Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Objective To explore the effect of individualized positive end expiratory pressure guided by driving pressure on lung protection after laparoscopic radical gastrectomy for elderly patients.Methods A total of 64 patients underwent elective laparoscopic radical gastrectomy for gastric cancer in the Second Affiliated Hospital of Anhui Medical University were selected.According to the random number table method,patients were divided into the driving the pressure guided individualized positive end-expiratory pressure(PEEP)group(experimental group)and the fixed PEEP group(control group),32 cases in each group.In the control group,PEEP = 5 cmH2O.In the experimental group,PEEP titration was performed according to the increasing method,and the PEEP corresponding to the lowest driving pressure was selected until extubation.Peak airway pressure(Ppeak),plateau airway pressure(Pplat)and PEEP were recorded at 5 min after intubation(T1),immediately after PEEP titration(T2),1 h after operation(T3),2 h after operation(T4),and 10 min after pneumoperitoneum release(T5).Driving pressure(ΔP)and lung dynamic compliance(Cdyn)were calculated.Arterial blood was collected at T1-5 for blood gas analysis,arterial partial pressure of oxygen(PaO2)was recorded,and oxygenation index(OI)was calculated.The occurrence of pulmonary complications(PPCs)within 7 days after operation was recorded.Modified clinical pulmonary infection score(mCPIS)was recorded on the second day after operation.The pulmonary function was evaluated before operation,1 day,3 days and 5 days after operation.Results Compared with T1,Ppeak,Pplat and ΔP were increased and Cdyn was decreased at T2-5,while OI was decreased at T4 in control group(P＜0.05).Compared with the control group,Ppeak,Pplat and Cdyn in the experimental group were increased at T2-5,ΔP was decreased,and OI was increased at T3-5(P＜0.05).Compared with the preoperative results,FVC at 1,3 and 5 days after surgery was decreased,and FEV1 and maximum expiratory flow(PEF)were decreased 1 and 3 days after surgery in the experimental groups(P＜0.05).Compared with the control group,FVC,FEV1 and PEF were higher 1 day after operation in the experimental group(P＜0.05).Compared with the preoperative results,mCPIS scores of the two groups were higher on the second day after surgery(P＜0.05).Compared with the control group,the mCPIS score was lower on day 2 after surgery in the experimental group(P＜0.05).The incidence of PPCs within 7 days after surgery was lower in the experimental group than that in the control group(15.6%vs.40.6%).Conclusion Individualized PEEP guided by drive pressure can improve lung compliance,reduce drive pressure,improve oxygenation function and early postoperative lung function,reduce the incidence of postoperative lung complications,and has a certain lung protection effect.

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO₂/FiO₂), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO₂/FiO₂ at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.
Humans ; Prevalence ; Critical Care ; Risk Factors ; Sepsis ; Intensive Care Units

Objective:To explore the role of N 6-methyladenosine (m6A) and its regulator METTL3 in the non-coding RNA of endometrial cancer.Methods:The expression levels of m6A and METTL3 were quantified in 20 paired carcinoma and adjacent clinical tissue samples from patients at from Jul. 2016 to Dec. 2020. HEC-1-A cell lines were constructed with METTL3 overexpression and knockdown. Western blot was used to detect the phosphorylation levels of key molecules in METTL3 and Akt/mTOR. The quantitative detection of mRNA levels were used qRT-PCR. The binding level of m6A to its receptor DGCR8 was determined by RNA immunoprecipitation.Results:The results of the m6A RNA methylation quantification kit showed that m6A (1.0±0.15) vs (1.7±0.34) ( P<0.01) and METTL3 levels were elevated in endometrial cancer cells, and METTL3 (1.0±0.13) vs (2.5±0.45) ( P<0.05) levels were elevated in endometrial cancer cells. Western blot and qRT-PCR detection of miR-17-92 cell clusters overexpressing METTL3, METTL3 overexpression significantly increased m6A modification on pri-miR-17-92 ( P<0.05) . Phosphorylation levels of AKT/mTOR pathway-related proteins were upregulated. In addition, RIP test results indicated that the binding of DGCR8 to pri-miR-17-92 was significantly facilitated. Conclusion:METTL3 modification of m6A facilitates the processing of pri-miR-1792 into the miR-17-92 clusters via m6A/DGCR8-dependent mechanism, which in turn activated the AKT/mTOR pathway.

