Objective Taking Sortilin as the entry point,this study aims to explore the mechanism of vascular calcification in chronic renal failure(CRF)and explore the influence of Sanqi on Sortilin,TLRs and vascular calcification,and to provide an effective method for clinical reduction of cardiovascular events in CRF.Methods Thirty-six male SD rats were randomly divided into normal group,model group,low-,medium-and high-dose Sanqi group and calcitriol group,with 6 rats in each.The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet.Aortic calcium salt deposition,serum creatinine(Scr),urea nitrogen(BUN),blood calcium(Ca),blood phosphorus(P),total cholesterol(TC),triglyceride(TG),TLRs and Sortilin protein in aorta and inflammatory factors were detected.Results In the model group,renal fibrosis was obvious and many adenine crystals were found in renal interstitium.Large deposits of calcium salts were found.Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups.Compared with those in the normal group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of the model group was ascended(P<0.01),while the level of Ca was descended(P<0.01).Compared with those in the model group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased(P<0.01),and the contents of Ca were significantly increased(P<0.05 or P<0.01).Compared with those in the normal group,the protein expression of BMP2,RUNX2,Sortilin,TLR7 and TLR9 in aortic tissue of rats in the model group was elevated(P<0.01),while the protein expression of SM22α was declined(P<0.01).Compared with those in the model group,the protein expression of BMP2,RUNX2,Sortilin,TLR7,and TLR9 in the low-,medium-,and high-dose Sanqi group and calcitriol group was decreased significantly(P<0.01);the protein expression of SM22α was increased significantly(P<0.05 or P<0.01),and the high-dose Sanqi group and calcitriol group had more significant effects.Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats,and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.

To investigate the association of triglyceride to high density lipoprotein-cholesterol ratio (TG/HDL-C) in early pregnancy with the risk of gestational diabetes mellitus (GDM).

[Objective]To explore the medication rule of TCM compound patent in the treatment of gout,and analyze the mechanism of action of the core herbs based on the national patent database.[Methods]The Chinese herbal compound patent database for gout treatment was retrieved and entered into the Website of China Patent Announcement of The State Intellectual Property Office.The characteristics of medications were analyzed by frequency statistics,Apriori algorithm,factor analysis and systematic clustering method.The Chinese herbs targets of the core herbs combinations were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the gout disease targets were obtained from Human Gene database(GeneCards)and Online Mendelian Inheritance in Man(OMIM)database.The intersection of the two targets was imported into Cytoscape 3.9.1 software,and the Cluego plug-in was used to complete the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the herb combinations.The intersection targets were imported into STRING database to obtain protein-protein interaction(PPI)network,and some key targets were selected for molecular docking with corresponding active compounds of Chinese herbs.[Results]A total of 508 Chinese herbal compound patents were included in the treatment of gout,involving 401 Chinese herbs,and the frequency of herbs was 6 082 times.Chinese herbs for diuresis-inducing and dampness-draining were mainly used,followed by herbs for tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis.The analysis of association rules obtained 3 binomial association rules and 5 trinomial association rules.Eight common factors were extracted by factor analysis.Three groups of herbs combinations were obtained by systematic clustering analysis,and 56 common biological pathways of herbs combination enrichment were found.Molecular docking results showed that the combination of Quercetin and tumor necrosis factor(TNF)was the best,followed by Baicalein and interleukin-6(IL-6),and the combination of Quercetin and adenosine triphosphate binding cassette super family G member 2(ABCG2)was good.[Conclusion]The national patent prescriptions for gout treatment based on the core pathogenesis of"turbid dampness and blood stasis"are mainly from three aspects of dampness,blood stasis and deficiency.The core herbs combinations are often supplemented or subtracted based on Simiao Powder,Fuling Zexie Decoction and Siwu Decoction.Chinese herbs mainly exert their effects through multiple signaling pathways such as TNF,hypoxia inducible factor-1(HIF-1),Toll-like receptors(TLRs)and IL-17 and promote excretion of uric acid.

