Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

Engineering Internal and External Low-Coordination Atoms in Nickel-Organic Framework Nanoarrays to Promote the Electrochemical Oxygen Evolution Reaction.

Monometallic nickel-organic frameworks based on a carboxylated ligand [2,6-naphthalenedicarboxylic acid (Ni-NDC)] have abundant and uniformly distributed single-atom Ni sites, enabling superior oxygen evolution reaction (OER) activity. In theory, most of the Ni atoms inside Ni-NDC microcrystals are coordinatively saturated except for the surface. Therefore, there are no accessible low-coordination atoms (LCAs) as electrocatalytic sites for the OER. One effective way is to expose more LCAs by preparing self-supporting Ni-NDC nanoarrays (Ni-NDC NAs) with hierarchical secondary structural units. Another effective method is to create more internal LCAs by removing partial ligands or coordination atoms attached to the Ni atoms. Herein, by combining the two strategies, we engineered LCAs in the interior and exterior of Ni-NDC to synergistically accelerate the OER. In brief, ultrathick "brick-like" Ni-NDC NAs were first prepared with dissolution and coordination effects of NDC on self-sacrificial templates of "agaric-like" nickel hydroxide nanoarrays [Ni(OH)2 NAs]. Subsequently, dual-coordinated NDC was partially replaced by monocoordinated 2-naphthoic acid (NA). The Ni-NDC NAs were further tailed into ultrathin "liner leaf-like" nanoneedle arrays (LCAs-Ni-NDC NAs). As a consequence, the LCAs-Ni-NDC NAs have more internal and external LCAs, which can deliver an OER performance that is superior to that of Ni-NDC NAs.

Utilizing disease transmission and response capacities to optimize covid-19 control in Malaysia.

OBJECTIVES: Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia. METHODS: Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed. RESULTS: CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic. CONCLUSIONS: The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia.

SHP2: its association and roles in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease. Src homology 2 domain containing protein tyrosine phosphatase (SHP2) is a member of the protein tyrosine phosphatases (PTPs) family. To date, relationship between SHP2 and SLE pathogenesis is not elucidated. METHOD: We measured plasma levels of SHP2 in 328 SLE patients, 78 RA patients, 80 SS patients and 79 healthy controls by ELISA, and discussed association of SHP2 in SLE patients, potential of plasma SHP2 as a SLE biomarker. Moreover, histological and serological changes were evaluated by flow cytometry, HE/Masson examination, immunofluorescence test in pristane-induced lupus mice after SHP2 inhibitor injection to reveal role of SHP2 in lupus development. RESULTS: Results indicated that SHP2 plasma levels were upregulated in SLE patients and correlated with some clinical, laboratory characteristics such as proteinuria, pyuria, and may be a potential biomarker for SLE. After SHP2 inhibitor treatment, hepatosplenomegaly and histological severity of the kidney in lupus mice were improved. SHP2 inhibitor reversed DCs, Th1, and Th17 cells differentiation and downregulated inflammatory cytokines (IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) and autoantibodies (ANA, anti-dsDNA) production in pristane-lupus mice. CONCLUSION: In summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.

16S full-length gene sequencing analysis of intestinal flora in breast cancer patients in Hainan Province.

Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P < 0.05 for all subgroups) . The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P < 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer.

Accelerating Electrochemical Water Oxidation Activity by Tailoring Morphology and Electronic Structure of Nickel Organic Framework Nanoarrays with a Fe Etching Effect.

