BACKGROUND: Hemorrhagic stroke (HS) is associated with significant disability and mortality. However, the relationship between meteorological factors and hemorrhagic stroke, as well as the potential moderating role of these factors, remains unclear. METHODS: Daily data on HS, air pollution, and meteorological conditions were collected from January 2015 to December 2021 in Ganzhou to analyze the relationship between meteorological factors and HS admissions. This analysis employed a time-stratified case-crossover design in conjunction with a distributional lag nonlinear model. Additionally, a bivariate response surface modelling was utilized to further investigate the interaction between meteorological factors and particulate matter. The study also stratified the analyses by gender and age. To investigate the potential impact of extreme weather conditions on HS, this study defined the 97.5th percentile as representing extremely high weather conditions, while the 2.5th percentile was classified as extremely low. RESULTS: In single-day lags, the risk of admissions for HS was significantly associated with extremely low temperature (lag 1-2 and lag 13-14), extremely low humidity (lag 1 and lag 9-12), and extremely high precipitation (lag 2-7). Females exhibited greater susceptibility to extremely low temperature than males within the single-day lag pattern in the subcomponent layer, with a maximum relative risk (RR) that was 7% higher. In the cumulative lag analysis, the risk of HS admissions was significantly associated with extremely high temperature (lag 0-8∼lag 0-14), extremely low humidity (lag 0-2∼lag 0-14), and extremely high precipitation (lag 0-4∼lag 0-14). Within the cumulative lag day structure of the subcomponent layer, both extremely low and extremely high temperature had a more pronounced effect on females and aged ≥65 years. The risk of HS admissions was positively associated with extremely high barometric pressure in the female subgroups (lag 0-1 and lag 0-2). The highest number of HS admissions occurred when high PM_2.5 concentrations coexisted with low precipitation. CONCLUSIONS Meteorological factors were significantly associated with the risk of hospital admissions for HS. Individuals who were female and aged ≥65 years were found to be more susceptible to these meteorological influences. Additionally, an interaction was observed between airborne particulate matter and meteorological factors. These findings contributed new evidence to the association between meteorological factors and HS.
China/epidemiology* ; Humans ; Female ; Male ; Aged ; Middle Aged ; Cross-Over Studies ; Hospitalization/statistics & numerical data* ; Adult ; Hemorrhagic Stroke/etiology* ; Meteorological Concepts ; Weather ; Particulate Matter/analysis* ; Air Pollution/adverse effects* ; Environmental Exposure/adverse effects* ; Aged, 80 and over ; Young Adult

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

To investigate the impact and underlying mechanism of NOP2/Sun RNA methyltransferase 2 (NSUN2) on gastric cancer progression, TCGA database was used and revealed a significant upregulation of NSUN2 expression in gastric cancer tissues. Western blot analysis revealed that NSUN2 was upregulated in gastric cancer cells compared with gastric mucosal epithelial cells. Colony formation assays demonstrated an enhanced colony-forming capacity in NSUN2-overexpressing cells. Furthermore, Transwell assays showed a marked increase in cell migration and invasion upon high NSUN2 expression. Moreover, TCGA database analysis suggested ARMC9 as a potential downstream target of NSUN2. Subsequently, MeRIP-qPCR analysis revealed that NSUN2 overexpression could increase m5C modification of ARMC9 mRNA, and reduce its degradation rate, thus enhancing protein expression. Additionally, ARMC9 overexpression augmented cellular colony formation and migratory and invasive capabilities. These findings indicate that NSUN2 promotes gastric cancer progression by elevating m5C modification of ARMC9 mRNA, increasing its stability and enhancing its expression, therefore, NSUN2 and ARMC9 may serve as potential therapeutic targets for gastric cancer.

Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme of the pentose phosphate pathway, which regulates the production of nicotinamide adenine dinucleotide phosphate (NADPH) in cells, and plays an important role in redox reactions. In addition, NADPH is necessary for biosynthesis reactions and is an essential hydrogen donor in the biosynthesis of cholesterol, fatty acids, and sex hormones. NADPH also plays an important role in maintaining intracellular redox homeostasis, converting intracellular oxidized glutathione into reduced glutathione (GSH), which is the main intracellular antioxidant. Therefore, G6PD plays an important role in maintaining intracellular redox homeostasis. Studies have shown that the decrease in G6PD activity can lead to a breakdown of the redox balance in the cells and tends to the oxidation state, which not only leads to dysregulation of cell growth and signaling, but also makes the host more susceptible to viruses. Previous studies have focused on the molecular characteristics of G6PD, anemia caused by G6PD deficiency, and the relationship between malignant tumors and G6PD. In recent years, more attentions have been paid to the importance of G6PD at the cellular level, development, and disease progression. To explore the effects of G6PD on viral life cycle, the relationship between G6PD and viral infections, including the clinical symptoms and virus-host interactions of hepatitis B virus (HBV), human papilloma virus (HPV), hepatitis E virus (HEV), influenza virus and dengue fever virus (DENV) will be reviewed, which will benefit the antiviral drugs development. Many studies had proved that patients with deficient G6PD are more susceptible to HBV infection. It has been reported that HBV infection activates the glycolytic pathway, promotes pentose phosphate pathway, and accelerates citric acid cycle to enhance nucleotide and fat biosynthesis, thereby promoting viral replication. During HPV infection, miR-206 up-regulates the expression of G6PD to facilitate viral replication. Thus, G6PD may be a new target for anti-cervical cancer therapy. It was reported that patients with G6PD deficiency are more susceptible to HEV infection, and more serious HEV infection-associated diseases are developed. However, the mechanism of why and how the deficiency of G6PD affect HEV infection is still unclear. The oxidative stress caused by G6PD deficiency provides a suitable environment for influenza virus replication. Furthermore, patients with G6PD deficiency are more susceptible to SARS-CoV-2 infection and lead to more severe clinical symptoms with a higher risk of thrombosis and hemolysis than general population. There is a correlation between DENV infection and G6PD deficiency, which increase the risk of hemolysis, however, the pathogenesis is still unknown. The deficiency of G6PD promotes HCoV 229E infection, possibly because the NF-κB signal pathway is suppressed when G6PD deficiency, which results in decreased innate antiviral immune, and increased susceptibility to HCoV 229E, finally leads to increased viral replication. Thus, the deficiency of G6PD play an important role during viruses’ infection, especially the susceptibility. More studies should be performed on the relicationship between G6PD deficiency and specific viral susceptibility, and more attentions shoud be paid to G6PD deficient patients, which will benefit the treatment of viral infection and the development of antiviral drugs.

Drug nanocrystals self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. There are more and more researches on DNSPE in the field of drug delivery in recent years. On the basis of summarizing the research status of DNSPE used as drug delivery systems, this paper comprehensively reviewed the research progress of three key issues, such as the main factors affecting construction of DNSPE, characterization methods of properties and structures, and in vivo fate, and looked forward to the industrialization prospect, which is beneficial to deepen the comprehensive research of DNSPE and promote its application in the field of drug delivery.

Objective Data mining technology was used to mine the medication rules of the prescriptions used in the treatment of pediatric atopic dermatitis by Chinese medical master XUAN Guo-Wei.Methods The medical records of effective cases of pediatric atopic dermatitis treated by Professor XUAN Guo-Wei at outpatient clinic were collected,and then the medical data were statistically analyzed using frequency statistics,association rule analysis and cluster analysis.Results A total of 242 prescriptions were included,involving 101 Chinese medicinals.There were 23 commonly-used herbs,and the 16 high-frequency herbs(frequency＞100 times)were Glycyrrhizae Radix et Rhizoma,Saposhnikoviae Radix,Glehniae Radix,Perillae Folium,Ophiopogonis Radix,Cynanchi Paniculati Radix et Rhizoma,Microctis Folium,Dictamni Cortex,Scrophulariae Radix,Coicis Semen,Cicadae Periostracum,Lilii Bulbus,Rehmanniae Radix,Kochiae Fructus,Sclerotium Poriae Pararadicis,and Euryales Semen.The analysis of the medicinal properties showed that most of the herbs were sweet and cold,and mainly had the meridian tropism of the spleen,stomach and liver meridians.The association rule analysis yielded 24 commonly-used drug combinations and 20 association rules.Cluster analysis yielded 2 core drug combinations.Conclusion For the treatment of pediatric atopic dermatitis,Professor XUAN Guo-Wei focuses on the clearing,supplementing and harmonizing therapies,and the medication principle of"supporting the healthy-qi to eliminate the pathogen,and balancing the yin and yang"is applied throughout the treatment.

