Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

Comparative study on left-sided versus right-sided hepatectomy for resectable peri-hilar cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Peri-hilar cholangiocarcinoma (pCCA) is a unique entity, and radical surgery provides the only chance for cure and long-term survival. But it is still under debate which surgical strategy (i.e., left-sided hepatectomy, LH or right-sided hepatectomy, RH) should be followed and benefitted. METHODS: We performed a systematic review and meta-analysis to analyze the clinical outcomes and prognostic value of LH versus RH for resectable pCCA. This study followed the PRISMA and AMSTAR guidelines. RESULTS: A total of 14 cohort studies include 1072 patients in the meta-analysis. The results showed no statistical difference between the two groups in terms of overall survival (OS) and disease-free survival (DFS). But compared to the LH group, the RH group exhibited more employment of preoperative portal vein embolization (PVE), higher rate of overall complications, post-hepatectomy liver failure (PHLF), and perioperative mortality, while LH was associated with higher frequency of arterial resection/reconstruction, longer operative time, and more postoperative bile leakage. There was no statistical difference between the two groups in terms of preoperative biliary drainage, R0 resection rate, portal vein resection, intraoperative bleeding, and intraoperative blood transfusion rate. CONCLUSIONS: According to our meta-analyses, LH and RH have comparable oncological effects on curative resection for pCCA patients. Although LH is not inferior to RH in DFS and OS, it requires more arterial reconstruction which is technically demanding and should be performed by experienced surgeons in high-volume centers. Selectin of surgical strategy between LH and RH should be based on not only tumor location (Bismuth classification) but also vascular involvement and future liver remnant (FLR).

Association between healthy lifestyle and the occurrence of cardiometabolic multimorbidity in hypertensive patients: a prospective cohort study of UK Biobank.

BACKGROUND: Cardiometabolic multimorbidity (CMM) is becoming increasingly common in patients with hypertension, and it is well established that healthy lifestyle plays a key role in the prevention of hypertension. However, the association between combined lifestyle factors and CMM in patients with hypertension is uncertain. METHODS: This prospective analysis included the data (obtained from the UK biobank) of participants with hypertension who did not have coronary heart disease (CHD), stroke, or diabetes. The outcome was the occurrence of CMM, defined as ≥ 1 disease of CHD, stroke, and diabetes that occurred in participants with hypertension. Four lifestyle factors (smoking, alcohol consumption, diet, and physical activity) were assessed using a weighted healthy lifestyle score, and participants were divided into four groups: the very unhealthy, unhealthy, healthy, and very healthy groups. The flexible parameter Royston-Parmar proportional hazard model was used to estimate hazard ratios (HRs) between lifestyles and CMM, as well as the difference in CMM-free life expectancy. RESULTS: During a median follow-up of 12.2 years, 9812 (18.4%) of the 53,397 hypertensive patients occurred CMM. Compared with the very unhealthy group, the very healthy group had a 41% reduction in the risk for CMM in hypertensive patients and a 32-50% reduction in the risk for specific cardiometabolic diseases such as CHD, stroke, and diabetes. For each lifestyle factor, non-smoking had the greatest protective effect against CMM (HR: 0.64, 95% confidence interval (CI) 0.60-0.68). A lifestyle combining multiple healthy factors extended CMM-free life expectancy (e.g., six years longer at age 45 years for participants in the very healthy group). CONCLUSIONS: Combined healthy lifestyle factors were associated with a lower risk for CMM in hypertensive patients. This suggests that combined healthy lifestyle should be supported to decrease disease burden.

Association of Healthy Lifestyle and Life Expectancy in Patients With Cardiometabolic Multimorbidity: A Prospective Cohort Study of UK Biobank.

