To analyze the disease burden of hypertension in the elderly population from 1990 to 2021 and to predict future trends in China and globally, thereby providing insights for public health decision-making regarding older adults with hypertension in China.

Hepatolenticular degeneration， also known as Wilson disease （WD）， is a hereditary disease caused by mutations in the ATP7B gene， leading to copper metabolism disorders. Gene mutations result in impaired synthesis of copper-binding protein， and abnormal excretion of copper through bile leads to pathological deposition of copper in various organs， ultimately causing multi-organ damage. The insidious onset and low specificity of symptoms make it difficult to diagnose this disease. On the basis of existing studies and the theory of latent toxin， this paper proposes that latent toxin in kidney collaterals is the main pathogenesis of renal injury in WD. It is pointed out that health Qi deficiency and latent pathogen are the premises for the occurrence of this disease， and the transformation of latent pathogen into toxin is the ley pathological process. Toxin damaging kidney collaterals is the ultimate result. According to the pathogenesis， this paper proposes the treatment principle of reinforcing healthy Qi and resolving toxin and treatment based on syndrome differentiation. This review provides new ideas for the diagnosis and treatment of renal injury in WD with traditional Chinese medicine.

As the third-level diagnosis of migraine， recurrent gastrointestinal disturbance is a group of disorders with recurrent episodic attacks of abdominal pain and/or discomfort and nausea and/or vomiting that may be associated with migraine， and it is a clinical syndrome with the core symptom of abdominal pain， with the presence of clinical and neurobiological associations. This article reviews the similarities of the two diseases from the aspects of epidemiological characteristics， gender distribution tendency， clinical course， auxiliary examination， and treatment response， as well as three potential mechanisms in pathophysiology. This strong association between functional recurrent abdominal pain and migraine suggests that although there is no definitive evidence， adult functional recurrent abdominal pain， or at least its specific subsets， may belong to the spectrum of migraine. In other words， functional recurrent abdominal pain itself without headache may be a “migraine phenomenon”. In the future， it is necessary to conduct more rigorously designed observational studies on the association between the two diseases to clarify such possibility， in order to provide strong supporting evidence for the diagnosis and treatment of patients with functional recurrent abdominal pain and migraine and relieve pain as soon as possible.

OBJECTIVE: To analyze the correlation between the expression levels of Tim-3, C-myc and the proportion of T lymphocyte subsets and prognosis in patients with acute lymphoblastic leukemia (ALL). METHODS: The research group selected 60 ALL patients admitted to our hospital from December 2019 to December 2021, while the control group selected 55 healthy volunteers who underwent physical examination in our hospital. The expression levels of Tim-3, C-myc mRNA and the proportion of T lymphocyte subsets in the two groups were detected. The mortality rate of ALL patients was calculated, and the correlation between the expression levels of Tim-3, C-myc, and the proportion of T lymphocyte subsets and pathological features and prognosis was analyzed. RESULTS: Compared with the control group, the levels of Tim-3, C-myc and CD8⁺ in the research group were increased, while the levels of CD3⁺ , CD4⁺ and CD4⁺ /CD8⁺ were decreased (all P < 0.001). The levels of Tim-3, C-myc mRNA, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were correlated with risk classification and extramedullary infiltration (all P < 0.05). The survival rate of patients with low expression of Tim-3, C-myc, and CD8⁺ was higher than that of patients with high expression, while the survival rate of patients with high expression of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ was higher than that of patients with low expression (all P < 0.05). Univariate analysis showed that the deceased patients had higher proportions of extramedullary infiltration and high-risk classification, as well as higher levels of Tim-3, C-myc, and CD8⁺ , while lower levels of CD3⁺ , CD4⁺ , and CD4⁺ /CD8⁺ compared with surviving patients (all P < 0.01). Multivariate logistic regression analysis showed that extramedullary invasion, risk classification, Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , CD4⁺ /CD8⁺ were the main factors affecting the prognosis of ALL patients (all P < 0.05). ROC curve analysis showed that the combination of Tim-3, C-myc, and T lymphocyte subsets had higher sensitivity and accuracy in predicting prognosis of ALL patients compared with the single diagnosis of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ , and CD4⁺ /CD8⁺ (P < 0.05). CONCLUSION ALL patients show higher levels of Tim-3, C-myc mRNA and CD8⁺ but lower levels of CD3⁺ , CD4⁺ and CD4⁺/CD8⁺. Moreover, the expression levels of Tim-3, C-myc, CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺/CD8⁺ are correlated with extramedullary invasion, high-risk classification and prognosis.
Humans ; Hepatitis A Virus Cellular Receptor 2/metabolism* ; Prognosis ; Proto-Oncogene Proteins c-myc/metabolism* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; T-Lymphocyte Subsets ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; RNA, Messenger