Fe-mediated nickel organic framework nanoarrays (NiFe-MOFs NAs) on carbon cloth were successfully constructed from ultrathin nanosheets via an etching effect. This strategy also combined the dissolution and coordination effect of acidic ligand (2,6-naphthalenedicarboxylic acid, NDC) to a self-sacrificial template of Ni(OH)2 NAs. Benefiting from the strong Fe etching effect, dense and thick brick-like Ni-NDC nanoplates were tailored into loose and ultrathin NiFe-NDC nanosheets with abundant squamous nanostructures, which were still tightly attached to carbon cloth. As a consequence, more coordinatively unsaturated metal sites (CUMSs) that served as active centers were exposed to accelerate oxygen production. Meanwhile, the electronic structure of active Ni centers was modulated by the incorporation of Fe atoms. The charge density redistribution between Ni and Fe ultimately optimized the energy barrier of the adsorption/desorption of oxygenated intermediates, promoting the kinetics for water oxidation.

IL-38, a potential therapeutic agent for lupus, inhibits lupus progression.

BACKGROUND: Previous studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown. METHODS: The therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38-/- mice. Thus, SLE was induced via pristane in WT and IL-38-/- mice. Afterwards, the liver, spleen, and kidney of each mouse were obtained. The flow cytometric analysis of the immune cells, serologic expression of inflammatory cytokines and autoantibodies, renal histopathology, and inflammatory signaling were evaluated. RESULTS: WT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38-/- mice whose lupus progressed, had elevated cells of CD14+, CD19+, CD3+, and Th1, upregulated inflammatory cytokines and autoantibodies, and severe pathological changes in kidney. Administration of recombinant murine IL-38 to pristane-treated IL-38-/- mice improved their renal histopathology, which depended on ERK1/2, JNK1/2, p38, NF-κB p65, and STAT5 signaling pathways. CONCLUSION: IL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE.

Introducing a Synergistic Ligand Containing an Exotic Metal in Metal-Organic Framework Nanoarrays Enabling Superior Electrocatalytic Water Oxidation Performance.

Designing and fabricating well-aligned metal-organic framework nanoarrays (MOF NAs) with high electrocatalytic activity and durability for water oxidation at large current density remain huge challenges. Here the vertical NiFc-MOF NAs constructed from agaric-like nanosheets were fabricated by introducing a ligand containing an exotic Fe atom to coordinate with Ni ion using Ni(OH)2 NAs as a self-sacrificing template. The NiFc-MOF NAs exhibited superior water oxidation performance with a very low overpotential of 161 mV at the current density of 10 mA cm-2. Chronoamperometry was tested at an overpotential of 250 mV, which delivered an initial industrial-grade current density of 702 mA cm-2 and still remained at 694 mA cm-2 after 24 h. Furthermore, it possessed fast reaction kinetics with a small Tafel slope of 29.5 mV dec-1. The superior electrocatalytic performance can be ascribed to the structural advantage of vertically grown agaric-like NAs and the synergistic electron coupling between Ni and Fe atoms, namely, electron transfer from Ni to Fe atoms in NiFc-MOF NAs. The exposed density and valence state of active Ni sites were synchronously increased. Furthermore, the energy barrier for the adsorption/desorption of oxygenated intermediates was ultimately optimized for water oxidation. This work provides a novelty orientation to accelerate electrocatalytic performance of MOF NAs by introducing self-sacrificing templates containing one metal and synergistic ligand containing dissimilar metal.

Higher dietary acid load is associated with hyperuricemia in Chinese adults: a case-control study.

