Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

The colonization of microorganisms planted on the surface of teeth and restoration materials is the main cause of oral disease and treatment failure. How to improve the antibacterial properties of dental materials is a hot topic in dentistry. Nano-sized antibacterial materials have attracted much attention. Among them, metal and metal oxide nanoparticles are prominent due to their strong and broad-spectrum antibacterial activity. Thus, in recent years, many studies have used metal and metal oxide nanoparticles to develop antimicrobial dental materials for resin restoration, root canal therapy, orthodontic treatment, and implant surface and removable denture repair and have found that the antibacterial properties of nano-sized materials are significantly enhanced. However, the mechanical properties and esthetic properties of the modified materials are affected, so it is still necessary to explore appropriate modification methods. In addition, most of the experiments are carried out in vitro, which cannot accurately simulate the oral environment. Therefore, the antibacterial effect, cytotoxicity and immune response of these materials in vivo still need further research and exploration. This paper reviewed the potential antibacterial mechanisms and the safety of those nanoparticles and their applications in dentistry.

ABSTRACT OBJECTIVE：To investigate the quality differences of Pinelliae Rhizoma with different diameter，and to providereference for the rational utilization of its resources. METHODS：A total of 65 batches of commercial Pinelliae Rhizoma from thefour major medicinal markets in China and two companies were collected as samples，the diameter of them were measured byvernier caliper，and then them were screened into samples with different diameter ranges（0.5 cm≤d≤0.8 cm，0.8 cm＜d≤1.0cm，1.0 cm＜d≤1.2 cm，1.2 cm＜d≤1.5 cm，1.5 cm＜d≤2.0 cm）by sieving. The content of organic acids（oxalic acid，citricacid，L-malic acid，succinic acid，fumaric acid，trans-aconitic acid and cis-aconitic acid）in Pinelliae Rhizoma samples of differentdiameter ranges were determined by HPLC，and the content of the extracts of Pinelliae Rhizoma samples of different diameterranges were determined by cold leaching method according to 2201 general principles in 2015 edition of Chinese Pharmacopoeia（Part Ⅳ），to evaluate the quality difference of Pinelliae Rhizoma in different diameter ranges.73 batches of Pinelliae Rhizoma fromcorresponding 10 main producing areas were collected as samples，to investigate its distribution of diameter. RESULTS：Dtermination of 65 batches of commercial Pinelliae Rhizoma showed that the content of organic acids and extracts in PinelliaeRhizoma increased with the increase of its diameter in general. However，there were no significant difference in organic acids andcontent of the extracts among Pinelliae Rhizoma samples of different diameter ranges in the same batch（P＞0.05）. The diameter distribution of 73 batches of Pinelliae Rhizoma from corresponding areas was mainly between 0.6 cm and 1.8 cm，with an averageweight of 95.54％. If the diameter standard（1-1.5 cm）specified in the 2015 edition of Chinese Pharmacopoeia（part Ⅰ）wasadopted，only 8 of 73 batches of Pinelliae Rhizoma meet the requirements，and the qualified rate was 10.96％；if the diameterrange was properly expanded to 0.7-1.5 cm，54 batches of Pinelliae Rhizoma meet the requirements，with a qualified rate of73.97％；when the diameter range was expanded to 0.7-1.6 cm，68 batches of Pinelliae Rhizoma meet the requirements，with aqualified rate of 93.15％ .CONCLUSIONS：There is no significant difference in the quality of Pinelliae Rhizoma with different diameters. Combined with the diameter distribution of Pinellia Rhizoma in different producing areas，the diameter range of 1-1.5cm specified in relative standard can be expanded to 0.7-1.6 cm，avoiding the waste of resources.

AIM: To evaluate the pharmacokinetics and bioequivalence of cetirizine hydrochloride tablets under fasting and fed conditions in Chinese healthy subjects. METHODS: This was a randomized, open-label, double-sequence, two-period, crossover designed study, and healthy subjects enrolled and administrated a single dose of 10 mg test and reference cetirizine hydrochloride tablets in each period under fasting or fed condition. The plasma concentrations of cetirizine were determined by a validated LC-MS/MS method. The pharmacokinetic parameters were calculated with WinNonlin 6.3 and the bioequivalence was evaluated through SAS 9.4 software. RESULTS: In the fasting condition, the major pharmacokinetic parameters of cetirizine of test and reference formulations were as follows, C

Chinese Pharmacopoeia provides nine pesticide Maximum Residual Limits(MRLs) of traditional Chinese medicines(TCMs), The number of pesticides used in production are far more than those listed in pharmacopoeia. The lack of the standards make it's hard to reflect the real situation of pesticide residues in TCMs correctly. The paper is aimed to analyze the data of pesticide residues in TCMs from 7 089 items in 140 reports, and judging the exceedance rate of pesticides in TCMs using the MRLs of European pharmacopoeia，which is widely accepted in many countries. The results show that：①Pesticide residues in 18 kinds of TCMs are higher than MRLs，while in 137 kinds are below MRLs, such as Atractylodis Macrocephalae Rhizoma, Menthae Haplocalycis Herba and Fritillariae Thunbergii Bulbus. The average exceedance rate of all TCMs is 1.72%. The average exceedance rates of organochlorine, organophosphorus and pyrethroid are 2.26%, 1.51%, 0.37%，respectively. ②The average exceedance rate of pesticides is 2.00%, and the exceedance rate is more than 5%, accounting for 8.33%, the exceedance rate is between 1%-5%, accounting for 18.75%. the exceedance rate is between 0%-1%, accounting for 18.75%. The remaining 29 kinds of pesticides were not exceeded, accounting for 60.42%.Some reports like Greenpeace's organization exaggerated the pesticide residues in TCMs.But the pesticide residue question is still worthy of attention, so we proposed to amend the Chinese Pharmacopoeia pesticide residues standards, to increase the pesticide species of traditional Chinese medicine in production on the basis of retaining the existing types of pesticide residues, to strengthen the system research of pesticide residues in TCMs, providing a basis for making standard and promoting import and export trade in TCMs.