Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study.

BACKGROUND: Although substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. OBJECTIVES: This study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. METHODS: This study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37-73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites' concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. RESULTS: The metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10-15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70-0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4-83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75-0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73-0.97; and P = 0.02, respectively). CONCLUSIONS: Our findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Surgical Management for Chronic Destructive Septic Hip Arthritis: Debridement, Antibiotics, and Single-Stage Replacement is as Effective as Two-Stage Arthroplasty.

OBJECTIVE: To compare the surgical outcomes of debridement, antibiotics, and single-stage total hip replacement (DASR) vs two-stage arthroplasty (two-stage arthroplasty) for chronic destructive septic hip arthritis (SHA). METHODS: Cases of chronic destructive SHA treated by DASR or two-stage arthroplasty in our department from January 2008 to October 2021 were retrospectively reviewed. Patient demographic information, perioperative inflammation markers, intraoperative blood loss, microbial culture, and metagenomic new generation sequencing results were recorded. The perioperative complications, hospital stay, hospitalization cost, infection recurrence rate, and Harris Hip Score (HHS) at the last follow-up were compared between the two groups. RESULTS: A total of 28 patients were included in the study, including 11 patients who received DASR and 17 patients who received two-stage arthroplasty. There was no significant difference in demographic information, preoperative serum inflammatory markers, synovial fluid white blood cell count, or percentage of polymorphonuclear leukocytes between the two groups. The DASR group demonstrated significantly lower intraoperative blood loss [(368.2 ± 253.3) mL vs (638.2 ± 170.0) mL, p = 0.002], hospital stay [(22.6 ± 8.1) days vs (43.5 ± 13.2) days, p < 0.0001], and hospitalization expenses [(81,269 ± 11,496) RMB vs (137,524 ± 25,516) RMB, p < 0.0001] than the two-stage arthroplasty group. In the DASR group, one patient had dislocation as a complication. There were no cases with recurrence of infection. In the two-stage arthroplasty group, there was one case complicated with spacer fracture, one case with spacer dislocation, and one case with deep vein thrombosis of the lower limbs. There were no cases with recurrence of infection. There were no significant differences in the readmission rate, complication rate, or HHS at the last follow-up between the two groups. CONCLUSIONS: Both DASR and two-stage arthroplasty achieved a satisfactory infection cure rate and functional recovery for chronic destructive SHA, and DASR demonstrated significantly lower intraoperative blood loss, hospital stay, and hospitalization costs than two-stage arthroplasty. For appropriately indicated patients, if microbial data are available and a standardized debridement protocol is strictly followed, DASR can be a treatment option.

Emerging role of air pollution in chronic kidney disease.

Chronic kidney disease (CKD), a global disease burden related to high rates of incidence and mortality, manifests as progressive and irretrievable nephron loss and decreased kidney regeneration capacity. Emerging studies have suggested that exposure to air pollution is closely relevant to increased risk of CKD, CKD progression and end-stage kidney disease (ESKD). Inhaled airborne particles may cause vascular injury, intraglomerular hypertension, or glomerulosclerosis through non-hemodynamic and hemodynamic factors with multiple complex interactions. The mechanisms linking air pollutants exposure to CKD include elevated blood pressure, worsening oxidative stress and inflammatory response, DNA damage and abnormal metabolic changes to aggravate kidney damage. In the present review, we will discuss the epidemiologic observations linking air pollutants exposure to the incidence and progression of CKD. Then, we elaborate the potential roles of several air pollutants including particulate matter and gaseous co-pollutants, environmental tobacco smoke, and gaseous heavy metals in its pathogenesis. Finally, this review outlines the latent effect of air pollution in ESKD patients undergoing dialysis or renal transplant, kidney cancer and other kidney diseases. The information obtained may be beneficial for further elucidating the pathogenesis of CKD and making proper preventive strategies for this disease.

Salmonella Osteomyelitis in Adults: A Systematic Review.

