Efficacy and safety of pharmacological intervention for smoking cessation in smokers with diseases: A systematic review and network meta-analysis.

OBJECTIVE: To investigate the most effective and best-tolerated drugs for treating diseased smokers. METHODS: Eight databases were searched for randomized controlled trials (RCTs) involving different pharmacological interventions for smoking cessation in disease patients (January 2023). Network meta-analysis was performed using STATA 15.1 software. The Cochrane Risk of Bias Tool assessed the risk of bias, and confidence in evidence was assessed using CINeMA. RESULTS: A total of 60 RCTs involving 13,009 patients of 12 disease categories were included. All trials reported 13 interventions, resulting in 78 comparisons. Network meta-analysis showed that varenicline (OR = 2.30, 95% CI (1.77, 3.00)) and bupropion (OR = 1.65, 95% CI (1.29, 2.11)) showed favorable abstinence effects compared to placebo in the cardiovascular disease population. Nicotine replacement therapy (NRT) had better withdrawal advantages than placebo (OR = 11.18, 95% CI (2.25, 55.54)) in the chronic obstructive pulmonary disease (COPD) population. Some combination treatments showed better results than monotherapy, such as bupropion + NRT was superior to bupropion (OR = 8.45, 95% CI (1.84, 38.89)) and NRT (OR = 4.98, 95% CI (1.25, 19.78)) in mental illness population. The final surface under the cumulative ranking curve indicated that bupropion + NRT achieved the best smoking cessation effect. Overall confidence in the evidence was low. In a comparison of drugs, the results showed that bupropion + NRT had the best safety. CONCLUSIONS: Most interventions show the benefit of quitting smoking compared with placebo, including monotherapy and combination therapy. Moreover, varenicline or bupropion combined with NRT is superior to some monotherapies.

Effectiveness and Safety of Varenicline for Smoking Cessation: An Overview and Meta-analysis.

OBJECTIVE: An overview, meta-analysis, and trial sequential analysis were conducted to evaluate the efficacy and safety of varenicline for smoking cessation. METHODS: Systematic reviews (SRs) and randomized controlled trials evaluating varenicline versus placebo for smoking cessation were included. A forest plot was used to summarize the effect size of the included SRs. Traditional meta-analysis and trial sequential analysis (TSA) were performed using Stata software and TSA 0.9 software, respectively. Finally, the Grades of Recommendation, Assessment, Development, and Evaluation approach was used to assess the quality of evidence for the abstinence effect. RESULTS: A total of 13 SRs and 46 randomized controlled trials were included. Twelve review studies showed that varenicline was superior to placebo for smoking cessation. The meta-analysis results showed that, compared with the placebo, varenicline significantly increased the odds of smoking cessation (odds ratio = 2.54, 95% confidence interval = 2.20-2.94, P < 0.05, moderate quality). Subgroup analysis showed that there were significant differences in smokers with disease and general smokers ( P < 0.05). Differences were also found in the follow-up time at 12, 24, and 52 weeks ( P < 0.05). The common adverse events were nausea, vomit, abnormal dreams, sleep disturbances, headache, depression, irritability, indigestion, and nasopharyngitis ( P < 0.05). The TSA results confirmed the evidence for the effect of varenicline on smoking cessation. CONCLUSIONS: Existing evidence supports the superiority of varenicline over a placebo for smoking cessation. Varenicline had mild to moderate adverse events but was well tolerated. Future trials should investigate varenicline in combination with other smoking cessation approaches and compare it with other interventions.

Lnc-TRTMFS promotes milk fat synthesis via the miR-132x/RAI14/mTOR pathway in BMECs.