Objective: To understand the epidemiological characteristics of pulmonary tuberculosis (PTB) in Shaanxi Province from 2016 to 2021, so as to provide the basis for improving PTB prevention and control strategies. Methods: The incidence data of PTB cases in Shaanxi Province were collected from the Tuberculosis Information Management System of the Chinese Disease Prevention and Control Information System from 2016 to 2021. The temporal, geographical, and demographic distribution characteristics of PTB were described. Results: A total of 121 280 PTB cases were reported in Shaanxi Province from 2016 to 2021, with the reported incidence rate decreasing from 56.30/105 in 2016 to 40.98/105 in 2021 (P<0.05). The etiological positivity rate increased from 16.61% in 2016 to 54.37% in 2021 (P<0.05). The average annual number of reported cases peaked in March (1 984.67 cases, accounting for 9.81%), followed by January (1 885.50 cases, accounting for 9.33%), and hit its lowest in October (1 458.50 cases, accounting for 7.22%). The incidence of PTB was relatively high in northern Shaanxi and southern Shaanxi, at 67.99/105 and 64.05/105, respectively, while it was relatively low in Guanzhong Region, at 44.83/105. The incidence rates of Ankang City (85.81/105), Fugu County (73.92/105), and Yulin City (72.20/105) ranked the top three. There were 80 111 male cases and 41 169 female cases of PTB, with a male-to-female ratio of 1.95︰1. The reported incidence rate of males (67.38/105) was significantly higher than that of females (36.61/105), and the difference was statistically significant (P<0.05). Among males, the highest average reported incidence rate was found in the 80 to <85 age group (179.46/105), while among females, the highest was in the 75 to <80 age group (104.38/105). The main occupations were farmers, accounting for 68.87% (83 526 cases). Conclusions The reported incidence rate of PTB in Shaanxi Province showed an overall downward trend from 2016 to 2021, with a high incidence in winter and spring. The epidemic in southern Shaanxi and northern Shaanxi is more severe than in Guanzhong Region of Shaanxi Province. The incidence of PTB is predominantly found among males, the elderly, and farmers.

Objective: To observe and compare the clinical effects of different electroacupuncture waveforms on primary dysmenorrhea. Methods: This was a prospective, randomized, three-group, parallel-controlled trial. Participants with primary dysmenorrhea were randomly divided into dense-sparse wave, continuous wave, and discontinuous wave groups in a 1:1:1 ratio. Two lateral Ciliao (BL 32) points were used. All three groups started treatment 3–5 days before menstruation, once a day for six sessions per course of treatment, one course of treatment per menstrual cycle, and three menstrual cycles. The primary outcome measure was the proportion with an average visual analog scale (VAS) score reduction of ≥50% from baseline for dysmenorrhea in the third menstrual cycle during treatment. The secondary outcome measures included changes in dysmenorrhea VAS scores, Cox Menstrual Symptom Scale scores and the proportion of patients taking analgesic drugs. Results: The proportion of cases where the average VAS score for dysmenorrhea decreased by ≥50% from baseline in the third menstrual cycle was not statistically significant (P > .05). Precisely 30 min after acupuncture and regarding immediate analgesia on the most severe day of dysmenorrhea, there was a statistically significant difference in the dense-sparse wave group compared with the other two groups during the third menstrual cycle (P < .05). Additionally, there was a statistically significant difference between the dense-sparse wave and discontinuous wave groups 24 h after acupuncture (P < .05). Conclusions Waveform electroacupuncture can alleviate primary dysmenorrhea and its related symptoms in patients. The three groups showed similar results in terms of short- and long-term analgesic efficacy and a reduction in the number of patients taking analgesic drugs. Regarding achieving immediate analgesia, the dense-sparse wave group was slightly better than the other two groups.

Objective To compare and explore the differences between the eight batches of drugs in the centralized procurement list and the 2018 edition of the national essential medicine list,and to provide reference for updating and improving the national essential medicine list and the national centralized procurement list of drugs.Methods The category,generic name variety,specification,and other information of drugs included in the centralized drug procurement were collected and compared with the 2018 edition of the national essential medicine list,and the reasons for differences were analyzed.Results A proportion of 39%of centralized procurement drugs were listed in national essential medicines.Forty pharmacological classifications were not involved in the drugs of centralized procurement.Only anticoagulant and thrombolytic drugs with dual attributes accounted for a smaller variety proportion than the specification proportion.Conclusion There are some differences between the centralized procurement list and the 2018 edition of the national essential medicine list,which have some rationality,but also some problems to be solved.