BACKGROUND: This study aims to explore the association between dietary acid load and hyperuricemia in Chinese adults. METHODS: A case-control study was conducted. Adult participants with hyperuricemia were recruited as the cases and those without hyperuricemia were as the controls. Food consumption was evaluated by food frequency questionnaire (FFQ). Dietary acid load was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Dietary acid load was divided into four levels: the first quartile (Q1), the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4). Logistic regression model was applied for exploring the association between dietary acid load (PRAL and NEAP) and hyperuricemia. Odds ratio (OR) and its correspondence confidence interval (CI) were computed. RESULTS: A total of 290 participants were eligible in this study, in which there were 143 individuals in case group and 147 in control group. A higher level of PRAL was found to be associated with odds of hyperuricemia. ORs of hyperuricemia for Q2, Q3 and Q4 of PRAL were 2.74 (95%CI: 1.94 ~ 3.88, p-value: 0.004), 2.90 (95%CI: 2.05 ~ 4.10, p-value: 0.002) and 3.14 (95%CI: 2.22 ~ 4.45, p-value: 0.001), respectively. There was a positive association between elevated NEAP and hyperuricemia. OR of hyperuricemia for Q2 was not material significance (OR:1.54, 95%CI: 0.93 ~ 2.53, p-value: 0.210), however, ORs of hyperuricemia for Q3 (OR: 2.40, 95%CI: 1.70 ~ 3.38, p-value: 0.011) and Q4 (OR: 3.27, 95%CI: 2.31 ~ 4.62, p-value: 0.001) were statistically significant. CONCLUSION: Higher level of dietary acid load was found to be associated with hyperuricemia in Chinese adults, indicative of advocation of a well-balanced diet in this population.

Progress in ZnO Nanosensors.

Developing various nanosensors with superior performance for accurate and sensitive detection of some physical signals is essential for advances in electronic systems. Zinc oxide (ZnO) is a unique semiconductor material with wide bandgap (3.37 eV) and high exciton binding energy (60 meV) at room temperature. ZnO nanostructures have been investigated extensively for possible use as high-performance sensors, due to their excellent optical, piezoelectric and electrochemical properties, as well as the large surface area. In this review, we primarily introduce the morphology and major synthetic methods of ZnO nanomaterials, with a brief discussion of the advantages and weaknesses of each method. Then, we mainly focus on the recent progress in ZnO nanosensors according to the functional classification, including pressure sensor, gas sensor, photoelectric sensor, biosensor and temperature sensor. We provide a comprehensive analysis of the research status and constraints for the development of ZnO nanosensor in each category. Finally, the challenges and future research directions of nanosensors based on ZnO are prospected and summarized. It is of profound significance to research ZnO nanosensors in depth, which will promote the development of artificial intelligence, medical and health, as well as industrial, production.

Association of MASP2 levels and MASP2 gene polymorphisms with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. MASP2 is a mediator that plays an important role in complement system. As dysregulation of the complement system has been demonstrated to correlate with SLE pathogenesis, the role of MASP2 in lupus has not been widely discussed. In the present study, serum levels of MASP2 were evaluated in 61 lupus patients and 98 healthy controls by training cohort, and then a validation cohort including 100 lupus, 100 rheumatoid arthritis, 100 osteoarthritis, 100 gout, 44 Sjogren's syndrome, 41 ankylosing spondylitis patients confirmed the findings. Receiver operating characteristic (ROC) curve analysis determined the discriminatory capacity for serum MASP2. PCR methods tested the association of MASP2 gene polymorphisms (rs7548659, rs17409276, rs2273346, rs1782455 and rs6695096) and SLE risk. Impact of polymorphism on MASP2 serum levels was evaluated as well. Results showed that serum levels of MASP2 were significantly higher in lupus patients and correlated with some clinical, laboratory characteristics in the training cohort, and were much higher as compared to that in different rheumatic diseases patients in the validation cohort. Serum MASP2 showed a good diagnostic ability for lupus. Genotype frequencies and allele frequency of polymorphisms rs7548659, rs2273346 were strongly related to SLE risk, and genotypes of rs17409276, rs1782455, rs76695096 were significantly correlated with lupus genetic susceptibility. Interestingly, patients carrying GA genotype of rs17409276, TT, TC genotype of rs6695096 showed higher levels of serum MASP2. The findings suggested that MASP2 may be a potential disease marker for lupus, and correlate with SLE pathogenesis.

IL-38: A novel cytokine in systemic lupus erythematosus pathogenesis.