As an important index to evaluate the quality of milk, milk fat content directly determines the nutrition and flavor of milk. Recently, growing evidence has suggested that long noncoding RNAs (lncRNAs) play important roles in bovine lactation, but little is known about the roles of lncRNAs in milk fat synthesis, particularly the underlying molecular processes. Therefore, the purpose of this study was to explore the regulatory mechanism of lncRNAs in milk fat synthesis. Based on our previous lncRNA-seq data and bioinformatics analysis, we found that Lnc-TRTMFS (transcripts related to milk fat synthesis) was upregulated in the lactation period compared to the dry period. In this study, we found that knockdown of Lnc-TRTMFS significantly inhibited milk fat synthesis, resulting in a smaller amount of lipid droplets and lower cellular triacylglycerol levels, and significantly decreased the expression of genes related to adipogenesis. In contrast, overexpression of Lnc-TRTMFS significantly promoted milk fat synthesis in bovine mammary epithelial cells (BMECs). In addition, Bibiserv2 analysis showed that Lnc-TRTMFS could act as a molecular sponge for miR-132x, and retinoic acid induced protein 14 (RAI14) was a potential target of miR-132x, which was further confirmed by dual-luciferase reporter assays, quantitative reverse transcription PCR, and western blots. We also found that miR-132x significantly inhibited milk fat synthesis. Finally, rescue experiments showed that Lnc-TRTMFS could weaken the inhibitory effect of miR-132x on milk fat synthesis and rescue the expression of RAI14. Taken together, these results revealed that Lnc-TRTMFS regulated milk fat synthesis in BMECs via the miR-132x/RAI14/mTOR pathway.

Milk fat is an important index to evaluate the quality of milk. The content of milk fat directly determines the quality and flavor of milk. Studies have shown that milk components can change with the expression of specific genes and noncoding RNA that regulate it in different lactation periods. In this study, after the interference and overexpression of Lnc-TRTMFS on milk fat metabolism in bovine mammany epithelial cells, we found that Lnc-TRTMFS could positively regulate milk fat synthesis in bovine mammary epithelial cells. The ceRNA network of Lnc-TRTMFS-miR-132x-RAI14 was constructed by software prediction and double fluorescein report test, and the salvage effect of Lnc-TRTMFS on milk fat synthesis was confirmed by salvage test. Most importantly, we found that Lnc-TRTMFS and miR-132x can regulate milk fat by regulating the mTOR pathway by regulating RAI14.

Network Meta-Analysis of Behavioral Programs for Smoking Cessation in Healthy People.

INTRODUCTION: Smoking is a risk factor for most chronic diseases and premature death, with a global prevalence of more than 1 billion people who smoke. This network meta-analysis aimed to investigate the impact of different behavioral interventions on smoking cessation. METHODS: Four electronic databases were searched for RCTs from inception to August 29, 2022. The risk of bias for the included RCTs was evaluated using the revised version of Cochrane tool for assessing risk of bias and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The network meta-analysis was performed using Stata 16SE and R 4.1.3 software. RESULTS: A total of 119 included RCTs enrolled 118,935 participants. For the 7-day-point prevalence abstinence rate, video counseling had a best intervention effect than brief advice, followed by financial incentives, self-help materials plus telephone counseling, motivational interview, health education, telephone counseling, and text messages. For the 30-day-point prevalence abstinence rate, face-to-face cognitive education and financial incentives were superior to brief advice. For the continuous abstinence rate, motivational interview and financial incentives were more effective than brief advice. The certainty of evidence was very low to moderate for these studies. DISCUSSION: From the results of the network meta-analysis, different behavioral interventions resulted in positive impacts on smoking cessation compared with that of brief advice, especially video counseling, face-to-face cognitive education, and motivational interviews. Owing to the poor quality of evidence, high-quality trials should be conducted in the future to provide more robust evidence.

Osteochondral Autograft From the Hamate for Treating Partial Defect of the Proximal Interphalangeal Joint.