The aim of this systematic review was to characterize the clinical features of adults with Salmonella osteomyelitis and summarize diagnosis and treatment methods to provide guidance for clinicians. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a literature search in the PubMed, EMBASE, and Cochrane Library databases. Article screening and data extraction were performed by two reviewers individually. All the included studies were independently evaluated by two reviewers using the Methodological Index for Non-Randomized Studies (MINORS) criteria. A total of 67 articles published between 1970 and 2019 were selected, which include 69 patients with an average age of 47.5 years (range, 18-79).The majority of cases (47.76%) occurred in immunocompetent adults without common risk factors. Aspiration and biopsy cultures were all positive in Salmonella osteomyelitis patients who underwent aspiration or biopsy. All infections were monomicrobial, and a total of 12 different serotypes were identified. The three most commonly reported Salmonella serotypes were Salmonella typhi (19 cases), Salmonella typhimurium (12 cases), and Salmonella enteritidis (11 cases). Only 12 of the 67 cases in our data (17.91%) had diarrhea symptoms, and 44 of the 67 cases (65.67%) had fever symptoms. Fifty-nine of the 67 cases (88.06%) had local inflammatory manifestations, such as erythema, swelling, and tenderness in the affected area. The commonly reported involved sites were the vertebrae, femur, and tibia. Antibiotic therapy alone was utilized in 30 cases, and 24 patients (80.00%) were eventually cured. In total, 75.68% of patients achieved satisfactory results after treatment with surgery and antibiotics. Third-generation cephalosporins were most commonly utilized, and antibiotic treatment was administered for an average of 11.3 weeks (95% CI, 8.31-14.37 weeks). Salmonella osteomyelitis should be considered in patients without any common risk factors. Aspiration or biopsy can facilitate the identification of pathogens to guide antibiotic choice. Empirical therapy with a third-generation cephalosporin is recommended until the susceptibility of the strain is determined.

Destination Joint Spacers: A Similar Infection-Relief Rate But Higher Complication Rate Compared with Two-Stage Revision.

OBJECTIVE: To evaluated the clinical outcomes of periprosthetic joint infection (PJI) patients with destination joint spacer compared with that of two-stage revision. METHODS: From January 2006 to December 2017, data of PJI patients who underwent implantation with antibiotic-impregnated cement spacers in our center due to chronic PJI were collected retrospectively. The diagnosis of PJI was based on the American Society for Musculoskeletal Infection (MSIS) criteria for PJI. One of the following must be met for diagnosis of PJI: a sinus tract communicating with the prosthesis; a pathogenis isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; four of the following six criteria exist: (i) elevated ESR and CRP; (ii) elevate dsynovial fluid white blood cell (WBC) count; (iii) elevated synovial fluid neutrophil percentage (PMN%); (iv) presence of purulence in the affected joint; (v) isolation of a microorganism in one periprosthetic tissue or fluid culture; (vi) more than five neutrophilsper high-power fields in five high-power fields observed from histological analysis of periprosthetic tissue at ×400 magnification. Age, sex, body mass index (BMI), and laboratory test results were recorded. All patients were followed up regularly after surgery, the infection-relief rates were recorded, Harris hip score (HHS) and knee society score (KSS) were used for functional evaluation, a Doppler ultrasonography of the lower limb veins was performed for complication evaluation. The infection-relief rates and complications were compared between destination joint spacer group and two-stage revision group. RESULTS: A total of 62 patients who were diagnosed with chronic PJI were enrolled, with an age of 65.13 ± 9.94 (39-88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group, namely, two-stage revision group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group, and this might be the primary reason for joint spacer retainment. As for infection-relief rate, there were three cases of recurrent infection (14.29%) in the destination joint spacer group and four cases of recurrent infection (9.76%) in the two-stage revision group, there were no significant differences with regard to infection-relief rate. Moreover, there two patients who suffered from spacer fractures, three cases of dislocation, one case of a periarticular fracture, and three cases of deep venous thrombosis in destination joint spacer group, while there was only one case of periprosthetic hip joint fracture, one case of dislocation, and one patient suffered from deep venous thrombosis of the lower extremity in two-stage revision. The incidence of complications in the destination joint spacer group was higher than that of two-stage revision. CONCLUSIONS: In summary, the present work showed that a destination joint spacer might be provided as a last resort for certain PJI patients due to similar infection-relief rate compared with two-stage revision.

