Yezo Virus Infection in Tick-Bitten Patient and Ticks, Northeastern China.

We identified Yezo virus infection in a febrile patient who had a tick bite in northeastern China, where 0.5% of Ixodes persulcatus ticks were positive for viral RNA. Clinicians should be aware of this potential health threat and include this emerging virus in the differential diagnosis for tick-bitten patients in this region.

Increased serine synthesis in cumulus cells of young infertile women with diminished ovarian reserve.

STUDY QUESTION: What are the differences in gene expression of cumulus cells (CCs) between young women with diminished ovarian reserve (DOR) and those of similar age with normal ovarian reserve (NOR)? SUMMARY ANSWER: Gene expression and metabolome profiling analysis demonstrate that the de novo serine synthesis pathway (SSP) is increased in the CCs of young women with DOR. WHAT IS KNOWN ALREADY: The incidence of DOR has risen, tending to present at younger ages. Its mechanisms and aetiologies are still poorly understood. Abnormal metabolism is present in luteinized CCs of patients with DOR. Previous studies have revealed that mitochondrial dysfunction and impaired oxidative phosphorylation in CCs are related to DOR in women of advanced age. The pathogenic mechanisms likely differ between young women with DOR and cases associated with advanced maternal age. Several studies have examined amino acid metabolism in the follicle, with a focus on embryo development, but less information is available about CCs. The physiological significance of de novo serine synthesis in follicles and oocytes remains largely unknown. STUDY DESIGN, SIZE, DURATION: CC samples were obtained from 107 young infertile women (age <38 years) undergoing ICSI, from July 2017 to June 2019, including 54 patients with DOR and 53 patients with NOR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte development data were analysed retrospectively. Comprehensive genome-wide transcriptomics of CCs was performed. Differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to categorize the functions of the DEGs and identify significantly enriched pathways. The transcript and protein levels of key enzymes involved in serine synthesis were verified in additional samples using quantitative real-time PCR (qRT-PCR) (n = 10) and capillary western blotting (n = 36). Targeted metabolomics of amino acids in CC extracts was performed by ultrahigh-performance liquid MS (UHPLC-MS/MS). MAIN RESULTS AND THE ROLE OF CHANCE: The number of oocytes (2.4 ± 2.2 versus 12.1 ± 5.3) and metaphase II oocytes (2.1 ± 2.0 versus 9.9 ± 4.9) retrieved was significantly decreased in the DOR versus the NOR group, respectively (P < 0.0001). The rates of fertilization (80.7% versus 78.8%), viable embryos (73.7% versus 72.5%), and high-quality embryos (42.8% versus 49.0%) did not differ between the DOR and NOR groups, respectively (P > 0.05). A total of 95 DEGs were found by transcriptome sequencing. GO and KEGG analyses demonstrated that the DEGs were linked to amino acid metabolism and suggested significantly higher activity of the de novo SSP in the CCs of young women with DOR. Further qRT-PCR and capillary western blotting revealed that key enzymes (PHGDH, PSAT1, PSPH, and SHMT2) involved in de novo serine synthesis were upregulated, and UHPLC-MS/MS analysis showed increases in serine and glycine (a downstream product of serine) levels in the CCs of young patients with DOR. Our data clearly demonstrate that the de novo SSP, which diverts 3-phosphoglycerate from glycolysis to serine synthesis, was upregulated in young DOR CCs. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Regarding the reproductive capacity of young patients DOR, the pregnancy outcomes were not analysed. The sample size was limited, and only women undergoing ICSI were examined since this was a prerequisite for the acquisition of CCs, which may cause selection bias. The exact mechanisms by which the SSP in CCs regulates ovarian reserve still require further study. WIDER IMPLICATIONS OF THE FINDINGS: Our research presents new evidence that alterations of the SSP in CCs of young infertile women are associated with DOR. We believe this is a significant contribution to the field, which should be key for understanding the cause and mechanisms of ovarian hypofunction in young women. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Ministry of Science and Technology of China (2018YFC1005001) and National Natural Science Foundation of China (31601197). There were no competing interests. TRIAL REGISTRATION NUMBER: N/A.

A New Segmented Virus Associated with Human Febrile Illness in China.

BACKGROUND: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected. METHODS: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients. RESULTS: We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness. CONCLUSIONS: A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).

The Association between Dietary Vitamin C Intake and the Risk of Esophageal Cancer: An Updated Dose-Response Meta-Analysis.

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections.

