OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Dazhui" (GV14) and "Ciliao" (BL32) on rats with bladder detrusor hyperreflexia (DH) after supersacral spinal cord transection, as well as the mechanism of EA in improving the urinary function by regulating the expression of Wnt-1, β-catenin and Neurogenin 1(Ngn1). METHODS: A total of 48 female Sprague-Dawley rats were randomly divided into sham-operation group, model control group, EA group, and EA control group, with 12 rats in each group. T10 spinal cord transection (SCT) was performed by surgery. The Basso, Beattie and Bresnahan (BBB) score was used to evaluate the motor function of SCT rat, and the Crede technique was used to assist urination. After the urine volume became stable, the urodynamic test was used to determine whether a rat model of DH was successfully established. The rats in the EA group were given EA at GV14 and BL32, and those in the EA control group were given EA (10 Hz/50 Hz, 20 min) at the acupuncture points at 1 cm next to GV14 and BL32 at both sides alternatively. EA was performed once a day for one week. Urodynamic parameters were used to evaluate urinary function. Western blot and immunohistochemistry were used to measure the expression of Wnt-1 and β-catenin in the spinal cord, and immunofluorescence assay was used to measure the expression of Ngn1 in the spinal cord. RESULTS: The BBB score of the model control group significantly decreased compared with that of the sham-operation group(P<0.01), and the EA group was significantly higher than the model control group and the EA control group. Compared with the sham-operation group, the model control group had significant increases in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant reductions in maximum bladder capacity and compliance (P<0.01). Compared with the model control group, the EA group had significant reductions in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant increases in maximum bladder capacity and compliance (P<0.01, P<0.05). Compared with the EA group, the EA control group had significant increases in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant reductions in maximum bladder capacity and compliance (P<0.01, P<0.05). Compared with the sham-operation group, the model control group had significant increases in the protein expression of Wnt-1 and β-catenin (P<0.05, P<0.01) and a signi-ficant reduction in the protein expression of Ngn1 in the spinal cord (P<0.01). Compared with the model control group, the EA group had significant increases in the protein expression of Wnt-1, β-catenin and Ngn1 in the spinal cord (P<0.01). Compared with the EA group, the EA control group had significant reductions in the protein expression of Wnt-1, β-catenin, and Ngn1 in the spinal cord (P<0.01). CONCLUSION: EA at GV14 and BL32 can significantly improve urinary function in rats with bladder DH due to SCT, partially by activating the Wnt/β-catenin signaling pathway and promoting the protein expression of Wnt-1, β-catenin and Ngn1.

Objective: Hippocampal neuron apoptosis contributes to autism, while METTL3 has been documented to possess great potentials in neuron apoptosis. Our study probed into the role of METTL3 in neuron apoptosis in autism and to determine the underlying mechanism. Methods: Bioinformatics analysis was used to analyze expressed genes in autism samples. Institute of Cancer Research mice were treated with valproic acid to develop autism models. The function of METTL3 in autism-like symptoms in mice was analyzed with behavioral tests and histological examination of their hippocampal tissues. Primary mouse hippocampal neurons were extracted for in vitro studies. Downstream factors of METTL3 were explored and validated. Results: METTL3, MALAT1, and Wnt/β-catenin signaling were downregulated, while SFRP2 was upregulated in the hippocampal tissues of a mouse model of autism. METTL3 stabilized MALAT1 expression by promoting m6A modification of MALAT1. MALAT1 promoted SFRP2 methylation and led to reduced SFRP2 expression by recruiting DNMT1, DNMT3A, and DNMT3B to the promoter region of SFRP2. Furthermore, SFRP2 facilitated activation of the Wnt/β-catenin signaling. By this mechanism, METTL3 suppressed autism-like symptoms and hippocampal neuron apoptosis. Conclusion This research suggests that METTL3 can reduce autism-like symptoms and hippocampal neuron apoptosis by regulating the MALAT1/SFRP2/Wnt/β-catenin axis.

BACKGROUNDThe chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPARalpha, PPARbeta/delta, and PPARgamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.

METHODSTissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), which can trans-activate PPARgamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNFalpha), and formation of carbonyl and nitrated proteins.

RESULTSThe expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARalpha protein in the kidney, liver, heart and brain increased by 130.76%, 91.48%, 306.24%, and 90.70%; PPARbeta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARgamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARgamma, the expression of C/EBPdelta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.

CONCLUSIONSThese findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.

