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Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.
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【Objective】 To determine the reference red blood cells with weak agglutination intensity of low positive quality control products by comparing RhD antigen expression intensity difference according to the serological results. 【Methods】 The RhD(+ ) red blood cells were detected by microcolumn gel method with 1 500 times diluted anti-D typing reagent. The samples with weak and strong RhD antigen expression intensity were selected as the reference red blood cells for weak agglutination intensity of low positive quality control products, and verification was performed. 【Results】 Ten RhD(+ ) red blood cells were detected with diluted anti-D typing reagent, of which 8 were 1+ and 2 were ±. Red blood cells with agglutination intensity of 1+ were used as the benchmark to determine the maximum dilution ratio of anti-D typing reagent when their agglutination intensity was 1+. As the preparation standard of low positive quality control products, the agglutination intensity of red blood cells with low RhD antigen expression intensity was extremely weak ±, which was difficult to ensure the stability of its control limit properties. Based on red blood cells with agglutination intensity of ±, the maximum dilution ratio of anti-D typing reagent with agglutination intensity of 1+ was re-determined as the preparation standard of low positive quality control products, and the results met the requirements of quality control product setting. 【Conclusion】 Using red blood cells with low RhD antigen expression intensity as the benchmark to set the weak agglutination intensity of the low positive quality control products can avoid the loss of control due to the low target value.
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【Objective】 To monitor the effectiveness and accuracy of the blood transfusion compatibility test system by self-made weakly positive internal quality control products. 【Methods】 Red blood cells from DAT(-) healthy subjects were selected, and B/RhD(-)E(-) red blood cells were selected as tube 1. A/RhD(+ )E(+ ) was selected as tube 2 to prepare blood group quality control products according to the principle of blood group antigen compatibility, and red blood cell preservation solution and corresponding ABO blood group reagent antibody were added to make the agglutination intensity of microcolumn gel method in reverse blood typing reach a low positive value (1+ ). Tube 3 and tube 4 were prepared with five different preservation media: plasma, serum, antibody diluent, mixture of equal plasma and antibody diluent, and mixture of equal serum and antibody diluent, respectively. IgM anti-E antibody was added to tube 3, and IgG anti-D antibody was added to tube 4, so that the agglutination intensity of microcolumn gel method reached a low positive value (1+ ). 【Results】 Comparison between the 5 different preservation media showed that the preservation medium of antibody diluent was the most stable for weakly positive antibody (F=11.35, P<0.05), Agglutination intensity 1+ is assigned 5 points by AABB Technical Manual, and its score was 5.25±1.75 points. 【Conclusion】 The use of self-made weakly positive quality control products can improve the effectiveness, accuracy and sensitivity of the monitoring system, thus achieving internal quality control and ensuring the safety of clinical blood use.
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Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8+ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.
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AIM: To compare the control effects between toric-designed orthokeratology and spherical orthokeratology on adolescents with moderate-to-low myopia.METHODS: The clinical data of 169 adolescents(290 eyes)with moderate-to-low myopia in Jiayuan Outpatient Department of Shanghai Demu Ophthalmology from July 2020 to June 2021 were analyzed retrospectively. The patients were divided into toric group and spherical group according to the type of orthokeratology, with 81 cases(135 eyes)and 88 cases(155 eyes)respectively. The changes of visual acuity and ocular axis before and after treatment were recorded to evaluate the therapeutic effect.RESULTS: The uncorrected visual acuity of both groups significantly improved at 1a after treatment(P<0.01), and the axial length increased compared to that before treatment(P<0.01). But there were no significant differences in uncorrected visual acuity(0.014±0.043, 0.017±0.047LogMAR)and axial growth(0.18±0.22, 0.19±0.22mm)between the two groups(P>0.05).CONCLUSION: Both toric-designed orthokeratology and spherical orthokeratology can improve the uncorrected visual acuity of adolescents with low-to-moderate myopia, and there is no significant difference in controlling effect on myopia.
