Drug-Related Side Effects and Adverse Reactions ; Emergency Service, Hospital ; Hospitals, General ; Humans ; Pharmaceutical Preparations ; Poisoning ; Retrospective Studies

Nonalcoholic fatty liver disease (NAFLD) is a common complication of type 2 diabetes mellitus (T2DM) and can progress to liver cirrhosis and even hepatocellular carcinoma, but there are still no effective pharmacotherapies for NAFLD at present. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) is a newly approved oral hypoglycemic agent and can effectively reduce blood glucose. Meanwhile, SGLT-2i can improve NAFLD by improving lipid accumulation and insulin resistance, exerting anti-inflammatory and anti-oxidative stress effects, reducing liver fibrosis degree, and delaying the progression to hepatocellular carcinoma. SGLT-2i also helps with the prevention of NAFLD by reducing the toxicity of high glucose, body weight, and blood uric acid and improving liver dysfunction. This article reviews the current status of T2DM with NAFLD, the mechanism of action of SGLT-2i, the effect of SGLT-2i in preventing T2DM with NAFLD, and the safety of SGLT-2i.

BACKGROUNDPersistent gastro-esophageal reflux (GER) due to various pathological factors often results in overt clinical symptoms and signs, which is termed as gastro-esophageal reflux disease (GERD). Affected children usually present with failure to thrive, recurrent pneumonia or apnea. Many neurologically impaired children have symptoms related to GERD. Although laparoscopic fundoplication has been established to be an effective treatment modality for children with GERD, data on its role and long-term efficacy for neurologically impaired patients remain sparse. The aim of this study was to review the results of such patients who underwent laparoscopic fundoplication.

METHODSA retrospective review was performed from 1998 to 2009. All children with neurological impairment who had laparoscopic fundoplication were included.

RESULTSFifty-nine GERD patients (male = 32, female = 27; mean age 6 years) were identified. All subjects showed symptoms of frequent emesis; 32 of them had history of hematemesis (54.2%); 54 had feeding difficulty; 35 (59.3%) had associated respiratory symptoms, including recurrent pneumonia. Gastrostomy was performed concurrently in 39 cases. There was no conversion to open procedure nor was there intra-operative complications and operative mortality. Emesis or hematemesis was controlled adequately in all. However, respiratory symptoms were not controlled in 10 patients (16.9%), and five of them required further respiratory assistance including nasal airway tube and tracheostomy. Clinical recurrence of GERD was not observed in any subject. Twelve patients died during follow-up (range from 3 months to 9 years) due to severe respiratory complications, cardiac arrest, and brain tumor.

CONCLUSIONSLaparoscopic fundoplication is an excellent procedure for controlling clinically significant symptoms in neurological impaired patients with GERD. Further studies are required to assess the improvement of the quality of life in such patients.

Child ; Female ; Fundoplication ; methods ; Gastroesophageal Reflux ; surgery ; Humans ; Laparoscopy ; methods ; Male ; Retrospective Studies ; Treatment Outcome

BACKGROUNDFalls are the most frequently reported adverse events in inpatient settings. We conducted a retrospective case-control study of inpatient falls within aged care wards in a tertiary hospital to investigate the associated characteristics of elderly patients suffering from falls and fall-related characteristics.

METHODSConsecutive retrospective cross-sectional design spanned July 2006 to December 2008.

PATIENT GROUPInformation on all aged care inpatients who suffered from 1 or more falls was extracted from Incident Information Management System (IIMS). Further details about the particular admission(s) were obtained from patients' medical records, e.g., patients' characteristics and circumstances surrounding the falls. Randomly selected aged care patients who did not suffer from a fall and who were discharged from the hospital in the same period served control group. Characteristics among patients with single fall and recurrent falls, as well as non-fallers were compared.

RESULTSOf the 438 falls evaluated, 71.9% occurred in patients' room and 18.9% in patients' bathroom/toilet. The common activities were moving/transferring and taking shower/toileting, respectively, 70.3%, 12.1% while occurring falls; and time of falls had a high peak during 9:00-11:00 a.m. Many were unassisted while falling. The common contributing factors for fall were intrinsic factors. Patients with recurrent falls were more likely to have lower Mini-Mental State Examination (MMSE) score. Logistic regression analysis showed length of stay longer than five weeks, dementia and stroke were independent risk factors for recurrent falls; and living in hostel/nursing home preadmission, needing assistance with mobility, cognitive impairment, stroke, incontinence and arthritis/osteoporosis were independent risk factors for fall.

CONCLUSIONSIn an aged care ward, falls are independently associated with recurrent factors. Cognitive impairment/dementia was a strong risk factor for falls, and main causes leading to fall were intrinsic factors. For patients with cognitive impairment/dementia and behavioral disorder providing special and effective interventions is of paramount importance for reducing the incidence of fall in an aged care ward in hospital settings.

Accidental Falls ; statistics & numerical data ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Male ; Nursing Homes ; statistics & numerical data ; Retrospective Studies ; Risk Factors

OBJECTIVECleidocranial dysplasia (CCD) is a rare skeletal disease with autosomal dominant inheritance associated with mutation in RUNX 2. The authors report a Chinese girl with CCD in whom the mutation in RUNX 2 was identified.

METHODSClinical diagnosis was based on physical examination, radiological findings, and biochemical tests. For mutation detection, genomic DNA was extracted from peripheral blood using standard method. All 7 coding exons of RUNX 2 and their flanking intronic sequences were amplified by polymerase chain reaction (PCR), and the PCR products were then subjected to automatic DNA sequencing.

RESULTSThe affected girl showed typical clinical manifestations of CCD, including patent fontanelles, absent clavicles, short stature and dental anomalies. Direct sequencing of PCR-amplified fragments revealed a recurrent missense mutation, R190W (568 C > T), in RUNX 2. The mutation was further confirmed by Hae III restriction analysis.