Animals ; Blood Pressure ; Blotting, Western ; E-Selectin ; genetics ; metabolism ; Gene Expression ; Hypertension ; genetics ; metabolism ; physiopathology ; Inflammation ; genetics ; metabolism ; physiopathology ; Interleukin-1beta ; genetics ; metabolism ; Male ; PPAR alpha ; genetics ; metabolism ; PPAR delta ; genetics ; metabolism ; PPAR gamma ; genetics ; metabolism ; Peroxisome Proliferator-Activated Receptors ; genetics ; metabolism ; Plethysmography ; methods ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

Objective To study the family rearing pattern of attention deficit hyperactivity disorder(ADHD)with or without anxiety disorder and to explore its risk factors.Methods 9495 children and their parents were sampled at random in Hunan province,using two-stage investigation.Those who were diagnosed ADHD and the normal control filled out Egna Minnen av Barndoms Uppfostran and family adaptability and cohesion scale bv themselves.Results The comparison of factors as:actual family cohesion,parents' punishments,reiection,mother's excessive protection,intervention and father's excessive protection were significantly difierent between ADHD with or without anxiety disorder and normal children(P＜0.05).The comparison of parents' punishments,reiection,excessive protection and intervention were obviously different between ADHD with anxiety disorder and simple ADHD(P＜0.05).Mother's reiection was the influencing factor of simple ADHD,with OR as 1.122.Ideal family cohesion,mother's rejection and father's punishments were the influencing factors of ADHD with anxiety disorder,with OR as 0.966.1.215 and 1.089 respectively.Conclusion There were some problems in the parental rearing pattern of ADHD with or without anxiety disorder.Mother's rejection,father's punishments and ideal family cohesion were suggested to be correlated with ADHD and anxiety disorder.

BACKGROUNDArrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the leading causes of sudden cardiac death. Recent studies have shown that ARVC, which is an inheritable genetic change, results from mutations in genes encoding desmosomal proteins. Plakophilin-2 is an important component of the desmosome. Because the full range of genetic variations related to ARVC is unknown and no related studies of the Chinese population have been reported, we aimed to investigate the genetic variation of plakophilin-2 in ARVC patients from the Southern Region of China.

METHODSGenomic DNA was isolated from peripheral blood samples of all 34 ARVC patients, who were screened through a clinical evaluation. They were used to detect variations in the sequences of the plakophilin-2 genes by polymerase chain reaction amplification in combination with direct sequencing.

RESULTSIn exon-1 of the plakophilin-2 gene, a deletion mutation (c.145_148 del GACA) was found in one family pedigree. The mutation was also found in exon-2, 4, and 11 of the plakophilin-2 gene. The QT interval dispersion of the ECG was considerably longer in the mutation group than in the non-mutation group of ARVC patients, and this result was statistically significant (P < 0.05).

CONCLUSIONWe discovered a plakophilin-2 mutation that prolongs the QT interval dispersion in the southern Chinese ARVC population.

Adult ; Arrhythmogenic Right Ventricular Dysplasia ; genetics ; Asian Continental Ancestry Group ; genetics ; Child ; China ; DNA Mutational Analysis ; Exons ; genetics ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Plakophilins ; genetics

OBJECTIVETo investigate the dynamic expression of hypoxia inducible factor-1alpha (HIF-1alpha) and its clinical values in hepatocellular carcinoma (HCC).

METHODSThe dynamic changes of liver pathology, HIF-1alpha transcription and expression were observed through the hepatoma model. The self-control specimens from 35 human HCC patients were collected and the expression, cellular distribution, and clinicopathological features of HIF-1alpha and its gene was analyzed by immunohistochemistry, western blotting and nested- PCR, respectively.

RESULTSBoth levels of hepatic HIF-1alpha and HIF-1alpha mRNA expression increased during the HCC development course. The incidence of HIF-1alpha and the ratio of HIF-1alpha to beta-actin was 0% and 0.16+/-0.02 in the control rats, 77.8% and 0.29+/-0.04 in the denatured rats, 88.9% and 0.52+/-0.03 in the precancerous rats, and 100% and 0.84+/-0.02 in the cancerous rats respectively, with significant difference between the control group and any of the experimental groups (P = 0.000). The positive HIF-1alpha was brown and granule-like and mainly presented in cytoplasm and few in nucleus. The incidence of HIF-1alpha was 80% (28/35) in HCC and 100% (35/35) in its surrounding tissues. The clinical pathological features indicated HIF-1alpha expression associated with tumor size and differentiation degree the of HCC. No correlation was found between HIF-1alpha and tumor numbers or positive-HBsAg.

CONCLUSIONSHIF-1alpha expression is associated with occurrence and development of HCC, and is perhaps a target molecule for HCC therapy.