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Objective To explore the predictive value of the model for end-stage liver disease (MELD) score, energy metabolism and serum thyroid hormone levels on the severity and prognosis of patients with liver failure and their correlation. Methods This study collected clinicopathological data from 60 liver failure patients, e.g., end-stage liver disease (MELD) score, energy metabolism, and serum thyroid hormone levels. The χ 2 test was performed to analyze the categorical variables, while the Mann-Whitney U test and independent sample t test were performed to assess the continuous variables between the two groups. Spearman correlation coefficient test was used to evaluate correlation of each index. The receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off points of serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels in predicting prognosis of the patients. Results The rates of low TT3 and FT3 levels in liver failure patients were 78.2% and 69.1%, respectively, whereas the low TT3 rates were 95.2% and 67.6% and the low FT3 rates were 90.5% and 55.9% in survival and non-survival groups of patients, respectively (both P < 0.05). Moreover, the MELD score was significantly higher in the non-survival patients than in survival patients [26.0(21.0-29.0) vs 21.0 (19.0-24.0), Z =-3.396, P =0.001], while TT3 and FT3 levels were significantly lower in the non-survival patients than in the survival patients [0.69(0.62-0.73) vs 0.83(0.69-0.94) and 2.17(1.99-2.31) vs 2.54(2.12-2.86), respectively; Z =-2.884、-2.876, all P < 0.01]. The MELD score was negatively associated with serum TT3, FT3, and thyroid stimulating hormone (TSH) levels and the respiratory quotient (RQ) ( r =-0.487、-0.329、-0.422、-0.350, all P < 0.01), whereas the RQ was associated with serum TT3 and FT3 levels ( r =0.271、0.265, all P < 0.05). The optimal cutoff values in predicting the severity and survival of patients was 0.75 nmol/L and 2.37pmol/L with the sensitivity values of 67.6% and 64.7% and the specificity of 90.5% and 81.0%, respectively. Conclusion Abnormal thyroid hormone levels and low respiratory quotient could be used to predict the severity and prognosis of patients with liver failure.
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Objective@#To explore the relationship between maternal emotional symptoms and emotional and behavioral problems (EBPs) of preschool offspring, and to provide reference for prevention and intervention of emotional and behavior problems in preschool children.@*Methods@#A total of 4 100 preschool children aged 3-6 in Fuyang City were enrolled by stratified cluster sampling method in June 2021. The Strengths and Difficulties Questionnaire (SDQ) and Depression Anxiety and Stress Scale (DASS-21) were used to investigate preschool children s EBPs and maternal emotional symptoms, respectively.@*Results@#The detection rates of preschool children s emotional symptoms, conduct problems, hyperactivity, peer interaction problems, prosocial behavior and difficulty scores were 15.7%, 17.4%, 20.0%, 32.3%, 15.1% and 15.8%, respectively. The detection rates of mother s depression, anxiety and stress symptoms were 7.9%, 12.7% and 4.8%, respectively. Multivariate Logistic regression analysis showed that, compared with children of mothers with no depression, anxiety and stress symptoms, offspring of mothers reported depression, anxiety and stress symptoms had significantly higher risks of emotional symptoms, conduct problems, hyperactivity, peer problems and total difficulties ( OR=1.76-6.35, P <0.01). Maternal emotional symptoms had the most significant effect on children s emotional symptoms, and there was no significant correlation between maternal stress symptoms and children s prosocial behavior ( OR=1.40, P >0.05). There was no significant gender difference in the relationship between maternal emotional symptoms and children s emotional and behavioral problems ( ROR=0.73-1.07, P >0.05). For only children whose mothers reported stress symptoms showed a higher risk of emotional and behavior problems than non singleton children ( ROR=2.03, P <0.05).@*Conclusion@#Maternal emotional symptoms are related to preschool children s emotional and behavioral problems. Early identification and intervention of mother s negative emotional symptoms, are beneficial to the prevention of preschool children s emotional and behavioral problems.
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Background/Aims@#Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). @*Methods@#The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC 50 ) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. @*Results@#circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDL-RAD3 knockdown decreased the IC 50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. @*Conclusions@#circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.
