Effect of L-carnitine combined with citicoline on the therapeutic effect of neonatal hypoxic-ischemic encephalopathy and serum NO and ET-1 / 国际检验医学杂志

Objective To explore the effects of L-carnitine combined with citicoline on the therapeutic effect of neonatal hypoxic-ischemic encephalopathy(NHIE)and serum nitric oxide(NO)and endothelin-1(ET-1).Methods A total of 95 children with HIE admitted to the hospital from April 2020 to January 2023 were selected and were divided into observation group(47 cases)and control group(48 cases)by random number table method.The control group was given citicoline,and the observation group was given citicoline combined with L-carnitine.The therapeutic effect was evaluated on 14 days after treatment,and the recovery time of original reflex,muscle tone and consciousness was calculated.The levels of oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD)]and vascular endothelial function indexes(NO,ET-1)were detected before treatment and 14 days after treatment.Neonatal neurobehavioral score(NBNA)was used to evaluate the neurological function of the children,and the safety of the treatment regimen was ob-served.Pearson correlation analysis was used to analyze the correlation between NBNA and vascular endothe-lial function indexes.Results The total effective rate in the observation group was 91.49％,which was higher than 72.92％in the control group(P＜0.05).The original reflex recovery time,muscle tone recovery time and consciousness recovery time of NHIE children in the observation group were shorter than those in the control group(P＜0.05).There was no significant difference in NBNA scores between the two groups before treatment(t=1.225,P=0.224).After treatment,the NBNA score in the observation group was higher than that in the control group(t=6.223,P＜0.001).After treatment,MDA level decreased and SOD level in-creased in two groups(P＜0.05).After treatment,the level of MDA in the observation group was lower than that in the control group,while the level of SOD was higher than that in the control group(P＜0.05).After treatment,the levels of NO and ET-1 were decreased in both groups(P＜0.05).The levels of NO and ET-1 in the observation group were lower than those in the control group after treatment(P＜0.05).The adverse drug reaction rates in observation group and control group were 17.02％and 8.33％,respectively,and there was no significant difference between two groups(P＞0.05).Pearson correlation analysis showed that serum NO,ET-1 and NBNA score in NHIE children were negatively correlated(r=-0.546,-0.608,P＜0.05).Conclusion L-carnitine combined with citicoline could improve the therapeutic effect of NHIE,shorten the re-covery time of clinical manifestations,and improve nerve function,oxidative stress and vascular endothelial function without increasing drugs and adverse reactions.In addition,vascular endothelial function indexes are negatively correlated with NBNA score,which could be used as auxiliary reference indexes for judging NHIE.

Correlation analysis of serum miR-939 and miR-15b expression and microvascular injury in diabetic retinopathy patients / 国际检验医学杂志

Objective To analyze the correlation between serum miR-939 and miR-15b expression and mi-crovascular injury in patients with diabetic retinopathy(DR).Methods A total of 176 patients with type 2 di-abetes diagnosed and treated in the Baoding Second Hospital from January 2021 to October 2022 were selected as the study objects.The subjects were divided into 74 patients without DR(NDR group),62 patients with non-proliferative DR(NPDR group)and 40 patients with proliferative DR(PDR group)according to whether or not DR occurred and the degree of lesions.Real-time fluorescent quantitative PCR was used to detect the relative expression levels of miR-939 and miR-15b in serum of all groups,the level of vascular endothelial growth factor(VEGF)was detected by enzyme-linked immunosorbent assay,and the count percentage of en-dothelial cells(ECs),endothelial progenitor cells(EPCs)and circulating progenitor cells(CPCs)was detected by flow cytometry.Serum levels of miR-939,miR-15b,VEGF and ECs,EPCs and CPCs were compared in 3 groups.Pearson correlation was used to analyze the correlation between serum miR-939 and miR-15b and VEGF,ECs,EPCs and CPCs.Multivariate Logistic regression was used to analyze the factors affecting the oc-currence of DR in patients with type 2 diabetes.Results The relative expression levels of miR-939 and miR-15b in PDR group and NPDR group were lower than those in NDR group,while the serum VEGF levels were higher than those in NDR group,with statistical significance(P＜0.05).ECs in PDR group and NPDR group were higher than those in NDR group,while EPCs and CPCs were lower than those in NDR group,the differ-ence was statistically significant(P＜0.05).Serum miR-939 was negatively correlated with VEGF and ECs(r=-0.407,-0.613,P＜0.05),and positively correlated with EPCs and CPCs(r=0.481,0.486,P＜0.05).Serum miR-15b was negatively correlated with VEGF and ECs(r=-0.539,-0.625,P＜0.05),and positively correlated with EPCs and CPCs(r=0.451,0.483,P＜0.05).Multivariate Logistic regression anal-ysis showed that the duration of type 2 diabetes,hemoglobin A1c,2-hour postprandial blood glucose,VEGF,miR-939 and miR-15b were the influencing factors for the occurrence of DR in type 2 diabetes patients(P＜0.05).Conclusion The expression of miR-939 and miR-15b in serum of DR patients is closely related to VEGF,ECs,EPCs and CPCs,and the expression of miR-939 and miR-15b in serum of DR patients can provide a certain reference for early judgment and evaluation of the degree of microvascular injury.