Renal fibrosis is a devastating consequence of progressive chronic kidney disease,representing a major public health challenge worldwide.The underlying mechanisms in the pathogenesis of renal fibrosis remain unclear,and effective treatments are still lacking.Renal tubular epithelial cells(RTECs)maintain kidney function,and their dysfunction has emerged as a critical contributor to renal fibrosis.Cellular quality control comprises several components,including telomere homeostasis,ubiquitin-proteasome system(UPS),autophagy,mitochondrial homeostasis(mitophagy and mitochondrial metabolism),endoplasmic reticulum(ER,unfolded protein response),and lysosomes.Failures in the cellular quality control of RTECs,including DNA,protein,and organelle damage,exert profibrotic functions by leading to senescence,defective autophagy,ER stress,mitochondrial and lysosomal dysfunction,apoptosis,fibro-blast activation,and immune cell recruitment.In this review,we summarize recent advances in un-derstanding the role of quality control components and intercellular crosstalk networks in RTECs,within the context of renal fibrosis.

Objective:To explore the expression levels and significance of programmed death factor 1 (PD-1)/programmed death factor ligand 1 (PDL-1) in T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs) in patients with unexplained recurrent spontaneous abortion (URSA).Methods:Forty-two URSA patients (as patient group), 34 healthy pregnant women (as normal pregnancy group) and 30 unpregnant healthy examination patients (as control group) were collected for retrospective analysis,all study subjects were from patients who were treated in Taizhou Hospital affiliated to Wenzhou Medical University from February 2020 to February 2022. Flow cytometry was used to detect the expression level of PD-1/PDL-1 in Treg cells, Breg cells and [T cells, B cells and natural killer cells (TBNK)] lymphocyte subsets, as well as the expression level of serum Th1 (IFN-γ, TNF-α)/Th2 (IL-4, IL-6, IL-10)/Th17 (IL-17) cytokine expression. The patients were treated with lymphocyte immunotherapy, the changes of PD-1/PDL-1 levels were detected at the end of treatment, and the pregnancy outcome was recorded during follow-up. Comparisons between multiple groups were performed by ANOVA, comparisons before and after treatment in URSA patients were performed by paired T-test, and correlation of each test index by bivariate correlation analysis.Results:The expression levels of PD-1/PDL-1 in Treg, Breg cells and T lymphocyte subsets in peripheral blood of patients with URSA was significantly lower than that of healthy pregnant women(all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was negatively correlated with the expression of serum Th1 cytokines Interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) (The r values were -0.44, -0.85, -0.33, and -0.94, respectively, all P<0.01). The expression level of PD-1/PDL-1 in CD4+T cells was positively correlated with the expression of serum Th2 cytokines interleukin 4(IL-4), interleukin 6(IL-6) and interleukin 10(IL-10)(The r values were 0.55, 0.47, 0.41, 0.33, 0.46, and 0.69, respectively,all P<0.01). The proportion of Breg cells and Treg cells were positively correlated with the level of serum IL-10 expression(The r values were 0.97, and 0.95 respectively, all P<0.01). The proportion of Treg cells was negatively correlated with the expression of IL-17( r=?0.95, P<0.01). The expression of PD-1/PDL-1 in Breg cells and Treg cells was positively correlated with the expression of serum IL-10(The r values were 0.95, 0.36, 0.96, and 0.95, respectively, all P<0.01). There was a negative correlation between serum IL-10 expression level and IL-17 expression level( r=?0.58, P<0.01). After URSA treatment, pregnancy was successful in 23 cases and failed in 19 cases. The expression of PD-1/PD-L1 on CD4, CD8, Tregs cells and Bregs cells in USRA treatment group was significantly higher than that before treatment( P<0.01), but there was no significant change in treatment failure group( P>0.05). Conclusion:The low expression of PD-1/PD-L1 in Treg cells, Breg cells and T cell subsets in peripheral blood of patients with URSA results in the immune imbalance of Th1/Th2 and Tregs/Th17, and the damage of maternal-fetal immune tolerance leads to pregnancy failure, which may be a potential therapeutic target.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.