AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.

Humans ; Benzodiazepines ; Hypnotics and Sedatives/therapeutic use* ; Intensive Care Units ; Midazolam

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life support technique for patients with severe respiratory failure. In the past, single lumen cannula was mostly used to constract the vascular pathway of extracorporeal membrane oxygenation. Compared with single-lumen cannula, double lumen cannula (DLC) can reduce recirculation fraction, reduce complications such as infection and bleeding, and facilitate patient's rehabilitation. DLC requires accurate positioning of the catheter. It has been gradually applied in China. This paper will review the key points related to the use of DLC, such as the insertion, position, and complications, etc. to provide guidance for clinical application practice.

Veno-veous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in the treatment for severe acute respiratory distress syndrome (ARDS). Up to now, the routine access to establish VV-ECMO involves two-sites single lumen cannula via femoral vein and internal jugular venous in adult and children, while few studies about the dual lumen cannula (DLC) in VV-ECMO implemented in adult and children have been reported. On December 16, 2021, an unconscious child with severe ARDS due to multiple trauma caused by fatal falling from a height was admitted to Taihe Hospital. The initial diagnosis was hemorrhagic shock, bilateral hemopneumothorax, sternal fracture, cavity organ perforation, splenic rupture, and pelvic fracture and severe ARDS. Despite mechanical ventilation, he progressed to refractory hypoxemia and was treated with VV-ECMO after successful DLC placement in the right internal jugular vein by the mobile ECMO team of intensive care unit of the Union Hospital eventually. In addition, he received endoscopic sputum aspiration, prone position ventilation, anti-infection and nutritional treatment. His oxygenation gradually improved and he was successfully weaned from ECMO after 11 days. In this case, DLC simplified the process without any related complications, suggesting that it can be safely and effectively used in the treatment of Child's severe ARDS.

Objective:To investigate the risk factors of venous thrombosis associated with peripherally inserted central catheter (PICC) in lymphoma patients undergoing chemotherapy.Methods:Using the convenient sampling method, a total of 135 patients with lymphoma undergoing chemotherapy who were admitted to Department of Oncology in Xinxiang Central Hospital from September 2019 to September 2020 were selected as the research objects. According to the occurrence of PICC-related venous thrombosis, they were divided into the thrombosis group ( n=23) and the non-thrombotic group ( n=112) . The general data, PICC catheter vein, catheter tip position, PICC catheter limb and other data were collected. Binomial Logistic regression analysis was used to analyze the risk factors of PICC-related venous thrombosis. Results:The incidence of PICC-related venous thrombosis in lymphoma patients undergoing chemotherapy was 17.04% (23/135) . Binomial logistic regression analysis showed that the catheterized vein was the cephalic vein, the catheter tip was located within the upper 2/3 of the superior vena cava, and the ratio of catheter diameter divided by vein diameter greater than or equal to 67% were independent risk factors of PICC-related venous thrombosis in lymphoma chemotherapy patients ( P<0.01) . Conclusions:The risk factors of PICC-related venous thrombosis in lymphoma chemotherapy patients mainly include the cephalic vein, the catheter tip within the upper 2/3 of the superior vena cava and the ratio of catheter diameter to vein diameter greater than or equal to 67%.Nursing staff should focus on high-risk population and actively take interventions to reduce the incidence of PICC-related venous thrombosis.