Effect of nutritional and environmental conditions on biofilm formation of avian pathogenic Escherichia coli.

AIMS: To study the effects of environmental stress and nutrient conditions on biofilm formation of avian pathogenic Escherichia coli (APEC). METHODS AND RESULTS: The APEC strain DE17 was used to study biofilm formation under various conditions of environmental stress (including different temperatures, pH, metal ions, and antibiotics) and nutrient conditions (Luria-Bertani [LB] and M9 media, with the addition of different carbohydrates, if necessary). The DE17 biofilm formation ability was strongest at 25°C in LB medium. Compared to incubation at 37°C, three biofilm-related genes (csgD, dgcC, and pfs) were significantly upregulated and two genes (flhC and flhD) were downregulated at 25°C, which resulted in decreased motility. However, biofilm formation was strongest in M9 medium supplemented with glucose at 37°C, and the number of live bacteria was the highest as determined by confocal laser scanning microscopy. The bacteria in the biofilm were surrounded by a thick extracellular matrix, and honeycomb-like or rough surfaces were observed by scanning electron microscopy. Moreover, biofilm formation of the DE17 strain was remarkably inhibited under acidic conditions, whereas neutral and alkaline conditions were more suitable for biofilm formation. Biofilm formation was also inhibited at specific concentrations of cations (Na+ , K+ , Ca2+ , and Mg2+ ) and antibiotics (ampicillin, chloramphenicol, kanamycin, and spectinomycin). The real-time quantitative reverse transcription PCR showed that the transcription levels of biofilm-related genes change under different environmental conditions. CONCLUSIONS: Nutritional and environmental factors played an important role in DE17 biofilm development. The transcription levels of biofilm-related genes changed under different environmental and nutrient conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings suggest that nutritional and environmental factors play an important role in APEC biofilm development. Depending on the different conditions involved in this study, it can serve as a guide to treating biofilm-related infections and to eliminating biofilms from the environment.

Intraoperative Nice knots assistance for reduction in displaced comminuted clavicle fractures.

PURPOSE: The Nice knots have been widely used in orthopedic surgeries to fix torn soft tissue and fracture in recent years. The study aims to investigate the clinical efficacy and prognosis of intraoperative and postoperative Nice Knots-assisted reduction in the treatment of displaced comminuted clavicle fracture. METHODS: From Jan 2014 to Dec 2019, 75 patients diagnosed with unilateral closed displaced comminuted clavicle fracture were treated with open reduction and internal fixation (ORIF) in this study. Nice knot group (the NK group) included 38 patients and the other 37 patients were in the traditional group (the TK group). The time of operation and the amount of bleeding during operation were recorded. Post-operative clinical outcomes and radiographic results were recorded and compared between these two groups. The Visual Analogue Scale (VAS), Neer score, Rating Scale of the American Shoulder and Elbow Surgeons, Constant-Murley score and complications such as infection, nonunion, implant loosening, fragment displacement and hardware pain were observed in the two groups. RESULTS: In the comparison between the two groups, there was no significant difference in age, sex, the cause of displaced clavicle fracture, and other basic information between the two groups. The operation time, intraoperative fluoroscopy time, and intraoperative blood loss were significantly reduced in the NK group (P < 0.01). There were 2 cases of plate fracture in the TK group. The follow-up results showed that there was no significant difference in VAS, Neer score, ASES, and Constant-Murley scores between the two groups. CONCLUSION: The use of Nice knot, in comminuted and displaced clavicle fractures can reduce intraoperative blood loss, shorten operation time, facilitate intraoperative reduction, and achieve satisfactory postoperative clinical results. This study demonstrates that Nice knot is a simple, safe, practical and effective auxiliary reduction method.

Evolution of an X-Linked miRNA Family Predominantly Expressed in Mammalian Male Germ Cells.