CONCLUSIONA Chinese case of CCD was confirmed and the disease-causing mutation was linked to a recurrent point mutation in RUNX 2.

Cleidocranial Dysplasia ; genetics ; Core Binding Factor Alpha 1 Subunit ; genetics ; Female ; Humans ; Mutation

OBJECTIVETo study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient.

METHODSLiver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured.

RESULTSIn the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation.

CONCLUSIONSPreconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.

Animals ; Liver Transplantation ; immunology ; Male ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Regulatory ; immunology ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; immunology ; Whole-Body Irradiation

Aim To investigate the effectiveness and safety of alfentanil in general anesthesia.Methods In this study, a multicenter randomized double-blind con¬trolled study was conducted.A total of 352 subjects were selected and randomly assigned to fentanyl group (group A, n =176) and alfentanil group (group 15, n = 176).Anesthesia induction: intravenous midazolam 0.03 mg • kg-1 + fentanyl 25 p.g • kg"'(group A) or alfentanil 4 p,g • kg-1 ( group 15) + propofol 2 mg • kg"1 + rocuronium 0.8 mg • kg"1.Sevoflurane + fent¬anyl ( group A ) or alfentanil ( group B ) + rocuronium were used for anesthesia.The vital signs of patients re¬covery time and extuhation time, anesthesia-related complications and the use of related remedial drugs during anesthesia induction and maintenance were compared between the two groups.Results During the induction and maintenance period of anesthesia, alfentanil and fentanyl could equally effectively inhibit the stress response induced by endotracheal intubation and surgical stimulation.Alfentanil also showed more effective inhibition on stress response induced by endo¬tracheal intubation and surgical stimulation than that of fentanyl ( P < 0.05 ) .However, there was no signifi¬cant difference in the incidence of intraoperative hypo¬tension and hypertension and the time of anesthesia re¬covery and extubation between the two groups.Conclu¬sions Both alfentanil and fentanyl can effectively in¬hibit the stress response induced by surgical stimulation and could be safely used in general anesthesia in sur¬gery.Alfentanil has more advantages in maintaining the stability of blood pressure and heart rate during an¬esthesia induction and maintenance.

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
Male ; Female ; Humans ; Child ; Stroke Volume ; Retrospective Studies ; Ventricular Function, Left ; Phenotype ; Cardiomyopathy, Dilated/diagnosis* ; Mutation ; ATPases Associated with Diverse Cellular Activities/genetics* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

Progranulin (PGRN) has recently emerged as a key player in a subset of frontotemporal dementias (FTD). Numerous mutations in the progranulin gene have been identified in patients with familial or sporadic frontotemporal lobar degeneration (FTLD). In order to understand the molecular mechanisms by which PGRN deficiency leads to FTLD, we examined activity of PGRN in mouse cortical and hippocampal neurons and in human neuroblastoma SH-SY5Y cells. Treatment of mouse neurons with PGRN protein resulted in an increase in neurite outgrowth, supporting the role of PGRN as a neurotrophic factor. PGRN treatment stimulated phosphorylation of glycogen synthase kinase-3 beta (GSK-3β) in cultured neurons. Knockdown of PGRN in SH-SY5Y cells impaired retinoic acid induced differentiation and reduced the level of phosphorylated GSK-3β. PGRN knockdown cells were also more sensitized to staurosporine-induced apoptosis. These results reveal an important role of PGRN in neurite outgrowth and involvement of GSK-3β in mediating PGRN activity. Identification of GSK-3β activation as a downstream event for PGRN signaling provides a mechanistic explanation for PGRN activity in the nervous system. Our work also suggest that loss of axonal growth stimulation during neural injury repair or deficits in axonal repair may contribute to neuronal damage or axonal loss in FTLD associated with PGRN mutations. Finally, our study suggests that modulating GSK-3β or similar signaling events may provide therapeutic benefits for FTLD cases associated with PGRN mutations.
Animals ; Apoptosis ; Cell Culture Techniques ; Cell Differentiation ; Cell Line ; Embryo, Mammalian ; Female ; Gene Knockdown Techniques ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; pharmacology ; physiology ; Mice ; Neurites ; physiology ; Neurons ; cytology ; physiology ; Phosphorylation ; Pregnancy ; Progranulins ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA Interference

OBJECTIVETo study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China.

METHODSThe kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2.

RESULTSA total of 603 children were surveyed (307 boys and 296 girls). There were 261 Han children, 194 Uyghur children, and 148 Kazak children. The overweight/obesity rates in Han, Uyghur, and Kazak children were 28.3%, 10.3%, and 31.1%, respectively (P<0.001). In Kazak children, the CNVs of IRX3_1 and MC4R_2 were associated with overweight/obesity (P<0.05). The multivariate logistic regression analysis showed that the risk of overweight/obesity in Han and Kazak children was 3.443 times (95%CI: 2.016-5.880) and 3.924 times (95%CI: 2.199-7.001), respectively, that in Uyghur children. The CNV of IRX3_1 was a risk factor for overweight/obesity (P=0.028, OR=2.251, 95%CI: 1.418-5.651).

CONCLUSIONSThe CNV of IRX3_1 is associated with overweight/obesity in Han, Uyghur, and Kazak children, and the association between the CNV of IRX3_1 and overweight/obesity in Kazak children should be taken seriously.

Child ; Child, Preschool ; China ; ethnology ; DNA Copy Number Variations ; Female ; Homeodomain Proteins ; genetics ; Humans ; Logistic Models ; Male ; Obesity ; etiology ; genetics ; Overweight ; etiology ; genetics ; Risk Factors ; Transcription Factors ; genetics