The Mechanism of Human Umbilical Mesenchymal Stem Cells (HUMSC) on Biological Behavior of Human Papillomavirus (HPV) Cells Through Restraining the Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1 (PD-1/PD-L1) Signal Pathway

Biological behavior of HPV cell was observed by HUMSC through restraining PD-1/PD-L1 signal pathway. And HUMSC was adopted as target cell for the treatment on HPV. The rat HPV model was established and divided into three groups including blank group, control group and test group according to different reagents being injected into rats. Use HE staining method to observe the cancerous transformation of tumor tissue sections. The gene presentation of PD-1/PD-L1 and lymphocyte was detected with Western blot. The invasion and migration condition of cancer cells was observed from experiment in vitro. The quantity of cancer cells in test group was the least. And invasion and migration ability in test group was the weakest. The control group was the second. The number of tumor cells in the blank group was the largest. Strongest ability to invade and migrate. The presentation of PD-L1 was restrained partly by HUMSC. The increasing of immune-associated cells could be prompted by HUMSC. The quantity of CD3+, CD4+ and CD8+ in PB was the most in test group. The expression of blank groups is the lowest than others restrained by HUMSC. And quantity of abundant immune cells including CD3+, CD4+ and CD8+ could be activated partly through activating immune action of body. And monitoring function of immune system on HPV cells could be increased effectively. The invasion and migration ability in vitro of HPV could be reduced partly.

NACA and LRP6 Are Part of a Common Genetic Pathway Necessary for Full Anabolic Response to Intermittent PTH

PTH induces phosphorylation of the transcriptional coregulator NACA on serine 99 through Gαs and PKA. This leads to nuclear translocation of NACA and expression of the target gene Lrp6, encoding a coreceptor of the PTH receptor (PTH1R) necessary for full anabolic response to intermittent PTH (iPTH) treatment. We hypothesized that maintaining enough functional PTH1R/LRP6 coreceptor complexes at the plasma membrane through NACA-dependent Lrp6 transcription is important to ensure maximal response to iPTH. To test this model, we generated compound heterozygous mice in which one allele each of Naca and Lrp6 is inactivated in osteoblasts and osteocytes, using a knock-in strain with a Naca99 Ser-to-Ala mutation and an Lrp6 floxed strain (test genotype: Naca99S/A; Lrp6+/fl;OCN-Cre). Four-month-old females were injected with vehicle or 100 μg/kg PTH(1-34) once daily, 5 days a week for 4 weeks. Control mice showed significant increases in vertebral trabecular bone mass and biomechanical properties that were abolished in compound heterozygotes. Lrp6 expression was reduced in compound heterozygotes vs. controls. The iPTH treatment increased Alpl and Col1a1 mRNA levels in the control but not in the test group. These results confirm that NACA and LRP6 form part of a common genetic pathway that is necessary for the full anabolic effect of iPTH.

Efficacy of Habb-e-Asab in diabetic peripheral neuropathy: a randomized placebo control study

Objectives Diabetic peripheral neuropathy (DPN) is a common diabetes complication. The prevalence of neuropathy is 55% for type 1 and 66% for type 2 diabetes. In Unani medicine neuropathy is known as Khidr (numbness). It is treated with drugs possessing hypoglycemic and analgesic properties, etc. Habb-e-Asab, a polyherbal Unani formulation used for the treatment of Waja-ul-Asab (neuralgia) is routinely used for its indications in neurological pain in Unani medicine. The aim of this study to investigate the efficacy of Habb-e-Asab in diabetic peripheral neuropathy. Methods Thirty patients with DPN were randomly assigned to test (n=20) and control (n=10) groups in a randomized single-blind placebo control study. For 45 days, the test group was given 250 mg Habb-e-Asab twice a day and the control group 250 mg placebo twice a day. The subjective parameters Pain in feet, burning in feet, and tingling in feet was assessed by the arbitrary scale and VAS fortnightly and objective parameters MNSI, and VPT was assessed in pre–post-treatment. Results The research drug revealed highly statistically significant with p<0.001 on VAS score and MNSI whereas VPT is significant with p<0.01 on few points. But control group exhibits no significant effect in any of the parameters. No adverse effects had been reported in either group. Conclusions Our finding indicated that the Habb-e-Asab for 45 days improved and reduced the severity of DPN in a patient with diabetes (CTRI/2018/02/011725).

