Icariin restrains NLRP3 inflammasome-mediated Th2 immune responses and ameliorates atopic dermatitis through modulating a novel lncRNA MALAT1/miR-124-3p axis.

CONTEXT: Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. OBJECTIVE: The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. MATERIALS AND METHODS: BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. RESULTS: Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. DISCUSSION AND CONCLUSIONS: The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

High-quality genomes reveal significant genetic divergence and cryptic speciation in the model organism Folsomia candida (collembola).

The collembolan Folsomia candida Willem, 1902, is widely distributed throughout the world and has been frequently used as a test organism in soil ecology and ecotoxicology studies. However, it is questioned as an ideal "standard" because of differences in reproductive modes and cryptic genetic diversity between strains from various geographical origins. In this study, we obtained two high-quality chromosome-level genomes of F. candida, for a parthenogenetic strain (named FCDK, 219.08 Mb, 25,139 protein-coding genes) and a sexual strain (named FCSH, 153.09 Mb, 21,609 protein-coding genes), reannotated the genome of the parthenogenetic strain reported by Faddeeva-Vakhrusheva et al. in 2017 (named FCBL, 221.7 Mb, 25,980 protein-coding genes) and conducted comparative genomic analyses of the three strains. High genome similarities between FCDK and FCBL based on synteny, genome architecture, mitochondrial and nuclear gene sequences suggest that they are conspecific. The seven chromosomes of FCDK are each 25%-54% larger than the corresponding chromosomes of FCSH, showing obvious repetitive element expansions and large-scale inversions and translocations but no whole-genome duplication. The strain-specific genes, expanded gene families and genes in nonsyntenic chromosomal regions identified in FCDK are highly related to the broader environmental adaptation of parthenogenetic strains. In addition, FCDK has fewer strain-specific microRNAs than FCSH, and their mitochondrial and nuclear genes have diverged greatly. In conclusion, FCDK/FCBL and FCSH have accumulated independent genetic changes and evolved into distinct species after 10 million years ago. Our work provides important genomic resources for studying the mechanisms of rapidly cryptic speciation and soil arthropod adaptation to soil ecosystems.

Training Benefits and Injury Risks of Standing Yoga Applied in Musculoskeletal Problems: Lower Limb Biomechanical Analysis.

Standing yoga poses strengthen a person's legs and helps to achieve the goal of musculoskeletal rehabilitation, but inadequate exercise planning can cause injuries. This study investigated changes in the electromyogram and joint moments of force (JMOFs) of lower extremities during common standing yoga poses in order to explore the feasibility and possible injury risk in dealing with musculoskeletal problems. Eleven yoga instructors were recruited to execute five yoga poses (Chair, Tree, Warrior 1, 2, and 3). The results revealed significant differences in hip, knee, and ankle JMOFs and varying degrees of muscle activation among the poses. Among these poses, rectus femoris muscle activation during the Chair pose was the highest, Warrior 2 produced the highest muscle activation in the vastus lateralis of the front limb, while Warrior 1 had the highest muscle activation in the vastus medialis of the back limb. Therefore, all three poses can possibly be suggested as a therapeutic intervention for quadriceps strengthening. Warrior 1 was possibly suggested as a therapeutic intervention in order to reduce excessive lateral overload of the patella, but the possible adverse effects of Warrior 2 with the highest knee adductor JMOF in the back limb could raise joint reaction forces across the medial condyles. In single-leg balance postures, Warrior 3 had unique training effects on the hamstring, and is therefore suggested as a part of hamstring rehabilitation exercises. The Tree pose induced low lower-extremity JMOFs and a low level of thigh muscle activations when it was performed by senior instructors with excellent balance control; however, for yoga beginners with insufficient stability, it will be a useful training mode for strengthening the muscles that help to keep one upright. This study quantified the physical demands of yoga poses using biomechanical data and elucidated the structures and principles underlying each yoga movement. This is crucial for yoga practitioners.

[Mechanism of Mahuang Lianqiao Chixiaodou Decoction in treating eczema by network pharmacology and molecular docking technology].

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.

A bifunctional enzyme belonging to cytochrome P450 family involved in the O-dealkylation and N-dealkoxymethylation toward chloroacetanilide herbicides in Rhodococcus sp. B2.