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

ObjectiveTo investigate the impact of metabolic associated fatty liver disease （MAFLD） on metabolic markers in patients with HIV infection， and to assess the risk of new-onset MAFLD in previously untreated HIV patients. MethodsA total of 161 HIV patients who attended the outpatient service of Zhongnan Hospital of Wuhan University from April 2020 to December 2021 were enrolled， and they were treated with the lamivudine/efavirenz/tenofovir disoproxil fumarate （3TC/EFV/TDF） regimen and were followed up for more than 36 months. According to the presence or absence of MAFLD， they were divided into MAFLD group with 42 patients and non-MAFLD group with 119 patients， and metabolic markers were compared between the two groups before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group before and after treatment； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Wilcoxon signed-rank test was used for comparison within each group before and after treatment； the chi-square test was used for comparison of categorical data between groups. Hepatic steatosis index （HIS） and Zhejiang University （ZJU） index were used to assess the risk of new-onset MAFLD after antiretroviral therapy. ResultsAfter 36 months of 3TC/EFV/TDF treatment， the MAFLD group had significant increases in body mass index （BMI） ［24.8 （23.2 — 25.9） kg/m² vs 25.3 （22.8 — 27.7） kg/m²， Z=-2.540， P=0.011］， total cholesterol （TC） （4.0±0.6 mmol/L vs 4.3±0.6 mmol/L， t=-2.388， P=0.022）， and high-density lipoprotein cholesterol （HDL-C） ［0.9 （0.8 — 1.1） mmol/L vs 1.1 （0.9 — 1.2） mmol/L， Z=-2.858， P=0.004］ and a significant reduction in serum uric acid （462.1±101.6 μmol/L vs 383.3±85.2 μmol/L， t=4.361， P<0.001）. There was a significant difference in BMI between the MAFLD group and the non-MAFLD group after 3TC/EFV/TDF treatment ［25.3 （22.8 — 27.7） kg/m² vs 21.6 （19.9 — 23.4） kg/m²， Z=-5.462， P<0.001］， while there were no significant differences between the two groups in serum uric acid， TC， triglyceride， HDL-C， low-density lipoprotein cholesterol， lipoprotein a， and CD4⁺ T cell count （all P >0.05）. Furthermore， for the patients in the non-MAFLD group after treatment， there was a significant increase in the proportion of patients at a high risk of MAFLD based on HSI and ZJU indices （χ²=10.829 and 5.658， P=0.001 and 0.017）. ConclusionAfter 36 months of 3TC/EFV/TDF treatment， there are increases in blood lipid levels in HIV patients with MAFLD， and there is an increase in the risk of new-onset MAFLD in HIV patients without MAFLD.

Objective To clarify the anti-inflammatory effect of chlorogenic acid on lipopolysaccharide(LPS)-induced inflamma-tion in macrophage RAW264.7,and to reveal its possible molecular mechanism.Methods The cellular activity of RAW264.7 after the intervention of different concentrations of chlorogenic acid was detected by CCK-8 method;the macrophage RAW264.7 was stimulated by LPS to preset cellular inflammatory state.The blank control group(K group,n=3),the model control group(L group,n=3),and the experimental group(S group,n=3)were administered separately,and the cell morphology was dynamically observed;cell precipita-tion and supernatants were obtained at 24 h and 48h,respectively.The concentrations of inflammatory cytokine interleukin(IL)-1β,monocyte chemoattractant protein-1(MCP-1),and arginase-1(Arg-1)in the cell supernatants were detected by enzyme-linked immunosorbent assay(ELISA);the mRNA expression of prostaglandin endoperoxide synthase 2(PTGS2),transforming growth factor-β1(TGF-β1),high mobility histone 1(HMGB1),and nuclear transcription factor-κB(NF-κB)were detected by quantitative real-time PCR(RT-qPCR).Results RAW264.7 cellular inflammatory state was successfully preset with 1 μg/ml LPS;12.5～200.0μg/ml chlorogenic acid had no distinct toxicity on RAW264.7.Chlorogenic acid at 50μg/ml and 200μg/ml had obvious proliferation effects on RAW264.7 cells(P＜0.05).Compared with the model control group,the content of IL-1 β protein in the supernatant of the experimental group was significantly decreased,while the content of Arg-1 was significantly increased(P＜0.05).Compared with the model control group,50μg/ml of chlorogenic acid significantly decreased the mRNA expressions of NF-κB,TGF-β1,PTGS2,and HMGB1 in LPS-induced inflammatory cells(P＜0.05).Conclusion Chlorogenic acid has a distinct inhibitory effect on LPS-induced RAW264.7 inflammatory response,which may be achieved by regulating molecular expression of the HMGB1-mediated NF-κB pathway.