Background: The prevalence of cardiometabolic multimorbidity (CMM), which significantly increases the risk of mortality, is increasing globally. However, the role of healthy lifestyle in the secondary prevention of CMM is unclear. Methods: In total, 290,795 participants with CMM, which was defined as coexistence of at least two of hypertension (HTN), diabetes mellitus (DM), coronary heart disease (CHD), and stroke (ST), and those without these four diseases at baseline were derived from UK Biobank. The associations between specific CMM patterns and mortality, and that between healthy lifestyle (including physical activity, smoking, alcohol consumption, and vegetable and fruit consumption) and mortality in patients with specific CMM patterns were calculated using the flexible parametric Royston-Parmar proportion-hazard model. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated. Results: During a median 12.3-year follow up period, 15,537 (5.3%) deaths occurred. Compared with participants without cardiometabolic diseases, the HRs for all-cause mortality were 1.54 [95% confidence interval (CI): 1.30, 1.82] in participants with HTN + DM, 1.84 (95% CI: 1.59, 2.12) in those with HTN + CHD, 1.89 (95% CI: 1.46, 2.45) in those with HTN + ST, and 2.89 (95% CI: 2.28, 3.67) in those with HTN + DM + CHD. At the age of 45 years, non-current smoking was associated with an increase in life expectancy by 3.72, 6.95, 6.75, and 4.86 years for participants with HTN + DM, HTN + CHD, HTN + ST, and HTN + DM + CHD, respectively. A corresponding increase by 2.03, 1.95, 2.99, and 1.88 years, respectively, was observed in participants with regular physical activity. Non-/moderate alcohol consumption and adequate fruit/vegetable consumption were not significantly associated with life expectancy in patients with specific CMM patterns. Conclusion: Cardiometabolic multimorbidity was associated with an increased risk of mortality. Regular physical activity and non-current smoking can increase life expectancy in patients with specific CMM patterns.

Slippery 3-dimensional porous bioabsorbable membranes with anti-adhesion and bactericidal properties as substitute for vaseline gauze.

Vaseline gauze is a common type of wound dressing that consist of absorbent gauze impregnated with white petrolatum. It has excellent anti-adhesive property which can reduce trauma during dressing changes. However, this kind of wound dressing doesn't have bacterial killing property. Thus, a new kind of wound dressing that has anti-adhesive and bactericidal properties is needed urgently. Creating slippery liquid-impregnated porous surfaces (SLIPS) that insensitive to the structure of porous solid are generally viewed as a new anti-adhesion strategy. To expand the potential utility of SLIPS as substitute for vaseline gauze, dual-functional slippery membranes with anti-adhesion and bactericidal properties by using triclosan, vegetable oils and polylactic acid (PLA) were prepared. It's demonstrated that the triclosan-loaded/vegetable oils-infused PLA membranes (T/V-PM) has good cytocompatibility in vitro. Notably, the T/V-PM can gradually release biocide molecule into surrounding aqueous media. Moreover, the T/V-PM can kill planktonic bacterial cells without loss of their antifouling property. The in vivo study revealed that the T/V-PM can prevent the secondary injuries during wound dressing changes. This simple and low-cost strategy can be applied to inhibit blood and bacterial adhesion, and prevent tissue adhesion at the wound site. It's confirmed that the T/V-PM have great potential as substitute for vaseline gauze.

Biomimetic nano-NOS mediated local NO release for inhibiting cancer-associated platelet activation and disrupting tumor vascular barriers.

Platelets attribute to the hypercoagulation of blood and maintenance of the tumor vascular integrity, resulting in limited intratumoral perfusion of nanoparticle into solid tumors. To overcome these adversities, we herein present an antiplatelet strategy based on erythrocyte membrane-enveloped proteinic nanoparticles that biomimic nitric oxide synthase (NOS)with co-loading of l-Arginine (LA) and photosensitizer IR783 for local NO release and inhibition of the activation of tumor-associated platelets specifically, thereby enhancing vascular permeability and accumulation of the nanoparticles in tumors. A cRGD-immobolized membrane structure is constructed to actively target platelets and cancer cells respectively, through overexpressed integrin receptors such as integrin αIIbß3 and αvß3, accelerating the inhibition of platelet activation and endocytosis of nanoparticles by tumor cells. Bio-mimicking the arginine/NO pathway in vivo, synergistical delivery of LA and IR783 enables LA molecules readily oxidize to NO with O2 that is mediated by activated IR783, the resulted NO not only retards the activity of platelets to disrupt the vascular integrity of tumor but also enhances toxicity to cancer cells. In addition, NIR-controlled release localizes the NO spatiotemporally to tumor-associated platelets and prevents undesirable systemic bleeding substantially. The reduction of the hypercoagulable state is further demonstrated by the down-regulation of tissues factor (TF) expression in tumor cells. Our study describes a promising approach to combat cancer, which advances the biomimetic NOS system as the potent therapeutic forces toward clinic applications.

