Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
Male ; Humans ; Aged ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Sjogren's Syndrome/diagnosis* ; Anemia, Hemolytic/complications* ; Dry Eye Syndromes/complications* ; Autoantibodies

Aim To study whether ginsenoside Rg1 could improve white matter injury caused by chronic cerebral ischemia.Methods C57BL/6 mice were randomly divided into Sham group,Model group,Donepezil group,and ginsenoside Rg1(10,5 mg·kg-1)group.BCAS was established by using bilateral common carotid artery stenosis.Drug treatment was started one day after the operation,and the stomach was given continuously for 30 days.During this period,the body weight and CBF changes were observed,and observed by climbing rods,new object recognition and Y maze experiments.The movement coordination and cognitive abilities of each group of animals were improved.The improvement of the myelin sheath of the corpus callosum was detected by LFB staining,the damage of corpus callosum neurons was observed by Nissl staining,and the expression level of MBP in the corpus callosum was detected by immunofluorescence and Western blot.Results The test results of body weight and CBF showed that compared with model group,ginsenoside Rg1 group did not significantly improve the animal's body weight and CBF values; the results of climbing rod,new object recognition,and Y maze experiment showed that ginsenoside Rg1 group significantly shortened the time it took animals to climb rods,and improved the animal's new object recognition index and the number of autonomous alternations; LFB and Nissl staining results showed that ginsenoside Rg1 group significantly improved the myelin and neuron damage of the animal corpus callosum.The results of immunofluorescence and Western blot showed that ginsenoside Rg1 group significantly increased the expression level of animal myelin basic protein MBP.Conclusion Ginsenoside Rg1 can significantly improve white matter injury caused by chronic cerebral ischemia.

Objective In recent years, many studies have reported that air pollution is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this systematic review and meta-analysis is to summarize the evidence about the association between exposure to air pollution and T2DM in developing countries. Methods The databases, including PubMed, EMBASE and Web of Science, were systematically searched for studies published up to 31 March 2022. Studies about the association between air pollution and T2DM prevalence or incidence in developing countries were included. The odds ratio (OR) was used as effect estimate. We synthesized the included studies in the meta-analysis. Results We included 8 cross-sectional studies and 8 cohort studies, all conducted in developing countries. Meta-analysis of 8 studies on PM_2.5 (particulate matter ≤ 2.5 μm in diameter) showed that T2DM prevalence was significantly associated with PM_2.5 exposure (OR=1.12; 95% CI: 1.07, 1.17; P<0.001). The association between air pollutants and T2DM incidence was not estimated due to the limited relevant studies. Conclusions The exposure to PM_2.5 would be positively associated with an increased prevalence of T2DM in developing countries. Some effective measures should be taken to reduce air pollutant exposure in people who are vulnerable to diabetes.
Humans ; Diabetes Mellitus, Type 2 ; Cross-Sectional Studies ; Developing Countries ; Environmental Exposure/analysis* ; Air Pollution/analysis* ; Particulate Matter ; Air Pollutants/analysis*