MicroRNAs (miRNAs) are important posttranscriptional regulators of gene expression. However, comprehensive expression profiles of miRNAs during mammalian spermatogenesis are lacking. Herein, we sequenced small RNAs in highly purified mouse spermatogenic cells at different stages. We found that a family of X-linked miRNAs named spermatogenesis-related miRNAs (spermiRs) is predominantly expressed in the early meiotic phases and has a conserved testis-specific high expression pattern in different mammals. We identified one spermiR homolog in opossum; this homolog might originate from THER1, a retrotransposon that is active in marsupials but extinct in current placental mammals. SpermiRs have expanded rapidly with mammalian evolution and are diverged into two clades, spermiR-L and spermiR-R, which are likely to have been generated at least in part by tandem duplication mediated by flanking retrotransposable elements. Notably, despite having undergone highly frequent lineage-specific duplication events, the sequences encoding all spermiR family members are strictly located between two protein-coding genes, Slitrk2 and Fmr1. Moreover, spermiR-Ls and spermiR-Rs have evolved different expression patterns during spermatogenesis in different mammals. Intriguingly, the seed sequences of spermiRs, which are critical for the recognition of target genes, are highly divergent within and among mammals, whereas spermiR target genes largely overlap. When miR-741, the most highly expressed spermiR, is knocked out in cultured mouse spermatogonial stem cells (SSCs), another spermiR, miR-465a-5p, is dramatically upregulated and becomes the most abundant miRNA. Notably, miR-741-/- SSCs grow normally, and the genome-wide expression levels of mRNAs remain unchanged. All these observations indicate functional compensation between spermiR family members and strong coevolution between spermiRs and their targets.

Postharvest benzothiazole treatment enhances healing in mechanically damaged sweet potato by activating the phenylpropanoid metabolism.

BACKGROUND: Sweet potato often suffers mechanical damage during harvest, handling, and transportation. Infections, water loss, and quality changes of sweet potato caused by mechanical damage pose great financial losses. Wound healing is an effective method to alleviate such problems. In this study, the effects of postharvest treatment with benzothiazole (BTH) on wound healing of sweet potato was investigated. RESULTS: Postharvest BTH treatment of sweet potatoes promoted lignin accumulation in wounded tissues, and 100 mg L-1 BTH exhibited better effects than 50 mg L-1 or 150 mg L-1 BTH. The biosynthesis of lignin in wounded tissues significantly decreased the weight loss of sweet potatoes. An increase in respiration intensity after BTH treatment was observed. The total phenolic and flavonoid contents and the activity of phenylalanine ammonia-lyase, peroxidase, and polyphenol oxidase were increased in BTH-treated sweet potatoes. This suggests that BTH increases phenylpropanoid metabolism. CONCLUSION: Postharvest 100 mg L-1 BTH treatment could promote wound healing in mechanically damaged sweet potatoes. The activation of the phenylpropanoid metabolism might be the mechanism of action of BTH in wound healing. © 2020 Society of Chemical Industry.

Tunable artificial microwave blackbodies based on metasurfaces.

Inspired by the classic hole-cavity blackbody model, we propose an open metasurface blackbody operating at microwave frequencies, whose unit cell is a dielectric resonator lying on an opaque metal plate. The resonator has a high temperature coefficient of dielectric constant, thus the blackbody can be thermally tunable. Furthermore, when the resonator is combined with ferrite, a magnetically tunable blackbody is also obtained. Absorption spectra of these two tunable blackbody unit cells are measured, and they agree very well with the simulated results. The proposed blackbodies offer a new opportunity for practical tunable microwave absorbers in applications.

The role of the ptsI gene on AI-2 internalization and pathogenesis of avian pathogenic Escherichia coli.

The LuxS/AI-2 quorum sensing mechanism can regulate the physiological functions of avian pathogenic Escherichia coli (APEC) through internalization of the small molecule autoinducer-2 (AI-2). The ptsI gene encodes enzyme I, which participates in the phosphotransferase system (PTS) that regulates the virulence and AI-2 internalization of bacteria. The aim of the present study was to determine the effect of ptsI on AI-2 internalization and other pathogenesis process in APEC using a ptsI mutant of the APEC strain DE17 (serotype O2), namely DE17ΔptsI. The results showed that deletion of the ptsI gene changed the rdar (red dry and rough) morphotype and decreased motility and biofilm formation in APEC (p < 0.05). Furthermore, scanning electron microscopy showed that the biofilm structure of DE17ΔptsI became sparse and more extracellular, as compared with the wild-type strain DE17. Moreover, AI-2 assay showed that AI-2 was internalized by DE17ΔptsI, while the recombinant PtsI protein had no AI-2 binding activity. Furthermore, deletion of the ptsI gene in APEC significantly increased adherence to DF-1 cells (p < 0.05). The 50% lethal dose of DE17ΔptsI was decreased by 17.8-fold and the bacterial loads of DE17ΔptsI were decreased by 13600-, 68.5-, 131-, and 3600-fold in the blood, liver, spleen, and kidney, respectively, as compared to the DE17. Moreover, histopathological analysis showed that the mutant DE17ΔptsI was associated with reduced pathological changes in the heart, liver, spleen, and kidney of ducklings, respectively, as compared to the wild-type strain DE17. The results of this study will benefit further studies on the functions of the ptsI in APEC.

Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.

Lung cancer is the second most common form of cancer worldwide Research points to the pivotal role of non-coding RNAs (ncRNAs) in controlling and managing the pathology by controlling essential pathways. ncRNAs have all been identified as being either up- or downregulated among individuals suffering from lung cancer thus hinting that they may play a role in either promoting or suppressing the spread of the disease. Several ncRNAs could be effective non-invasive biomarkers to diagnose or even serve as effective treatment options for those with lung cancer, and several molecules have emerged as potential targets of interest. Given that ncRNAs are contained in exosomes and are implicated in the development and progression of the malady. Herein, we have summarized the role of ncRNAs in lung cancer. Moreover, we highlight the role of exosomal ncRNAs in lung cancer.

Formation mechanism and optical properties of InAs quantum dots on the surface of GaAs nanowires.

Formation mechanism and optical properties of InAs quantum dots (QDs) on the surface of GaAs nanowires (NWs) were investigated. This NW-QDs hybrid structure was fabricated by Au-catalyzed metal organic chemical vapor deposition. We found that the formation and distribution of QDs were strongly influenced by the deposition time of InAs as well as the diameter of GaAs NWs. A model based on the adatom diffusion mechanism was proposed to describe the evolution process of the QDs. Photoluminescence emission from the InAs QDs with a peak wavelength of 940 nm was observed at room temperature. The structure also exhibits a decoupling feature that QDs act as gain medium, while NW acts as Fabry-Perot cavity. This hybrid structure could serve as an important element in high-performance NW-based optoelectronic devices, such as near-infrared lasers, optical detectors, and solar cells.

Surgical resection of primary tumors improves survival in patients with lung metastases: a population-based SEER analysis.

Background: The lung is a common site for cancer metastasis. Some cancer patients would develop lung metastases throughout the course of their illness. However, choosing surgical resection of the primary tumor (SRPT) or palliative treatment in patients with lung metastases remains controversial. Methods: Lung metastatic patients diagnosed from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients were divided into two subgroups (surgery and non-surgery). Further, all the 58 tumor types were classified into 13 subtypes. The clinical and demographic features were examined by the Fisher's exact test, chi-squared test, or z-test. Overall survival (OS) was analyzed using the Kaplan-Meier (K-M) estimator and a log-rank test for each primary tumor type. Multivariable survival analyses of OS were performed using the Cox proportional hazards model. Results: Among the 118,088 patients selected for study, 18,688 (15.83%) patients had undergone surgery. The analyses demonstrated that there was a significant association between SRPT and better OS in patients with lung metastases. The median survival time increased from 4.0 months in the non-surgery group to 19.0 months in the surgery group. Multivariate Cox regression analyses further validated that patients who underwent SRPT had an improved OS. Conclusions: The current study demonstrated that patients with lung metastases can benefit from SRPT. SRPT should be considered in patients with lung metastases. Properly designed prospective randomized clinical trials would be required to further verify the conclusion.

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway.

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.

The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters.

The piRNA pathway is essential for female fertility in golden hamsters and likely humans, but not in mice. However, the role of individual PIWIs in mammalian reproduction remains poorly understood outside of mice. Here, we describe the expression profiles, subcellular localization, and knockout-associated reproductive defects for all four PIWIs in golden hamsters. In female golden hamsters, PIWIL1 and PIWIL3 are highly expressed throughout oogenesis and early embryogenesis, while knockout of PIWIL1 leads to sterility, and PIWIL3 deficiency results in subfertility with lagging zygotic development. PIWIL1 can partially compensate for TE silencing in PIWIL3 knockout females, but not vice versa. PIWIL1 and PIWIL4 are the predominant PIWIs expressed in adult and postnatal testes, respectively, while PIWIL2 is present at both stages. Loss of any PIWI expressed in testes leads to sterility and severe but distinct spermatogenesis disorders. These findings illustrate the non-redundant regulatory functions of PIWI-piRNAs in gametogenesis and early embryogenesis in golden hamsters, facilitating study of their role in human fertility.

Epidemiological evidence for associations between variants in CHRNA genes and risk of lung cancer and chronic obstructive pulmonary disease.

