Objective To explore the effects of Shuanglu Tongnao Formula on neuroinflammation in ischemic stroke (IS) rats via the P2X purinoceptor 7 receptor (P2X7R)/NLR family pyrin domain-containing 3 (NLRP3) pathway. Methods The rats were divided into five groups: the IS group, control group, Shuanglu Tongnao Formula group, P2X7R inhibitor brilliant blue G (BBG) group, and Shuanglu Tongnao Formula combined with P2X7R activator adenosine triphosphate (ATP) group, with 18 rats in each group. Except for the control group, rats in all other groups were used to construct an IS model using the suture method. After successful modeling, the drug was given once a day for 2 weeks. Neurological function scores and cerebral infarction volume ratios were measured in rats. Pathological examination of the ischemic penumbra brain tissue was performed. Immunofluorescence staining was used to quantify the proportions of microglia co-expressing both inducible nitric oxide synthase (iNOS) and ionized calcium-binding adapter molecule 1 (Iba1), as well as arginase 1 (Arg1) and Iba1, in the ischemic penumbra brain tissue. ELISA was used to detect tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6) and IL-10 in the ischemic penumbra brain tissue. Western blotting was used to measure P2X7R, NLRP3, and IL-1β proteins in the ischemic penumbra brain tissue. Results Compared with the control group, the IS group showed disordered neuronal arrangement, nuclear condensation, and obvious infiltration of inflammatory cells in the ischemic penumbra; significantly elevated neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with reduced proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. Compared with the IS group, the Zhuang medicine Shuanglu Tongnao Formula and BBG groups demonstrated alleviated brain tissue damage; reduced neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with increased proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. ATP reversed the effects of Zhuang medicine Shuanglu Tongnao Formula on microglial polarization and neuroinflammation in IS rats. Conclusion Zhuang medicine Shuanglu Tongnao Formula may promote the transformation of microglia from M1 type to M2 type by inhibiting the P2X7R/NLRP3 pathway, thereby improving neuroinflammation in IS rats.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Ischemic Stroke/pathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Brain Ischemia/drug therapy* ; Microglia/metabolism*

Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund's complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young's modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
Animals ; NF-kappa B/metabolism* ; Temporomandibular Joint Disorders/pathology* ; Temporomandibular Joint Disc/metabolism* ; Rats ; Rats, Sprague-Dawley ; Disease Models, Animal ; Male ; Collagen/metabolism* ; Cells, Cultured ; Joint Dislocations/pathology* ; Interleukin-1beta ; Arthritis, Experimental

Objective: To understand the prevalence of elevated blood pressure and its association with dietary patterns in children and adolescents in China, providing evidence for developing dietary intervention of hypertension in children and adolescents. Methods: Data were derived from the China Children s Nutrition and Health System Survey and Application Project(2019-2021). A stratified cluster random sampling method was used to include 7 933 participants from 28 survey sites in seven major regions of Northeast, North, Northwest, East, Central, South and Southwest China. Multivariate Logistic regression models were used to analyze associations between demographic characteristics, nutritional status and elevated blood pressure. Exploratory factor analysis identified dietary patterns, which were divided into three quartile groups (T3, T2, T1) based on factor scores (compliance for dietary pattern) from high to low, and multivariate Logistic regression model assessed the correlation between elevated blood pressure and dietary patterns. Results: The prevalence of elevated blood pressure was 15.4% among Chinese children aged 7-17 years. Significant differences were observed across nutritional status (reference: underweight; normal weight: OR =1.57; overweight: OR = 2.61 ; obesity: OR =3.85), urban/rural residence (reference: rural; urban: OR =0.86), and paternal education (reference: junior high school and below; bachelor degree or above: OR =0.68) ( P <0.05). The detection rates of high blood pressure in T3 group children and adolescents with four dietary patterns (staple food, animal based food, snacks, vegetables and fruits) were 15.7%, 14.6%, 16.8%, and 15.8%, respectively. After adjusting for residence, paternal education, and nutritional status, the "snack dietary pattern" (mainly candy, sugar sweetened beverages, and processed snacks) showed positive associations with elevated blood pressure in T2 ( OR =1.21) and T3 ( OR =1.19) tertiles ( P <0.05). Conclusions The snack dietary pattern is a related factor for elevated blood pressure in children and adolescents. Restricting unhealthy snack intake may promote cardiovascular health.

Objective:To construct the evaluation indicator system of medical insurance capacity, healthcare service capacity, and pharmaceutical supply security capacity, and explore the process and law of medical-insurance-medicine linkage reform in the 12 years since the Sanming medical reform.Methods:Data from documents such as Development of Healthcare in Sanming City and Financial Performance Report of Public Medical Institutions in Sanming City were collected. The TOPSIS and coupled coordination models were used to measure the degree of medical-insurance-medicine linkage reform, and correlation analysis was employed to explore the relationship between medical insurance capacity, healthcare service capacity, pharmaceuticals supply securty capacity and the degree of medical-insurance-medicine linkage reform.Results:The degree of medical-insurance-medicine linkage reform in Sanming medical reform increased from 0.220 before the reform to the highest of 0.346, 0.642 and 0.831 in the stages of " governing chaos and blocking waste", " establishing rules and systems" and " treating diseases before they occur and promoting general health" respectively. The coupling coordination status advanced from moderate imbalance to sound coordination. The r-values of medical insurance capacity, healthcare service capacity, and pharmaceutical supply security capacity with the degree of medical-insurance-medicine linkage were 0.940, 0.926, and 0.789 respectively ( P<0.01), among which medical insurance had the highest correlation with the degree of medical-insurance-medicine linkage. Conclusions:Since the Sanming medical reform, the service security capacities in the fields of medical insurance, healthcare service, and pharmaceuticals, as well as the degree of medical-insurance-medicine linkage reform, have been continuously improved, showing the characteristics of differentiated development in different stages. Among them, medical insurance has played an engine role in the medical-insurance-medicine linkage reform of Sanming medical reform.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.

Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.

Objective:To construct the evaluation indicator system of medical insurance capacity, healthcare service capacity, and pharmaceutical supply security capacity, and explore the process and law of medical-insurance-medicine linkage reform in the 12 years since the Sanming medical reform.Methods:Data from documents such as Development of Healthcare in Sanming City and Financial Performance Report of Public Medical Institutions in Sanming City were collected. The TOPSIS and coupled coordination models were used to measure the degree of medical-insurance-medicine linkage reform, and correlation analysis was employed to explore the relationship between medical insurance capacity, healthcare service capacity, pharmaceuticals supply securty capacity and the degree of medical-insurance-medicine linkage reform.Results:The degree of medical-insurance-medicine linkage reform in Sanming medical reform increased from 0.220 before the reform to the highest of 0.346, 0.642 and 0.831 in the stages of " governing chaos and blocking waste", " establishing rules and systems" and " treating diseases before they occur and promoting general health" respectively. The coupling coordination status advanced from moderate imbalance to sound coordination. The r-values of medical insurance capacity, healthcare service capacity, and pharmaceutical supply security capacity with the degree of medical-insurance-medicine linkage were 0.940, 0.926, and 0.789 respectively ( P<0.01), among which medical insurance had the highest correlation with the degree of medical-insurance-medicine linkage. Conclusions:Since the Sanming medical reform, the service security capacities in the fields of medical insurance, healthcare service, and pharmaceuticals, as well as the degree of medical-insurance-medicine linkage reform, have been continuously improved, showing the characteristics of differentiated development in different stages. Among them, medical insurance has played an engine role in the medical-insurance-medicine linkage reform of Sanming medical reform.

OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.