Objective To investigate the effect of tumor-infiltrating B cells on the therapeutic efficacy of programmed death ligand-1[PD-(L)1]inhibitors and elucidate the potential mechanisms.Methods Based on immunotherapy cohorts for melanoma patients in public databases,the relationship of B cells with progression-free survival (PFS) and response to immune checkpoint inhibitors treatment was analyzed.TC-1 and B16-OVA cells were implanted subcutaneously and in the liver in 6-8-week-old female C57BL/6 mice to establish tumor xenograft models.The effect of B cell clearance on PD-(L)1 therapy was compared.Flow cytometry was performed on the 15th day of TC-1 tumor microenvironment (TME)to confirm the number,function and phenotypic changes of T cells.Flow cytometry and quantitative real-time polymerase chain reaction (qPCR)were used to detect B cell surface molecules and cytokines.Results Based on ERP105482 data from the ICBatlas public database,high CD19 expression in the tumors was associated with longer PFS in melanoma patients (753 vs 95 d,HR=0.3,95％CI:0.13～0.65,P=0.003).B cells were significantly enriched in immunotherapy-responsive patients (P=0.01).In a mouse TC-1 liver-loaded tumor model,PD-(L)1 antibody treatment reduced tumor mass (P<0.01),whereas B-cell clearance attenuated the therapeutic efficacy.B cells enhanced PD-(L)1 antibody treatment by promoting T cell infiltration and function,and the treatment resulted in changes in B cell subsets,as evidenced by an increase in PD-1 low-expressing subsets (P<0.01).Conclusion After PD-(L)1 treatment,a decrease in PD-1 expression on B cell subsets might be one of the potential mechanisms by which B cells enhance the efficacy of PD-(L)1 therapy.

Objective To deeply explore the principles of drug combinations in the treatment of vitiligo by traditional Chinese medicine master XUAN Guo-Wei by data mining technology,and to analyze the potential mechanism of action of the core drug pairs by network pharmacology.Methods The original case records of Professor XUAN Guo-Wei in treating vitiligo were compiled,and then TCM inheritance Computing Platform was used to analyze the frequency of drugs in the prescriptions,the association rules between drugs,and the core combinations of drugs by the association rule method,and the core drug pairs of Professor XUAN Guo-Wei's treatment of vitiligo were obtained based on the results of the data mining,additionally,the mechanism of the core pairs of drugs was analyzed by using the method of network pharmacology.Results A total of 243 prescriptions were collected,among which the high-frequency drugs were Glycyrrhizae Radix et Rhizoma,Tribuli Fructus,Ecliptae Herba,Cuscutae Semen,Scrophulariae Radix,Angelicae Dahuricae Radix,etc.,and the core pair was Tribuli Fructus-Ecliptae Herba.The main components of Tribuli Fructus-Ecliptae Herba for the treatment of vitiligo were quercetin,kaempferol,etc.,there were 47 targets for the intersection of the active ingredients with the disease,among which TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,and IL4 may be the core targets for the treatment of vitiligo by Tribuli Fructus-Ecliptae Herba.The main pathways of Tribuli Fructus-Ecliptae Herba drug pairs against the disease were PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.Conclusion The core drug pair of Professor XUAN Guo-Wei in the treatment of vitiligo is Tribuli Fructus-Ecliptae Herba,which involves targets such as TP53,TNF,IL-1β,CASP3,VEGFA,PTGS2,IL10,IL2,IFNG,IL4,etc.,Tribuli Fructus-Ecliptae Herba drug pair maybe exert an effect in the treatment of vitiligo through PI3K-Akt signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway and MAPK signaling pathway.

