This study aims to explore the synergistic effects of the main components in salvianolic acids for Injection(SAFI) on key pathological events in cerebral ischemia, elucidating the pharmacological characteristics of SAFI in neuroprotection. Two major pathological gene modules related to endothelial injury and neuroinflammation in cerebral ischemia were mined from single-cell data. According to the topological distance calculated in network medicine, potential synergistic component combinations of SAFI were screened out. The results showed that the combination of caffeic acid and salvianolic acid B scored the highest in addressing both endothelial injury and neuroinflammation, demonstrating potential synergistic effects. The cell experiments confirmed that the combination of these two components at a ratio of 1∶1 significantly protected brain microvascular endothelial cells(bEnd.3) from oxygen-glucose deprivation/reoxygenation(OGD/R)-induced reperfusion injury and effectively suppressed lipopolysaccharide(LPS)-induced neuroinflammatory responses in microglial cells(BV-2). This study provides a new method for uncovering synergistic effects among active components in traditional Chinese medicine(TCM) and offers novel insights into the multi-component, multi-target acting mechanisms of TCM.
Brain Ischemia/metabolism* ; Neuroprotective Agents/pharmacology* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Benzofurans/pharmacology* ; Mice ; Drug Synergism ; Caffeic Acids/pharmacology* ; Polyphenols/pharmacology* ; Humans ; Alkenes/pharmacology* ; Endothelial Cells/drug effects* ; Depsides

OBJECTIVE: To investigate the clinical efficacy and safety of venetoclax (VEN) in combination with hypomethylating agent (HMA) in the treatment of patients with high-risk myelodysplastic syndromes (MDS). METHODS: A total of 30 patients with high-risk MDS who received the combination of VEN and HMA from March 2019 to November 2022 were included. The overall response rate (ORR), modified overall response rate (mORR), overall survival (OS), progression-free survival (PFS), and adverse events of all included patients were evaluated. RESULTS: Among the 30 high-risk MDS patients treated with VEN combined with HMA regimen, 24 cases achieved complete response (CR)/ marrow complete response (mCR), 2 cases achieved partial response (PR), the ORR was 24/30, the median OS was 28.1 months, and the median PFS was 28.1 months. In addition, patients who achieved complete remission / marrow complete remission after treatment had a significantly longer OS than those who did not. Moreover, 12 patients were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). There were grade 3 or higher hematologic adverse events including thrombocytopenia (14 cases), neutropenia (14 cases), febrile neutropenia (10 cases) and anemia (7 cases) as well as gastrointestinal adverse events of any grade, such as vomiting (7 cases), diarrhea (5 cases), and constipation (4 cases). CONCLUSION VEN in combination with HMA is an effective and safe treatment option in patients with high-risk MDS. This regimen combined with allo-HSCT can improve the prognosis of these patients. Continuous attention to the monitoring and management of adverse events is essential for the patients' safety in this combination therapy.
Humans ; Myelodysplastic Syndromes/drug therapy* ; Sulfonamides/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Female ; Male ; Treatment Outcome ; Middle Aged ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Adult

OBJECTIVE: To analyze the effect of altitude on NIH-CPSI score in patients with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) Methods: Clinical data and the results of NIH-CPSI Questionnaire of the 321 patients with CP/CPPS at different altitudes were collected from March 2021 to March 2022. And the influence of altitudes on NIH-CPSI score of CP/CPPS was analyzed. RESULT: The NIH-CPSI score of patients living at an altitude of 4 300 m was significantly higher than that of patients living at an altitude of 1 500 m and 2 200 m. The CP/CPPS patients who lived in the higher altitude had more severe symptoms of pain and urination as well as lower scores of life quality (P<0.05). CONCLUSION NIH-CPSI score increased significantly with higher altitude, indicating more severe symptoms and decreased quality of life in CP/CPPS patients. These findings highlight the need for management strategies for specific heights in patients with CP/CPPS.
Humans ; Male ; Prostatitis ; Altitude ; Quality of Life ; Surveys and Questionnaires ; Pelvic Pain ; Adult ; Chronic Disease ; Middle Aged

