Development and validation of a point-of-care nursing mobile tool to guide the diagnosis of malnutrition in hospitalized adult patients: a multicenter, prospective cohort study.

Malnutrition is a prevalent and severe issue in hospitalized patients with chronic diseases. However, malnutrition screening is often overlooked or inaccurate due to lack of awareness and experience among health care providers. This study aimed to develop and validate a novel digital smartphone-based self-administered tool that uses facial features, especially the ocular area, as indicators of malnutrition in inpatient patients with chronic diseases. Facial photographs and malnutrition screening scales were collected from 619 patients in four different hospitals. A machine learning model based on back propagation neural network was trained, validated, and tested using these data. The model showed a significant correlation (p < 0.05) and a high accuracy (area under the curve 0.834-0.927) in different patient groups. The point-of-care mobile tool can be used to screen malnutrition with good accuracy and accessibility, showing its potential for screening malnutrition in patients with chronic diseases.

A-site defective La2-xCuO4 perovskite-type oxides for efficient oxidation of cyclohexylbenzene.

Phenol production through the oxidation of cyclohexylbenzene (CHB) and the subsequent decomposition of tertiary hydroperoxide has attracted more and more attention. In this study, defective La2-xCuO4 perovskite-type oxide catalysts with tunable A-site deficient structures and abundant surface oxygen vacancies were developed for the liquid phase oxidation of CHB to produce cyclohexylbenzene-1-hydroperoxide (CHBHP). By tuning the amount of A-site La ions in the perovskite structure, more surface oxygen vacancies and Cu+ species were formed in catalysts. The A-site-deficient La1.9CuO4 catalyst achieved significant catalytic efficiency along with a high CHBHP yield of 27.6% at 48.6% CHB conversion under reaction conditions (i.e., 120 °C and 12 h), outperforming those of other transition metal-based catalysts previously reported in the literature. A series of structural characterization methods and catalytic reactions highlighted the crucial roles of surface oxygen vacancies and metal La and Cu ions in the oxidation process. It was revealed that metal ions favored CHB adsorption and activation, while surface oxygen vacancies facilitated the creation of active adsorbed oxygen species. The present study offers an opportunity for the future design of new high-efficiency heterogeneous catalyst systems for CHB oxidation to obtain phenol.

Use of intercellular proximity labeling to quantify and decipher cell-cell interactions directed by diversified molecular pairs.

FucoID is an intercellular proximity labeling technique for studying cell-cell interactions (CCIs) via fucosyltransferase (FT)-meditated fucosyl-biotinylation, which has been applied to probe antigen-specific dendritic cell (DC)-T cell interactions. In this system, bait cells of interest with cell surface-anchored FT are used to capture the interacting prey cells by transferring a biotin-modified substrate to prey cells. Here, we leveraged FucoID to study CCIs directed by different molecular pairs, e.g., programmed cell death protein-1(PD-1)/programmed cell death protein-ligand-1 (PD-L1), and identify unknown or little studied CCIs, e.g., the interaction of DCs and B cells. To expand the application of FucoID to complex systems, we also synthesized site-specific antibody-based FT conjugate, which substantially improves the ability of FucoID to probe molecular signatures of specific CCI when cells of interest (bait cells) cannot be purified, e.g., in clinical samples. Collectively, these studies demonstrate the general applicability of FucoID to study unknown CCIs in complex systems at a molecular resolution.

Heterogeneity of IGF-1 Levels in Children with hCG-Induced Precocious Puberty.