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice / 神经科学通报·英文版

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

Discussion on the performance reform of administrative and logistics personnel in a large public hospital / 中华医院管理杂志

Because the work of administrative and logistics personnel in public hospitals is difficult to quantify and evaluate, its performance reform is difficult. A large public hospital in Wuhan has explored and established a distribution incentive mechanism that combines department performance appraisal, individual classification and grading, and secondary distribution within the department. Taking into account the completion of performance appraisal indicators of the national tertiary public hospital in the department, the results of the institutional " Excellent Management Team Ranking" , personal job grades, working years and other factors, a relatively mature and operable system has been formed, which could provide reference for the performance reform of other hospitals.

SARS-CoV-2 causes human BBB injury and neuroinflammation indirectly in a linked organ chip platform

COVID-19 is a multi-system disease affecting many organs outside of the lungs, and patients generally develop varying degrees of neurological symptoms. Whereas, the pathogenesis underlying these neurological manifestations remains elusive. Although in vitro models and animal models are widely used in studies of SARS-CoV-2 infection, human organ models that can reflect the pathological alterations in a multi-organ context are still lacking. In this study, we propose a new strategy to probe the effects of SARS-CoV-2 on human brains in a linked alveolus-BBB organ chip platform. The new multi-organ platform allows to recapitulate the essential features of human alveolar-capillary barrier and blood-brain barrier in a microfluidic condition by co-culturing the organ-specific cells. The results reveal direct SARS-CoV-2 exposure has no obvious effects on BBB chip alone. While, infusion of endothelial medium from infected alveolus chips can cause BBB dysfunction and neuroinflammation on the linked chip platform, including brain endothelium disruption, glial cell activation and inflammatory cytokines release. These new findings suggest that SARS-CoV-2 could induce neuropathological alterations, which might not result from direct viral infection through hematogenous route, but rather likely from systemic inflammation following lung infection. This work provides a new strategy to study the virus-host interaction and neuropathology at an organ-organ context, which is not easily obtained by other in vitro models. This will facilitate to understand the neurological pathogenesis in SARS-CoV-2 and accelerate the development of new therapeutics. SUMMARYO_LIA linked human alveolus-BBB chip platform is established to explore the influences of SARS-CoV-2 on human brains in an organ-organ context. C_LIO_LISARS-CoV-2 infection could induce BBB injury and neuroinflammation. C_LIO_LIThe neuropathological changes are caused by SARS-CoV-2 indirectly, which might be mediated by systemic inflammation following lung infection, but probably not by direct viral neuroinvasion. C_LI

Modeling SARS-CoV-2 infection in vitro with a human intestine-on-chip device

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has given rise to a global pandemic. The gastrointestinal symptoms of some COVID-19 patients are underestimated. There is an urgent need to develop physiologically relevant model that can accurately reflect human response to viral infection. Here, we report the creation of a biomimetic human intestine infection model on a chip system that allows to recapitulate the intestinal injury and immune response induced by SARS-CoV-2, for the first time. The microengineered intestine-on-chip device contains human intestinal epithelium (co-cultured human intestinal epithelial Caco-2 cells and mucin secreting HT-29 cells) lined in upper channel and vascular endothelium (human umbilical vein endothelial cells, HUVECs) in a parallel lower channel under fluidic flow condition, sandwiched by a porous PDMS membrane coated with extracellular matrix (ECM). At day 3 post-infection of SARS-CoV-2, the intestine epithelium showed high susceptibility to viral infection and obvious morphological changes with destruction of intestinal villus, dispersed distribution of mucus secreting cells and reduced expression of tight junction (E-cadherin), indicating the destruction of mucous layer and the integrity of intestinal barrier caused by virus. Moreover, the endothelium exhibited abnormal cell morphology with disrupted expression of adherent junction protein (VE-cadherin). Transcriptional analysis revealed the abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., up-regulated cytokine genes, TNF signaling and NF-kappa B signaling-related genes). This bioengineered in vitro model system can mirror the human relevant pathophysiology and response to viral infection at the organ level, which is not possible in existing in vitro culture systems. It may provide a promising tool to accelerate our understanding of COVID-19 and devising novel therapies.