Research on diagnosis method of series arc fault of three-phase load based on SSA-ELM

Arc fault in the three-phase load circuit may cause fire, resulting in production interruption and even worse, it will cause casualties. In order to effectively detect the arc fault in the three-phase circuit, series arc fault experiments of three-phase motor load and frequency converter were carried out under different current conditions. Firstly, variational mode decomposition (VMD) was performed for each cycle of A-phase current, and then the VMD energy entropy and sample entropy were calculated. Secondly, the noise-dominated component was removed according to the permutation entropy, then the average value after first-order difference of the half-cycle reconstructed signal was obtained. An arc fault diagnosis model of extreme learning machine (ELM) optimized by sparrow search algorithm (SSA) was established. The feature vectors were divided into training group and test group to train the model and test its fault diagnosis accuracy. Compared with GA-ELM, PSO-ELM, support vector machine (SVM) and SSA-SVM, the experimental results show that the proposed method can identify the series arc fault accurately and more quickly.

Evaluating the association of TRPA1 gene polymorphisms with pain sensitivity: a protocol for an adaptive recall by genotype study

Background Pain is a complex polygenic trait whose common genetic underpinnings are relatively ill-defined due in part to challenges in measuring pain as a phenotype. Pain sensitivity can be quantified, but this is difficult to perform at the scale required for genome wide association studies (GWAS). Existing GWAS of pain have identified surprisingly few loci involved in nociceptor function which contrasts strongly with rare monogenic pain states. This suggests a lack of resolution with current techniques. We propose an adaptive methodology within a recall-by-genotype (RbG) framework using detailed phenotyping to screen minor alleles in a candidate ‘nociceptor’ gene in an attempt to estimate their genetic contribution to pain. Methods/design Participants of the Avon Longitudinal Study of Parents and Children will be recalled on the basis of genotype at five common non-synonomous SNPs in the ‘nociceptor’ gene transient receptor potential ankylin 1 (TRPA1). Those homozygous for the common alleles at each of the five SNPs will represent a control group. Individuals homozygous for the minor alleles will then be recruited in a series of three sequential test groups. The outcome of a pre-planned early assessment (interim) of the current test group will determine whether to continue recruitment or switch to the next test group. Pain sensitivity will be assessed using quantitative sensory testing (QST) before and after topical application of 10% cinnamaldehyde (a TRPA1 agonist). Discussion The design of this adaptive RbG study offers efficiency in the assessment of associations between genetic variation at TRPA1 and detailed pain phenotypes. The possibility to change the test group in response to preliminary data increases the likelihood to observe smaller effect sizes relative to a conventional multi-armed design, as well as reducing futile testing of participants where an effect is unlikely to be observed. This specific adaptive RbG design aims to uncover the influence of common TRPA1 variants on pain sensation but can be applied to any hypothesis-led genotype study where costly and time intensive investigation is required and / or where there is large uncertainty around the expected effect size. Trial registration: ISRCTN, ISRCTN16294731. Retrospectively registered 25th November 2021.

PENGARUH MODEL PEMBELAJARAN KOOPERATIF TEAM ASSISTED INDIVIDUALIZATION TERHADAP HASIL BELAJAR MOTOR BENSIN SISWA JURUSAN TKR SMK NEGERI 1 MOTOLING