IL-38 is a newly identified cytokine that belongs to the IL-1 family. In our previous study, we found elevated plasma levels of IL-38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL-38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL-38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane-induced murine lupus model was used to further demonstrate the effects of IL-38 on cytokines in vivo and discuss the significance of IL-38 in lupus development. The results showed that mRNA expression of IL-38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL-38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF-α, IL-1ß, IL-6 and IL-23 were elevated in patients with SLE and were related to plasma levels of IL-38. In vitro, PBMCs of patients with SLE stimulated with IL-38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL-38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down-regulated inflammatory cytokines. In conclusion, IL-38 may suppress synthesis of pro-inflammatory cytokines and therefore regulate lupus pathogenesis.

Surfactant-Free Approach for Engineering an Ultrathin Ti-Doped Ni(OH)2 Nanosheet on Carbon Cloth: Experimental and Theoretical Insight into Boosted Alkaline Water Oxidation Activity.

Ti-based layered double hydroxides (LDHs) have enormous potential in photocatalysis, electrocatalysis, and photoelectrocatalysis. However, Ti-based LDHs are rarely reported because of the difficulties of the preparation process, in which the Ti precursors are more prone to hydrolysis into titanium hydroxide. In this work, toward robust, efficient, and earth-abundant electrocatalysts for water oxidation in alkaline environments, we have engineered Ti-doped Ni(OH)2 nanosheet arrays on carbon cloth [Ti-Ni(OH)2/CC] with a facile solvothermal and surfactant-free method. The experimental tests show that the activity of Ti-Ni(OH)2-1/CC (∼12.5 atom % Ti substitution) is optimal among these materials. In addition, the activity is correlated with the Ti substitution ratio and reversed with higher Ti doping level (≥25 atom % Ti substitution). Therein, η10 of Ti-Ni(OH)2-1/CC is as low as 196 mV, and it is still maintained at 210 mV after a long-term chronopotentiometry (CP) test at a constant current density of 10 mA cm-2 for 32 h, demonstrating superior activity and long-term durability. Density functional theory calculations further reveal that dilute Ti substitution produces extra active sites and promotes more optimal OH* adsorption to the surface of the electrocatalyst.

Insights into IL-29: Emerging role in inflammatory autoimmune diseases.

Interleukin-29 (IL-29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL-29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL-29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL-29. The information collected revealed the regulatory role of IL-29 and may give important implications for its potential in clinical treatment.

Gene polymorphisms and serum levels of TL1A in patients with rheumatoid arthritis.

Recent findings showed elevated expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) in rheumatoid arthritis (RA) patients and arthritis mice. However, whether TL1A gene polymorphisms may correlate with RA susceptibility needs to be discussed. This case-control study was performed on 350 RA patients and 556 healthy subjects to identify TL1A genetic variants (rs3810936, rs6478109, and rs7848647) and their possible association with TL1A levels, susceptibility to and severity of RA. Odds ratio and 95% confidence interval were calculated to represent the correlation between TL1A polymorphisms and RA. The TL1A serum levels were evaluated. Results showed that frequencies of TC, TT + TC genotypes of rs3810936, rs7848647 in RA patients were significantly lower in RA patients compared with controls. Patients with C allele showed more severe disease course (disease activity index: erythrocyte sedimentation rate, rheumatoid factor) than in carriers of T allele. However, the allele or genotype frequencies of rs6478109 were not associated with RA. In addition, TL1A genetic variants conferred higher TL1A levels in RA patients compared with controls. In conclusion, these findings indicated an association between TL1A rs3810936, rs7848647 variation and the susceptibility of RA in a sample of Chinese individuals, and TL1A may correlate with severity of RA.

Targeting IL-34 in inflammatory autoimmune diseases.

Interleukin-34 (IL-34) shares a common receptor with macrophage colony-stimulating factor (M-CSF), and can bind to CSF-1R, induces lymphocytes differentiation, proliferation, and regulates the synthesis of inflammatory components. Recent findings reported aberrant expression of IL-34 in several autoimmune disorders, such as lupus, arthritis, systemic sclerosis, inflammatory bowel diseases. The functional analysis further demonstrated that IL-34 may perform significantly in these inflammatory autoimmune disorders. IL-34 might consider as a biomarker for these diseases. I hope this collection of the findings in this review will improve knowledge of the role of IL-34, and targeting IL-34 may give the potential for these autoimmune diseases.