A human disease model of SARS-CoV-2-induced lung injury and immune responses with a microengineered organ chip

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that seriously endangers human health. There is an urgent need to build physiological relevant human models for deep understanding the complex organ-level disease processes and facilitating effective therapeutics for COVID-19. Here, we first report the use of microengineered alveolus chip to create a human disease model of lung injury and immune responses induced by native SARS-CoV-2 at organ-level. This biomimetic system is able to reconstitute the key features of human alveolar-capillary barrier by co-culture of alveolar epithelial and microvascular endothelial cells under microfluidic flow. The epithelial cells on chip showed higher susceptibility to SARS-CoV-2 infection than endothelial cells identified by viral spike protein expression. Transcriptional analysis showed distinct responses of two cell types to SARS-CoV-2 infection, including activated type I interferon (IFN-I) signaling pathway in epithelium and activated JAK-STAT signaling pathway in endothelium. Notably, in the presence of circulating immune cells, a series of alveolar pathological changes were observed, including the detachment of endothelial cells, recruitment of immune cells, and increased production of inflammatory cytokines (IL-6, IL-8, IL-1{beta} and TNF-). These new findings revealed a crucial role of immune cells in mediating lung injury and exacerbated inflammation. Treatment with antiviral compound remdesivir could suppress viral copy and alleviate the disruption of alveolar barrier integrity induced by viral infection. This bioengineered human organ chip system can closely mirror human-relevant lung pathogenesis and immune responses to SARS-CoV-2 infection, not possible by other in vitro models, which provides a promising and alternative platform for COVID-19 research and preclinical trials.

Clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone / 中国综合临床

Objective To investigate the clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone.Methods One hundred and twenty cases of functional dyspepsia were randomly divided into the control group and observation group,60 cases in each group.The control group was treated with trimebutine 0.2 g,3 times/d and the observation group was treated with trimebutine 0.2 g,3 times/d and Xiangsha Pingwei 10 g,2 times/d.Both groups were treated for four weeks,a course of treatment.Clinical efficacy and the influence on gastrointestinal hormone levels were compared between the two groups.Results The symptoms scores in both groups all decreased significantly after treatment.While the postprandial fullness scores,early satiety scores and epigastric pain scores in the observation group were significantly lower than those in the control group (0.62±0.12 vs.1.85±0.25,0.56±0.14 vs.1.46±0.21,0.48±0.15 vs.1.32±0.12,t=34.36,27.62,33.87,P<0.05).The total effective rate in the observation group was significantly higher than that in the control group (90.00% vs.73.33%,χ2=5.57,P<0.05).MOT and GAS levels in both groups increased significantly.While MOT and GAS levels in the observation group were significantly higher than those in the control group (MOT: (355.2±78.1) ng/L vs.(288.7±82.4) ng/L;GAS:(96.5±17.6) ng/L vs.(88.4±16.0) ng/L,t=4.54,2.64,P<0.05).The somatostatin (SS) level in both groups decreased significantly.While the SS level in the observation group was significantly lower than that in the control group ((41.1±11.1) ng/L vs.(48.9±12.9) ng/L,t=3.55,P<0.05).Conclusion Trimebutine combined with Xiangsha Pingwei can significantly improve the clinical symptoms and gastrointestinal hormone in patients with functional dyspepsia.

