[Mechanism of Huangqin Qingre Chubi Capsules in improving rheumatoid arthritis based on METTL3-SFRP4/Wnt/ß-catenin pathway].

The effect and mechanism of Huangqin Qingre Chubi Capsules(HQC) on rheumatoid arthritis(RA) were studied.Seventy male SPF rats were randomly divided into normal group, model group, low-(0. 18 g·kg~(-1)), middle-(0. 36 g·kg~(-1)), and high-(0. 72 g·kg~(-1)) dose groups of HQC, methotrexate group(MTX, 0. 75 mg·kg~(-1)), and negative control group(NC group, model +saline). Adjuvant arthritis fibroblast-like synoviocytes(AA-FLS) were divided into normal group, model group, low-, middle-, and high-dose groups of HQC, and negative control group. RT-qPCR and Western blot were used to detect the m RNA and protein expressions of METTL3, SFRP4, ß-catenin, CCND1, c-Myc, MMP3, and fibronectin. The protein expression of MMP3 and ß-catenin was detected by immunofluorescence. The gene expression level of METTL3 on AA-FLS was knocked down to further examine the expression of each gene. ELISA measured the levels of IL-1ß, IL-6, and IL-8. The results showed that compared with the normal group, rats in the model group found redness and swelling in their limbs and significantly increased joint swelling. Compared with the model group, the joint swelling degree of each treatment group significantly decreased(P<0. 05). The paw retraction threshold and body weight mass index both significantly increased(P<0. 05). METTL3 was highly expressed on AA and negatively correlated with the expression of SFRP4. After treatment, the m RNA and protein expression of METTL3, ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 were significantly decreased on AA-FLS(P< 0. 05). Compared with the model group, knocking down METTL3 resulted in reduced m RNA and protein expression of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3(P< 0. 05). At the same time, the m RNA and protein expressions of ß-catenin, CCND1, c-Myc, fibronectin, and MMP3 in the HQC+METTL3 knockdown group were significantly lower than those in the METTL3 knockdown group(P<0. 05). HQC could reduce the levels of IL-1ß, IL-6, and IL-8 to varying degrees(P<0. 05). The results indicate that HQC has a significant improvement effect on arthritis in AA rats. The expression of METTL3 is significantly increased in synovial tissue and AA-FLS of AA rats, which may be a potential target for the diagnosis and treatment of RA. HQC improves RA through the METTL3-SFRP4/Wnt/ß-catenin signaling pathway and has significant antiinflammatory and anti-rheumatic effects.

RUNX3-mediated circDYRK1A inhibits glutamine metabolism in gastric cancer by up-regulating microRNA-889-3p-dependent FBXO4.

BACKGROUND: Targeting glutamine metabolism is previously indicated as a potential and attractive strategy for gastric cancer (GC) therapy. However, the underlying mechanisms responsible for the modification of glutamine metabolism in GC cells have not been fully elucidated. Accordingly, the current study sought to investigate the physiological mechanisms of RUNX3-mediated circDYRK1A in glutamine metabolism of GC. METHODS: Firstly, GC tissues and adjacent normal tissues were obtained from 50 GC patients to determine circDYRK1A expression in GC tissues. Next, the binding affinity among RUNX3, circDYRK1A, miR-889-3p, and FBXO4 was detected to clarify the mechanistic basis. Moreover, GC cells were subjected to ectopic expression and knockdown manipulations of circDYRK1A, miR-889-3p, and/or FBXO4 to assay GC cell malignant phenotypes, levels of glutamine, glutamic acid, and α-KG in cell supernatant and glutamine metabolism-related proteins (GLS and GDH). Finally, nude mice were xenografted with GC cells to explore the in vivo effects of circDYRK1A on the tumorigenicity and apoptosis. RESULTS: circDYRK1A was found to be poorly expressed in GC tissues. RUNX3 was validated to bind to the circDYRK1A promoter, and circDYRK1A functioned as a miR-889-3p sponge to up-regulate FBXO4 expression. Moreover, RUNX3-upregulated circDYRK1A reduced levels of glutamine, glutamic acid, and α-KG, and protein levels of GLS and GDH, and further diminished malignant phenotypes in vitro. Furthermore, in vivo experimentation substantiated that circDYRK1A inhibited the tumorigenicity and augmented the apoptosis in GC. CONCLUSION: In conclusion, these findings highlighted the significance and mechanism of RUNX3-mediated circDYRK1A in suppressing glutamine metabolism in GC via the miR-889-3p/FBXO4 axis.