Association between TL1A gene polymorphisms and systemic lupus erythematosus in a Chinese Han population.

Our previous studies showed elevated tumor necrosis factor-like ligand 1 aberrance (TL1A) expression in systemic lupus erythematosus (SLE). However, TL1A polymorphisms with SLE susceptibility remain to be elucidated. In addition, we made meta-analysis to evaluate the relationship of TL1A polymorphisms and autoimmune diseases owing to inconsistent results. The present research was carried out by 404 SLE, 150 primary Sjogren's syndrome (pSS) patients, and 574 healthy individuals. Three TL1A polymorphisms (rs3810936, rs6478109, rs7848647) were genotyped using TaqMan genotyping assay. Then, the meta-analysis was performed by collecting the present case-control study and previously published research. Results showed that genotypes of rs3810936, rs7848647 were different between SLE patients and healthy controls, whereas no significant association was observed in the three polymorphisms and pSS patients. Genotypes distribution of rs6478109, rs7848647 were strongly related to lupus nephritis within SLE (p = 0.004, p = 0.011), respectively. Moreover, combined meta-analysis consisted of ten comparative research involving 4,305 patients and 5,600 controls. An association between autoimmune diseases and rs6478109 polymorphism was found. Our findings indicate that gene polymorphisms (rs3810936, rs7848647) of TL1A might correlate with lupus.

High incidence of drug-resistant Mycobacterium tuberculosis in Hainan Island, China.

OBJECTIVES: To assess the proportion of drug-resistant tuberculosis (TB) cases and to identify independent risk factors associated with drug-resistant TB in Hainan. METHODS: Descriptive analysis of demographic and clinical data of culture-positive TB patients to assess the trends in drug-resistant TB at the Provincial Clinical Center on Tuberculosis of Hainan between 2014 and 2017. RESULTS: 994 patients were recruited into the study. Overall, the proportion of patients resistant to at least one TB drug tested was 36.1% (359/994). The most frequent resistance was to isoniazid (INH, 29.8%), followed by rifampin (RIF, 29.3%), streptomycin (19.3%), ofloxacin (OFX, 17.4%), ethambutol (9.5%) and kanamycin (KAN, 3.2%). Of 291 RIF-resistant isolates, 228 (78.4%) were also resistant to INH, while the remaining 63 (21.6%) were susceptible to INH. Among those with multidrug-resistant tuberculosis (MDR-TB), 41.2% had additional resistance to OFX and 3.9% to KAN. 8.8% of MDR-TB patients were affected by extensively drug-resistant (XDR-TB). Females were more likely to infected with MDR-TB than males, and young people (<20 years old) were more likely to have MDR-TB; patients exhibited decreasing MDR-TB risk with increasing age. CONCLUSIONS: Our data provide the first primary understanding of the drug-resistant TB epidemic in Hainan. The high incidence of drug resistance, especially RIF and FQ resistance, highlight the importance of interventions for preventing epidemics of drug-resistant TB. Younger age is an independent predictor of MDR-TB, reflecting the potential transmission in this population.

