Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

Objective:To assess the changes of selenium nutrition of school-age children in Kashin-Beck disease (KBD) areas of Linzhou County, Lhasa City and Xietongmen County, Shigatse City in Tibet Autonomous Region (referred to as Tibet), and provide a scientific basis for evaluating the effectiveness of prevention and control measures.Methods:According to the historical condition of KBD, a total of 344 children's hair samples were collected to determine the content of selenium in Kazi (KBD area) and Jiangxia townships (non-KBD area) of Linzhou County in 2013 and 2021, Renqinze (KBD area) and Tongmen townships (non-KBD area) of Xietongmen County in 2015 and 2021.Results:Compared to 2013/2015, in 2021, the hair selenium level of children in the four townships increased ( P < 0.001). The selenium nutritional level of more than 90% of the children reached medium or above (hair selenium > 0.25 μg/g) in 2021. The hair selenium levels of girls in the two KBD areas (Kazi and Renqinze townships) were lower than those of boys ( Z = - 2.83, - 2.83, P < 0.05). Conclusions:The selenium nutrition level of school-age children in KBD areas in Linzhou and Xietongmen counties has increased rapidly in recent years. However, the selenium nutrition level of girls is significantly lower than that of boys. It is necessary to strengthen prevention, controlling and monitoring, and to further improve the dietary structure of school-age children through the joint efforts of families and schools, to increase the proportion of exogenous high selenium food intake.

Objective: To investigate the epidemiological characteristics of sexually transmitted diseases (STDs) in Zhejiang Province from 2018 to 2022, so as to provide insights into improving STDs prevention and control strategies. Methods: Data of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections reported in Zhejiang Province from 2018 to 2022 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, spatial and population distribution of STDs were analyzed, and the trends in incidence of STDs were evaluated using annual percent change (APC). Results: A total of 386 770 STDs cases were reported in Zhejiang Province from 2018 to 2022, with mean annual reported incidence of 127.80/105. The mean annual reported incidence from high to low was syphilis (44.11/105), genital Chlamydia trachomatis infections (40.20/105), gonorrhea (24.92/105), condyloma acuminatum (13.32/105), and genital herpes (5.34/105). The incidence of STDs appeared a tendency towards a decline from 2018 to 2022 (APC=-9.332%, P<0.05), with an average annual growth rate of -9.41%. Syphilis (APC=-11.536%, P<0.05), condyloma acuminatum (APC=-7.509%, P<0.05), and genital Chlamydia trachomatis infections (APC=-9.009%, P<0.05) showed a appeared a tendency towards a decline. The top three highest reported incidence were reported in Hangzhou City (185.98/105), Taizhou City (133.85/105) and Lishui City (122.73/105), respectively. The mean annual reported incidence of females was higher than that of males (140.60/105 vs. 117.83/105; P<0.05). Most STDs cases were at ages of 20 to 49 years (265 314 cases, 68.60%). Farmers (118 096 cases, 30.53%), household and unemployed personnel (85 924 cases, 22.22%) were the predominant occupation. Conclusions The incidence of STDs appeared a tendency towards a decline in Zhejiang Province from 2018 to 2022, with regional differences in incidence. People at ages of 20 to 49 years, farmers, household and unemployed personnel are high-risk populations for STDs.

N6-Methyladenosine (m⁶A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m⁶A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m⁶A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

Objective: To observe the efficacy of mild moxibustion combined with arthroscopic meniscal repair in the treatment of meniscal injury and to explore its action mechanism. Methods: Ninety-eight patients with meniscal injury were divided into a surgery group and a moxibustion plus surgery group by the random number table method, with 49 cases in each group. Both groups received arthroscopic meniscal repair, and the moxibustion plus surgery group was treated with add-on mild moxibustion. The Lysholm score, visual analog scale (VAS) score, and mobility of the affected knee were measured before and after treatment, and transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) levels were measured in the fluid of the affected knee joint. The healing of the meniscus was recorded at a follow-up visit 3 months after the surgery. Results: After treatment, the Lysholm score increased, the VAS score decreased in both groups, and the intra-group differences in both groups were statistically significant (P<0.05). The Lysholm score was higher in the moxibustion plus surgery group than in the surgery group, and the VAS score was lower in the moxibustion plus surgery group than in the surgery group. The differences between groups in both scores were statistically significant (P<0.05). The mobility of the affected knee joint increased in both groups (P<0.05), and it was greater in the moxibustion plus surgery group than in the surgery group (P<0.05). When compared with pretreatment, the levels of TGF-β1 and PDGF in the fluid of the knee joint increased in both groups (P<0.05), and the levels of TGF-β1 and PDGF in the fluid of the affected knee joint were higher in the moxibustion plus surgery group than in the surgery group (P<0.05). The healing of the meniscus in the moxibustion plus surgery group was significantly better than that in the surgery group at the follow-up visit 3 months after the surgery (P<0.05). Conclusion: The effect of mild moxibustion combined with arthroscopic meniscal repair is better than the surgery alone in improving knee function, relieving pain, increasing mobility of the affected knee, and promoting meniscal healing, which may be related to the up-regulation of TGF-β1 and PDGF levels in the fluid of knee joint.