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ObjectiveTo investigate the patterns of changes in routine blood parameters, thyroid hormone levels, and their correlations with thyroid peroxidase antibodies (TPOAb) among women at different stages of pregnancy, so as to provide a theoretical basis for maternal and child health care and diagnosis and treatment. MethodsA total of 732 pregnant women at different stages of pregnancy who underwent health examinations at the First Maternity and Infant Hospital affiliated to Tongji University from May 2020 to August 2022 were selected as the observation group. The group comprised 245 women in the first trimester (≤12 weeks), 247 women in the second trimester (between13 and 27 weeks) and 240 women in the third trimester (≥28 weeks). Additionally, 240 non-pregnant, healthy women of child-bearing age who conducted their health checkups in the same hospital were selected as the control group. All the research subjects were required to provide peripheral venous blood samples to measure hemoglobin (Hb), standard deviation of red blood cell distribution width (RDW-SD), coefficient of variation of red blood cell distribution width (RDW-CV), platelet (Plt) count, platelet distribution width (PDW), as well as thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and TPOAb. The results were statistically analyzed. ResultsWith advancing gestational age, Hb levels were significantly lower in the second and third trimesters than in the first trimester and the control group (F=68.25, P<0.001), while RDW-SD and RDW-CV were significantly higher (F=41.34, P<0.001; F=3.64, P=0.012). Plt levels throughout pregnancy were significantly lower than that in the control group (F=43.21, P<0.001). TSH levels were significantly lower in the first and second trimesters than in the control group (Z=53.49, P<0.001), but gradually increased with gestational age. TT3 and TT4 levels were significantly higher than those in the control group throughout pregnancy (F=148.25, P<0.001; F=210.83, P<0.001), while FT3 and FT4 levels were significantly lower in the second and third trimesters than in the first trimester and the control group (F=42.95, P<0.001; F=101.73, P<0.001). The abnormal rate of TPOAb was significantly higher than that in the control group throughout pregnancy (χ2=25.61, P<0.001). Among pregnant women, those with TPOAb positivity had significantly higher TSH levels and RDW-CV than those with TPOAb negativity (Z=5.70, P<0.001; t=2.39, P=0.018). ConclusionThe levels of Hb, Plt, and thyroid hormones in pregnant women are closely related to gestational age. With increasing gestational age, the abnormal rate of TPOAb decreases, but the TSH levels and RDW-CV of TPOAb positive pregnant women are higher, requiring clinical attention and screening to improve maternal and child health.
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Furcation involvement (FI) is the lesion and destruction of periodontium that spread to the root furcation of multi-root teeth, where periodontal pockets, loss of periodontal attachment and resorption of alveolar bone are formed. Furcation involvement is a common concomitant lesion of periodontitis. The severity of furcation involvement can directly affect the prognosis of periodontitis. However, the specificity of the anatomical structure of the root furcation greatly increases the difficulty of treatment. Therefore, early detection and treatment of furcation involvement is crucial for the prevention and control of periodontitis. This paper briefly describes the pathogenesis of furcation involvement and discusses the diagnosis, classification and treatment of this disease, which is helpful to improve the clinical diagnosis and treatment of furcation involvement.
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Humains , Molaire , Anomalies de furcation/thérapie , Parodontite/complications , Poche parodontale , PronosticRÉSUMÉ
In the case of periodontitis, local microecological imbalance can cause a large number of plaque biofilm accumulations, leading to the destruction of periodontal tissue and attachment loss, which makes it particularly difficult for the periodontal regenerative healing. In order to overcome the clinical treatment dilemma of periodontitis, periodontal tissue regeneration therapy assisted by new biomaterials has become a hot topic in recent years, among which electrospinning biomaterials with good biocompatibility have attracted wide attention. In this paper, based on periodontal clinical problems, the importance of functional regeneration is presented and clarified. Besides, according to the application of electrospinning biomaterials reported in previous researches, their effects of promoting functional periodontal tissue regeneration are analyzed. In addition, the internal mechanism of periodontal tissue repair by electrospinning materials is discussed and the future research direction is also proposed, in order to provide a new strategy for clinical treatment of periodontal diseases.
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Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.
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Objective: To investigate the current situation of job involvement of nurses in military hospitals in Henan Province and analyze the influencing factors, so as to provide reference for improving the level of job involvement of military nurses. Methods: In February 2022, the employed nurses of 4 military hospitals in Henan Province were investigated by convenient sampling method. A total of 663 questionnaires were collected, including 632 valid questionnaires, with an effective recovery rate of 95.32%. The self-designed questionnaire was used to investigate the basic information of nurses, the Job Involvement Scale was used to investigate the job involvement of nurses, the Emotional Labor Scale for Nurses was used to investigate nurses' emotions, and the Work-Family Conflict Scale was used to investigate the work-family conflict of nurses. Independent sample t-test and univariate analysis of variance were used to compare the job involvement of military employed nurses with different demographic characteristics, Pearson correlation analysis was used to explore the correlation between emotional labor, work-family conflict and job involvement, and hierarchical regression analysis was used to explore the impact of relevant variables on the job involvement of military employed nurses. Results: The total average score of job involvement of military employed nurses was (3.68±1.13), and the scores of vitality, dedication and focus were (3.64±1.15), (3.74±1.25) and (3.67±1.21) respectively. The total score of emotional labor of nurses was 33-80 (62.95±8.12), with an average score of (3.93±0.51). The total score of work-family conflict was 18-94 (55.16±13.53), with an average score of (3.06±0.75). Professional emotional regulation, patient-centered emotional inhibition and standardized emotional play were positively related to the job involvement (r=0.46, 0.41, 0.22, P<0.01). Time-based conflict, stress-based conflict and behavior-based conflict had negative correlation with the job involvement (r=-0.12, -0.23, -0.20, P<0.01). In hierarchical regression analysis, after controlling demographic variables, emotional labor and work-family conflict accounted for 17.2% and 4.2% of the variation of job involvement. Conclusion: The job involvement of military employed nurses tends to be at a moderate level. Emotional labor and work-family conflict can significantly affect their job involvement.