BACKGROUND: The chloroacetamide herbicides pretilachlor is an emerging pollutant. Due to the large amount of use, its presence in the environment threatens human health. However, the molecular mechanism of pretilachlor degradation remains unknown. RESULTS: Now, Rhodococcus sp. B2 was isolated from rice field and shown to degrade pretilachlor. The maximum pretilachlor degradation efficiency (86.1%) was observed at a culture time of 5 d, an initial substrate concentration 50 mg/L, pH 6.98, and 30.1 °C. One novel metabolite N-hydroxyethyl-2-chloro-N-(2, 6-diethyl-phenyl)-acetamide was identified by gas chromatography-mass spectrometry (GC-MS). Draft genome comparison demonstrated that a 32,147-bp DNA fragment, harboring gene cluster (EthRABCDB2), was absent from the mutant strain TB2 which could not degrade pretilachlor. The Eth gene cluster, encodes an AraC/XylS family transcriptional regulator (EthRB2), a ferredoxin reductase (EthAB2), a cytochrome P450 monooxygenase (EthBB2), a ferredoxin (EthCB2) and a 10-kDa protein of unknown function (EthDB2). Complementation with EthABCDB2 and EthABDB2, but not EthABCB2 in strain TB2 restored its ability to degrade chloroacetamide herbicides. Subsequently, codon optimization of EthABCDB2 was performed, after which the optimized components were separately expressed in Escherichia coli, and purified using Ni-affinity chromatography. A mixture of EthABCDB2 or EthABDB2 but not EthABCB2 catalyzed the N-dealkoxymethylation of alachlor, acetochlor, butachlor, and propisochlor and O-dealkylation of pretilachlor, revealing that EthDB2 acted as a ferredoxin in strain B2. EthABDB2 displayed maximal activity at 30 °C and pH 7.5. CONCLUSIONS: This is the first report of a P450 family oxygenase catalyzing the O-dealkylation and N-dealkoxymethylation of pretilachlor and propisochlor, respectively. And the results of the present study provide a microbial resource for the remediation of chloroacetamide herbicides-contaminated sites.

Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China.

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population.

Family history of liver cancer may modify the association between HBV infection and liver cancer in a Chinese population.

BACKGROUND & AIMS: The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. METHODS: We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. RESULTS: Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). CONCLUSIONS: Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.

Tobacco Smoking Modifies the Association between Hormonal Factors and Lung Cancer Occurrence among Post-Menopausal Chinese Women.

Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case-control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at >54 vs. <46 years old) was associated with increased risk of lung cancer (SBOR, semi-Bayes adjusted odds ratio = 1.61, 95% PI, posterior interval = 1.10-2.36). More pregnancies (2 or 3 vs. 0 or 1) was associated with decreased risk (SBOR = 0.71, 95% PI = 0.53, 0.95). Ever being a smoker and having two or fewer pregnancies in one's lifetime could jointly increase the odds of lung cancer (RERI, relative excess risk due to interaction = 1.71, 95% CI = 0.03, 3.38). An increased number of ovulatory cycles was associated with increased risk of lung cancer (SBOR for 13 ovulatory cycles = 1.02, 95% CI = 1.00+, 1.04).

Consumption of garlic and its interactions with tobacco smoking and alcohol drinking on esophageal cancer in a Chinese population.

Garlic consumption has been associated inversely with esophageal cancer (EC); however, its interactions with tobacco smoking and alcohol consumption have never been evaluated in an epidemiological study. We evaluated the potential interactions between garlic intake and tobacco smoking as well as alcohol consumption in a population-based case-control study with 2969 incident EC cases and 8019 healthy controls. Epidemiologic data were collected by face-to-face interviews using a questionnaire. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated and additive and multiplicative interactions were evaluated using unconditional logistic regression models, adjusting for potential confounding factors. Semi-Bayes (SB) adjustments were used to reduce potential false-positive findings. EC was associated inversely with raw garlic intake [SB-adjusted OR for more than once a week=0.68, 95% CI: 0.57-0.80], with a strong dose-response pattern in the overall analysis and in the stratified analyses by smoking and drinking. EC was associated positively with smoking and alcohol drinking, with SB-adjusted OR of 1.73 (95% CI: 1.62-1.85) and 1.37 (95% CI: 1.28-1.46) in dose-response effects of increased intensity and longer duration of smoking/drinking. Moreover, garlic intake interacts with smoking [synergy index (S)=0.83, 95% CI: 0.67-1.02; ratio of OR=0.88, 95% CI: 0.80-0.98] and alcohol drinking (S=0.73, 95% CI: 0.57-0.93; ratio of OR=0.86, 95% CI: 0.77-0.95) both multiplicatively and additively. Our findings suggested that high intake of raw garlic may reduce EC risk and may interact with tobacco smoking and alcohol consumption, which might shed a light on the development of EC as well as a potential dietary intervention among high-risk smokers and drinkers for EC prevention in the Chinese population.