Background: Genetic studies have previously reported that single-nucleotide polymorphisms (SNPs) in CHRNA genes (such as CHRNA3, CHRNA4, CHRNA5, or CHRNA3-CHRNA5-CHRNB4 clusters) are linked to the risk of neoplastic and non-neoplastic diseases. However, these conclusions were controversial and no systematic research synopsis has been available. We aimed to synthesize current knowledge of variants in the CHRNA genes on the risk of diseases. Methods: We systematically searched for publications using PubMed, Medline, and Web of Science on or before 25 August 2021. A total of 1,818 publications were identified, of which 29 were deemed eligible for inclusion that could be used to perform meta-analysis based on at least three data sources to assess whether the morbidity associated with neoplastic and non-neoplastic diseases can be attributed to SNPs in CHRNA genes. To further evaluate the authenticity of cumulative evidence proving significant associations, the present study covered the Venice criteria and false-positive report probability tests. Through the Encyclopedia of DNA Elements (ENCODE) project, we created functional annotations for strong associations. Results: Meta-analyses were done for nine genetic variants with two diseases {chronic obstructive pulmonary disease (COPD) and lung cancer (LC)}that had at least three data sources. Interestingly, eight polymorphisms were significantly related to changes in the susceptibility COPD and LC (p < 0.05). Of these, strong evidence was assigned to six variants (28 significant associations): CHRNA3 rs1051730, CHRNA3 rs6495309, and CHRNA5 rs16969968 with COPD risk, and CHRNA3 rs1051730, CHRNA3 rs578776, CHRNA3 rs6495309, CHRNA3 rs938682, CHRNA5 rs16969968, and CHRNA5 rs588765 with LC risk; moderate evidence was assigned to five SNPs (12 total associations) with LC or COPD risk. Data from ENCODE and other public databases showed that SNPs with strong evidence may be located in presumptive functional regions. Conclusions: Our study summarized comprehensive evidence showing that common mutations in CHRNA genes are strongly related to LC and COPD risk. The study also elucidated the vital function of CHRNA genes in genetic predispositions to human diseases.

Pan-cancer analysis of the prevalence and associated factors of lung metastasis and the construction of the lung metastatic classification system.

This study first presents an analysis of the prevalence and associated factors of the lung metastasis (LM) database and then uses this analysis to construct an LM classification system. Using cancer patient data gathered from the surveillance, epidemiology, and end results (SEER) database, this study shows that the prevalence of LM is not consistent among different cancers; that is, the prevalence of LM ranges from 0.0013 [brain; 95% confidence interval (95% CI); 0.0010-0.0018] to 0.234 ("other digestive organs"; 95% CI; 0.221-0.249). This study finds that advanced age, poor grade, higher tumor or node stage, and metastases including bone, brain, and liver are positively related to LM occurrence, while female gender, income, marital status, and insured status are negatively related. Then, this study generates four categories from 58 cancer types based on prevalence and influence factors and satisfactorily validates these. This classification system reflects the LM risk of different cancers. It can guide individualized treatment and the management of these synchronous metastatic cancer patients and help clinicians better distribute medical resources.

Polymorphisms in ERCC4 and ERCC5 and risk of cancers: Systematic research synopsis, meta-analysis, and epidemiological evidence.

The variants of DNA repair genes have been widely reported to be associated with cancer risk in the past decades. As were two crucial members of nucleotide excision repair pathway, ERCC4 and ERCC5 polymorphisms are linked with susceptibility to multiple cancers, but the conclusions were controversial. In this updated meta-analysis concerned with ERCC4 and ERCC5 single-nucleotide polymorphisms (SNPs), 160 eligible publications were identified, and we exerted the meta-analysis of correlations between 24 variants and 19 types of cancer. Venice criteria and the false-positive report probability were used to evaluate a cumulative evidence of significant associations. We conducted functional annotations for those strong associations using data from the Encyclopedia of DNA Elements (ENCODE) Project. We obtained 11 polymorphisms significantly related to changed susceptibility to 11 cancers (p < 0.05). Strong evidence was assigned to four variant-related cancer risks in Asians (ERCC4 rs744154 with bladder cancer, ERCC5 rs2296147 with esophageal cancer, ERCC5 rs17655 with laryngeal cancer and uterine cancer, and ERCC5 rs751402 with gastric cancer), moderate to six SNPs with a risk of eight cancers, and weak to nine SNPs with nine cancers. Data from ENCODE and other public databases showed that the loci of these SNPs with strong evidence might fall in putative functional regions. In conclusion, this paper summarizes comprehensive evidence that common variants of ERCC4 and ERCC5 genes are strongly associated with the risk of bladder cancer, esophageal cancer, laryngeal cancer, uterine cancer, and gastric cancer and elucidates the crucial role of the DNA repair genes in the genetic predisposition to human cancers.