Objective: Sex steroid stimulates growth hormone release during puberty. However, the role of IGF-1 levels in human-chorionic-gonadotropin-induced precocious puberty remains unclear. Methods: A retrospective study reviewing thirty patients with precocious puberty due to human-chorionic-gonadotropin-secreting intracranial germ cell tumors was performed. Changes in IGF-1 levels were collected. Result: All patients included were boys. At diagnosis, the median IGF-1 standard deviation was 0.87 (0.1, 1.87). When human-chorionic-gonadotropin normalized, the median IGF-1 standard deviation was 1.58 (-0.53, 2.55), which is slightly higher than baseline (p = 0.408). When patients completed their therapeutic plan, the median IGF-1 standard deviation was 0.10 (-1.05, 0.68), which was significantly lower than that of baseline (p = 0.004) and of human-chorionic-gonadotropin being normalized (p = 0.003). At the last visit, the mean IGF-1 standard deviation was -1.11(-1.97, 0.76), which is slightly lower than that of baseline (p = 0.109) and post-therapy levels (p = 0.575), but significantly lower than that of human-chorionic-gonadotropin being normalized. Two patients had IGF-1 levels above 2 standard deviations at diagnosis, eight at the time when human-chorionic-gonadotropin normalized, and two at the end of therapy. Only one patient had an IGF-1 level below 2 standard deviations at diagnosis and at the time when human-chorionic-gonadotropin normalized, and two patients at the end of therapy. At the last follow-up, all patients had normal IGF-1 levels. Conclusion: IGF-1 levels in patients with human-chorionic-gonadotropin-induced precocious puberty have heterogeneity, but IGF-1 standard deviations are mostly within the normal range. If elevated, it might decline later with a decrease in human-chorionic-gonadotropin level. IGF-1 levels seem not valuable enough to assess human-chorionic-gonadotropin-induced precocity regression.

The role of adenosine A1 receptor on immune cells.

BACKGROUND: Adenosine, acting as a regulator by mediating the activation of G protein-coupled adenosine receptor families (A1, A2A, A2B, and A3), plays an important role under physiological and pathological conditions. As the receptor with the highest affinity for adenosine, the role of adenosine A1 receptor (A1R)-mediated adenosine signaling pathway in the central nervous system has been well addressed. However, functions of A1R on immune cells are less summarized. Considering that some immune cells express multiple types of adenosine receptors with distinct effects and varied density, exogenous adenosine of different concentrations may induce divergent immune cell functions. MATERIALS AND METHODS: The literatures about the expression of A1R and its regulation on immune cells and how it regulates the function of immune cells were searched on PubMed and Google Scholar. CONCLUSION: In this review, we discussed the effects of A1R on immune cells, including monocytes, macrophages, neutrophils, dendritic cells, and microglia, and focused on the role of A1R in regulating immune cells in diseases, which may facilitate our understanding of the mechanisms by which adenosine affects immune cells through A1R.

Dynamic Immune Landscape and VZV-Specific T Cell Responses in Patients With Herpes Zoster and Postherpetic Neuralgia.

Objectives: Varicella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN. Methods: We used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation. Results: We investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4+ and CD8+ T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1+CD4+ T cells, VZV-specific PD-1+CD4+ T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner. Conclusions: Our results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN.

Targeted downregulation of HIF-1α for restraining circulating tumor microemboli mediated metastasis.

Tumor metastasis is directly correlated to poor prognosis and high mortality. Circulating tumor cells (CTCs) play a pivotal role in metastatic cascades, of which CTC clusters is highly metastatic compared to single CTCs. Although platelets and neutrophils within the bloodstream could further exacerbate the pro-metastatic effect of single CTCs, the influence of platelets and neutrophils on CTC clusters mediated metastasis remains unclear. In this study, a pro-metastatic complex composed of CTC clusters, platelets and neutrophils, namely circulating tumor microemboli (CTM), was identified in vivo among different metastatic tumor, which was demonstrated with highly upregulation of hypoxia-inducible factor-1α (HIF-1α). While knock-out of HIF-1α or therapeutically downregulating of HIF-1α via HIF-1α inhibitor (BAY87-2243)-loaded neutrophil cyto-pharmaceuticals (PNEs) could efficiently restrain CTM mediated lung metastasis. The underlying mechanism of metastasis inhibition was attributed to the downregulation of HIF-1α-associated PD-L1, which would enhance immune response for inhibiting metastatic cells. Thus, our work here illustrates that hypoxia was an essential factor in promoting CTM colonization in lung. More importantly, we provide a promising strategy by targeted downregulation of HIF-1α in CTM via neutrophil cyto-pharmaceuticals for treatment of CTM mediated metastasis.

Internet-based platform for a low-calorie dietary intervention involving prepackaged food for weight loss in overweight and obese individuals in China: protocol for a randomised controlled trial.