Poly(γ-glutamic acid)-based electrospun nanofibrous mats with photodynamic therapy for effectively combating wound infection.

Pathogenic bacterial infections associated with wound healing progress usually result in serious complications. Herein, biocompatible and antimicrobial electrospun nanofibrous mats with photodynamic therapy (PDT) effect were fabricated to accelerate the infected wound healing. The nanofibrous mats were fabricated by co-electrospining of polyanionic poly(γ-glutamic acid) (γ-PGA) and cationic photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra (p-toluenesulfonate) (TMPyP) in aqueous solution and stabilized by the chemical crosslinking. The as-prepared nanofibrous mats can not only confer the moist microenvironment to the wound bed, but also provide potent bactericidal activity upon visible light irradiation by releasing the cytotoxic reactive oxygen species (ROS). The antibacterial assay in vitro showed that they can effectively eradicate the board-spectrum bacteria at a relatively low loading dose of TMPyP (e.g., 0.1 wt%). Meanwhile, those nanofibrous mats showed good biocompatibility with no obvious adverse effects on mammalian cells and red blood cells (RBCs). The animal test in vivo suggested that the restrained inflammatory reaction and better wound healing could be achieved upon timely and effective antibacterial treatment with negligible local toxicities. This biocompatible and antibacterial γ-PGA-TMPyP nanofibrous mat may show great potential in practical infection-resistant applications, particularly for wound dressing applications.

E4BP4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases.

T follicular helper (Tfh) cells are indispensable for the formation of germinal center (GC) reactions, whereas T follicular regulatory (Tfr) cells inhibit Tfh-mediated GC responses. Aberrant activation of Tfh cells contributes substantially to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). Nonetheless, the molecular mechanisms mitigating excessive Tfh cell differentiation are not fully understood. Herein we demonstrate that the adenovirus E4 promoter-binding protein (E4BP4) mediates a feedback loop and acts as a transcriptional brake to inhibit Tfh cell differentiation. Furthermore, we show that such an immunological mechanism is compromised in patients with SLE. Establishing mice with either conditional knockout (cKO) or knockin (cKI) of the E4bp4 gene in T cells reveals that E4BP4 strongly inhibits Tfh cell differentiation. Mechanistically, E4BP4 regulates Bcl6 transcription by recruiting the repressive epigenetic modifiers HDAC1 and EZH2. E4BP4 phosphorylation site mutants have limited capability with regard to inhibiting Tfh cell differentiation. In SLE, we detected impaired phosphorylation of E4BP4, finding that this compromised transcription factor is positively correlated with disease activity. These findings unveiled molecular mechanisms by which E4BP4 restrains Tfh cell differentiation, whose compromised function is associated with uncontrolled autoimmune reactions in SLE.

Hydrogen Peroxide and Glutathione Dual Redox-Responsive Nanoparticles for Controlled DOX Release.

Polymer nanoparticulate drug delivery systems that respond to reactive oxygen species (ROS) and glutathione (GSH) simultaneously at biologically relevant levels hold great promise to improve the therapeutic efficacy to cancer cells with reduced side effects of chemo drugs. Herein, a novel redox dual-responsive amphiphilic block copolymer (ABP) that consists of a hydrophilic poly (ethylene oxide) block and a hydrophobic block bearing disulfide linked phenylboronic ester group as pendant is synthesized, and the DOX loaded nanoparticles (BSN-DOX) based on ABPs with varied hydrophobic block length are fabricated for DOX delivery. The self-immolative leaving reaction of phenylboronic ester triggered by extracellular ROS and the cleavage of disulfide linkages induced by intracellular GSH both lead to rapid DOX release from BSN-DOX, resulting in an on-demand DOX release. Moreover, BSN-DOX show better tumor inhibition and lower side effects in vivo compared with free drug.

One-step hydrophobization of tannic acid for antibacterial coating on catheters to prevent catheter-associated infections.

