A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

Congenital Cutaneous Sinus at the Sternoclavicular Joint.

A 32-year-old female patient presented with chronic discharging sinus with recurrent infection at the left sternoclavicular joint. What is your diagnosis?

Effect of acupuncture on tic disorder: a randomized controlled clinical trial based on energy metabolomics and infrared thermography.

BACKGROUND: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder. METHODS: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline. DISCUSSION: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023).

Correlation between Disc Imaging Observations and Clinical Efficacy after Percutaneous Endoscopic Lumbar Discectomy: A 1-Year Follow-up Study.

OBJECTIVE: The connection between alterations in the disc structure following percutaneous endoscopic lumbar discectomy (PELD) and symptoms in patients postsurgery has not been reported yet. The purpose of the present study was to discuss the potential correlation between the changes in the morphological characteristics of various reference surfaces of the intervertebral disc after percutaneous endoscopic lumbar discectomy (PELD) and clinical outcomes, to identify the morphological parameters that affect efficacy and provide an evidence-based foundation for assessing postoperative efficacy. METHODS: From October 2019 to October 2021, after percutaneous endoscopic lumbar discectomy (PELD), 98 individuals were enrolled. MRI DICOM data of the lumbar spine were obtained before and after surgery, specifically around 3 months. The morphological parameters of the operated and adjacent segments of the discs were measured using T2-weighted images from three reference planes. Outcomes were assessed using the Oswestry disability index (ODI), visual analogue pain scores for the back and leg (VAS-back/VAS-leg), Japanese Orthopaedic Association (JOA) scores, and recovery rates. Postoperative changes in disc parameters and outcomes were compared between patients with different severity and types of LDH based on the MSU staging. Patients completed the questionnaire during outpatient follow-up appointments 3, 6, and 12 months after the surgery. The follow-up period was 14.69 ± 4.21 months, ranging from 12 to 24 months. RESULTS: Parameters such as area and circumference of intervertebral discs in the cross-section were not associated with the change in the efficacy index. Postoperatively, a negative correlation between the variation of the disc height, disc height index, and protrusion distance and the difference in VAS scores for low back pain at 3 and 6 months was observed among the two sagittal change parameters. Differences between changes in disc imaging parameters and postoperative efficacy were not statistically significant between various types of lumbar disc herniation. CONCLUSION: For the patients after percutaneous endoscopic lumbar discectomy, the changes in parameters such as disc area and circumference in the cross-sectional plane are not associated with efficacy, and the changes in disc height and herniation distance in the sagittal plane provide a morphologic basis for the assessment of short-term postoperative efficacy. In addition, the changes in disc morphologic parameters and postoperative efficacy do not differ between various types of lumbar disc herniation.

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.

Comparative study on inhibitory effects of ginsenosides on human pancreatic lipase and porcine pancreatic lipase: structure-activity relationships and inhibitory mechanism.

The inhibitory effects of twenty-six ginsenosides on human pancreatic lipase (hPL) and porcine pancreatic lipase (pPL) were studied. Study reveals that nine ginsenosides have moderate inhibitory effects against hPL, and good selectivity over pPL. By contrast, (S)-Rh2 showed good inhibitory effects on pPL over hPL. SAR analysis indicated that introduction of the O-glycosyl group(s) at C-3/C-7 site is unbeneficial for hPL inhibition, ginsenosides with A-skeleton is more beneficial than ginsenosides with B-/C-skeleton. Inhibition kinetic analysis indicated that Rg3 and (S)-Rh2 inhibited hPL-catalyzed DDAO-ol hydrolysis in a mixed manner. Molecular docking studies have confirmed that Rg3 and (S)-Rh2 inhibit hPL via many Pi-hydrogen interactions and hydrogen bonds with catalytic residues of hPL. These results indicated that pPL as an enzyme source could not fully represent the inhibitory effect of the tested compounds on hPL, and hPL should be used as far as possible to evaluate the inhibitory effect of PL.

A Hump-like Neck Mass in a Child.

A 7-year-old boy with no medical history of trauma, infection, or surgery presented with a slowly growing, asymptomatic lump on his left lower neck since birth. What is your diagnosis?

[Spatial Distribution Characteristics and Source Analysis of Heavy Metals in Soil of a Lead Plant in Sanmenxia].

At present, a large-scale relocation of industrial enterprises is taking place in major cities in China, and a large number of contaminated relocation sites are being generated, among which the heavy metal pollution is particularly serious. In order to analyze the pollution status, spatial distribution, and sources of heavy metals in the soil of a lead factory in Sanmenxia, the spatial variation and distribution characteristics of heavy metals in the soil were analyzed using geostatistics, and the main sources of heavy metals in the soil were analyzed using a PMF model. The results showed that the average values of As, Cd, Cu, Pb, Hg, and Ni in the soil far exceeded the background values of the soil environment in Henan province; the contents of As, Cd, Pb, and Hg exceeded the screening values of soil pollution risk; and the contents of As, Pb, and Hg exceeded the control values of soil pollution risk. The high-value area was located on the northern part of the slag yard; the Cr, Ni, and Cd high-value area was located in the north and south of the slag yard; the high-value As area was located in the slag yard between the southern area and the living quarters; the Cu and Pb high-value area was relatively scattered, mainly concentrated in the central part of the raw material storage area and furnace area; and Ni and Cd and Cu and Pb had the same spatial distribution characteristics. Based on the PMF model, it can be seen that there were three main sources of the seven heavy metals, and Cd was mainly from waste residue accumulation, with a contributing rate of 87.60%. Cu, Pb, and Hg were mainly soil parent material, with contribution rates of 92.50%, 75.20%, and 95.40%, respectively. Cr, Ni, and As were mainly raw material dust exhaust gas sources, with contribution rates of 80.80%, 83.30%, and 62.00%, respectively.