Adult ; Aged ; Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Liver ; metabolism ; pathology ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

Objective: To prospectively evaluate the outcomes of ultrasound (US)-guided radiofrequency ablation (RFA) in tertiary hyperparathyroidism (THPT). Materials and Methods: Patients with THPT underwent RFA between September 2017 and January 2022. Laboratory parameters, including serum intact parathyroid hormone (iPTH) levels, were monitored for 48 months after RFA and compared with the levels at baseline. Complications related to RFA and changes in hyperparathyroidism-related clinical symptoms were recorded before and after RFA. Results: A total of 42 patients with THPT were recruited for this study. Ultimately, 36 patients with renal failure and 2 patients who underwent successful renal transplantation (male:female, 17:21; median age, 54.5 years) were enrolled. The follow-up time was 21.5 ± 19.0 months in the 36 patients with renal failure. In these 36 patients, iPTH levels were significantly decreased to 261.1 pg/mL at 48 months compared with the baseline value of 1284.9 pg/mL (P = 0.012). Persistent hyperparathyroidism, defined as iPTH levels maintained at > 585.0 pg/mL for 6 months after treatment, occurred in 4.0% of patients (1/25). Recurrent hyperparathyroidism, defined as iPTH levels > 585.0 pg/mL after 6 months, were 4.0% (1/25) and 0.0% (0/9) at 6 months and 4 years after treatment, respectively. In two patients with THPT after successful renal transplantation, iPTH decreased from the baseline value of 242.5 and 115.9 pg/mL to 171.0 and 62.0 pg/mL at 6 months after treatment. All complications resolved within 6 months of ablation without medical intervention, except in 10.5% (4/38) patients with permanent hypocalcemia. The overall symptom recovery rate was 58.8% (10/17). The severity scores for bone pain, arthralgia, and itchy skin associated with hyperparathyroidism improved after treatment (P < 0.05). Conclusion US-guided RFA is an effective and safe alternative to surgery in the treatment of patients with TPTH and improves hyperparathyroidism-related clinical symptoms.Keywords: Ultrasound; Radiofrequency ablation; Te

Objective To investigate the clinical and neuroimaging features of cerebral microbleeds(CMBs)in patients with ischemic stroke. Methods MRI,including gradient-echo T2~*-weighted MRI,was performed in 85 patients with acute ischemic stroke.Their clinical information and imaging characteristics were analyzed. Results One hundred and twenty-four CMBs were noted in 26 patients(30.6%)with the number of CMBs ranged from 1 to 16 per patient.CMBs were more frequently presentcd in the cortical-subcortical region and thalamus-basal ganglia than in the cerebellum and brain stem legions.Some CMBs in the brain stem had related neurological symptoms and signs.CMBs,the age of the patient,the number of lacunar infarcts and the white matter changes were correlative(r=0.243,P=0.025;r=0.337,P=0.025;r=0.438,P=0.000).CMBs could be well demonstrated in the gradient-echo T2~*-weighted MRI and some larger ones could be demonstrated in the apin-echo T2~*-weighted MRI and DWI. Conclusion CMBs are the sighs for microangiopathy in the brain with advanced age,mutiple lacunar infartion and leukoaraiosis as its main prognosis factors.

OBJECTIVETo analyze the clinical characteristics of severely and critically ill children with 2009 influenza A (H1N1) infection.

METHODClinical data of 150 cases with 2009 influenza A (H1N1) virus infection confirmed with the use of a real-time polymerase-chain-reaction assay on nasopharyngeal swab specimens were analyzed.

RESULTAmong 150 severely and critically ill children with 2009 influenza A (H1N1) virus infection, 103 were male, 47 were female; the median age was 5 years, 81(55%) were 5 years of age or older; 21 (14%) had underlying chronic diseases. The most common presenting symptoms were fever (95%), cough (89%), vomiting (23%), wheezing (19%), abdominal pain (16%), lethargy (7%), seizures (6%), myalgia (6%), and diarrhea (6%). The common laboratory abnormalities were increased or decreased white blood cells counts (40%), elevated of CRP (33%), LDH (29%), CK (25%) and AST (19%). Clinical complications included pneumonia (65%), encephalopathy (12%), myocarditis (5%), encephalitis (1%) and myositis (1%). All patients had received antibiotics before admission or on admission; 73% of patients had received oseltamivir treatment, 23% of patients had received corticosteroids; 32 (21%) were admitted to an ICU, 13 patients were intubated and mechanically ventilated. Fourteen patients with dyspnea who were irresponsive to the treatment experienced bronchoalveolar lavage with flexible bronchoscopy, and the branching bronchial casts were removed in 5 patients. Totally 145 (97%) patients were discharged, five (3%) died, three previously healthy patients died from severe encephalopathy, one patient died from ARDS, one previously healthy patient died from secondary fungal meningitis.

CONCLUSIONSeverely and critically ill children with 2009 influenza A (H1N1) virus infection may occur mainly in older children without underlying chronic disease. The clinical spectrum and laboratory abnormality of the patients can have a wide range. Neurologic complications may be common and severe encephalopathy can lead to death in previously healthy children. Early use of bronchoalveolar lavage with flexible bronchoscopy may reduce death associated with pulmonary complications.

Child ; Child, Hospitalized ; Child, Preschool ; China ; epidemiology ; Critical Care ; Critical Illness ; Female ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; diagnosis ; drug therapy ; epidemiology ; pathology ; Male

Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.