Catheter-associated infections (CAIs) caused by bacterial colonization are significant problems in clinics. Thus, effective antibacterial coatings for biomedical catheters to prevent bacterial infections are urgently needed. Ideal coatings should include the advantage of potent antibacterial properties and being easily and economically modified on the catheter surface. Due to their advantages of adhesive capability on various substrates, an increasing number of coatings based on plant polyphenols have been developed. However, the hydrophilicity of plant polyphenols limits their utilization in coatings. Herein, hydrophobic tannic acid (TA) was synthesized via the one-step electrostatic assembly of TA and benzalkonium chloride (BAC) with the green solvent water as the medium. The as-prepared hydrophobic TA (TBA) facilely formed a stable and colorless coating on the luminal and outer surface of biomedical catheters with broad-spectrum antibacterial activity and biocompatiblity. It was demonstrated that the TBA-coated surfaces displayed excellent bactericidal activity toward Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and more than 99% of the above bacteria were killed by the TBA-coated films. The test of the coated catheters in vitro also showed the excellent antibacterial activity of both the outer and luminal surfaces of the catheter. Moreover, in an in vivo mouse model, the coated catheters relatively prevented bacterial colonization compared to the uncoated catheters. Meantime, no significant cytotoxicity and host response for Cell Counting Kit-8 (CCK-8) and tissue compatibility in vivo were observed, indicating the better biocompatibility of the TBA coating. This preparation method overcomes the limitation of the traditional hydrophilic tannic acid as a coating and provides a new method for preventing medical indwelling device-associated infections.

Inhibition of Inflammation-Associated Thrombosis with ROS-Responsive Heparin-DOCA/PVAX Nanoparticles.

Inflammation-associated thrombosis is a non-negligible source of mortalities and morbidities worldwide. To manipulate inflammation-associated coagulation, nanoparticles that contain anti-inflammatory polymer (copolyoxalate containing vanillyl alcohol, PVAX) and anti-thrombotic heparin derivative deoxycholic acid (Hep-DOCA) are prepared. The strategy takes advantage of the reducted side effects of heparin through heparin conjugation, achievement of long-term anti-inflammation by inflammation-trigged release of anti-inflammatory agents, and formation of PVAX/heparin-DOCA nanoparticles by co-self-assembly. It is demonstrated that the Hep-DOCA conjugate and PVAX are synthesized successfully; PVAX and Hep-DOCA nanodrugs (HDP) are obtained by co-assembly; the HDP nanoparticles effectively reduce the inflammation and coagulation without inducing lethal bleeding both in vivo and in vitro. The method provided here is versatile and effective, which paves new way to develop nanodrugs to treat inflammation-associated thrombosis safely.

Biomimicking Dual-Responsive Extracellular Matrix Restoring Extracellular Balance through the Na/K-ATPase Pathway.

Biomedical implant mimicking the physiological extracellular matrix (ECM) is a new strategy to modulate the cell microenvironment to improve implant integrity and longevity. However, the biomimicking ECM suffers from low sensitivity to pathological change and low efficiency to restore the physiological state in vivo. To overcome these problems, reactive oxygen species (ROS) and K+ dual-responsive micro-/nanofibers that encapsulate ascorbic acid-2-glucoside (AA-2G) are fabricated on an elastomer substrate with electrospinning to mimic the ECM. The strategy is based on the fact that ROS and K+ dual responsiveness enhance the sensitivity of the ECM to pathological changes and delivery of AA-2G from the ECM to cell membrane promotes reactivating Na/K-ATPase and shifting cellular diseased conditions to the normal state. We demonstrate that the ROS and K+-responsive tripolymer of poly(ethylene glycol)diacrylate, 1,2-ethanedithiol, and 4-nitrobenzo-18-crown-6-ether (PEGDA-EDT-BCAm) are synthesized successfully; the ECM composed of acylated poly(caprolactone)/PEGDA-EDT-BCAm/AA-2G micro-/nanofibers is prepared through reactive electrospinning; the ECM is sensitive to ROS and K+ concentration in the microenvironment to release AA-2G, which targets the membrane to remove the excessive ROS and reactivate Na/K-ATPase; as a result, the ECM reduces oxidative stress and restores the extracellular physiological state both in vitro and in vivo. This work provides basic principles to design an implant that can adjust the extracellular microenvironment while avoiding pathogenicity to improve implant integrity and longevity in vivo.

Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression.

Ten-eleven translocation (TET) proteins regulate DNA methylation and gene expression by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Although Tet2/Tet3 deficiency has been reported to lead to myeloid cell, B-cell and invariant natural killer T (iNKT) cell malignancy, the effect of TET on regulatory T cells (Tregs) has not been elucidated. We found that Tet2/Tet3 deficiency in Tregs led to lethal hyperproliferation of CD4+Foxp3+ T cells in the spleen and mesenteric lymph nodes after 5 months of age. Additionally, in aged Treg-specific Tet2/Tet3-deficient mice, serum IgG1, IgG3, IgM and IgE levels were markedly elevated. High IL-17 expression was observed in both Foxp3+ and Fopx3- CD4+ T cells, and adoptive transfer of Tet2/Tet3-deficient Tregs into lymphopenic mice inhibited Foxp3 expression and caused conversion into IL-17-producing cells. However, the conserved non-coding DNA sequence-2 (CNS2) region of the Foxp3 gene locus, which has been shown to be particularly important for stable Foxp3 expression, was only partly methylated. We identified novel TET-dependent demethylation sites in the Foxp3 upstream enhancer, which may contribute to stable Foxp3 expression. Together, these data indicate that Tet2 and Tet3 are involved in Treg stability and immune homeostasis in mice.

Bioinspired Antioxidant Defense System Constructed by Antioxidants-Eluting Electrospun F127-Based Fibers.

Cells were continuously exposed to oxidative damage by overproduction of reactive oxygen species (ROS) when they contacted implanted biomaterials. The strategy to prevent cells from oxidative injures remains a challenge. Inspired by the antioxidant defense system of cells, we constructed a biocompatible and ROS-responsive architecture on the substrate of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS). The strategy was based on fabrication of architectures through reactive electrospinning of mixture including SEBS, acylated Pluronic F127, copolymer of poly(ethylene glycol) diacrylate and 1,2-ethanedithiol (PEGDA-EDT), and antioxidants (AA-2G) and ROS-triggered release of AA-2G from microfibers to detoxify the excess ROS. We demonstrated that the stable and hydrophilic architecture was constructed by phase separation of SEBS/F127 components and cross-linking between polymer chains during electrospinning; the ROS-responsive fibers controlled the release of AA-2G and the interaction of AA-2G with ROS reduced the oxidative damage to cells. The bioinspired architecture not only reduced mechanical and oxidative damage to cells but also maintained normal ROS level for physiological hemostasis. This work provides basic principles to design and develop antioxidative biomaterials for implantation in vivo.

Anti-N-methyl-d-aspartate receptor encephalitis in children of Central South China: Clinical features, treatment, influencing factors, and outcomes.

BACKGROUND AND PURPOSE: We analyzed the clinical manifestations of children with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis in Central South China and the factors influencing the effectiveness of treatment. METHODS: A retrospective study of children (0-14years old) with anti-NMDAR encephalitis in Central South China was carried out from March 2014 to November 2016. Demographics, clinical features, treatment, outcome, and the factors influencing the effectiveness of treatment were reviewed. RESULTS: Fifty-one patients with anti-NMDAR encephalitis were enrolled (age from 4months to 14years old; median age, 8years; 30 females). Forty-five patients (88%) presented with psychiatric symptoms, 40 (78%) with dyskinesia and movement disorders, 39 (77%) with sleep disturbances, 34 (67%) with seizures, 30 (59%) with a decreased level of consciousness (Glasgow score<15), 28 (55%) with speech disturbances, and twelve (24%) with autonomic instability. None presented with hypoventilation, and only one patient (female, 14years old) had an ovarian teratoma. All patients received first-line immunotherapy, 25 patients both received firstline and second-line immunotherapy. Forty-four of the 51 patients achieved good outcomes (score on the modified Rankin Scale [mRS] of 0-2), while the other seven had poor outcomes (mRS score of 3-5). CONCLUSIONS: This study investigated the clinical characteristics of children (aged 14 or younger) with anti-NMDAR encephalitis in Central South China. Patients with decreased consciousness, PICU stay and autonomic instability were more likely to have no or limited response to first-line immunotherapy and to require second-line or even more aggressive immunotherapy. Children with anti-NMDAR encephalitis in China have a much lower incidence of tumors, lower mortality rates, and a lower proportion of lethal autonomic instability than adults.