Interaction between tobacco smoking and hepatitis B virus infection on the risk of liver cancer in a Chinese population.

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population-based case-control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti-HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi-Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33-1.96) among male and 0.82 (95% CI: 0.53-1.26) among female. Age at first cigarette, duration of smoking and pack-years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg-negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03-1.52) for HBsAg-negative ever smokers, 7.66 (95% CI: 6.05-9.71) for HBsAg-positive never smokers, and 15.68 (95% CI: 12.06-20.39) for HBsAg-positive ever smokers. These different odds ratios indicated super-additive (RERI: 7.77, 95% CI: 3.81-11.73) and super-multiplicative interactions (ROR: 1.64, 95% CI: 1.17-2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.

Beneficial effects of Huaiqihuang on hyperglycemia-induced MPC5 podocyte dysfunction through the suppression of mitochondrial dysfunction and endoplasmic reticulum stress.

The present study was performed to investigate the effect of Huaiqihuang (HQH) on hyperglycemia (HG)-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress in MPC5 podocytes. The effects of HQH and HG on cell viability were assessed using an MTT assay. mRNA and protein expression levels were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell apoptosis was assessed using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling, whereas reactive oxygen species production and alterations in mitochondrial membrane potential were assessed using flow cytometry. DNA damage was evaluated using a comet assay. The results demonstrated that treatment of podocytes with HQH markedly suppressed the HG­induced generation of reactive oxygen species. HQH also significantly improved mitochondrial membrane potential in podocytes exposed to HG. When the podocytes were treated with HG, Ca2+ levels were significantly increased, compared with those in the control group, whereas treatment of the podocytes with HQH significantly reversed the HG­induced upregulation of Ca2+ secretion. Treatment of the podocytes with HQH significantly reversed the HG­induced upregulation of glucose­related protein 78 (GRP78) and C/EBP­homologous protein, which were used as indicators of ER stress. Furthermore, GRP78 loss­of­function attenuated HG­induced podocyte dysfunction, including cell apoptosis and DNA damage. In conclusion, beneficial effects of HQH on HG­induced MPC5 podocyte dysfunction were observed, and occurred through the suppression of mitochondrial dysfunction and ER stress.

A Novel and Efficient Method for Bacteria Genome Editing Employing both CRISPR/Cas9 and an Antibiotic Resistance Cassette.

As Cas9-mediated cleavage requires both protospacer and protospacer adjacent motif (PAM) sequences, it is impossible to employ the CRISPR/Cas9 system to directly edit genomic sites without available PAM sequences nearby. Here, we optimized the CRISPR/Cas9 system and developed an innovative two-step strategy for efficient genome editing of any sites, which did not rely on the availability of PAM sequences. An antibiotic resistance cassette was employed as both a positive and a negative selection marker. By integrating the optimized two-plasmid CRISPR/Cas system and donor DNA, we achieved gene insertion and point mutation with high efficiency in Escherichia coli, and importantly, obtained clean mutants with no other unwanted mutations. Moreover, genome editing of essential genes was successfully achieved using this approach with a few modifications. Therefore, our newly developed method is PAM-independent and can be used to edit any genomic loci, and we hope this method can also be used for efficient genome editing in other organisms.

[Pollution Characteristics of PCDD/Fs in Ambient Air and Exposure Risk Assessment Around a Municipal Solid Waste Incinerator in Beijing].