Rare Occurrence of Acute Hematogenous Periprosthetic Joint Infection Due to Fusobacterium Nucleatum in the Background of a Dental Procedure: A Case Report.

OBJECTIVE: Fusobacterium nucleatum is an anaerobic gram-negative bacilli that is one of the oral and other mucosal surface microbiota. It involves a wide range of human diseases and was first found in periodontal diseases, but reports of bone-related infections caused by F. nucleatum are rare, especially periprosthetic joint infections (PJI). METHODS: Here, we present the first case of acute hematogenous PJI of the hip joint caused by F. nucleatum, and debridement, antibiotics, and implant retention (DAIR) was performed. RESULTS: The patient was successfully treated with DAIR, identification of isolates by metagenomics next-generation sequencing was confirmed by polymerase chain reaction. CONCLUSIONS: For stable acute hematogenous PJI after hip replacement, quick and accurate diagnosis, the identification of pathogenic microorganisms, and the use of DAIR combined with sufficient sensitive antibiotics have a certain clinical effect and can achieve the purpose of both preserving the prosthesis and infection control.

Total Knee Arthroplasty in Patients with Unsuspected Tuberculosis of the Joint: A Report of Four Cases and a Systematic Review of the Literature.

OBJECTIVES: To provide a case series and systematic review that explores the clinical manifestations, treatments, and methods for defining tuberculosis diagnoses in patients who have undergone total knee arthroplasty (TKA). METHODS: Four patients (three women, one man; average age, 59.5 ± 8.89 years; range, 48-69 years) underwent TKA and were subsequently treated for previously unsuspected knee tuberculosis between January 2013 and December 2019. We also reviewed published cases of tuberculous periprosthetic joint infections (TBPJIs) following TKA through databases of MEDLINE/PubMed, the Cochrane Library, and EMBASE. We reviewed studies that were published between January 1980 and December 2019. RESULTS: In our four cases, the preoperative diagnoses were osteoarthritis (n = 2), rheumatoid arthritis (one case), and Charcot's arthropathy (one case). The main clinical manifestations were knee swelling and pain, without fever, weakness, or weight loss. Comorbidities included multiple joints with rheumatoid arthritis or Charcot's arthropathy, diabetes mellitus, and uremia. One patient had a history of lumbar tuberculosis treated with debridement and intervertebral fusion. Preoperative elevated erythrocyte sedimentation rates (ESRs) were detected in all cases, and elevated C-reactive protein (CRP) levels were observed in three cases. The tuberculosis diagnoses were confirmed via histopathologic analysis (three cases) and second-generation sequencing (one case). Three patients received antituberculosis therapy for 1 year, without surgical intervention. Two-stage exchange arthroplasty was performed in one patient because of prosthesis loosening. Within an average follow-up period of 24.75 months, tuberculosis reactivation was not observed and overall functional improvement was demonstrated. Forty-four TBPJI cases were reported in the literature between January 1980 and December 2019. Most (59.09%) occurred within the first year after the index arthroplasty, and the diagnoses were confirmed by culturing Mycobacterium tuberculosis in 88.64% of cases. Favorable outcomes were achieved in 90.91% of the patients who did not undergo surgery, 71.43% of those treated with debridement, 93.33% undergoing revision arthroplasty, and in 90.91% of those undergoing resection and arthrodesis. CONCLUSIONS: Clinical manifestations of knee tuberculosis and TBPJI are atypical. Thus, attention should be paid to finding the causes of increased ESRs and CRP levels, particularly in patients with weakened immune functioning, before performing TKA. Pathological examination is an effective method for diagnosing tuberculosis, although sending multiple specimens for pathological examination is necessary.