Objective:To analyze spatiotemporal distribution characteristics of syphilis in Zhejiang province from 2016 to 2020, to explore cluster areas of syphilis cases, and to provide a theoretical basis for accurate prevention and control of syphilis.Methods:Data on reported syphilis cases in Zhejiang province from 2016 to 2020 were collected from the notifiable infectious disease surveillance system in China Disease Control and Prevention Information System. The ArcGIS10.2 software was used as a data management and presentation platform to establish a database for spatial analysis of syphilis in Zhejiang province from 2016 to 2020, and spatial autocorrelation analysis of reported syphilis incidence was conducted. The SaTScan 9.6 software was used for spatiotemporal scanning analysis.Results:A total of 158 420 cases of syphilis were reported in Zhejiang province from 2016 to 2020, and the average annual reported incidence rate was 49.07 per 100 000 in all counties and districts (range: 20.52 per 100 000-124.29 per 100 000) . The overall spatial distribution pattern of syphilis cases in Zhejiang province was characterized by higher reported syphilis incidence in the West area and lower incidence in the middle area. Global autocorrelation analysis showed that all the global Moran′s I indices from 2016 to 2020 were over 0, Z values were over 1.96, and P values were below 0.001, suggesting the spatial clustering of reported syphilis cases. Local autocorrelation analysis showed that there were 2 high-high clustering areas (Tonglu and Chun′an counties in Hangzhou city, Jingning county in Lishui city) , and 1 low-low clustering area (Jindong district, Dongyang and Yongkang county-level cities in Jinhua city) . Local hot-spot analysis with G statistic showed that there were 6 positive hot-spot areas and 8 negative hot-spot areas of syphilis cases in Zhejiang province. SaTScan spatiotemporal scanning analysis revealed 3 clustering areas, mainly distributed in Taizhou and Zhoushan cities along the eastern coast, and some counties and districts in the southwestern mountainous areas. Conclusions:The reported incidence rate of syphilis in Zhejiang province is characterized by spatial clustering. In the future, prevention and control of syphilis should be strengthened in southwestern mountainous areas, eastern islands, and other remote areas as well as areas with poor transportation.

Objective: To assess the implementation of National Leprosy Control Plan (2011-2020) in Zhejiang Province, so as to provide insights into leprosy control. Methods: Leprosy control data were collected from the National Leprosy Management Information System of China, and health administrative sectors, centers for disease control and prevention and professional leprosy control institutions at each level in Zhejiang Province. According to the scheme for the final evaluation of National Leprosy Control Plan (2011-2020), the implementation of 12 indicators in Zhejiang Province in 2020 was investigated, including the current number of leprosy patients, prevalence of leprosy, proportion of training on leprosy control skills, proportion of regular leprosy treatment, proportion of treatment of adverse reactions, annual examination rate of close contacts, proportion of early case identification and awareness of leprosy control knowledge. Results: There were 50 registered leprosy cases in Zhejiang Province by the end of 2020, with a decrease of 50.98% relative to in 2010. The prevalence of leprosy was less than 1/105 in 93 counties (districts) of Zhejiang Province, and the rate of training on leprosy control skills, rate of regular leprosy treatment, rate of treatment of adverse reactions, annual examination rate of close contacts, rate of early case identification were all 100% in Zhejiang Province. There were no new confirmed cases with diagnosis of leprosy having grade 2 deformity or disability, or no new cases with deformity or disability within 2 years following anti-leprosy therapy. In addition, the awareness of leprosy control knowledge was 91.67% among the public and 98.12% among the close contacts. All of the 12 indicators reached the requirements of the National Leprosy Control Plan (2011-2020). Conclusions The implementation of the National Leprosy Control Plan (2011-2020) in Zhejiang Province had achieved the targets defined in the final evaluation of the plan. Intensifying multi-sectoral joint leprosy prevention and control and improving early identification and standardized therapy of leprosy cases are recommended for future leprosy control in Zhejiang Province.

Objective:To construct the core competence evaluation indicators for clinical teaching nurses,provide quantifiable indicators for the core competency of clinical teaching nurses.Methods:Using literature review, survey of nursing students, interview of clinical teaching nurses, and two-round Delphi expert consultation for 18 clinical teaching nurses, the core competence evaluation indicators was constructed.Results:The response rates for two rounds of expert consultation were 18/18 and 16/18, authority coefficients were 0.83 and 0.85, and coordination coefficients at all levels ranged from 0.096-0.503( P<0.05). The core competence evaluation indicators for clinical teaching nurses consisted of 7 first-class indicators, 25 second-class indicators and 43 third-class indicators. Conclusions:The enthusiasm, authority, concentration degree and coordination degree of experts are comparatively high. It can provide references for standardized evaluation, training and management of clinical teaching nurses.