Objective To explore the metabolism and chronic complication features of type 2 diabetes mellitus patients with hyperferritemia. Methods:A total of 268 type 2 diabetic patients with a disease course of more than 5 years, who were hospitalized in our hospital between January to December 2019 were included in this retrospective study. Serum ferritin was measured by Chemiluminescence in each participant. Patients with other diseases, which might affect serum ferritin level, were excluded. According to the results of serum ferritin, the patients were divided into hyperferritemia group ( n=115) and normal ferritin group ( n=153). The metabolic indexes, including C-reactive protein, blood glucose, blood lipid, liver and kidney function, were measured. Chronic complications and comorbidities, including diabetic retinopathy, urinary microalbumin excretion, hypertension, coronary heart disease and cerebrovascular disease were evaluated. The correlation between hyperferritemia and various variables was analyzed. Results:Body mass index, the levels of serum urea nitrogen, uric acid, C-reactive protein, alanine aminotransferase and γ-glutamyltranspeptidase, as well as prevalence of diabetic retinopathy, microalbuminuria, hypertension and coronary heart disease, were significantly higher in hyperferritemia group than in normal ferritin group (all P<0.05). Hyperferrinemia was positively correlated with C-reactive protein ( r=0.262, P<0.001), coronary heart disease ( r=0.232, P<0.001), alanine transpeptidase ( r=0.216, P<0.001), urea nitrogen ( r=0.201, P=0.001), diabetic retinopathy ( r=0.169, P=0.008) and microalbuminuria ( r=0.176, P=0.004). Multivariate logistic regression analysis showed that hyperferrinemia was an independent risk factor of coronary heart disease and diabetic retinopathy ( OR=2.246, 95% CI 1.310-3.849, P=0.003; OR=2.232, 95% CI 1.287-3.870, P=0.004, respectively) in this patient cohort. Stepwise linear regression showed that there was a significant correlation between hyperferrinemia and microalbuminuria (β=0.165, P=0.009). Conclusions:Our results show that the level of serum C-reactive protein, alanine aminotransferase, γ-glutamyltranspeptidase, urea nitrogen, uric acid and microalbuminuria are significantly increased and the risk of coronary heart disease and diabetic retinopathy are higher in type 2 diabetic patients with hyperferritemia.

Objective:To investigate the pathogenesis, precaution and treatment of neonatal congenital complete heart block (CCHB) in twins.Methods:The clinical data of a case of premature twins with neonatal CCHB from the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed and related literature was reviewed.Results:(1)Case review: the 37-year-old gravida had no symptoms.Fetal ultrasound cardiogram(fUCG)at 23 weeks of gestation indicated bradycardia and CCHB.Then, the mother was diagnosed with undifferentiated connective tissue disease.After treatment with human immunoglobulin, dexamethasone and hydroxychloroquine, fUCG at 31 weeks of gestation still suggested CCHB.An emergency cesarean section was performed on the diagnosis of threatened preterm labor.With weakly positive neonatal antinuclear antibody (ANA), and positive Ro60 and Ro52 autoantibodies, twins were diagnosed with CCHB by 24 hour-Holter monitors.One of the twins was discharged with CCHB (ventricular rate of 80-90 times/min) after systemic therapy, but the weight increased to 2 200 g. The other one of the twins suffered from the sudden decrease of heart rate and blood pressure and finally died of sudden cardiac arrest.(2) Literature search: two cases in Chinese and 9 cases in English were reviewed.Among them, 9 cases were sjogren syndrome type A (SSA)/Ro and sjogren syndrome type B(SSB)/La related CCHB, and 2 cases were idiopathic CCHB.Conclusions:The placental transfer of anti-SSA or anti-SSB is an important mechanism of neonatal CCHB in twins, and other factors may also be involved.Current treatments are unsatisfactory.Most patients need pacemaker implantation.Early diagnosis and prenatal management can improve the prognosis.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Exosomes, as a kind of extracellular vesicles generated by inward budding of the endosomes to form multi-vesicular bodies (MVBs), are secreted into the extracellular milieu and the systemic circulation thereafter. By endocytosis, direct fusion or receptor-ligand interactions, exosomes can interact with receptor cells and involve in various pathophysiological processes. Accumulating evidence have indicated that exosomes may play crucial roles in the pathogenesis of many neurodegenerative diseases including Parkinson's disease (PD), Huntington's disease (HD), Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS). In this paper, the roles of exosomes in the pathogenesis, diagnosis and treatment of PD and ALS are reviewed.