Tujuan penelitian ini adalah untuk mengetahui pengaruh model pembelajaran kooperatif TAI (Team Assisted Individualization) terhadap hasil siswa pada mata pelajaran Motor Bensin kelas XI di SMK Negeri 1 Motoling. Penelitian ini dikategorikan dalam penelitian Eksperimen Semu (quasi exsperimental). Desain penelitian yang digunakan pada penelitian ini adalah desain jenis pre-test dan post-test group design. Berdasarkan uji hipotesis diperoleh nilai t hitung sebesar 4,4360 dan nilai t tabel 1,6772 artinya nilai t hitung lebih besar dari t tabel maka signifikan. Hasil tersebut menunjukkan bahwa terdapat perbedaan yang signifikan pada penggunaan model pembelajaran Kooperatif TAI (Team Assisted Individualization) dan konvensional terhadap pencapaian hasil belajar siswa di SMK N 1 Motoling. Kata Kunci: Hasil Belajar, Team Assisted Individualization. The purpose of this study was to determine the effect of the TAI (Team Assisted Individualization) cooperative learning model on student outcomes in the XI class of gasoline motorbike subjects at SMK Negeri 1 Motoling. This research is categorized as a quasi-experimental research. The research design used in this study was a pre-test and post-test group design. Based on the hypothesis test, the t value is 4.4360 and the t table value is 1.6772, which means that the t value is greater than the t table, so it is significant. These results indicate that there is a significant difference in the use of the cooperative learning model TAI (Team Assisted Individualization) and conventional to the achievement of student learning outcomes at SMK N 1 Motoling. Keywods: Learning Outcomes, Team Assisted Individualization.

Prioritization of Quality Principles for Health Apps Using the Kano Model: Survey Study

Background Health apps are often used without adequately taking aspects related to their quality under consideration. This may partially be due to inadequate awareness about necessary criteria and how to prioritize them when evaluating an app. Objective The aim of this study was to introduce a method for prioritizing quality attributes in the mobile health context. To this end, physicians were asked about their assessment of nine app quality principles relevant in health contexts and their responses were used as a basis for designing a method for app prioritization. Ultimately, the goal was to aid in making better use of limited resources (eg, time) by assisting with the decision as to the specific quality principles that deserve priority in everyday medical practice and those that can be given lower priority, even in cases where the overall principles are rated similarly. Methods A total of 9503 members of two German professional societies in the field of orthopedics were invited by email to participate in an anonymous online survey over a 1-month period. Participants were asked to rate a set of nine app quality principles using a Kano survey with functional and dysfunctional (ie, positively and negatively worded) questions. The evaluation was based on the work of Kano (baseline), supplemented by a self-designed approach. Results Among the 9503 invited members, 382 completed relevant parts of the survey (return rate of 4.02%). These participants were equally and randomly assigned to two groups (test group and validation group, n=191 each). Demographic characteristics did not significantly differ between groups (all P>.05). Participants were predominantly male (328/382, 85.9%) and older than 40 years (290/382, 75.9%). Given similar ratings, common evaluation strategies for Kano surveys did not allow for conclusive prioritization of the principles, and the same was true when using the more elaborate approach of satisfaction and dissatisfaction indices following the work of Timko. Therefore, an extended, so-called “in-line-of-sight” method was developed and applied for this evaluation. Modified from the Timko method, this approach is based on a “point of view” (POV) metric, which generates a ranking coefficient. Although the principles were previously almost exclusively rated as must-be (with the exception of resource efficiency), which was not conducive to their prioritization, the new method applied from the must-be POV resulted in identical rankings for the test and validation groups: (1) legal conformity, (2) content validity, (3) risk adequacy, (4) practicality, (5) ethical soundness, (6) usability, (7) transparency, (8) technical adequacy, and (9) resource efficiency. Conclusions Established survey methodologies based on the work of Kano predominantly seek to categorize the attributes to be evaluated. The methodology presented here is an interesting option for prioritization, and enables focusing on the most important criteria, thus saving valuable time when reviewing apps for use in the medical field, even with otherwise largely similar categorization results. The extent to which this approach is applicable beyond the scenario presented herein requires further investigation.

The Impact of COVID-19 Infection on Macular Capillary Perfusion

Purpose: To evaluate the impact of a prior non-severe COVID-19 infection on retinal microcirculation with optical coherence tomography angiography (OCTA).Methods:A total of 83 eyes of 43 patients with a history of non-severe COVID-19 infection confirmed with a positive PCR test (Group 1) and 30 age-matched healthy controls (Group 2) underwent detailed eye examination including Spectral-Domain OCT (Topcon-Triton Swept Source) and OCTA (RTVue-XR Avanti) scanning. OCTA images (6x6mm) images were used to assess vessel densities (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) and foveal avascular zone (FAZ). Results:The mean duration between the COVID-19 positive PCR test and ocular examination was 144.6±82.2 days (range: 30-270). VD of SCP and DCP in the foveal and perifoveal regions were significantly lower in Group 1 compared to Group 2 (p<0.05). Conclusion:Non-severe COVID-19 infection may cause a decrease in VD of retinal SCP and DCP.