Cup-Cage Solution for Massive Acetabular Defects: A Systematic Review and Meta-Analysis.

Our systematic review compiled multiple studies and evaluated survivorship and clinical outcomes of cup-cage construct usage in the management of massive acetabular bone defects. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Various combinations of "acetabular", "pelvis", "cup cage" and their corresponding synonyms were used to search relevant articles in the Cochrane, EMBASE, and PubMed databases. Basic information of the functional scores, implant revision rate, and complication rate were selected as outcomes for analysis. Finally, a total of 11 articles published between 1999 and 2019 were selected, which include 232 patients with an average age of 68.5 years (range, 30-90). The mean follow-up period was 48.85 months (range, 1-140). Our study shows that the cup-cage construct has a good clinical outcome with a low revision rate and a low complication rate. Improved clinical outcomes of cup-cage constructs were seen with a revision rate of 8% and an all-cause complication rate of 20%. The most commonly reported complication was dislocation, followed by aseptic loosening, infection, and nerve injuries. In summary, it is a promising method for managing large acetabular bone defects in total hip revision.

Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infection.

OBJECTIVE: To report on our clinical outcomes and on the experience of managing acute periprosthetic joint infection (PJI) with debridement, antibiotics, and implant retention (DAIR). METHODS: We performed a retrospective review of all patients who were diagnosed with acute PJI after primary hip or knee replacement surgeries and who were managed with DAIR in our prospective joint replacement registry from 2008 to 2019. The diagnosis of PJI was made according to the 2011 Musculoskeletal Infection Society (MSIS) criteria. The symptom onset duration, inflammatory marker levels (i.e. C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], white cell count [WBC], and synovial WBC count), functional scores including the Knee Society Score (KSS), the KSS functional score and the Harris Hip Score (HHS), bacteriology, and surgical outcomes of the patients were tracked and recorded. A paired sample of joint fluid and tissues was also sent for a metagenomic next-generation sequencing (mNGS) test. A paired-samples t-test was used to compare the differences in the inflammatory markers and functional scores before and after surgery. RESULTS: A total of 24 patients with 7 infections after hip replacements and 17 infections after knee replacements were included. A total of 21 patients exhibited early postoperative infections, and 3 exhibited late acute hematogenous infections. During a mean follow-up time of 29.2 ± 15.1 months, 22 patients were successfully treated, whereas 2 patients were unsuccessfully treated and required repeated DAIR. The overall success rate of DAIR was 91.7%. For staphylococcal infections, DAIR had a 100% success rate. Five patients who presented with symptoms between 4 and 8 weeks also achieved a 100% success rate. At the last follow-up, the mean CRP level decreased from 52.6 ± 34.0 to 5.4 ± 3.5 (P < 0.001), and the mean ESR level decreased from 72.3 ± 34.3 to 20.2 ± 12.1 (P < 0.001). The mean KSS score increased from 44.8 ± 12.2 to 81.4 ± 9.2 (P < 0.001), and the mean KSS functional score increased from 38.1 ± 3.5 to 73.9 ± 23.0 (P < 0.001), and the mean HHS score increased from 34.4 ± 6.9 to 84.1 ± 15.1 (P < 0.001). The overall pathogen identification rate was 91.7% (22/24 cases). The success rates for Staphylococcus, Streptococcus, and the other pathogens were 100% (9/9 cases), 71.4% (5/7 cases), and 100% (6/6 cases), respectively. CONCLUSION: Debridement, antibiotics, and implant retention has a high success rate for the treatment of acute PJI and may be performed in selected patients whose symptoms have been sustained for over 4 weeks. A high rate of success for staphylococcal infections was reported with the use of DAIR.

Association between prenatal exposure to household inhalants exposure and ADHD-like behaviors at around 3 years of age: Findings from Shenzhen Longhua Child Cohort Study.

BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of ADHD or ADHD-like behaviors. But we still lack a comprehensive assessment of household air pollutants exposure on the development of ADHD-like behaviors during childhood. OBJECT: We aimed to assess whether prenatal household inhalants exposure is associated with preschoolers' ADHD-like behaviors in a nonclinical population. METHODS: This study used the baseline data of the Longhua Child Cohort Study. During 2015-2017, we recruited 42,983 mothers and their kindergarten-aged children who enrolled at kindergarten in the Longhua district of Shenzhen, to obtain the demographic data and relevant exposure information through self-administrated questionnaire survey. The source of prenatal household inhalants exposure include cooking fumes, environmental tobacco smoke, mosqutio coils, home renovated and indoor burning incense. Logistic and censored least absolute deviations (CLAD) models were used to reveal the association between prenatal exposure to household air pollutants and hyperactive behaviors in child. RESULTS: We found that exposure to five types of household inhalants during pregnancy were independently associated with an increased risk of child hyperactive behaviors. Moreover, we observed a significant interaction between exposure to environmental tobacco smoke and cooking fumes during gestation on child hyperactive behaviors in CLAD models. We also found a significant joint effect between burning mosquito coils and incense during gestation for child hyperactive behaviors risk both in CLAD and Logistic models. Furthermore, a household inhalants exposure index was used to demonstrate a dose-response relationship between the cumulative effect of exposure to the five household air pollutants and child hyperactivity. CONCLUSIONS: Our results suggest that prenatal exposure to different household inhalants might increase the risk of children's hyperactive behaviors at around 3 years of age with the presence of interaction effects between some inhalants.

MiR-137-3p rescue motoneuron death by targeting calpain-2.

Brachial plexus root avulsion (BPRA) is a type of injury that leads to motor function loss as a result of motoneurons (MNs) degeneration. Here we identified that the reduced expression of rat miR-137-3p in the ventral horn of spinal cord was associated with MNs death. However, the pathophysiological role of miR-137-3p in root avulsion remains poorly understood. We demonstrated that the calcium-activated neutral protease-2 (calpain-2) was a direct target gene of miR-137-3p with miR-137-3p binding to the 3'-untranslated region of calpain-2. Silencing of calpain-2 suppressed the expression of neuronal nitric oxide synthase (nNOS), a primary source of nitric oxide (NO). After avulsion 2 weeks, up-regulation of miR-137-3p in the spinal cord reduced calpain-2 levels and nNOS expression inside spinal MNs, resulting in an amelioration of the MNs death. These events provide new insight into the mechanism by which upregulation of miR-137-3p can impair MN survival in the BPRA.

Detecting the Presence of Bacterial DNA and RNA by Polymerase Chain Reaction to Diagnose Suspected Periprosthetic Joint Infection after Antibiotic Therapy.

OBJECTIVE: To explore the diagnostic efficiency of DNA-based and RNA-based quantitative polymerase chain reaction (qPCR) analyses for periprosthetic joint infection (PJI). METHODS: To determine the detection limit of DNA-based and RNA-based qPCR in vitro, Staphylococcus aureus and Escherichia coli strains were added to sterile synovial fluid obtained from a patient with knee osteoarthritis. Serial dilutions of samples were analyzed by DNA-based and RNA-based qPCR. Clinically, patients who were suspected of having PJI and eventually underwent revision arthroplasty in our hospital from July 2014 to December 2016 were screened. Preoperative puncture or intraoperative collection was performed on patients who met the inclusion and exclusion criteria to obtain synovial fluid. DNA-based and RNA-based PCR analyses and culture were performed on each synovial fluid sample. The patients' demographic characteristics, medical history, and laboratory test results were recorded. The diagnostic efficiency of both PCR assays was compared with culture methods. RESULTS: The in vitro analysis demonstrated that DNA-based qPCR assay was highly sensitive, with the detection limit being 1200 colony forming units (CFU)/mL of S. aureus and 3200 CFU/mL of E. coli. Meanwhile, The RNA-based qPCR assay could detect 2300 CFU/mL of S. aureus and 11 000 CFU/mL of E. coli. Clinically, the sensitivity, specificity, and accuracy were 65.7%, 100%, and 81.6%, respectively, for the culture method; 81.5%, 84.8%, and 83.1%, respectively, for DNA-based qPCR; and 73.6%, 100%, and 85.9%, respectively, for RNA-based qPCR. CONCLUSIONS: DNA-based qPCR could detect suspected PJI with high sensitivity after antibiotic therapy. RNA-based qPCR could reduce the false positive rates of DNA-based assays. qPCR-based methods could improve the efficiency of PJI diagnosis.

