Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of total paeony glycoside(TPG)on airway remodeling in bronchial asthma mice and its underlying mechanisms.Methods Forty-eight BALB/c mice were randomly divided into control group,model group,ovalbumin+budesonide group(OVA+BUD group),and OVA+TPG group,with 12 mice in each group.Except the control group,mice in other groups were sensitized by intraperitoneal injection of 10%OVA aluminum hydroxide suspension,and then stimulated by atomized inhalation of 1%OVA to establish mouse asthma model.One hour before each inhalation of OVA,mice in OVA+BUD group were atomized with 2 ml BUD suspension,and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration.Lung tissues and bronchoalveolar lavage fluid(BALF)of mice from each group were collected,and the pathological morphology of the lung tissues was detected by hematoxylin-eosin(HE)and periodic acid schiff(PAS)staining.Inflammatory cell counts[white blood cell(WBC),neutrophil(NEU),eosinophils(EOS),and leukomonocyte(LYM)]in BALF were detected by Wright-giemsa staining.The contents of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in BALF were determined by ELISA.Airway remodeling proteins[fibronectin,α-smooth muscle actin(α-SMA),collagen Ⅰ]and NOD-like receptor protein 3(NLRP3)inflammasome-related proteins[NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein(ASC)]levels were detected by Western blotting.Human bronchial smooth muscle cells(HBSMCs)were divided into control group(normal culture),transforming growth factor(TGF)-β1 group(culture medium containing 10 ng/ml TGF-β1),and TGF-β1+TPG group(culture medium containing 10 ng/ml TGF-β1 and 50 μg/ml TPG).Cell proliferation was detected by CCK-8 method,and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins.Results Compared with control group,model group exhibited increased infiltration of inflammatory cell in lung tissues,mucosal epithelium hyperplasia,narrowed bronchial lumen narrowed,tube wall thickened,increased cup cells and mucus secretion,and an elevated pathological score of lung injury(P<0.05);the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF were increased(P<0.05),and the expressions of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were elevated(P<0.05).Compared with model group,BUD or TPG treatment effectively reduced asthma symptoms,improved lung histopathology injury,inhibited bronchial wall thickening,significantly reduced the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the content of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF,and inhibited expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Compared with control group,the proliferation rate of HBSMCs was increased,and the protein expression levels of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were increased in TGF-β1 group(P<0.05).Compared with TGF-β1 group,TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins,inhibiting NLRP3 inflammasome activation,and reducing the inflammatory response.

Objective To evaluate the efficacy and safety of percutaneous vertebroplasty(PVP)using a 17 G puncture needle for the treatment of painful cervical osteolytic metastases.Methods The clinical data of 42 patients with cervical osteolytic metastases(53 lesions in total),who were treated with PVP at the Affiliated Zhongda Hospital of Southeast University of China from March 2012 to March 2024,were retrospectively analyzed.Visual Analog Scale(VAS)was used to evaluate the clinical efficacy and procedure-related complications at one week,one month,3 months,6 months,and one year after PVP.Follow-up CT scan was performed at 1-3 days after PVP so as to evaluate the condition of bone cement filling and leakage.Results Successful PVP using a 17 G puncture needle was accomplished for all the 53 diseased cervical vertebrae.Among them,one patient had one diseased vertebra of C1 and each in 5 patients had one diseased vertebra of C2,and all the 6 lesions were treated with CT-guided PVP;each in 6 patients had one diseased vertebra of C2 and 30 patients had 41 diseased vertebrae of C3-C6,and all the 47 lesions were treated with DSA fluoroscopy-guided PVP.The mean volume of bone cement injected in each vertebra was(1.9±0.45)mL,and the mean bone cement filling rate in each vertebra was(83.5±9.7)％.The preoperative average VAS score was 8.2 points,and it decreased by 5.6,6.1,6.2,5.9,and 5.7 points at one week,one month,3 months,6 months,and one year after PVP,respectively.There was a statistically significant difference in VAS score between one week after PVP and before PVP(P＜0.01),but no statistically significant differences in VAS scores existed within one year after PVP(all P＞0.05).Asymptomatic leakage of bone cement occurred in 14(26.4％)cervical vertebrae.One patient developed pharyngeal infection(adopting the anterior oblique puncture approach),which was cured after anti-infection treatment.No procedure-related complications such as neck bleeding,hematoma,etc.were observed.The lesion control rates at 3,6,and 12 months after PVP were 94.3％,93.9％,and 88.9％,respectively,there was no statistically significant difference in lesion control rates among the follow-up time-points(P=0.580).Conclusion For the treatment of painful cervical osteolytic metastases,PVP using a 17 G puncture needle is clinically safe and feasible.PVP can quickly relieve cervical pain and maintain cervical stability for a long time.Bone cement filling has a good control effect on cervical osteolytic metastatic tumors,although this control effect will decrease over time.