INTRODUCTION: Obesity is a global health issue that impacts quality of life. A calorie-restricted diet with high-intensity consultation provided via the internet may be an effective way to lose weight. The objective of this study was to assess the effectiveness of a practitioner-guided, mobile internet-based low-energy dietary intervention in overweight and obese populations in China. METHODS AND ANALYSIS: This open-label randomised controlled trial enrolled 220 overweight and obese adults aged 18-70 years who met the inclusion criteria. Participants were assigned to the control group (n=110) or trial group (n=110). The trial group will be enrolled in the MetaWell programme, a weight loss programme using diet replacement products, wireless scales and a mobile phone app. Participants in the control group will receive paper material containing a sample diet for weight loss. The follow-up period will be 1 year, and measurements will occur at 3, 6 and 12 months. Dual-emission X-ray absorptiometry and abdominal quantitative CT will be performed to estimate the percentage of overall body fat and areas of visceral and subcutaneous fat, alongside several cardiometabolic measurements. The primary outcome of this study is the change in body mas index (BMI) at 6 months after enrolment. A mixed-effects model will be used to compare BMI and body fat changes between the two groups. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the Hospital of Chengdu Office of the People's Government of the Tibetan Autonomous Region. Advertisements for recruitment will be sent via official accounts using WeChat. The results will be disseminated via publications in academic journals and our clinic. Our study group will maintain contact with the participants to inform them of the study findings. TRIAL REGISTRATION NUMBER: ChiCTR1900021630.

A novel and efficient synthetic route to perfluoroisobutyronitrile from perfluoroisobutyryl acid.

A novel synthetic route to perfluoroisobutyronitrile from perfluoroisobutyryl acid which has mild conditions and low toxicity is described. This study introduces detailed synthetic protocols and characterization including GC-MS, 13C NMR and 19F NMR spectroscopy of perfluoroisobutyryl acid, perfluoroisobutyryl chloride, perfluoroisobutyl amide and perfluoroisobutyronitrile. Besides, this route is superior to the established patent and shows potential application in high voltage electrical equipment.

[The Effects of All-trans Retinoic Acid on the Expression of Inflammatory Cytokines and Cartilage Damage Related Protease in Rats with Collagen Induced Arthritis].

OBJECTIVES: To investigate the effects of all-trans retinoic acid (ATRA) on arthritis and the expressions of inflammatory cytokines and cartilage damage related proteases of the collagen-induced arthritis model (CIA) rats in vivo. METHODS: The CIA model of rheumatoid arthritis was induced with C2 and incomplete Freund's adjuvant. The rats were randomly divided into control group, CIA model group and two ATRA dose groups (ATRA 0.50 mg/kg group and ATRA 1.00 mg/kg group). ATRA were given three times per week for six weeks in ATRA groups. Morphological changes, arthritis index (AI) scores, the semi-quantitative scores of pathology damage, the protein expressions of cartilage damage related proteases and the serum levels of TNF-α, IL-17A, IFN-γ, IL-4, IL-10 were observed. RESULTS: The AI scores of ATRA groups were similar to CIA model group ( P<0.05). Apparent morphological disorders in knee and ankle joints were observed in the CIA model group and ATRA 1.00 mg/kg group. The structure of knee joint was improved slightly in ATRA 0.50 mg/kg group. The serum levels of TNF-α, IFN-γ and IL-17A were decreased in both ATRA groups; ATRA also can increase the serum level of IL-4. Compared to CIA model group, the protein expressions of ADAMTS-4, MMP3, MMP1 were decreased in both ATRA groups ( P<0.05). CONCLUSIONS: ATRA, which was able to inhibit pro-inflammatory cytokines secretion, could correct the imbalance of Th1/Th2 and Th17/Treg. ATRA also can reduce the expressions of cartilage damage related proteases, which proved that ATRA may have a beneficial effect on rheumatoid arthritis.

Beneficial effects of tripterygium glycosides tablet on biomarkers in patients with ankylosing spondylitis.