【Objective】 To analyze the viability of covering blood cost in medical insurance in China and discuss the necessity and practicability, so as to provide references for the improvement of medical insurance mechanism. 【Methods】 A questionnaire was designed and issued to blood centers covering 31 provinces /municipalities/autonomous regions in June 2019, and respective information regarding basic medical diagnosis and treatment directory, as well as normative documents on the official websites was collected and analyzed. 【Results】 13 out of 31 provinces /municipalities/autonomous regions had introduced the relevant policies of covering blood cost in medical insurance. Concerning the other 18 respondents, a total of 52 cities in 9 provinces had issued relevant policies. 5.01 billion RMB was included in medical insurance in 2017, accounting for 61.00% of the total clinical blood cost. 【Conclusion】 Less economic burden and less impact on voluntary blood donation recruitment could be realized by setting clinical blood price by the government.

The pathogenesis of diabetic retinopathy (DR) is complex.Antisense non-coding RNA (ANRIL) in the INK4 locus in long-chain non-coding RNA (lncRNA) is closely related to cell proliferation,differentiation,and individual development.It plays an important role in the dysplasia of retinal vascular endothelial cells and is a new field in the study of the pathogenesis of DR.According to the researches at present,ANRIL may plays its role in the occurrence and development of DR through the signal pathway of nuclear factor-κB and ROS/polyadenylation diphosphate ribose polymerase,and interact with p300,miR-200b,and EZH2 to regulating the expression and function of VEGF.Specific blocking ANRIL and its related pathwaysmay become a new target in the treatment of DR.

Objective To investigate and analyze the similarities of allergens in children of the same family with susceptibility to the same genetic background and environmental factors. Methods From January 2013 to December 2017,a total of 142 pairs of children with allergic diseases aged 0-15 years and their siblings ( 284 cases) were collected from the outpatient or hospitalized treatment of Pediatrics and otolaryngology department of the First People′s Hospital of Foshan City,the Third Affiliated Hospital of Sun Yat-sen University. The elder group was brother or sister (142 cases),and the younger group was brother or sister ( 142 cases ) . The serum allergen sIgE was tested by Allergy Screen allergen detection system (developed by Germany MEDIWISS Company) and the similarity of allergens was analyzed. Results A total of 142 siblings ( 284 cases ) had systemic symptoms of allergic diseases in varying degrees, including respiratory symptoms ( cough ( 47 cases in the old group,32 cases in the young group), χ2 ＝3. 946, P＝0. 047),nasal obstruction ( 41 cases in the old group,19 cases in the young group, χ2 ＝ 10. 227, P ＝0. 001),runny nose (46 cases in the old group,26 cases in the young group,χ2＝7. 442,P＝0. 006), gastrointestinal symptoms (abdominal pain (11cases in the old group,7 cases in the young group,χ2＝4. 63, P＝0. 031),skin symptoms(urticaria (18 cases in the old group,8 cases in the young group,χ2＝4. 234,P＝0. 037)) and so on,the difference was statistically significant. Some children have multiple organ system symptoms at the same time. There was no significant difference between the old group and the young group in the early use of antibiotics,mode of production and feeding mode within 6 months (all P＞0. 05). Among the two groups,house dust mite and cockroach (r＝0. 831,P＜0. 05),dog hair and house dust ( r＝0. 717,P＜0. 05),cypress,elm,willow,birch,oak,maple,walnut,sycamore,poplar and Dianqing,branching,yanqu, and heiqu ( r ＝ 0. 683, P＜ 0. 05 ) . Conclusion With the same genetic background and the same environmental factors,the allergens in siblings are similar.

In order to figure out phylogenetic relationship and genetic diversity of different geographical populations,genetic analyses of Aedes albopictus were performed based on mitochondrial gene COI.Based on samples collected from most distribution regions in China,mitochondrial gene Cytochrome C Oxidase Subunit I was obtained through PCR and DNA sequence.Together with some COI sequences downloaded from GenBank,60 COI sequences with the final length of 598 bp were used for subsequent analyses.Results showed that there was no obvious divergence according to phylogenetic analyse,all sequences were clustered together in Maximum Likelihood tree.Sixteen haplotypes were detected,and four of them shared haplotypes.Haplotype diversity (Hd) was 0.737,nucleotide diversity (π) was 0.20 ％.Population genetic differentiation analyses demon strated that Hainan population showed obvious divergences.In the network of haplotypes,H1 and H6 was found to be the primary haplotypes,and they formed two radical centers.All these results indicate that A.albopictus populations of China are expanding presently,and Hainan population become differential with other geographical populations,which probably attribute to geographical isolations.

The study of protein-surface interactions represents one of the most important topics in the field of biomaterials.It is believed that blood cells do not actually contact the biomaterial surface directly,but rather interact with the molecular structure of the adsorbed protein layer.Therefore,protein plays a key role in regulation and induction of cells.It provides ideas for biomaterials designing that exploring the molecular mechanism of controlling protein adsorption and regulating cell response.This paper reviews the research progress of the interactions of protein and surfaces,and prospects the future research direction.