COMPARISON OF HEPATOPROTECTIVE ACTIVITY OF NISHA LAUHA (NL) AND NISHA LAUHA WITHOUT LAUHA BHASMA (NLWL) AGAINST CCL4 INDUCED HEPATOTOXICITY IN WISTAR RATS

Introduction: Many herbal drugs are used to treat liver diseases, but the dose of the herbal drug is high, and they have lesser palatability. An ideal medicine is a medicine that is effective, easy palatable and produces quick action in a low dose. It is possible by adding metals like Lauha (Iron) to the herbal drugs. Objective: To compare the hepatoprotective effect of Nisha Lauha (NL) and Nisha Lauha without Lauha Bhasma (NLWL) in experimental rats. Materials and methods: 40 rats were taken divided into five groups, and each group contained eight rats. Among these groups, four groups receive 0.2 ml of injection containing the 0.1 ml CCL4 plus 0.1 ml liquid paraffin given intraperitoneally for 28 days to induce Hepatotoxicity. Both Test groups received NL and NLWL at a dose of 45mg/kg bd. wt. and 450mg/kg bd. wt. respectively for 28 days. The standard group receives silymarin at a 100 mg/kg bd dose. wt. for 28 days by oral route. The hepatoprotective effect was analyzed using biochemical parameters and histopathological study of the liver. Results: Both the Test and standard groups do not show toxic effects against CCL4 induced hepatotoxicity and lower the dose of the herbal drug due to the addition of Lauha. Conclusion: The result suggests that both test group NL and NL without Lauha Bhasma shows the hepatoprotective activity as equivalent to standard drug silymarin. The addition of Lauha Bhasma to herbal drugs decreases the dose without affecting the drug’s efficacy against the hepatoprotective effect.

Inflammatory Cytokines, Adipocytokines, and Th17/Treg Balance in Patients with Nonalcoholic Fatty Liver Disease following Administration of Dahuang Zhechong Pills

Objectives. The occurrence and development of nonalcoholic fatty liver disease (NAFLD) is related to lipid peroxidation, imbalance of inflammatory response factors, and immune function disorder. This study was conducted with the purpose of investigating the expression levels of inflammatory cytokines and adipocytokines and Th17/Treg balance in NAFLD patients treated with Dahuang Zhechong pills (DHZCPs). Methods. The study recruited 100 NAFLD patients who were then arranged into the test group and control group. Patients in the test group were treated with DHZCPs, while patients in the control group were untreated. Peripheral TH17 and Treg cells were detected by flow cytometry, and peripheral IL-17, IL-10, hs-CRP, and TNF-α expression levels were determined by enzyme-linked immunosorbent assay (ELISA) methods. The concentrations of ghrelin, leptin, and adiponectin were quantitatively examined. Results. The levels of TC, TG, ALT, and AST were declined but the level of HDL-C was increased in NAFLD patients treated with DHZCPs compared with untreated patients ( P < 0.05 ). The ratio of Th17/Treg in NAFLD patients treated with DHZCPs was (1.52 ± 0.21), which was significantly lower than (2.39 ± 0.45) of untreated patients ( P < 0.05 ). The levels of IL-17, hs-CRP, and TNF-α were lower, but the level of IL-10 was higher in NAFLD patients treated with DHZCPs than that in untreated patients ( P < 0.05 ). The expression levels of ghrelin and adiponectin in NAFLD patients treated with DHZCPs were evidently higher than those in untreated patients ( P < 0.01 ), and the expression level of leptin in NAFLD patients treated with DHZCPs was evidently lower than that in untreated patients ( P < 0.01 ). Conclusions. Administration of DHZCPs regulates the immune function of NAFLD patients by keeping Th17/Treg balance and affecting the levels of inflammatory cytokines and adipocytokines.