The relationship of plasma homocysteine level and apolipoprotein E gene polymorphism with Alzheimer's disease / 中华老年医学杂志

Objective To investigate the correlations of plasma homocysteine(Hcy)level and apolipoprotein E gene polymorphism with Alzheimer' s disease(AD)and mild cognitive impairment (MCI).Methods A case-control study in 66 AD patients(AD group),64 MCI patients(MCI group) and 54 healthy controls(control group)was conducted.Plasma Hcy level and ApoE polymorphism were determined and analyzed.Results Plasma Hcy levels were significantly higher in AD and MCI groups than in control subjects(both P＜0.001).AD patients also showed increased plasma Hcy levels as compared with MCI patients(P＜0.001).Logistic regression analysis indicated that the increased plasma Hcy level was a risk factor for AD and MCI(OR＝ 1.435 and 1.312,both P＜0.001).ApoE ε3/3 was the most common genotype in AD,MCI and control groups,and ε3/4 and ε4/4 genotypes were more common in AD group and MCI group than in control group(both P＜0.05).The ε4 allele frequency of ApoE was 24.2％ and 23.4％ in AD or MCI group respectively,and 6.5％ in control group(AD or MCI vs.control,P＜0.05).The analysis by multiplicative interaction model showed that the odd ratio for MCI was 23.3 in patients with only hyperhomocysteinemia(Hhcy,Hcy＞ 15 μmol/L),12.6 in patients with carrying ε4 allele,and 46.7 in patients with both Hhcy and carrying ε4 allele,which indicated that there was interaction between hyperhomocysteinemia and carrying e4 allele.Conclusions Hyperhomocysteinemia and ApoE ε4 allele are correlated with dementia and also have additive interactions.

The role of calcium/calmodulin dependent serine protein kinase in embryonic development and related diseases / 中华医学遗传学杂志

Calcium/calmodulin dependent serine protein kinase (CASK), which belongs to the family of membrane associated guanylate kinase (MAGUK) proteins, has several isoforms. CASK expresses differently in embryonic tissues and adult tissues. It can be modulated by phosphorylation and SUMOylation. CASK plays an important role in neural development, spermatozoal development and renal development. Dysfunction of CASK may lead to diseases. CASK is distributed extensively in the brain, regulating synapse formation. Mutation of CASK can lead to several neurologic diseases. CASK is also involved in the development and maturation of sperm and fertilization. It also can influence renal development through interaction with DLG1.

Emergency endoscopic intervention in acute obstructive suppurative cholangitis complicated with septic shock / 中华消化内镜杂志

Objective To evaluate the efficacy of emergency endoscopic intervention in acute obstructive suppurative cholangitis (AOSC) complicated with septic shock.Methods A total of 54 patients with AOSC and septic shock who underwent therapeutic emergency ERCP were included in this retrospective study,and were evaluated by the shock index (SI).Results ERCP was performed for all patients in 24hours after hospitalization,and the average ERCP operation time was 23.8 ± 12.5 min.All 54 patients underwent EST,46 of whom received ENBD,7 biliary stenting and 1 transferred to surgery due to bleeding.The post-ERCP mortality rate was 0,and the complications included 1 case of pancreatitis and 2 cases of pneumonia.The positive rate ofGram-Negative bacillus before ERCP was 46.9％ (15/32).The SI before ERCP was 1.250 ±0.200,which decreased to 0.950 ±0.119 at 2hr after the procedure (P ＜0.001 ),and decreased further to 0.598 ± 0.099 ( P ＜ 0.001 ) at 24 hours after ERCP.Conclusion Therapeutic emergency ERCP is of great importance in the treatments for AOSC complicated with septic shock.

Regulation of the protein stability of POSH and MLK family

Sequential activation of the JNK pathway components, including Rac1/Cdc42, MLKs (mixed-lineage kinases), MKK4/7 and JNKs, plays a required role in many cell death paradigms. Those components are organized by a scaffold protein, POSH (Plenty of SH3's), to ensure the effective activation of the JNK pathway and cell death upon apoptotic stimuli. We have shown recently that the expression of POSH and MLK family proteins are regulated through protein stability. By generating a variety of mutants, we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell death. In addition, POSH's ability to induce apoptosis is correlated with its stability as well as its MLK binding ability. MLK family's stability, like that of POSH, requires activation of JNKs. However, we were surprised to find out that the widely used dominant negative (d/n) form of c-Jun could down-regulate MLK's stability, indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.

Characteristics of parental rearing pattern in schizophrenics with brilliant school records / 中国组织工程研究

Objective To explore the features of the parental rearing behavior in schizophrenics with a brilliant school records.Methods 51 schizophrenics in remission with brilliant records were tested by EMBU.36 healthy volunteers were randomized into the controls group.Result Subjects with schizophrenia had abnormal parental rearing behavior,such as overprotection, predilection over intervention and over punishment of parents.Most of them come from peasant family.Conclusion The factors such as abnormal parental rearing behavior probably influence the development of schizophrenics.