Probiotics may not prevent the deterioration of necrotizing enterocolitis from stage I to II/III.

BACKGROUND: Probiotic therapy can reduce the incidence of NEC. Therapeutic use of probiotics after NEC diagnosis reduces the severity of NEC in preterm infants or full-term infants is unclear. To evaluate the effect of probiotics on preventing the deterioration of necrotizing enterocolitis (NEC) from stage I to II/III. METHODS: A retrospective matched cohort study was performed. Included patients were ultimately divided into two groups: the probiotic treatment group (probiotics were used ≥4 days) and the no probiotic treatment group. The differences in deterioration trends between the two groups were compared. Additionally, the risk factors associated with the deterioration of NEC were further analyzed with a case-control study. RESULTS: A total of 231 infants met the inclusion criteria. Eighty-one pairs were matched according to similar gestational age and birth weight. Before matching, we found that the rate of deterioration of NEC from stage I to II/III in the group with probiotic treatment was similar to that in the group without probiotic treatment (23.1% [25/108] vs 26.0% [32/123], P = 0.614). After matching, the rate of deterioration of NEC between the two groups still had no significant difference (21.0% [17/81] vs 27.2% [22/81], P = 0.358). Logistic regression analysis showed that sepsis after NEC was an independent risk factor for NEC deteriorating from stage I to II/III (OR 2.378, 95% CI 1.005-5.628, P = 0.049). CONCLUSION: Probiotics may not prevent the deterioration of NEC from stage I to II/III in infants, but this conclusion should be treated with caution.

DOA Tracking Based on Unscented Transform Multi-Bernoulli Filter in Impulse Noise Environment.

Aiming at the problem of multiple-source direction of arrival (DOA) tracking in impulse noise, this paper models the impulse noise by using the symmetric α stable (SαS) distribution, and proposes a DOA tracking algorithm based on the Unscented Transform Multi-target Multi-Bernoulli (UT-MeMBer) filter framework. In order to overcome the problem of particle decay in particle filtering, UT is adopted to select a group of sigma points with different weights to make them close to the posterior probability density of the state. Since the α stable distribution does not have finite covariance, the Fractional Lower Order Moment (FLOM) matrix of the received array data is employed to replace the covariance matrix to formulate a MUSIC spatial spectra in the MeMBer filter. Further exponential weighting is used to enhance the weight of particles at high likelihood area and obtain a better resampling. Compared with the PASTD algorithm and the MeMBer DOA filter algorithm, the simulation results show that the proposed algorithm can more effectively solve the issue that the DOA and number of target are time-varying. In addition, we present the Sequential Monte Carlo (SMC) implementation of the UT-MeMBer algorithm.

Expression of Caenorhabditis elegans-expressed Trans-HPS, partial aminopeptidase H11 from Haemonchus contortus.

Aminopeptidase H11 present in the surface of intestine microvilli in Haemonchus contortus was identified as the most effective antigen candidate. However, its recombinant forms produced in Escherichiacoli, insect cells and yeast could not provide promising protection against H. contortus challenge, probably due to the inappropriate glycosylation and/or conformational folding. Herein, partial H11 containing the potential zinc-binding domain and two predicted glycosylation sites (nt 1 bp-1710 bp, Trans-HPS) was subcloned downstream of 5' flanking region of Caenorhabditis elegans cpr-1 gene in pPD95.77 vector, with the deletion of GFP gene. The recombinant was expressed in C. elegans and verified by blotting with anti-H11 and anti-Trans-HPS rabbit polyclonal antibodies and anti-His monoclonal antibody. Stably inherited Trans-HPS in worm descendants was achieved by integration using UV irradiation. Immunization with the crude Trans-HPS extracted from transgenic worms resulted in 37.71% reduction in faecal egg counts (FEC) (P<0.05) and 24.91% reduction in worm burden, but an upward curve with moderate rate of daily FEC in goats. These results suggested an apparent delay against H. contortus egg-laying in goats, which differed from that with bacteria-origin form of partial H11 (nt 670 bp-1710 bp, HPS) (26.04% reduction in FEC and 18.46% reduction in worm burden). These findings indicate the feasibility of sufficient C. elegans-expressed H11 for the immunological research and vaccine development.