Objective:To analyze the correlation between homocysteine (Hcy), ferritin and gestational anemia in advanced age pregnant women, and the effect on adverse pregnancy outcomes.Methods:The clinical data of 344 advanced age pregnant women in Handan City Maternal and Child Health Hospital from March 2021 to June 2022 were retrospectively analyzed. The adverse pregnancy outcomes were followed up and recorded. The pregnant women were divided into anemia group (114 cases) and control group (230 cases) according to the diagnostic criteria for anemia. The levels of Hcy and ferritin, etc. were compared between two groups, different degrees of anemia and different pregnancy outcomes. Pearson method was used to analyze the correlation between Hcy, ferritin and hemoglobin. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcomes in advanced age pregnant women with gestational anemia.Results:The Hcy in anemia group was significantly higher than that in control group: (31.39 ± 3.34) mol/L vs. (9.28 ± 1.44) mol/L, the ferritin was significantly lower than that in control group: (69.81 ± 5.08) μg/L vs. (96.43 ± 7.52) μg/L, and there were statistical differences ( P<0.01). Among 114 advanced age pregnant women with gestational anemia, 64 cases were mild anemia (mild anemia group), 35 cases were moderate anemia (moderate anemia group), and 15 cases were severe anemia (severe anemia group). The levels of Hcy in the control group, mild anemia group, moderate anemia group and severe anemia group were gradually increased: (9.28 ± 1.44), (24.79 ± 3.25), (37.63 ± 5.51) and (45.01 ± 7.23) mol/L, the levels of ferritin were gradually decreased: (96.43 ± 7.52), (81.19 ± 5.14), (64.82 ± 4.47) and (32.96 ± 2.01) μg/L, and the difference between pairwise comparisons were statistically significant ( P<0.05). Pearson correlation analysis result showed that Hcy was negatively correlated with hemoglobin ( r = - 0.596, P<0.01), and ferritin was positively correlated with hemoglobin ( r = 0.685, P<0.01). Among 114 advanced age pregnant women with gestational anemia, 35 cases had adverse pregnancy outcomes, and 79 cases had normal pregnancy outcomes. The age, gestational reproductive tract infection rate and Hcy in advanced age pregnant women with adverse pregnancy outcomes were significantly higher than those in advanced age pregnant women with normal pregnancy outcomes: (41.17 ± 3.74) years old vs. (38.25 ± 4.28) years old, 28.57% (10/35) vs. 10.13% (8/79) and (49.56 ± 4.12) mol/L vs. (23.34 ± 2.63) mol/L, the ferritin was significantly lower than that in advanced age pregnant women with normal pregnancy outcomes: (38.36 ± 3.08) μg/L vs. (83.74 ± 6.25) μg/L, and the degree of gestational anemia was more serious than that in advanced age pregnant women with normal pregnancy outcomes, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that age, gestational reproductive tract infection, Hcy, ferritin and the degree of gestational anemia were the independent risk factors of adverse pregnancy outcomes in advanced age pregnant women with gestational anemia ( OR = 1.570, 1.758, 1.865, 1.556 and 1.652; 95% CI 1.154 to 2.136, 1.181 to 2.617, 1.223 to 2.842, 1.100 to 2.201 and 1.175 to 2.323; P<0.01). Conclusions:The level of Hcy in advanced age pregnant women with gestational anemia is relatively higher, and the level of ferritin is relatively lower. The ferritin and Hcy levels are risk factors for adverse pregnancy outcomes in advanced age pregnant women with gestational anemia, and may be involved in the occurrence and development of gestational anemia in advanced age pregnant women.