OBJECTIFS: Evaluer la proportion de cas de tuberculose (TB) résistante aux médicaments et identifier les facteurs de risque indépendants associés à la TB résistante à Hainan. MÉTHODES: Analyse descriptive des données démographiques et cliniques de patients TB à culture positive pour évaluer les tendances de la TB résistante au Centre Clinique Provincial de la TB de Hainan entre 2014 et 2017. RÉSULTATS: 994 patients ont été recrutés dans l'étude. Au total, la proportion de patients résistant à au moins un antituberculeux testé était de 36,1% (359/994). La résistance la plus fréquente était à l'isoniazide (INH, 29,8%), suivi par la rifampine (RIF, 29,3%), la streptomycine (19,3%), l'ofloxacine (OFX, 17,4%), l'éthambutol (9,5%) et la kanamycine (KAN, 3,2%). Sur les 291 isolats résistants au RIF, 228 (78,4%) étaient également résistants à l'INH, tandis que les 63 restants (21,6%) étaient sensibles à l'INH. Parmi ceux avec la multirésistance (TB-MDR), 41,2% présentaient une résistance supplémentaire à l'OFX et 3,9% à la KAN. 8,8% des patients atteints de TB-MDR étaient atteints d'une TB ultrarésistante (TB-XDR). Les femmes étaient plus susceptibles d'être infectées par la TB-MDR que les hommes et les jeunes (<20 ans) étaient plus susceptibles d'être atteints de TB-MDR; les patients présentaient un risque décroissant de TB-MDR avec l'âge. CONCLUSIONS: Nos données fournissent la première compréhension importante de l'épidémie de TB résistante à Hainan. L'incidence élevée de la résistance aux médicaments, en particulier des résistances RIF et FQ, souligne l'importance des interventions pour prévenir les épidémies de TB résistante. L'âge plus jeune est un facteur indépendant de prédiction de la TB-MDR, reflétant le potentiel de transmission dans cette population.

Panax notoginseng Saponins Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Human SH-SY5Y Cells by Regulating the Expression of Inflammatory Factors through miR-155.

Panax notoginseng saponins (PNS) have been widely used in China to treat stroke. Accumulating evidence has found that microRNA (miR)-155 plays critical roles in the pathology of ischemic stroke. Here we investigated whether PNS plays a protective effect against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced focal inflammation and injury in SH-SY5Y cells by regulating miR-155 expression. Treatment with PNS at a concentration less than 160 µg/mL had no effect on the proliferation of SH-SY5Y cell. In OGD/R-induced SH-SY5Y cells, 160 µg/mL PNS treatment promoted cell proliferation and cell cycle progression, as well as decreased inhibited apoptosis and miR-155 expression. However, overexpression of miR-155 attenuated the promotion effects of PNS on cell proliferation and cell cycle, apoptosis inhibition in OGD/R-induced SH-SY5Y cells. Moreover, 160 µg/mL PNS treatment decreased the levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in OGD/R-induced SH-SY5Y cells, whereas overexpression of miR-155 reversed PNS-induced decreases in the levels of IL-1ß, IL-6, and TNF-α in OGD/R-treated SH-SY5Y cells. In conclusion, PNS attenuated OGD/R-induced injury in human undifferentiated SH-SY5Y cells by regulating the expression of inflammatory factors through miR-155.

Isolated Influences of Surgery Repair on Maxillofacial Growth in Complete Unilateral Cleft Lip and Palate.

PURPOSE: The purpose of this study was to investigate the maxillofacial morphologic characteristics of children with complete unilateral cleft lip and palate (UCLP) with and without surgical correction and better understand the relation between surgery and inhibition of maxillary growth. MATERIAL AND METHODS: Lateral cephalometric radiography was performed in 3 groups of 9-year-old children: 1) 20 whose UCLP was repaired in infancy; 2) 20 who had no surgical repair or any relevant treatments; and 3) 20 without UCLP who served as controls. RESULTS: Marked morphologic deviations of patients in groups 1 and 2 compared with the control group were observed in the cranial base angle, maxillary heights, length and shape of the mandible, and anteroposterior jaw relation. Facial morphology was similar between groups 1 and 2 except for less vertical maxillary height and more obtuse gonial angle in group 1. CONCLUSION: The facial morphology of children with UCLP differs markedly from that of normal children. The differences can be ascribed to the difference in the primary anomaly in the UCLP groups, but isolated surgery has minor effects on growth disturbances.