Comparison of prognostic value of red cell distribution width and NT-proBNP for short-term clinical outcomes in acute heart failure patients.

Comparison of the prognostic value of red cell distribution width (RDW) and N-terminal pro B-type natriuretic peptide (NT-proBNP) for short-term clinical outcomes in acute heart failure (AHF) patients has not been fully investigated.A total of 128 patients with AHF were enrolled and followed for 3 months. Primary endpoints were cardiovascular (CV) events, defined as cardiac death and/or readmission for HF. Baseline RDW and NT-proBNP were measured at admission.The 30-day and 90-day CV event rates were 16.4% and 35.9%, respectively. NT-proBNP was higher in people with cardiovascular events at both time points, while RDW was significantly higher only at the 90-day time point. The area under the ROC curve of RDW (area under the ROC curve = 0.695) for the prediction of CV events was higher than that of NT-proBNP (area under the ROC curve = 0.610) at the 90-day time point, but lower at the 30-day time point. Cox hazard analysis revealed RDW and NT-proBNP were independent predictive factors of a 90-day CV event (RDW, hazard ratio, 4.610, 95% confidence interval 1.935-10.981, P = 0.001; NT-proBNP, hazard ratio, 3.661, 95% confi dence interval 1.125-11.907, P = 0.031). Kaplan-Meier survival analysis revealed that patients with an RDW level > 14.5% and NT-proBNP > 1471.5 pg/mL were at highest risk for a CV event (P < 0.001).RDW and NT-proBNP are strong independent predictors of 90-day cardiovascular events in patients hospitalized with AHF. RDW can add prognostic value to NT-proBNP for predicting early cardiovascular events.

Molecular bonding characteristics of Self-plasticized bamboo composites.

Bamboo biomass fibers were gradually separated, prepared, and then self-plasticized for immune composites. The molecular bonding characteristics of the self-plasticized bamboo composites were investigated by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and thermo gravimetric analysis (TG). The important results were as follows. (1) During self-plasticizing of bamboo biomass, the cross-linking between celluloses mainly depended on carboxylic acid anhydrides and carboxylic acid esters, that between cellulose and lignin depended on carboxylic acid esters and C=O groups of aliphatic hydrocarbons, and that of hemi cellulose had a ether bond and ester bond bridging effect between lignin and cellulose. The cross-linking effects of hemi cellulose, lignin, and cellulose could be stacked and coupled. (2) After self-plasticization, the crystallinity of the lingo cellulosic biomass, lignin cellulose, and cellulose were increased by 5.8%, 2.28%, and 11.67%, respectively. While the TG curves of all samples were basically similar in shape, the weight loss rate turning points of the self-plasticized samples were delayed compared with those of the bamboo biomass fibers. This result demonstrated that the molecular integration of the bamboo biomass was increased after self-plasticization, and confirmed that bond cross-linking between the hemi cellulose, lignin and cellulose of the bamboo biomass had occurred.

Immune effects of extractives on bamboo biomass self-plasticization.

Bamboo is a fast-growing renewable bioresource. However, bamboo resources are wasted, and bamboo products release toxic gases. Bamboo biomass was therefore extracted and self-plasticized, and the immune effects of bamboo extractives were determined and investigated using nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopies, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The results showed the following. (1) The 1H-NMR signals at ~5.5, 4-8, 7.4-10.2, and 12.22-12.37 ppm were attributed to the chemical shifts of active protons on carbons adjacent to R-OH, RAr-OH, oximes, and -COOH, respectively. This showed that there were highly reactive hydrogen atoms in bamboo benzene/ethanol extractives. The 13C-NMR spectrum gave further confirmation. (2) The extents of the effects of key process parameters were different: temperature > hot pressure > time. The optimal self-plasticizing conditions were temperature 170°C, hot pressure 9 MPa, time 40 min, and extraction of bamboo. (3) SEM, FT-IR, and XRD showed that contact and linkages among bamboo cells were significantly decreased by extractives, so the internal bond strengths of the self-plasticized samples were all higher after bamboo extraction. It was also found that the extractives created a significant barrier to bamboo self-plasticization as a result of their structure and chemical linkage reactions.

