Effects of calcitonin on lumbar spinal stenosis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: There is some controversy about the effects of calcitonin (CT) on lumbar spinal stenosis (LSS). This systematic review and meta-analysis is to assess the strength of the evidence supporting the use of CT in the treatment of patients with LSS. MATERIAL AND METHOD: We performed an electronic search depicting randomized controlled trials (RCTs) through 4 databases from the date of database creation to January 2023. 3 different researchers conducted independent literature screening, data extractions, and quality assessments. The outcome measures included visual analogue scale (VAS), walking distance, and oswestry disability index (ODI). Meta-analysis and trial sequence analysis (TSA) were carried out using RevMan 5.4, Stata 16.0, and TSA 0.9. GRADE 3.6 was used to evaluate the evidence quality. RESULTS: We accepted 9 studies with 496 participants. The meta-analysis revealed that CT offered no significant improvement in VAS, walking distance, or ODI in patients with LSS. CONCLUSION: There is no evidence that CT has a benefit in patients with LSS, either alone or in combination with other treatments, or depending on the route of administration, according to the systematic review and meta-analysis of relevant RCTs.

Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria.

BACKGROUND: Diabetic kidney disease is one of the common complications of type 2 diabetes (T2D). There are no typical symptoms in the early stage, and the disease will progress to moderate and late stage when albuminuria reaches a high level. Treatment is difficult and the prognosis is poor. At present, the pathogenesis of diabetic kidney disease is still unclear, and it is believed that it is associated with genetic and environmental factors. AIM: To explore the relationship between the glucokinase regulatory protein (GCKR) gene rs780094 polymorphism and T2D with albuminuria. METHODS: We selected 252 patients (126 males and 126 females) with T2D admitted to our hospital from January 2020 to October 2020, and 66 healthy people (44 females and 22 males). According to the urinary albumin/creatinine ratio, the subjects were divided into group I (control), group II (T2D with normoalbuminuria), group III (T2D with microalbuminuria), and group IV (T2D with macroalbuminuria). Additionly, the subjects were divided into group M (normal group) or group N (albuminuria group) according to whether they developed albuminuria. We detected the GCKR gene rs780094 polymorphism (C/T) of all subjects, and measured the correlation between GCKR gene rs780094 polymorphism (C/T) and T2D with albuminuria. RESULTS: Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium. Genotype frequency was significantly different among the four groups (P = 0.048, χ2 = 7.906). T allele frequency in groups II, III, and IV was significantly higher than that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT + TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor. CONCLUSION: CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individuals carrying susceptible genes to delay the onset of T2D.

Mps one binder 2 gene upregulation in the stellation of astrocytes induced by cAMP-dependent pathway.

Astrocytes, the major glial population in the central nervous system (CNS), play an important role in neuronal homeostasis, neurogenesis, and synaptogenesis. The cells have a stellate shape with elaborated processes in the developing CNS. Cultured astrocytes become stellate when the cells undergo differentiation in response to stimuli. Nevertheless, the molecular mechanism for astrocytic stellation is poorly understood. Here, we showed that the addition of serum induced a flat polygonal shape in cultured astrocytes with a reduced level of Mps one binder 2 (Mob2) that is involved in neurite growth by forming stable complex with a nuclear Ser/Thr kinase Dbf2-related protein kinase 1 (NDR1). Furthermore, exposure to a membrane permeable cAMP analogue, dbcAMP, not only induced astrocytic stellation, but also caused an increase in Mob2 expression. Similarly, the upregulation of Mob2 mRNA expression was induced by exposure of astrocytes to pituitary adenylyl cyclase-activating polypeptide (PACAP). Pretreatment with a cAMP/protein kinase A (PKA) inhibitor, KT-5720, significantly blocked the effect of dbcAMP and PACAP on induced upregulation of Mob2 mRNA expression in astrocytes. In addition, the process withdrawal of dbcAMP-treated astrocytes was caused by the inhibition of Mob2 expression using lentivirus-mediated Mob2 shRNA delivery system. Based on our findings, we suggest that Mob2 is involved in PKA signaling-mediated astrocytic stellation.

Promoter hypermethylation-induced transcriptional down-regulation of the gene MYCT1 in laryngeal squamous cell carcinoma.