Ambient air was sampled and analyzed around a municipal solid waste incinerator (MSWI) in Beijing from April 2014 to January 2015 to investigate the concentrations, profiles and seasonal variations of PCDD/Fs in the region using HRGC-HRMS technique. The mass concentrations and TEQ of 2,3,7,8-substituted PCDD/Fs in the air samples ranged from 8.9 to 140 pg·m-3 and from 0.11 to 1.8 pg·m-3, respectively. The concentration values at 4 sampling sites in haze day in autumn and all 7 sampling sites in winter were higher than the ambient air standard of 0.6 pg·m-3 for dioxins regulated in Japan. 1,2,3,4,6,7,8-HpCDF and OCDD dominated PCDD/Fs in all the samples for all four seasons with average contribution fractions of 20.5% and 14.0%, respectively, while 2,3,4,7,8-PeCDF was the dominant congener contributing to TEQ (43.3%). The spatial distribution basically exhibited a trend that the concentrations at all sites were comparable and not related to the distances from the source. Seasonal variation showed obviously higher concentration in winter than the other three seasons, which may attribute to the high concentration of ambient particulate matter due to domestic heating and worse atmospheric dispersion that occurred in winter. The homologue and congener profiles of PCDD/Fs in the air samples differed from those of the flue gas emission from the MSWI, consistent with the principle component analysis results. Dioxin inhalation exposure dose estimation showed that the dioxin inhalation exposure risk of residents living in the studied area was at a relatively safe level[0.060-0.224 pg·(kg·d)-1]. However, the dioxin inhalation exposure risk in heavily polluted seasons still needs great concerns.

[Suggestions for standardized management of nomenclature and classification of neonatal diseases].

Nomenclature and classification of diseases are not only related to clinical diagnosis and treatment, but also involved in the fields such as management and exchange of medical information, medical expense payments, and medical insurance payment. In order to standardize clinical physicians' diagnostic and treatment activities, medical records, and the first page of medical records, this article elaborates on the basic principles and methods for nomenclature and classification of diseases with reference to international nomenclature of diseases and international classification of diseases. Meanwhile, in view of the problems in clinical practice, this article proposes the classification of neonatal diseases, the basic procedure and writing rules in the diagnosis of neonatal diseases, and death diagnosis principles.

Recurrent rhabdomyolysis and glutaric aciduria type I: a case report and literature review.

BACKGROUND: Glutaric acidemia type I (GA-I) is a rare metabolic disorder caused by mutation of the glutaryl- CoA dehydrogenase (GCDH) gene. The occurrence of rhabdomyolysis with GA-I is extremely rare. METHODS: We reported a child with recurrent rhabdomyolysis and undiagnosed glutaric acidemia type I (GA-I). And a literature review was performed. RESULTS: A 4.5-year-old girl was admitted to our hospital due to recurrent rhabdomyolysis for 3 times within three years. At the third admission, she was diagnosed with GA-I by biochemical testing and mutation analysis. The girl was found to have a serine to leucine replacement mutation of the GCDH gene in exon 8 at position 764. Other three patients with rhabdomyolysis and GA-I were discovered by literature searching. CONCLUSIONS: This report highlights that patients with GA-I may have an increased risk of rhabdomyolysis.

24h Urinary Protein Levels and Urine Protein/Creatinine Ratios Could Probably Forecast the Pathological Classification of HSPN.

This study aimed to assess the relevance of laboratory tests in Henoch-Schönlein purpura nephritis (HSPN) classification, and determine accurate classification factors. This prospective study included 694 HSPN patients who underwent ultrasound-guided percutaneous renal biopsy (PRB). Renal specimens were scored according to International Study of Kidney Disease in Children (ISKDC) classification. Meanwhile, blood samples were immediately collected for laboratory examination. The associations between laboratory parameters and HSPN classification were assessed. Significant differences in levels of serum Th1/Th2 cytokines, immunoglobulins, T-lymphocyte subsets, complement, and coagulation markers were obtained between HSPN patients and healthy children. Interestingly, 24h urinary protein (24h-UPRO) levels and urine protein/urine creatinine ratios could determine HPSN grade IIb, IIIa, and IIIb incidences, with areas under ROC curve of 0.767 and 0.731, respectively. At 24h-UPRO >580.35mg/L, prediction sensitivity and specificity were 75.2% and 70.0%, respectively. These values became 53.0% and 82.3%, respectively, with 24h-UPRO exceeding 1006.25mg/L. At urine protein/urine creatinine > 0.97, prediction sensitivity and specificity were 65.5% and 67.2%, respectively, values that became 57.4% and 80.0%, respectively, at ratios exceeding 1.2. Cell and humoral immunity, coagulation and fibrinolytic systems are all involved in the pathogenesis of HSPN, and type I hypersensitivity may be the disease trigger of HSPN. 24h-UPRO levels and urine protein/creatinine ratios could probably forecast the pathological classification of HSPN.