High expression of TRIP13 is associated with tumor progression in H. pylori infection induced gastric cancer.

BACKGROUND/OBJECTIVE: H. pylori is a recognized bacterial carcinogen in the world to cause gastric cancer (GC). However, the molecular mechanism of H. pylori infection-induced GC is not completely clear. Thus, there is an urgent need to reveal the precise mechanisms regulating cancer development due to H. pylori infection. METHODS: GEO microarray databases and TCGA databases were extracted for the analysis of different expression genes (DEGs). Then, Kaplan-Meier Plotter was used for prognostic analysis. Functional enrichment analysis of TRIP13 was performed by metascape database and TIMER database. Specific role of TRIP13 in GC with H. pylori infection was confirmed by CCK8, cell cycle analysis and WB. RESULTS: A total 10 DEGs were substantially elevated in GC and H. pylori+ tissues and might be associated with H. pylori infection in GC and only the highly expressed TRIP13 was statistically associated with poor prognosis in GC patients. Meanwhile, TRIP13 were upregulated in both CagA-transfected epithelial cells and GC cells. And TRIP13 deficiency inhibited cell proliferation and arrested the cell cycle at the G1 phase. CONCLUSION: Our study suggested that high expression of TRIP13 can promote the proliferation, cell cycle in GC cells, which could be used as a biomarker for H. pylori infection GC.

O-GlcNAcylation: a pro-survival response to acute stress in the cardiovascular and central nervous systems.

O-GlcNAcylation is a unique monosaccharide modification that is ubiquitously present in numerous nucleoplasmic and mitochondrial proteins. The hexosamine biosynthesis pathway (HBP), which is a key branch of glycolysis, provides the unique sugar donor UDP-GlcNAc for the O-GlcNAc modification. Thus, HBP/O-GlcNAcylation can act as a nutrient sensor to perceive changes in nutrient levels and trigger O-GlcNAc modifications of functional proteins in cellular (patho-)physiology, thereby regulating diverse metabolic processes. An imbalance in O-GlcNAcylation has been shown to be a pathogenic contributor to dysfunction in metabolic diseases, including type 2 diabetes, cancer, and neurodegeneration. However, under acute stress conditions, protein O-GlcNAc modification exhibits rapid and transient upregulation, which is strongly correlated with stress tolerance and cell survival. In this context, we discuss the metabolic, pharmacological and genetic modulation of HBP/O-GlcNAc modification in the biological system, the beneficial role of O-GlcNAcylation in regulating stress tolerance for cardioprotection, and neuroprotection, which is a novel and rapidly growing field. Current evidence suggests that transient activation of the O-GlcNAc modification represents a potent pro-survival signalling pathway and may provide a promising strategy for stress-related disorder therapy.

[Association study of insulin-like growth factor-1 polymorphisms with extreme high myopia].