Objective: To understand the prevalence of HIV, hepatitis C virus (HCV) and syphilis and related factors among cross-border couples in Mangshi county, Dehong autonomous prefecture, Yunnan province. Methods: From May, 2017 to April, 2019, 2 500 couples with 5 000 cross-border marriages were selected by using cluster sampling method. The demographic characteristics, AIDS-related health services, HIV, HCV, syphilis infection and other information were collected through questionnaires and laboratory tests. The influencing factors of HIV, HCV and syphilis infection were analyzed by multivariate logistic regression model. Results: A total of 2 500 couples with cross-border marriage were investigated, among which 2 438 (97.5%) couples were Chinese men with Myanmar women. The average age of 5 000 participants was (34.16±9.00) years. Most of them were minority groups (59.9%), farmers (98.5%), education years ≤6 years (81.4%), marriage years>3 years (80.0%), and from mountainous areas (61.7%). The HIV prevalence of Chinese and Myanmar populations was 1.7% (43/2 500) and 2.0% (49/2 500), respectively. The HCV infection rates were 2.0% (49/2 500) and 1.3% (32/2 500), respectively and the infection rates of syphilis were 0.4% (10/2 500) and 0.2% (4/2 500), respectively. There were no statistically significant differences in the prevalence of three diseases among Chinese and Myanmar populations (P>0.05). The multivariate analysis showed that compared with those aged ≤ 30 years, having lower AIDS awareness, never receiving HIV testing, without HCV and syphilis infection, HIV prevalence was higher among those aged>30 years (OR=3.21, 95%CI: 1.80-5.73), having higher AIDS awareness (OR=17.41, 95%CI: 4.27-70.91), receiving HIV testing (OR=4.93, 95%CI: 2.72-8.92), with HCV infection (OR=5.64, 95%CI: 2.72-11.70) and syphilis infection (OR=8.37, 95%CI: 1.63-43.08). Compared with those aged ≤ 30 years, having marriage years ≤ 3 years, and with HIV negatives, HCV infection rate was higher among those age>30 years (OR=3.02, 95%CI: 1.69-5.38), having marriage years>3 years (OR=2.24, 95%CI: 1.34-3.74), and with HIV positives (OR=6.69, 95%CI: 3.29-13.59). Compared with those having HIV negatives, the syphilis infection rate was relatively higher among participants with HIV positives (OR=9.07, 95%CI: 2.00-41.10). Conclusion: The prevalence of HIV, HCV, and syphilis among cross-border couples in Mangshi county, Dehong autonomous prefecture of Yunnan province is relatively high. Age, AIDS awareness, HIV testing history, and the length of marriage are associated with the HIV, HCV, and syphilis infection.
Acquired Immunodeficiency Syndrome ; China/epidemiology* ; Female ; HIV Infections/epidemiology* ; Hepacivirus ; Hepatitis C/epidemiology* ; Humans ; Male ; Prevalence ; Risk Factors ; Syphilis/epidemiology*

This study investigates the protective role of IMM-H004, a novel coumarin derivative, on hepatic ischemia-reperfusion injury (HIRI) in mice. All animal experiments in this paper have been approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The experimental animals were divided into three groups, including sham group, model group, and IMM-H004 treatment group. Serum biochemical indicators were detected and H&E staining was used to assess liver damage. Real-time quantitative PCR (qPCR) was performed to analysis the mRNA content of inflammatory factors. Immunohistochemistry and immunofluorescence were used to observe neutrophil infiltration. Western blot was used to examine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and interleukin-1β (IL-1β). The results showed that IMM-H004 could significantly reduce the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH). H&E results showed IMM-H004 could alleviate liver damage caused by HIRI. The mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-6 (IL-6) were decreased by IMM-H004 administration. Meanwhile, IMM-H004 could markedly inhibit neutrophil infiltration. Furthermore, IMM-H004 could significantly down-regulate the protein expression of NLRP3, ASC, caspase-1, and IL-1β, inhibiting the activation of NLRP3 inflammasome pathway. Our results confirmed that IMM-H004 could protect mice from HIRI and provide a theoretical foundation for IMM-H004 application for treating HIRI.

Objective: Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model . Methods: A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.
Animals ; Anti-Bacterial Agents ; pharmacology ; Disease Models, Animal ; Moxifloxacin ; pharmacology ; Mycobacterium Infections, Nontuberculous ; drug therapy ; Mycobacterium abscessus ; drug effects ; Zebrafish

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.
Bone Marrow ; Erythrocyte Indices ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.
Humans ; Primary Myelofibrosis ; Prognosis ; Retrospective Studies ; Thrombocytopenia

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.
Danazol ; Drug Combinations ; Humans ; Nitriles ; Pilot Projects ; Prednisone ; Primary Myelofibrosis/drug therapy* ; Pyrazoles/therapeutic use* ; Pyrimidines ; Thalidomide/therapeutic use* ; Treatment Outcome