The aim of the current study was to explore the effects and possible mechanisms of tripterygium glycosides tablet (TGT) in the treatment of active ankylosing spondylitis (AS). Thirty-six patients with active AS were given a 20 mg TGT treatment three times per day for 12 weeks, and 21 unrelated healthy controls were recruited as the control group. Efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior and subsequent to TGT treatment. Serum dickkopf homolog 1 (DKK1) and interleukin-17 (IL-17) levels before and after TGT treatment were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA assay. The levels of several serum biomarkers were determined by ELISA, including receptor activator of nuclear factor κ-B ligand (RANKL), osteoprotegerin (OPG), bone alkaline phosphatase (BAP), bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-3 (MMP-3), cross-linked telopeptide of type II collagen (CTX-II), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). After 12 weeks of TGT treatment, the BASDAI score of the patients was significantly reduced (P<0.05), their levels of ESR and CRP were significantly reduced to a normal level (P<0.05, P<0.05), RT-PCR and ELISA showed a significant increase in the level of DKK1 expression (P<0.05) and a significant decreased IL-17 expression (P<0.05), there was a significant increase in the expression of OPG, BAP and BMP-2 (P<0.01, P<0.01, P<0.01) and a significant reduction in the expression levels of RANKL, CTX-II. MMP-3, PGE2, and VEGF (P<0.01, P<0.01, P<0.01, P<0.05, P<0.01) compared with those of the controls. TGT is effective at improving the signs and symptoms of patients with AS through the regulation of serum biomarkers, and the mechanisms may be associated with the anti-inflammatory effect, inhibition of new bone formation and potential bone-protective effects.

[Establishment of a rotary aerobic culture system for in vitro culture of mouse testis].

OBJECTIVE: To establish an in vitro model of cultured mouse testis using rotary aerobic culture. METHODS: Rotary aerobic incubation with optimized culture conditions was used for in vitro culture of mouse testis, and the morphology of the cultured testicular tissues was compared with that cultured in Transwell chambers. The changes in the testicular tissue structure were examined using HE staining, and the cell proliferation was assessed with BrdU staining. Testosterone concentrations in the culture medium were tested with radioimmunoassay and the expression of the functionally related proteins in the testis was detected using immunohistochemistry. RESULTS: The testicular tissue cultured by optimized rotary aerobic culture presented with more intact histological structure with the size of the testis ranged from 0.3 to 0.8 mm(3). In the two culture systems, the prolifeation index of the spermatogonia increased and that of Sertoli cells decreased with time, and such changes in spermatogonia and Sertoli cell proliferation indices became statistically significant at 3 days (P<0.05) and 5 days (P<0.05) of culture, respectively, as compared with those at 1 day. The concentration of testoerone in the culture media decreased significantly with incubation time (P<0.05). At 3 days of culture, the protein expression of 3ß-hydroxysteroid dehydrogenase, cytochrome P450 17α-hydroxylase and cholesterol side-chain cleavage enzyme was detected in Leydig cell cytoplasm and vimentin expression in Sertoli cell cytoplasm. CONCLUSION: An in vitro model of cultured mouse testis has been successfully established using rotary aerobic incubation.

[Estrogen Receptor Subtype-mediated Luciferase Reporter Gene Assays for Determining (anti) Estrogen Effect of Chemicals].

OBJECTIVE: To establish gene assays for determining (anti) estrogen effect of environmental chemicals; and to compare the reactivity and sensitivity of two assays with different estrogen subtype. METHODS: Human estrogen receptor a (hERalpha) and hERbeta mediated reporter gene assays employing firefly luciferase (Luc) were developed. The expression plasmid hERalpha or hERbeta was constructed and transiently co-transfected into LLC-MK2 cells with pERE-minP-Luc2P reporter plasmid and the control plasmid pGL4.74. Estradiol (E2) and diethylstilbestrol (DES) served as positive test substances to verify the performance of the assays. The effectiveness of the assays for detecting anti-estrogenic activity was tested using 10(-5) mol/L ICI 182, 780 under different concentrations of E2. The performance of the two subtype-mediated assays was verified and compared using bisphenol A (BPA) and genistein (GS). RESULTS: The hERalpha mediated assay found expression of reported gene at 1.9 x 10(-11) mol/L E2; and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 30.7-fold of vehicle control. The hERbeta mediated assay found expression of reporter gene at 2.2 x 10(11) mol/L E2, and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 14.4-fold of vehicle control. ICI 182, 780 inhibited estrogenic activity of E2 significantly. In both assays, E2 failed to induce luciferase activity without hER-pcDNA3.1. BPA and GS induced luciferase activity. CONCLUSION: Both assays have high sensitivity and reproducibility for detecting (anti) estrogen effect. The pGL4-based hERbeta has lower sensitivity than the hERalpha- mediated reporter gene assay. BPA shows stronger estrogenic activity than GS in hERalpha mediated reporter gene assay; whereas, GS shows stronger estrogenic activity than BPA in hERbeta mediated reporter gene assay.