OBJECTIVE: To investigate whether the polymorphisms of insulin-like growth factor-1 (IGF-1) gene and its regulatory regions are associated with extreme high myopia. METHODS: A case-control analysis of 302 subjects with extreme high myopia and 401 controls was undertaken. Genomic DNA was obtained from peripheral blood. Seven tag single nucleotide polymorphisms (tSNP) across the IGF-1 gene region were selected to capture the majority of genetic variation. All tSNP were genotyped using the MassArray platform and MALDI-TOF analysis. Genotypic distribution was tested for Hardy-Weinberg equilibrium. Statistical analyses were performed using the SPSS (version 13.0: SPSS Science, Chicago, IL) software. The genotype and allele frequencies were evaluated using the χ(2) tests and performed by Bonferroni corrections for multiple comparisons. The significance of the differences in the estimated haplotype frequencies between the myopia and control groups was examined on Haploview 4.2 using χ(2) tests, and haplotypes were corrected by using permutation test after running 50 000 times. RESULTS: Among seven different IGF-1 tSNP tested, the allele frequencies of four tSNP-rs5742629(A/G), rs12423791(G/C), rs35766 (G/A) and rs1457601(T/A) in the myopia and the control groups were A(56.5%, 62.3%)/G(43.5%, 27.7%), G(70.4%, 77.1%)/C(29.6%, 22.9%), G(33.9%, 28.8%)/A(66.1%, 71.2%), T(72.5%, 77.3%)/A(27.5%, 22.7%), respectively. And they showed significant differences (χ(2) = 4.968, 8.059, 4.250, 4.245, P < 0.05) between the two groups. However, only rs12423791 remained significance after Bonferroni correction. The haplotype GC of rs5742629-rs12423791 was associated with extreme high myopia (P = 0.033) after 50 000 permutations for multiple comparisons as well. CONCLUSIONS: The polymorphism of rs12423791 in IGF-1 may be associated with extreme high myopia in the Chinese population.

The complex impact of family caregiver kinship type on the rehabilitation of patients with mental disorders in rural communities of China.

BACKGROUND: In 2009, the Chinese government incorporated severe mental disorders into the central subsidized local health funding project for the effective management, treatment, and reintegration of patients with severe mental disorders from hospitals into the community (Project 686). The conditions that were classified as 'severe' by this project included: schizophrenia, schizoaffective disorders, paranoid disorders, bipolar disorders, mental disorders caused by epilepsy, and mental retardation accompanying mental disorders. Patients in rural communities received better care after project implementation, of which 62.91% were farmers. OBJECTIVE: This paper attempts to investigate the complex impact of Project 686 on the levels of rehabilitation of patients by their families. METHODS: The last follow-up visit of the community psychiatrists in city H in 2020 was used as the time point. Finally, 174 samples were used in the analysis model. The type of kinship between family caregivers and patients with mental disorders was operationalized according to the information provided under the 'primary caregiver' item within the basic information section of the follow-up form. The software Stata15 was used to perform descriptive statistics, baseline regression model analysis, and a robustness test on the types of kinship identified and patients' recovery. RESULTS: The types of kinship, current symptoms, and medication use all affected patients' recovery, were found to have regression coefficients of -0.148, -1.756, and 0.902, respectively. Parents of patients with mental disorders remain in the caregiver category with the largest proportion. Community acceptance of patients is high; current symptoms, medication use, and types of caregiver-patient relationships influence patients' recovery levels. CONCLUSIONS AND DISCUSSION: Project 686 has solved some of the rehabilitation and living difficulties of patients with mental disorders in rural communities. The types of kinship between family caregivers and patients with mental disorders in rural communities affect patients' rehabilitation levels. Patients' current symptoms and medication use can effectively moderate the impact of kinship type on patients' recovery in terms of complete self-knowledge, productive work, and life and good social relationships. It is necessary for mental illness prevention-treatment organizations to establish supplemental, replacement, and substitution mechanisms for the life and rehabilitation of patients with mental disorders in rural communities. Furthermore, the sense of reward and concern for family caregivers should be actively enhanced, and greater scientific use of the rehabilitation function of the 'family care + village doctor management' model should be made.

EFHD1 expression is correlated with tumor-infiltrating neutrophils and predicts prognosis in gastric cancer.

Background: Gastric cancer (GC) ranks third in terms of mortality worldwide. The tumor microenvironment is critical for the progression of gastric cancer. This study investigated the association between EF-hand domain containing 1 (EFHD1) expression and its clinical significance in the tumor microenvironment (TME) of gastric cancer. Methods: We used bioinformatic analyses to assess the relevance of EFHD1 mRNA in the TME of gastric carcinoma tissues and its relationship with clinical features. Therefore, we performed multiplex immunohistochemistry analyses to determine the potential role of the EFHD1 protein in the TME of gastric cancer. Results: EFHD1 expression increased dramatically in gastric cancer tissues compared to levels in non-cancerous tissue samples (t = 6.246, P < 0.001). The EFHD1 protein presentation was associated with invasion depth (χ2 = 19.120, P < 0.001) and TNM stages (χ2 = 14.468, P = 0.002). Notably, EFHD1 protein expression was significantly related to CD66b + neutrophil infiltration of the intratumoral (r = 0.420, P < 0.001) and stromal (r = 0.367, P < 0.001) TME in gastric cancer. Additionally, Cox regression analysis revealed that EFHD1 was an independent prognostic predictor (hazard ratio [HR] = 2.262, P < 0.001) in patients with gastric cancer. Conclusions: Our study revealed the pattern of EFHD1 overexpression in the TME of patients with gastric cancer and demonstrated its utility as a biomarker for unfavorable clinical outcomes, thereby providing a potential immunotherapy target.