Objective To explore the association of the magnitude of systolic blood pressure reduction(SBPr)with post-procedure 24 h symptomatic intracranial hemorrhage(sICH)and 90-day clinical outcomes in patients with successful endovascular thrombectomy(EVT).Methods Consecutively registered patients with EVT caused by anterior circulation large vessel occlusion stroke(LVOS)in the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital)between July 2015 and April 2023 and patients with successful reperfusion were analyzed.Demographic data,medical history(hypertension,diabetes),the trial of Org 10172 in acute stroke treatment(TOAST)classification,the baseline National Institutes of Health Stroke Scale(NIHSS)score and the baseline Alberta stroke early CT(ASPECT)score of patients were collected.And procedure related parameters(including time from onset to puncture,time from onset to reperfusion,occluded site[internal carotid artery,M1 segment of middle cerebral artery,M2 segment of middle cerebral artery],collateral circulation status[determined based on preoperative occluded angiography showing the range of collateral circulation in the occluded vessel area,defined as good collateral circulation with a reflux range of ≥ 50％and poor collateral circulation with a reflux range of＜50％]),immediate postoperative reperfusion status(evaluated using the modified thrombolysis for cerebral infarction[mTICI]grading,successful reperfusion defined as mTICI grading of 2b-3),24 hours sICH,and 90 days clinical outcomes(evaluated using the modified Rankin scale score at 90days after EVT,with a score ≤ 2indicating a good prognosis and a score＞2indicating a poor prognosis).SBPr was defined as(baseline SBP-mean SBP)/baseline SBP x 100％.According to the the magnitude of SBPr,SBPr is divided into 5 categories(＜-10％,-10％-10％,＞10％-20％,＞20％-30％and＞30％).Based on the clinical outcomes at 90 days and the occurrence of sICH at 24 hours after EVT,patients were divided into a good prognosis group and a poor prognosis group,as well as an sICH group and a non-sICH group.The relationship between SBPr and postoperative 90 days clinical prognosis or sICH was analyzed using a binary Logistic regression model.Subgroup analysis was conducted based on a history of hypertension(yes and no),continuous intravenous hypotensive therapy(yes and no),baseline ASPECT scores(3-5 and 6-10),and collateral circulation status(good and bad).Using a restricted cubic plot to depict the relationship between SBPr and sICH and clinical prognosis at 90days.Results(1)In total,731 patients were included.The median age was 71(62,77)years and 424(58.0％)were men.The median baseline NIHSS score was 14(12,18),the median baseline ASPECT was 9(7,10),405(55.4％)patients achieved 90-day modified Rankin scale score 0-2,and 35 patients(4.8％)developed sICH.(2)Multivariate analysis showed that the older age(OR,1.036,95％CI 1.017-1.056),the higher baseline NIHSS score(OR,1.095,95％CI1.049-1.144),the lower baseline ASPECT score(OR,0.704,95％CI 0.636-0.780),diabetes(OR,1.729,95％CI 1.084-2.758),bad collateral circulation(good collateral circulation vs.bad collateral circulation,OR,0.481,95％CI 0.332-0.696)and SBPr＞30％(SBPr-10％-10％as a reference,OR,2.238,95％CI 1.230-4.071),the higher the risk of poor clinical outcomes at 90 days(all P＜0.05).Continuous intravenous hypotensive therapy is a risk factor for postoperative 24 h sICH(OR,2.278,95％CI 1.047-4.953;P=0.038),while SBPr 20％-30％is associated with a lower risk of postoperative 24 h sICH(SBPr-10％-10％as a reference,OR,0.362,95％CI0.131-0.998;P=0.049).(3)The restrictive cube plot shows that there is a U-shaped relationship between SBPr after EVT and poor clinical outcomes at 90 days,while there is a nearly linear relationship with the occurrence of sICH.The more SBP reduction,the lower the incidence of sICH.(4)In the subgroup analyses,in the non-hypertension history and the good collateral circulation group,SBPr＞30％has a higher risk of poor clinical outcomes compared to SBPr-10％-10％(OR and 95％CI were 2.921[1.000-8.528]and 2.363[1.078-5.183],respectively,with P=0.05 or P＜0.05);After EVT,the group receiving continuous intravenous hypotensive therapy and the baseline ASPECT score 6-10 groups showed a significant correlation between SBPr＞30％and poor clinical outcomes at 90 days(SBPr-10％-10％as a reference,OR and 95％CI were 2.646[1.168-5.993]and 2.481[1.360-4.527],respectively,with P＜0.05).The correlation between SBPr and lower incidence of sICH was only found in the subgroup of poor collateral circulation(SBPr-10％-10％as a reference,SBPr＞20％-30％:OR,0.133,95％CI 0.027-0.652;SBPr＞30％:OR,0.104,95％CI 0.013-0.864;all P＜0.05).Conclusions Among patients who achieved successful reperfusion with EVT,SBPr might be related to a worse functional outcome at 90 days and sICH 24 h after operation.However,the relationship may exhibit significant heterogeneity across different subgroups.Baseline ASPECT score,history of hypertension,collateral circulation,and the use of continuous venous hypertension after EVT have been highlighted in individualized blood pressure management after EVT.