Perillanolides A and B, new monoterpene glycosides from the leaves of Perilla frutescens

Abstract Two new monoterpene glycosides, perillanolides A and B, together with a known compound reported from the genus Perilla for the first time were isolated and characterized from the leaves of Perilla frutescens (L.) Britton, Lamiaceae, a garnish and colorant for foods as well as commonly used for traditional medicine. The structures of the isolated compounds were elucidated on the basis of extensive spectroscopic evidences derived from nuclear magnetic resonance experiments, mass spectrometry and by comparing their physical and spectroscopic data of literature. These compounds, together with the previously isolated secondary metabolites of this species, were investigated for their inhibitory effects on xanthine oxidase in vitro. Of the compounds, luteolin showed the strongest inhibitory activity with an IC50 value of 2.18 µM. Esculetin and scutellarein moderately inhibited the enzyme, while perillanolides A and B, and 4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside exerted weak activities.

Lithium accelerates functional motor recovery by improving remyelination of regenerating axons following ventral root avulsion and reimplantation.

Brachial plexus injury (BPI) often involves the complete or partial avulsion of one or more of the cervical nerve roots, which leads to permanent paralysis of the innervated muscles. Reimplantation surgery has been attempted as a clinical treatment for brachial plexus root avulsion but has failed to achieve complete functional recovery. Lithium is a mood stabilizer drug that is used to treat bipolar disorder; however, its effects on spinal cord or peripheral nerve injuries have also been reported. The purpose of this study was to investigate whether lithium can improve functional motor recovery after ventral root avulsion and reimplantation in a rat model of BPI. The results showed that systemic treatment with a clinical dose of lithium promoted motor neuron outgrowth and increased the efficiency of motor unit regeneration through enhanced remyelination. An analysis of myelin-associated genes showed that the effects of lithium started during the early phase of remyelination and persisted through the late stage of the process. Efficient remyelination of the regenerated axons in the lithium-treated rats led to an earlier functional recovery. Therefore, we demonstrated that lithium might be a potential clinical treatment for BPI in combination with reimplantation surgery.

Long noncoding RNAs: novel insights into gastric cancer.

Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Recent advances in the non-protein coding part of human genome analysis have discovered extensive transcription of large RNA transcripts that lack coding protein function, termed non-coding RNA (ncRNA). It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in diverse diseases are not yet fully understood. Thus, it is anticipated that more efforts should be made to clarify the lncRNA world. Moreover, accumulating evidence has demonstrated that many lncRNAs are dysregulated in gastric cancer (GC) and closely related to tumorigenesis, metastasis, and prognosis or diagnosis. In this review, we will briefly outline the regulation and functional role of lncRNAs in GC. Finally, we discussed the potential of lncRNAs as prospective novel targets in GC treatment and biomarkers for GC diagnosis.

5,10-Methylenetetrahydrofolate reductase polymorphisms and colon cancer risk: a meta-analysis.

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.

E2F1: a potential therapeutic target for systematic lupus erythematosus.

E2F1 is a transcriptional activator, which binds to DNA, and regulates the expression of genes involved in the cell cycle progression. Many elegant studies have revealed that E2F1 plays a crucial role in regulating the apoptosis process of DC and T cells. In addition, the pathogenesis of SLE involves marked immune dysfunction, and in particular, the function of immunosuppressive elements of the immune system is impaired, including regulatory T cell function and DC. Thus, therapeutic agents targeting E2F1 might result in important innovative therapies for SLE.