Benign prostatic hyperplasia associated with white matter hyperintensities in men.

PURPOSE: Benign prostatic hyperplasia (BPH) describes common noncancerous prostate enlargement. BPH is usually associated with lower urinary tract symptoms and an increased risk of cerebrovascular diseases, such as stroke and its recurrence. White matter hyperintensities (WMHs), markers of cerebral injury, increase the risk of stroke, cognitive impairment, dementia, and death. The relationship between BPH and WMHs remains unclear. This study aimed to determine the association between BPH and WMHs. METHODS: A total of 788 male patients from the First Affiliated Hospital of Kunming Medical University from July 2019 to September 2021 were enrolled in this cross-sectional study. BPH was assessed by abdominal ultrasound, and three independent neuroradiologists rated the presence or absence of WMHs. Multiple imputations of chained equations were used to handle missing data. Logistic regression was used to assess the relationship between BPH and WMHs. RESULTS: Patients with BPH presented an increased risk of WMHs with a crude odds ratio (OR) of 2.76 (95% CI, 2.02-3.79) and an adjusted OR of 1.75 (95% CI, 1.24-2.48) after controlling for potential confounding factors in the multivariate logistic regression. CONCLUSION: We found that BPH was closely associated with WMHs in male Chinese individuals.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020.

Objective: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. Methods: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. Results: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. Conclusion: The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Regulation of mitochondrial network homeostasis by O-GlcNAcylation.

O-GlcNAcylation, a ubiquitous post-translational modification, rapidly modulates protein activity through the reversible addition and removal of O-GlcNAc groups from serine or threonine residues in target proteins, and is involved in multiple metabolic pathways. With the discovery of enzymes and substrates for O-GlcNAc cycling in mitochondria, mitochondrial O-GlcNAc modification and its regulatory role in mitochondrial function deserve extensive attention. Adaptive regulation of the O-GlcNAc cycling in response to energy perturbations is demonstrated to be important in maintaining mitochondrial homeostasis. Dysregulation of O-GlcNAcylation in mitochondria has been associated with various mitochondrial dysfunctions, such as abnormal mitochondrial dynamics, reduced mitochondrial biosynthesis, disruption of the electron transport chain, oxidative stress and the calcium paradox, as well as activation of mitochondrial apoptosis pathways. Here, we outline the current understanding of O-GlcNAc modification in mitochondria and the key discovery of O-GlcNAcylation in regulating mitochondrial network homeostasis. This review will provide insights into targeting mitochondrial O-GlcNAcylation, as well as the mechanisms linking mitochondrial dysfunction and disease.

The basic chemical substances of three medicinal parts from Rhododendron molle G. Don.

Rhododendron Molle G. Don belongs to Ericaceae family. As a toxic traditional Chinese medicine, its roots, flowers, and fruit are often mixed and substituted arbitrarily to treat rheumatoid arthritis in clinic. To clarify the main chemical basis of each medicinal part, and provide sufficient scientific basis for clinical application, analysis using HPLC-ELSD of the roots, flowers, and fruit from R. molle was established, and characteristic chemical constituents of them were separated by tracking. The structures were determined by NMR methods. Finally, 16, 21, and 18 compounds were obtained from the roots, flowers, and fruit, respectively. Overall, 49 compounds were obtained, of which 25 were identified for the first time in R. molle. Meanwhile, among the obtained compounds, 12, 11, and 6 characteristic peaks were identified from the roots, flowers, and fruit, respectively. Thus, the basic chemical substances of the medicinal parts of R. molle were determined initially.