Cumulative evidence for associations between genetic variants in interleukin 17 family gene and risk of human diseases.

Background: Genetic association studies have elucidated the link of variants in the interleukin 17 (IL-17) family genes with susceptibility to human diseases, yet have obtained controversial outcomes. Therefore, we sought to update comprehensive synopsis of variants in the IL-17 family genes with susceptibility to human diseases. Methods: Our study screened the Pubmed and Web of Science to enroll eligible articles and performed a meta-analysis, then graded the cumulative evidence of significant association using Venice criteria and false-positive report probability test, and finally assessed the function of variants with strong evidence. Results: Seven variants in IL-17 family genes had significant relationships with susceptibility to 18 human diseases identified by meta-analyses. Strong evidence was assigned to 4 variants (IL-17A rs2275913, IL-17A rs8193037, IL-17F rs1889570, IL-17F rs763780) with susceptibility to 6 human diseases (lung and cervical cancer, spondyloarthritis, asthma, multiple sclerosis, rheumatoid arthritis), moderate to 2 variants with risk of 5 diseases, weak to 5 variants with risk of 10 diseases. Bioinformatics analysis suggested that the variants with strong evidence might fall in putative functional regions. Additionally, positive relationships for 5 variants with risk of 4 diseases (based on two datasets) and 14 variants with risk of 21 diseases (based on one dataset) were considered noteworthy. Conclusions: This study offers updated and comprehensive clues that variants in the IL-17 family genes are significantly linked with susceptibility to cervical, lung cancer, asthma, multiple sclerosis, rheumatoid arthritis and spondyloarthritis, and elucidates the crucial role of the IL-17 regions in the genetic predisposition to cancer or noncancerous diseases.

The Treatment of Subtrochanteric Fracture with Reversed Contralateral Distal Femoral Locking Compression Plate (DF-LCP) Using a Progressive and Intermittent Drilling Procedure in Three Osteopetrosis Patients.

OBJECTIVE: To describe the application of reversed contralateral distal femoral locking compression plate (DF-LCP) inserted through a progressive and intermittent drilling procedure in the treatment of osteopetrotic subtrochanteric fracture (OSF). METHODS: Three patients (one male and two females with an average age of 45.33 ± 11.09 years) with OSF hospitalized between September 2015 and September 2020, were included in this present study. Lateral approach was applied in all patients who accepted open reduction and internal fixation (ORIF) with a reversed contralateral DF-LCP inserted through a progressive and intermittent drilling procedure. The operation time and intraoperative blood loss were recorded to evaluate the efficiency of this surgical method. Physical examination and imaging examination of the fracture site were used to evaluate the fracture union status, the position and stability of the implant, and the alignment of the injured limb at 1, 3, 6, and 12 months after operation, then a subsequent visit was conducted at least once a year. Harris Hip Score (HHS) was used to evaluate the hip joint function at 6 and 12 months after operation. RESULTS: The average operation time was 140 ± 21.60 min (110, 160, and 150 min); The average intraoperative blood loss was about 333.33 ± 23.57 ml (300, 350, and 350 ml). The average follow-up time was 22.33 ± 7.41 months (29, 26, and 12 months). All patients achieved bone union with an average time of 6.67 ± 0.94 months (6, 8, and 6 months). At the time of 6 months after operation, case 1 and 3 were almost pain-free and could walk with full weight bearing while case 2 could walk only with partial weight bearing using a crutch. The HHS scores of cases 1, 2, and 3 were 84/100, 74/100, and 92/100, respectively. At the follow-up at 12 months after operation, the HHS score improved to 91/100, 81/100, and 96/100, respectively. The contralateral incomplete old subtrochanteric fracture was deteriorated in case 1 at 26 months after operation. After 3 months of limited weight bearing using a crutch, bone union was verified in radiograph imaging. Fresh contralateral subtrochanteric fracture occurred in case 2 at 26 months after operation, which was treated using a similar surgical approach, and its clinical outcome is under follow-up. Moreover, no perioperative complications including operation-related death, vascular/nerve injury, deep venous thrombosis, pulmonary embolism, and incision infection, and long-term complications involving malunion, nonunion, implant failure, ankylosis, heterotopic ossification, osteonecrosis, and osteomyelitis were identified. CONCLUSION: The application of reversed contralateral DF-LCP in OSF is practicable and reliable. Progressive and intermittent drilling is a safe and efficient method for implant insertion in this complicated situation.