Recurrent exercise-induced acute kidney injury by idiopathic renal hypouricemia with a novel mutation in the SLC2A9 gene and literature review.

BACKGROUND: Idiopathic renal hypouricemia (iRHUC) is an autosomal recessive hereditary disorder, characterized by impaired tubular uric acid transport, re-absorption insufficiency and/or the acceleration of secretions. Some patients present with severe complications, such as exercise-induced acute kidney injury (EIAKI) and nephrolithiasis. CASE PRESENTATION: Herein, we report the case of a girl with severe iRHUC (serum urate 0.05 mg/dL, fractional excretion of uric acid 295.99%) associated with recurrent EIAKI, in whom the disease was caused by a homozygous mutation (g.68G > A in exon 3) in the SLC2A9 gene. Her family members (father, mother and brother) carried the same mutation but were heterozygous, without any signs of severe hypouricemia. CONCLUSIONS: Our findings indicate that iRHUC is a rare disorder but that it should also be considered in patients with EIAKI, especially in those patients who manifest with moderately elevated or normal serum concentrations of uric acid during the acute phase of AKI. Mutational screening of the SLC2A9 gene is necessary for the diagnosis of iRHUC, and homozygous mutations of the SLC2A9 alleles can cause severe hypouricemia. Careful attention should be paid to any signs of hypouricemia during the recovery phase of AKI and long-term follow-up.

Persistent asymptomatic isolated hematuria in children: clinical and histopathological features and prognosis.

BACKGROUND: This study involving 351 children who had undergone kidney biopsy secondary to persistent asymptomatic isolated hematuria was undertaken to assess histological diagnosis of the disease and its natural history and prognosis. METHODS: The patients were divided into two groups: 215 patients with asymptomatic isolated microhematuria (AIMH; proteinuria <0.1 g/day) and 136 patients with persistent asymptomatic microhematuria, recurrent macrohematuria and/or proteinuria (AMHP; proteinuria 0.1-0.25 g/day). After kidney biopsy, the patients were monitored for 2-10 years. RESULTS: Normal biopsies or minor abnormalities were more frequent in AIMH patients than those in AMHP patients, who exhibited IgA nephropathy more frequently. During the 2- to 10-year follow-up period, adverse renal events (i.e., development of proteinuria, hypertension, or impaired renal function) were observed in 13/215 (6.0%) patients with AIMH and 31/136 (22.8%) patients with AMHP (χ(2)=15.521, P<0.001). CONCLUSIONS: Normal biopsies or minor abnormalities were more frequently observed in AIMH patients, whereas IgA nephropathy and adverse renal events were more frequent in AMHP. Microscopic hematuria, especially when accompanied by macroscopic hematuria and proteinuria, may represent an important risk factor for the development of chronic kidney disease.

Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China.

Alcohol drinking is a major risk factor for esophageal cancer (EC) and the metabolism of ethanol has been suggested to play an important role in esophageal carcinogenesis. Epidemiologic studies, including genomewide association studies (GWAS), have identified single nucleotide polymorphisms (SNPs) in alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs) to be associated with EC. Using a population-based case-control study with 858 EC cases and 1,081 controls conducted in Jiangsu Province, China, we aimed to provide further information on the association of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) polymorphisms with EC in a Chinese population. Results showed that ADH1B (rs1229984) was associated with EC with odds ratios (ORs) of 1.34 [95% confidence interval (CI): 1.08-1.66] for G-allele carriers compared to A/A homozygotes. No heterogeneity was detected on this association across different strata of alcohol drinking and tobacco smoking. Statistical interaction between ALDH2 (rs671) and alcohol drinking on EC susceptibility in both additive and multiplicative scales was observed. Compared to G/G homozygotes, A-allele carriers were positively associated with EC among moderate/heavy drinkers (OR = 1.64, 95% CI: 1.12-2.40) and inversely associated with EC among never/light drinks (OR = 0.75, 95% CI: 0.54-1.03). In addition, statistical interaction between ALDH2 and ADH1B polymorphisms on EC susceptibility among never/light drinkers was indicated. We did not observe association of ADH1C polymorphism with EC. In conclusion, our findings indicated that ADH1B (rs1229984) was associated with EC independent of alcohol drinking and tobacco smoking status and alcohol drinking interacted with ALDH2 (rs671) on EC susceptibility in this high-risk Chinese population.