Glomerular filtration Rate, urine Albumin/ creatinine ratio and current perception threshold in patients with diabetic kidney disease.

BACKGROUND: Diabetic microvascular complications, including diabetic kidney disease (DKD), retinopathy (DR), and neuropathy (DN), were major causes of morbidity and mortality in diabetic patients worldwide. It has been suggested that urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were not the only indicators of renal function impairment in DKD and that they were also associated with diabetic peripheral neuropathy (DPN) which might affect nerve conduction velocity (NCV). As 30-40% of DPN patients had no subjective symptoms, while current perception threshold (CPT) could detect sensory nerve damage at an early stage. As a result, we aimed to investigate correlation between UACR, eGFR and CPT in DKD patients. METHODS: A total of 273 DKD patients from the First Affiliated Hospital of Kunming Medical University from January 2018 to June 2020 were enrolled to complete the CPT test. CPT values of the bilateral median nerve and superficial and deep peroneal nerves at 2000 Hz, 250 Hz, and 5 Hz were collected. RESULTS: In normoesthesia and hypaesthesia patients with DKD, MDRD-eGFR correlated negatively with TC (r = -0.135, P = 0.037), left superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.205, P = 0.001) and right superficial peroneal and deep peroneal nerve 2000 Hz CPT (r = -0.154, P = 0.017). Besides, left and right superficial peroneal and deep peroneal nerve 2000 Hz CPT correlated with CKD-EPI-eGFR and UACR. Multivariate logistic regression analysis found left superficial peroneal and deep peroneal nerve 2000 Hz CPT was independently associated with both MDRD-eGFR and CKD-EPI-eGFR. CONCLUSION: Decreased MDRD-eGFR and CKD-EPI-eGFR were expected to be a predictor of peripheral nerve injury in normoesthesia and hypaesthesia patients with DKD.

Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits.

Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-ß-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg-1·d-1) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides.

Are you using the third definition to diagnose sepsis in clinic?-A survey among Chinese intensivists.

BACKGROUND: Since sepsis-3 definition is more accurate and sensitive than previous sepsis definition, implementation the newest diagnosis criteria could definitely bring more benefit to sepsis patients. This study was done to identify the level of current intensivists' knowledge regarding the third international consensus definitions for sepsis and septic shock and its implementation for the diagnosis of sepsis among Chinese adult intensive care units (ICUs). METHODS: A nationwide survey amongst critical care physicians was designed. The questionnaires measured the understanding and the frequency of diagnosis of sepsis and septic shock according to the third international consensus definitions for sepsis and septic shock. One thousand random physician members of Chinese Society of Critical Care Medicine were involved in the survey. A 5-point Likert scale (totally understand, partially understand, understand, hardly understand, do not understand) was used to elicit answers about the degree of understanding the sepsis-3 definition. The other 5-point Likert scale (always, often, sometimes, rarely, never) was used to elicit answers about the frequency of diagnosing sepsis according to the sepsis-3 definition. RESULTS: There were 59 (16.1%) intensivists who could completely understand the sepsis-3 definition. Less practiced intensivists could understand the sepsis-3 definition better than more practiced intensivists (P<0.001). Intensivists from university teaching hospitals understand the sepsis-3 definition better than the intensivists from the community hospitals (P<0.001). Intensivists from small-sized ICUs understand the sepsis-3 definition better than intensivists from big-sized ICUs (P<0.001). There were 60 (16.4%) intensivists who always diagnose sepsis according to the sepsis-3 definition since sepsis-3 published. Less practiced intensivists prefer using the sepsis-3 definition to diagnose sepsis compared with more practiced intensivists (P<0.001). Intensivists from university teaching hospitals prefer using the sepsis-3 definition to diagnose sepsis compared with the intensivists from the community hospitals (P<0.001). Intensivists from small-sized ICUs prefer adapting sepsis-3 definition to diagnosis sepsis compared with intensivists from big-sized ICUs (P<0.001). CONCLUSIONS: In current China, the sepsis-3 definition is well understood and accepted by intensivists.