Sleep Duration and Cardiometabolic Risk Among Chinese School-aged Children: Do Adipokines Play a Mediating Role?

Study Objectives: To assess the associations between sleep duration and cardiometabolic risk factors in Chinese school-aged children and to explore the possible mediating role of adipokines. Methods: Sleep duration was collected in 3166 children from the Beijing Child and Adolescent Metabolic Syndrome study. Glucose homeostasis and other cardiometabolic risk factors were assessed. Serum adipokines including leptin, total and high-molecular-weight (HMW) adiponectin, resistin, fibroblast growth factor 21 (FGF21), and retinol binding protein 4 (RBP4) were determined. Results: Among the 6- to 12-year-old children, after adjusting for covariates including puberty, short sleep duration was associated with increased body mass index (BMI), waist circumference, fasting glucose, insulin and homeostasis model assessment of insulin resistance (all p < .0001), higher triglyceride and lower high-density lipoprotein cholesterol (p < .05), along with increased leptin (p < .0001), FGF21 (p < .05) and decreased HMW-adiponectin (p ≤ .01); the association with leptin remained significant after further adjustment for BMI. However, these associations, except for glucose (p < .0001), disappeared after further adjusted for leptin. For the 13-18 years old group, short sleep duration was associated with higher BMI, waist circumference, and RBP4 (all p < .05), but the association with RBP4 was attenuated after adjusting for BMI (p = .067). Conclusions: Short sleep duration is strongly associated with obesity and hyperglycemia (in 6-12 years old), along with adverse adipokine secretion patterns among Chinese children. The associations with cardiometabolic risk factors appear to be more pronounced in younger children, and could be explained, at least partially, by leptin levels.

Organ-specific biomarkers in lupus.

Systemic lupus erythematosus (SLE) is a complex and highly heterogeneous disease, which affects multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nerve system. While the etiopathogenesis of SLE still remains unclear, genetic susceptibilities and aberrant epigenetic modifications are believed to be involved. For precision therapy, it is necessary to assess accurately and objectively organ involvements and disease activity, which is difficult by current clinical laboratory tests. Biomarkers, which are a biologic, genetic, epigenetic or a chemical characteristic and conveniently detectable, serve as measures of disease diagnosis, activity, prognosis, and manifestation prediction, thereby providing instruction for individualized therapy. In addition, biomarkers differ according to different manifestations, since the disease activity index and treatments vary significantly. For example, unlike other non-renal SLE, lupus nephritis requires significant immunosuppressive drugs. Over the past decades, the research on biomarkers in lupus has been strengthened and numerous promising biomarkers have been identified at levels of genomics, transcriptomics and proteomics. In this review, we summarize the conventional and novel biomarkers in the tissue-specific manner, and discuss their roles in specific organ diagnosis, future manifestation prediction, disease activity assessment and their correlation with histology results. By doing so, it aims to shed a light on individualized treatment.

Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients.

Xeroderma pigmentosum (XP) is a rare genetic disorder which is divided into eight complementation groups: XP-A to XP-G and XP-V. Some XP patients demonstrate severe cutaneous and neurological manifestations, management of which requires timely diagnosis and intervention. We performed clinical evaluation and genetic analysis on 19 patients, the largest cohort of XP to date in China. Twenty-three mutations from six groups were identified, 16 of which were novel. All patients developed marked freckle-like pigmentation on sun-exposed sites while patients with XP-A, XP-D, XP-F and XP-G showed acute sunburn reactions. Only XP-A patients displayed progressive neurological degeneration. A relatively larger proportion of XP-A and XP-C were found in Chinese XP patients. One XP case and two carriers were prenatally determined. This study extended the mutation spectrum of XP in China and may aid in the diagnosis and treatment of Chinese XP patients.