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Nitrogen narcosis is a neurological syndrome that manifests when humans or animals encounter hyperbaric nitrogen, resulting in a range of motor, emotional, and cognitive abnormalities. The anterior cingulate cortex (ACC) is known for its significant involvement in regulating motivation, cognition, and action. However, its specific contribution to nitrogen narcosis-induced hyperlocomotion and the underlying mechanisms remain poorly understood. Here we report that exposure to hyperbaric nitrogen notably increased the locomotor activity of mice in a pressure-dependent manner. Concurrently, this exposure induced heightened activation among neurons in both the ACC and dorsal medial striatum (DMS). Notably, chemogenetic inhibition of ACC neurons effectively suppressed hyperlocomotion. Conversely, chemogenetic excitation lowered the hyperbaric pressure threshold required to induce hyperlocomotion. Moreover, both chemogenetic inhibition and genetic ablation of activity-dependent neurons within the ACC reduced the hyperlocomotion. Further investigation revealed that ACC neurons project to the DMS, and chemogenetic inhibition of ACC-DMS projections resulted in a reduction in hyperlocomotion. Finally, nitrogen narcosis led to an increase in local field potentials in the theta frequency band and a decrease in the alpha frequency band in both the ACC and DMS. These results collectively suggest that excitatory neurons within the ACC, along with their projections to the DMS, play a pivotal role in regulating the hyperlocomotion induced by exposure to hyperbaric nitrogen.
Animals ; Gyrus Cinguli/drug effects* ; Male ; Mice, Inbred C57BL ; Locomotion/drug effects* ; Neurons/drug effects* ; Mice ; Nitrogen/toxicity* ; Inert Gas Narcosis/physiopathology* ; Corpus Striatum/physiopathology*

Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

AIM To establish a GC-MS method for the simultaneous content determination of sixteen pesticide residues in Lycii Fructus and perform safety assessment.METHODS The analysis was performed on DB-5MS chromatographic column(30 m×0.25 mm,0.25 μm)subjected to the programmed heating,with splitless injection of 1.0 μL dissolved sample at a flowing rate of 1.0 mL/min.Other parameters were as follows:injection port temperature of 250℃,electron impact ionization(EI),electron energy of 70 eV;ion source temperature of 230℃,multi-reaction monitoring mode,and collision gas.of high-purity N2.Pesticide residues with relatively high dietary risk were analyzed and discussed with regard to residue levels,dietary intake risk,risk ranking and cumulative exposure assessment.RESULTS Sixteen pesticides showed good linear relationships within their own ranges(r≥0.994 4),whose average recoveries were 70%-114%,with the RSDs of less than 2%.The highest average cyfluthrin residue of 0.999 2 mg/kg in Lycii Fructus of production regions and the highest average cypermethrin residue of 0.088 4 mg/kg in Lycii Fructus commodities were both detected.In Lycii Fructus of production regions with chronic hazard index(HI)value of 0.012 9 and acute HI value of 0.065 5 and their commodities with chronic HI of 0.001 2 and acute HI of 0.005 4,the pesticide residue of cypermethrin was the leading cause of chronic and acute dietary risk,and additionally,pyridaben within maximum residue limit(MRL)was the only detectectable highly toxic pesticide among the other most concerning pestcides of deltamethrin,pyridaben,chlorpyrifos,dichlorvos and methidathion.CONCLUSION There exist pesticide residues within MRL values in some samples of Lycii Fructus and the use of cypermethrin should be well-controlled.

Objective To investigate the clinical efficacy of Bushen Yijing Decoction for the treatment of xerophthalmia of kidney yang deficiency type and to observe its effect on serum Th1/Th17 cytokines.Methods From January 2021 to January 2023,a total of 96 patients with xerophthalmia of kidney yang deficiency type were selected as the study objects.According to the treatment methods,the patients were divided into observation group and control group,with 48 cases in each group.The control group was treated with Sodium Hyaluronate Eye Drops externally,and the observation group was given oral use of Bushen Yijing Decoction together with Sodium Hyaluronate Eye Drops externally.The course of treatment for the two groups covered 21 days.The changes of tear film break-up time(BUT),corneal fluorescein staining(FL)score,SchirmerⅠtest(SIT)value,serum Th1/Th17 cytokines,Ocular Surface Disease Index(OSDI)questionnaire scores,and 25-Item National Eye Institute Visual Function Questionnaire(NEI-VFQ-25)score in the two groups were observed before and after treatment.Moreover,the clinical efficacy and incidence of adverse reactions were compared between the two groups.Results(1)After 21 days of treatment,the total effective rate of the observation group was 95.83%(46/48),and that of the control group was 70.83%(34/48).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the ocular surface function indicators of BUT and SIT values in the two groups were higher and the FL values were lower than those before treatment(P＜0.05).The increase of BUT and SIT values and the decrease of FL values in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the levels of serum cytokines of interleukin 17(IL-17),tumor necrosis factor alpha(TNF-α)and interferon gamma(IFN-γ)in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-17,TNF-α and IFN-γ levels in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the questionnaire scores of OSDI in the two groups were lower and the NEI-VFQ-25 scores were higher than those before treatment(P＜0.05).The decrease of OSDI scores and the increase of NEI-VFQ-25 scores in the observation group were significantly superior to those in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.17%(2/48),and that in the control group was 8.33%(4/48).There was no significant difference between the two groups(P＞0.05).Conclusion Bushen Yijing Decoction can enhance the clinical efficacy of xerophthalmia of kidney yang deficiency type,and the decoction is effective on alleviating the eye discomforts,improving the ocular surface function of patients,regulating the levels of Th1/Th17 cytokines,and relieving the inflammatory response without inducing severe adverse reactions while with high safety.