BACKGROUND: MYCT1, previously named MTLC, is a novel candidate tumor suppressor gene. MYCT1 was cloned from laryngeal squamous cell cancer (LSCC) and has been found to be down-regulated in LSCC; however, the regulatory details have not been fully elucidated. METHODS: Here, we sought to investigate the methylation status of the CpG islands of MYCT1 and mRNA levels by bisulfite-specific PCR (BSP) based on sequencing restriction enzyme digestion, reverse transcription and real-time quantitative polymerase chain reaction (RQ-PCR). The function of specific sites in the proximal promoter of MYCT1 in LSCC was measured by transient transfection, luciferase assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation assay (ChIP). RESULTS: The results suggested hypermethylation of 12 CpG sites of the promoter in both laryngeal cancer tissues and the laryngeal cancer line Hep-2 cell. The hypermethylation of the site CGCG (-695 to -692), which has been identified as the c-Myc binding site, was identified in laryngeal cancer tissues (59/73) compared to paired mucosa (13/73); in addition, statistical analysis revealed that the methylation status of this site significantly correlated with cancer cell differentiation(p < 0.01). The mRNA level of MYCT1 increased in Hep-2 cells treated with 5-aza-C (p < 0.01). The luciferase activity from mutant transfectants pGL3-MYCT1m (-852/+12, mut-695-C > A, mut-693-C > G) was significantly reduced compared with the wild type pGL3-MYCT1 (-852/+12), while the luciferase activity from wild transfectants pGL3-MYCT1 (-852/+12) rose after 5-aza treatment in Hep-2 cells. Finally, EMSA and ChIP confirmed that the methylation of the CGCG (-695 to -692) site prevented c-Myc from binding of the site and demethylation treatment of the 5' flanking region of MYCT1 by 5-aza induced the increased occupation of the core promoter by c-Myc (p < 0.01). CONCLUSION: In summary, this study concluded that hypermethylation contributed to the transcriptional down-regulation of MYCT1 and could inhibit cancer cell differentiation in LSCC. DNA methylation of the CGCG site (-695 to -692) of MYCT1 altered the promoter activity by interfering with its binding to c-Myc in LSCC. Epigenetic therapy of reactivating MYCT1 by 5-aza should be further evaluated in clinical trails of LSCC.

After-hour trauma-radiograph interpretation in the emergency centre of a District Hospital.

Introduction: Plain radiographs remain a first-line trauma investigation. Most trauma radiographs worldwide are reported by junior doctors. This study assesses the accuracy of after-hour acute trauma radiograph reporting by emergency centre (EC) doctors in an African district hospital. Methods: An institutional review board approved retrospective descriptive study over two consecutive weekends in February 2020. The radiologist report on the admission radiographs of adult trauma patients was compared with the initial EC interpretation. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for EC interpretation were calculated with 95% confidence intervals (95%CI). The association between reporting accuracy and anatomical region, mechanism of injury, time of investigation, and the number of abnormalities per radiograph was assessed. Results: 140 radiographs were included, of which 49 (35%) were abnormal. EC doctors recorded (95%CI) 77% (69-84%) accuracy, 38% (25-54%) sensitivity, 97% (91-99%) specificity, 86% (65-95%) PPV and 76% (71-80%) NPV. Performance was associated with the anatomical region (p=0.02), mechanism of injury (p=<0.01) time of day (p=0.04) and the number of abnormalities on the film (p=<0.01). The highest sensitivity was achieved in reports of the appendicular skeleton (42%) and in the setting of simple blunt trauma (62%). Overall accuracy was in line with the range (44%-99%) reported in the international literature. Discussion: Accurate reporting of acute trauma radiographs is challenging. Key factors impact performance. Further training of junior doctors in this area of clinical practice is recommended. Future work should focus on assessing the impact of such training on reporting performance.

Study on the Effect of Antiplatelet and Gastric Mucosal Protection of Traditional Chinese Medicine Invigorating Qi and Hemostasis.

BACKGROUND: To investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model. METHODS: A pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested. RESULTS: The area under the curve (AUC; 0-T, 300.342 ± 35.832 mg/L* h; AUC 0-∞, 320.462 ± 40.213 mg/L* h), the plasma peak concentration (30.622 ± 9.917 mg/L*), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05). CONCLUSION: TCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.