Effects of Tripterygium glycosides on interleukin-17 and CD4+CD25+CD127low regulatory T-cell expression in the peripheral blood of patients with ankylosing spondylitis.

The aim of this study was to investigate the possible mechanisms of action of Tripterygium glycosides (TG) in the treatment of ankylosing spondylitis (AS). In total, 20 patients with active AS received treatment with 20 mg TG tablet (TGT) 3 times per day for 6 weeks. In addition, 20 healthy age- and gender-matched individuals were recruited as the control group. The efficacy measures included the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. The serum interleukin (IL)-17 levels were measured using ELISA. The expression of CD4+CD25+CD127low regulatory T cells (Tregs) in the peripheral blood was evaluated by flow cytometry. A bivariate correlation analysis was used to determine the association of IL-17 levels with BASDAI, ESR, CRP and CD4+CD25+CD127low Tregs in AS patients. Prior to treatment, the BASDAI, ESR and CRP levels in AS patients were found to be elevated compared to those in healthy controls and were significantly reduced following TGT treatment (P<0.05, P<0.05 and P<0.05, respectively). Prior to treatment, the AS patients exhibited significantly higher IL-17 levels compared to those in healthy controls (P<0.05). Following TGT treatment, the IL-17 levels were significantly reduced in AS patients (P<0.01) but were not significantly different in the control subjects (P>0.05). In addition, prior to treatment, the ratio of CD4+CD25+CD127low Tregs in AS patients was significantly lower compared to that in healthy controls (P<0.05) and it was significantly increased following TGT treatment (P<0.05). The correlation analysis between the BASDAI, ESR or CRP levels and IL-17 revealed a positive linear correlation (P<0.001, P<0.001 and P<0.01, respectively), whereas CD4+CD25+CD127low Tregs were found to be negatively correlated with IL-17 (P<0.01). In conclusion, TGT is efficient for the treatment of AS patients and its mechanism of action may be correlated with the upregulation of CD4+CD25+CD127low Tregs and the downregulation of IL-17 in the peripheral blood.

[The effects of equol on enzymes related to testosterone synthesis and vimentin in the testis of perinatal mice by organ culture in vitro].

OBJECTIVE: To investigate the effects of Equol on genes and protein expression of testosterone synthesis related enzymes and Vimentin in testis of perinatal mice in vitro. METHODS: Testes were isolated and cultured in infiltrating type rotating device for 72 h. The testes were randomly divided into five groups and treated with Equol (DMSO control, 0.01, 0.10, 1.00, 10.00 µmol/L Equol). Morphological changes were observed by HE staining under optical microscope. Expressions of 3ß-hydroxysteroid dehydrogenase (3ß-HSD),P450 side-chain cleavage enzyme (P450scc), Vimentin were detected by real-time PCR and immunohistochemistry. RESULTS: No apparent morphological change in testes was observed compared to control group. The mRNA expression of 3ß HSD, P450Scc, Vimentin show no statistical significance(P> 0. 05) in all Equol group, while the protein expressions of 3ß-HSD, Vimentin, P450scc increased in 0. 10 µmol/L and decreased in 10.00 µmol/L Equol group. CONCLUSION: Equol exposure can affect 3ß-HSD, P450Scc, Vimentin expression in testes in vitro, means Equol may have potential adverse effects on testosterone production and spermatogenesis.