based on moving averages, regression-adjusted real-time QC, neural networks and anomaly detection are described and contrasted. As Artificial Intelligence tools become more available to laboratories, user-friendly and computationally efficient, the major disadvantages, such as complexity and the need for high computing resources, are reduced and become attractive to implement in PBRTQC applications.

Purpose: Vascular calcification (VC) is a common complication of end-stage renal disease (ESRD). This study aimed to examine changes in the expression of miR-21-5p in ESRD patients with VC and to explore its clinical value in predicting the occurrence and progression of uremic VC. Materials and Methods: 120 ESRD patients were divided into patients without VC group (n=38) and patients with VC group (n=82). All patients were followed up for 2 years to evaluate VC progression. qRT-PCR was used to detect serum miR-21-5p levels.Receiver operating characteristic curves were constructed to assess diagnostic value. Kaplan-Meier and log-rank methods were utilized to calculate associations between VC progression and risk factors. Results: Serum miR-21-5p levels were significantly higher in ESRD patients with VC than in those without VC and increased progressively with increasing disease severity. Serum miR-21-5p levels were able to distinguish patients with VC from those without VC, with an area under the curve value of 0.883, a sensitivity of 81.7%, and a specificity of 84.2%. After 2 years of follow-up, miR-21-5p expression had increased in patients with worse VC severity, compared with those with stable VC severity. Patients with high miR-21-5p levels were more likely to develop more severe VC, indicating an association between miR-21-5p and VC progression (log-rank p=0.002). Multivariable Cox regression analysis suggested that serum miR-21-5p is an independent predictive factor of VC progression in ESRD patients (hazard ratio=2.064, 95% confidence interval=1.225–3.478, p=0.006). Conclusion miR-21-5p is overexpressed in the serum of ESRD patients with VC. Our results suggest that overexpression of miR-21-5p is closely associated with VC progression.

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Objective To investigate the value of arterial spin labeling (ASL) MRI in evaluation of renal cortex perfusion in patients with type 2 diabetes.Methods Fifty patients with type 2 diabetes were enrolled and divided into simple diabetes (SD) group (n=25) and diabetes kidney disease (DKD) group (n=25) according to suffering from DKD or not.Based on estimated glomerular filtration rate (eGFR),DKD group were further divided into mild disease subgroup (n=11,eGFR≥ 60 ml/[min · 1.73m2]) and moderate-severe disease subgroup (n=14,eGFR＜60 ml/[min · 1.73m2]).Twenty-five healthy volunteers were recruited as control group at the same time.ASL MRI were performed on all participants.The cortical renal blood flow (RBF) of bilateral kidneys were measured by 2 radiologists.The consistency between 2 radiologists was analyzed.Statistical analysis were conducted to analysis the differences in cortical RBF among different groups.Correlation analysis were performed to evaluate the relationship between RBF and eGFR in type 2 diabetes patients.Results Cortical RBF values measured by two radiologists showed high consistency (all ICC＞0.90).There was significant difference in cortical RBF among control group ([269.71±33.28]ml/[100 g · min]),SD group ([258.52±42.30]ml/[100 g · min]),mild disease group ([242.86±56.86]ml/[100 g · min]) and moderate-severe disease group ([173.39±27.16]ml/ [100 g· min];F=20.66,P＜0.01).Moreover,the RBF in moderate-severe disease group was significantly lower than those in other groups (all P＜0.01).And no significant differences of RBF was found among the remainder groups (P=0.064,0.320).RBF in type 2 diabetes patients was positively correlated to eGFR (r=0.646,P＜0.001).Conclusion ASL MRI is a valuable tool to quantitatively assess the renal perfusion in patients with type 2 diabetes mellitus,which can provide potential imaging indicator as RBF for the functional evaluation of kidney.

Objective To investigate the relationship between IL‐10 SNPs and breast cancer susceptibility .Methods Collect‐ed 156 blood samples of breast cancer patients as case group and 156 blood samples of health as control .Genotype SNPs of IL‐10‐592 ,‐1082 were analyzed by genomic DNA extraction ,PCR amplification and TOF mass spectrometry .The data was used by statis‐tical analysis .Results IL‐10‐592 C/C ,C/A and A/A site the genotype frequencies were not diversity between two groups(χ2 =3 .26 ,P>0 .05) .IL‐10‐1082 G/G、G/A、A/A site the genotype frequencies were statistically significant between two groups(χ2 =14 .07 ,P<0 .01) .In Logistic multivariate regression analysis found that :be compared with IL‐10‐592 A/A ,carrying IL‐10‐592 C/A ,C/C group respectively the risk of breast cancer were OR=1 .039(95% CI:0 .484 -2 .233) ,P=0 .922 ,OR= 1 .635(95% CI:0 .683-3 .915) ,P =0 .270 ,which had no statistical significance .In Logistic multivariate regression analysis found that :be com‐pared with IL‐10‐1082 A/A ,carrying IL‐10‐1082 G/A、G/G group respectively the risk of breast cancer were OR=0 .424(95% CI:0 .210-0 .855) ,P=0 .016 ,OR=0 .455(95% CI:0 .178 -1 .163) ,P= 0 .100 .Conclusion IL‐10‐592 may be not associated with breast cancer susceptibility .IL‐10‐1082 G/A may be a protection factor with breast cancer susceptibility .