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Humains , États-Unis , Hôpitaux militaires , Conflit familial , Enquêtes et questionnaires , Analyse de régression , Infirmières et infirmiers , Satisfaction professionnelleRÉSUMÉ
OBJECTIVE@#To improve the rat model of cervical spondylosis of vertebral artery type (CSA) induced by injecting sclerosing agent. To evaluate the efficacy of injecting sclerosing agent to induce CSA.@*METHODS@#Forty Health SPF SD rats(20 males and 20 females), were randomly divided into two groups:the model group (20) and the blank group (20). All the animals were followed up for 4 weeks for the observation of general situation, transcranial Doppler(TCD) detection of blood flow velocity, pulsatility index and resistive index of the vertebral artery, measurement of mental distress by open-field test.@*RESULTS@#One to two days after establish the animal model, rats in the model group appeared apathetic with decreased autonomic activities, trembling, squinting, increased eye excrement, etc., and no rats died during the experiment. The mean blood flow velocity of the model group was lower than that of the blank group (P<0.05), and the pulsatilit index and resistive index of the model group were higher than that of the blank group (P<0.05). The mental distress of the model group was significantly higher than that of the blank group.@*CONCLUSION@#The modified injection of sclerosing agent is a practical method to establish the rat model of CSA, with high success rate, high stability, low mortality and simple operation.
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Mâle , Animaux , Femelle , Rats , Sclérothérapie , Solutions sclérosantes/usage thérapeutique , Rat Sprague-Dawley , Spondylose/thérapie , Rachis , Artère vertébraleRÉSUMÉ
OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg-1·d-1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.
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Souris , Animaux , Sécrétion d'insuline , Diabète de type 2/traitement médicamenteux , Ilots pancréatiques/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Insuline/usage thérapeutique , Diabète expérimental , Souris de lignée ICR , Glucose/usage thérapeutique , Interleukine-6/métabolisme , Petit ARN interférent/pharmacologie , Adénosine triphosphate , dGTPases/usage thérapeutiqueRÉSUMÉ
ObjectiveTo investigate the effect of xenon post-conditioning on autophagy after spinal cord ischemia/reperfusion injury (SCIRI) in rats and its relationship with protein kinase B (Akt) signaling pathway. MethodsA total of 30 male rats were randomized into sham-operated group (sham group), spinal cord ischemia/reperfusion injury group (I/R group) and I/R + xenon post-conditioning group (Xe group), with ten rats in each group. In the latter two groups, SCIRI was induced by clamping the abdominal aorta for 85 minutes followed by reperfusion for four hours. Xe group inhaled xenon and oxygen (1∶1) for one hour at one hour after initiation of reperfusion, while the other groups inhaled nitrogen and oxygen (1∶1) for one hour. After the reperfusion, they were assessed with Basso-Beattie-Bresnahan (BBB) scale and slanting board test. And then, their spinal cords of L3-5 were obtained. Nissl staining was used to count the number of normal neurons. Western blotting was used to detect the protein expression of Akt, p-Akt, p62, Beclin 1, microtubule-associated protein 1 light chain 3 (LC3) Ⅰ, LC3 Ⅱ. The mRNA expression of Beclin 1, p62 and LC3 Ⅱ in the spinal cord was measured with reverse transcription real-time quantitative polymerase chain reaction. ResultsCompared with the sham group, the BBB score and the maximum inclination of the slanting board test decreased, the count of normal neurons decreased, the protein expression of p62 and the p-Akt/Akt ratio decreased (P < 0.01), the protein and mRNA expression of Beclin 1 and LC3 Ⅱ, and the LC3 Ⅱ/LC3 Ⅰ ratio increased, the p62 mRNA expression decreased (P < 0.01) in the I/R group. Compared with the I/R group, the BBB score and the maximum inclination of the slanting board test increased, the count of normal neurons increased, the protein expression of p-Akt and p62 increased, the p-Akt/Akt ratio increased, the protein and mRNA expression of Beclin 1, LC3 Ⅱ and LC3 Ⅱ/LC3 Ⅰ ratio decreased, and the mRNA expression of p62 increased (P < 0.01) in Xe group. ConclusionXenon post-conditioning may relieve SCIRI in rats, which is related to activating Akt signaling pathway to inhibit autophagy.
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Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.