Oxidative Stress Marker Aberrations in Multiple Sclerosis: A Meta-Analysis Study.

Oxidative stress has been suggested to play a key role in multiple sclerosis (MS), but clinical data on oxidative stress markers in MS patients were inconsistent. This study sought to quantitatively summarize the data of oxidative stress markers in the blood and cerebrospinal fluid (CSF) of patients with MS in the literature. We conducted a systematic search of PubMed and Web of Science and included studies if they provided data on the concentrations of oxidative stress markers in the peripheral blood and CSF of MS patients and healthy control (HC) subjects. The systematic search resulted in the inclusion of 31 studies with 2,001 MS patients and 2,212 HC subjects for meta-analysis. Random-effects meta-analysis demonstrated that patients with MS had significantly increased concentrations of blood oxidative stress markers compared with HC subjects for malondialdehyde (MDA; Hedges' g, 2.252; 95% CI, 1.080 to 3.424; p < 0.001) and lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH; Hedges' g, 0.383; 95% CI, 0.065 to 0.702; p = 0.018). In contrast, concentrations of albumin (Hedges' g, -1.036; CI, -1.679 to -0.394; p = 0.002) were significantly decreased in MS patients when compared with those in HC subjects. However, the other analyzed blood oxidative stress markers did not show significant differences between cases and controls. Furthermore, this meta-analysis showed significant association between CSF MDA and MS (Hedges' g, 3.275; 95% CI, 0.859 to 5.691; p = 0.008). Taken together, our results revealed increased blood and CSF MDA and decreased blood albumin levels in patients with MS, strengthening the clinical evidence of increased oxidative stress in MS.

Effect of Nutritional Intervention Programs on Nutritional Status and Readmission Rate in Malnourished Older Adults with Pneumonia: A Randomized Control Trial.

Pneumonia leads to changes in body composition and weakness due to the malnourished condition. In addition, patient family caregivers always have a lack of nutritional information, and they do not know how to manage patients' nutritional intake during hospitalization and after discharge. Most intervention studies aim to provide nutritional support for older patients. However, whether long-term nutritional intervention by dietitians and caregivers from patients' families exert clinical effects-particularly in malnourished pneumonia-on nutritional status and readmission rate at each interventional phase, from hospitalization to postdischarge, remains unclear. To investigate the effects of an individualized nutritional intervention program (iNIP) on nutritional status and readmission rate in older adults with pneumonia during hospitalization and three and six months after discharge. Eighty-two malnourished older adults with a primary diagnosis of pneumonia participated. Patients were randomly allocated to either a nutrition intervention (NI) group or a standard care (SC) group. Participants in the NI group received an iNIP according to energy and protein intake requirements in addition to dietary advice based on face-to-face interviews with their family caregivers during hospitalization. After discharge, phone calls were adopted for prescribing iNIPs. Anthropometry (i.e., body mass index, limb circumference, and subcutaneous fat thickness), blood parameters (i.e., albumin and total lymphocyte count), hospital stay, Mini-Nutritional Assessment-Short Form (MNA-SF) score, target daily calorie intake, total calorie intake adherence rate, and three-major-nutrient intakes were assessed during hospitalization and three and six months after discharge. Both groups received regular follow-up through phone calls. Furthermore, the rate of readmission resulting from pneumonia was recorded after discharge. During hospital stay, the NI group showed significant increases in daily calorie intake, total calorie intake adherence rate, and protein intake compared with the SC group (p < 0.05); however, no significant difference was found in anthropometry, blood biochemical values, MNA-SF scores, and hospital stay. At three and six months after discharge, the NI group showed significantly higher daily calorie intake and MNA-SF scores (8.2 vs. 6.5 scores at three months; 9.3 vs. 7.6 scores at six months) than did the SC group (p < 0.05). After adjusting for sex, the readmission rate for pneumonia significantly decreased by 77% in the NI group compared with that in the SC group (p = 0.03, OR: 0.228, 95% CI: 0.06-0.87). A six-month iNIP under dietitian and patient family nutritional support for malnourished older adults with pneumonia can significantly improve their nutritional status and reduce the readmission rate.