ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

OBJECTIVES: To study the impact of family socioeconomic status on children's reading fluency and the chain mediation effect of family reading environment and children's living and learning styles in this relationship. METHODS: A total of 473 children from grades 2 to 6 in two primary schools in Nanjing were selected through stratified random sampling. The children's reading fluency was assessed, and a questionnaire was used to collect information on family socioeconomic status, family reading environment, and children's living and learning styles. The mediation model was established using the Process macro in SPSS, and the Bootstrap method was employed to test the significance of the mediation effects. RESULTS: Family socioeconomic status, family reading environment, and children's living and learning styles were significantly positively correlated with reading fluency (P<0.001). The family reading environment and children's living and learning styles mediated the relationship between family socioeconomic status and children's reading fluency. Specifically, the independent mediation effect of family reading environment accounted for 11.02% of the total effect, while the independent mediation effect of children's living and learning styles accounted for 10.79%. The chain mediation effect of family reading environment and children's living and learning styles accounted for 7.41% of the total effect. CONCLUSIONS Family socioeconomic status can affect children's reading fluency through three pathways: family reading environment, children's living and learning styles, and the chain mediation effect of family reading environment and children's living and learning styles.
Humans ; Child ; Male ; Female ; Reading ; Learning ; Social Class ; Family

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

BACKGROUND: Blood glucose and serum albumin have been associated with cardiovascular disease prognosis, but the impact of admission-blood-glucose-to-albumin ratio (AAR) on adverse outcomes in critical ill coronary artery disease (CAD) patients was not investigated. METHODS: Patients diagnosed with CAD were non-consecutively selected from the MIMIC-IV database and categorized into quartiles based on their AAR. The primary outcome was 1-year mortality, and secondary endpoints were in-hospital mortality, acute kidney injury (AKI), and renal replacement therapy (RRT). A restricted cubic splines model and Cox proportional hazard models assessed the association between AAR and adverse outcomes in CAD patients. Kaplan-Meier survival analysis determined differences in endpoints across subgroups. RESULTS: A total of 8360 patients were included. There were 726 patients (8.7%) died in the hospital and 1944 patients (23%) died at 1 year. The incidence of AKI and RRT was 63% and 4.3%, respectively. High AAR was markedly associated with in-hospital mortality (HR = 1.587, P = 0.003), 1-year mortality (HR = 1.502, P < 0.001), AKI incidence (HR = 1.579, P < 0.001), and RRT (HR = 1.640, P < 0.016) in CAD patients in the completely adjusted Cox proportional hazard model. Kaplan-Meier survival analysis noted substantial differences in all endpoints based on AAR quartiles. Stratified analysis and interaction test demonstrated stable correlations between AAR and outcomes. CONCLUSIONS The results highlight that AAR may be a potential indicator for assessing in-hospital mortality, 1-year mortality, and adverse renal prognosis in critical CAD patients.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

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*

Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction of blood vessels at the lesion site. Here, a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke, including anti-inflammation, anti-oxidant, and promotion of angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide (NO) and ISO-1 (inhibitor of macrophage migration inhibitory factor, MIF). The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), and MIF. In a mouse stroke model, hydrogels, when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release, would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect. Concurrently, NO was sustained release to facilitate angiogenesis and provide neuroprotective effects. Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score, rotarod test, and open field test. These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.