Sujet(s)
Humains , Virus de l'hépatite B , Encéphalopathie hépatique/complications , Insuffisance hépatique aigüe sur chronique/diagnostic , Maladie du foie en phase terminale/complications , Indice de gravité de la maladie , Facteurs de risque , Courbe ROC , Pronostic , Études rétrospectivesRÉSUMÉ
OBJECTIVE@#To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis.@*METHODS@#Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe3+ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue.@*RESULTS@#Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (μmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group.@*CONCLUSIONS@#Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.
Sujet(s)
Souris , Mâle , Animaux , Aldehyde dehydrogenase, mitochondrial , Ferroptose , Espèces réactives de l'oxygène , Lésions hépatiques chroniques d'origine chimique ou médicamenteuse , Diméthylsulfoxyde , Souris de lignée C57BL , Sepsie , Modèles animaux de maladie humaineRÉSUMÉ
Objective:To report the experience of using CT-guided cochlear implant surgery in difficult cases such as severe inner ear deformities and anatomical abnormalities, and to discuss the application value of intraoperative CT-assisted localization in difficult cases of cochlear implant surgery. Methods:Retrospectively analyzed the clinical data of 23 cases of difficult cochlear implant surgery cases completed by our team with the assistance of intraoperative CT, and collected their medical data, including preoperative imaging manifestations, surgical conditions, and intraoperative imaging images for evaluation. Results:During the study period, 23 difficult cases(27 ears) underwent cochlear implantation under the guidance of intraoperative CT, and 4 cases were bilaterally implanted. Including 6 cases of incomplete segmentation type Ⅰ(IP-Ⅰ), 1 case of incomplete segmentation type Ⅱ(IP-Ⅱ), 10 cases of incomplete segmentation type Ⅲ(IP-Ⅲ), 3 cases of common cavity deformity(CC) and 3 cases of cochlear ossification after meningitis. Facial nerve anatomy was abnormal in 9 cases, cerebrospinal fluid "blowout" was serious in 14 cases, electrode position was abnormal in 3 cases requiring intraoperative adjustment of electrode position, anatomical difficulties required intraoperative CT to assist in finding anatomical landmarks in 2 cases, and electrodes were not fully implanted in 3 cases. Conclusion:When faced with difficult cases with challenging and complex temporal bone anatomy, intraoperative CT can accurately evaluate the electrode position and provide intraoperative anatomical details, allowing immediate adjustment of the electrode position if necessary, providing safety guarantee for difficult cases of cochlear implant surgery and ensure accurate implantation of electrodes.
Sujet(s)
Humains , Implantation cochléaire/méthodes , Études rétrospectives , Tomodensitométrie/méthodes , Cochlée , Implants cochléairesRÉSUMÉ
Objective To explore the effect of circ_0038467 on angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte damage and its possible mechanism.Methods Ang Ⅱ was used to induce rat cardiomyocyte H9C2 to establish a cell injury model.si-NC,si-circ_0038467,miR-NC,miR-495 mimics were transfected into H9C2 cells and then treated with 1 μmol/L Ang Ⅱ for 24 h.si-circ_0038467 and anti-miR-NC,si-circ_0038467 and anti-miR-495 were co-transfected into H9C2 cells and treated with 1 μmol/L Ang Ⅱ for 24 h.qRT-PCR method was used to detect the expression levels of circ_0038467 and miR-495.A kit was used to detect the level of MDA and the activity of LDH and SOD.Flow cytometry was used to detect the rate of apoptosis.The dual lu-ciferase reporter experiment was used to detect the targeting relationship between circ_0038467 and miR-495.Western blot was used to detect the protein expression of cleaved Caspase-3 and cleaved Caspase-9,Bcl-2,p-P65 and p-IKBa.Results The expres-sion of circ_0038467 in H9C2 cells induced by Ang Ⅱ was increased(P<0.05),while the expression of miR-495 was decreased(P<0.05).After transfection of si-circ_0038467 or miR-495 mimics,the activity of LDH and the level of MDA were decreased(all P<0.05),the rate of apoptosis and the protein levels of cleaved Caspase-3,cleaved Caspase-9 were decreased(all P<0.05),while the activity of SOD was increased(P<0.05).Circ_0038467 could target miR-495.Co-transfection of si-circ_0038467 and anti-miR-495 could antagonize the effect of si-circ_0038467 on Ang Ⅱ-induced oxidative stress and apoptosis of H9C2 cells.In addition,circ_0038467 could activate the NF-κB pathway by targeting miR-495.Conclusion circ_0038467 regu-lates oxidative stress and apoptosis of cardiomyocytes by targeting miR-495/NF-KB pathway.