PURPOSE: The management of a proximal interphalangeal (PIP) joint fracture dislocation becomes more challenging when the joint surface is damaged because of severe comminution or inadequate treatment in the acute phase. The purpose of this study was to evaluate the clinical outcomes of an osteochondral autograft for the reconstruction of the joint surface in patients with a partial PIP joint defect. METHODS: Twelve patients underwent osteochondral autograft surgery from May 2007 to July 2018. The average age at the time of surgery was 38 years (range, 21-67 years), and there were 10 men and 2 women. Plain radiographs and computed tomography scans showed a partial middle phalangeal base defect in all the cases. The surgeries were performed 2 weeks to 20 months after the fracture or a previous surgery. Partial hamate grafts were harvested to reconstruct volar lip (n = 7), middle portion (n = 2), and dorsal lip (n = 3) defects of the middle phalangeal base. Bone healing, postoperative range of motion, instability, and pain were evaluated. The average follow-up duration was 27.8 months (range, 12-53 months). RESULTS: Radiographic graft union was observed in all the patients 6-8 weeks after the surgery. The deformity was corrected in 11 patients. The active range of motion of the involved PIP joint was improved from 28.3° (range, 0°-60°) to 75.0° (range, 25°-95°). Complications were observed during follow-up, including degenerative arthritis (n = 2), instability (n = 3), and stiffness (n = 5). CONCLUSIONS: Various types of partial joint defects of the middle phalangeal base following a PIP fracture dislocation can be reconstructed using an osteochondral autograft from the hamate. The functional recovery is generally acceptable, with a well-restored joint architecture. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

ORFV can carry TRAP gene expression via intracellular CRISPR/Cas9 gene editing technology.

Orf is an acute and highly contracted human and animal infection caused by orf virus (ORFV), which mainly affects sheep, goats, and other species. Clinically, opportunistic or conditional pathogens such as Staphylococcus aureus (S. aureus) are often detected in cases of orf, which greatly increases the risk of disease progression and clinical death. It has been reported that TRAP gene products of S. aureus can broadly influence bacterial life and pathogenicity in vivo, and introduction of exogenous TRAP genes may help to inhibit the proliferation of bacteria. In order to achieve the combined control of ORFV and S. aureus, a novel approach to design a S. aureus TRAP gene vaccine using a live attenuated ORFV vector is proposed. In this study, CRISPR/Cas9 gene editing technology was used to disable vascular endothelial growth factor E of ORFV (VEGF-v) and introduced TRAP gene into this position. TRAP gene expression was detected in keratinocytes infected with recombinant virus. The construction and experimental verification of recombinant ORFV (ORFV-v/TRAP) will provide a reference for in-depth studies on the prevention and control of mixed infectious disease.

Pharmacological interventions on smoking cessation: A systematic review and network meta-analysis.

Objective: A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation. Methods: English databases were searched to obtain randomized controlled trials reporting the effect of pharmacological interventions on smoking cessation. The risk of bias for the included trials was assessed using Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and GRADE approach was used to assess the evidence credibility on the effects of different interventions on smoking cessation. Results: A total of 159 studies involving 60,285 smokers were included in the network meta-analysis. The analysis involved 15 interventions and which yielded 105 pairs of comparisons. Network meta-analysis showed that varenicline was more helpful for smoking cessation than other monotherapies, such as nicotine replacement therapy [Odds Ratio (OR) = 1.42, 95% confidence interval (CI) (1.16, 1.73)] and bupropion [OR = 1.52, 95% CI (1.22, 1.89)]. Furthermore, combined interventions were superior to monotherapy in achieving smoking cessation, such as varenicline plus bupropion over bupropion [OR = 2.00, 95% CI (1.11, 3.61)], varenicline plus nicotine replacement therapy over nicotine replacement therapy [OR = 1.84, 95% CI (1.07, 3.18)], and nicotine replacement therapy plus mecamylamine over naltrexone [OR = 6.29, 95% CI (1.59, 24.90)]. Finally, the surface under the cumulative ranking curve value indicated that nicotine replacement therapy plus mecamylamine had the greatest probability of becoming the best intervention. Conclusion: Most pharmacological interventions demonstrated a benefit in smoking cessation compared with placebo, whether monotherapy or combination therapy. Moreover, confirmed evidence suggested that some combination treatments, such as varenicline plus bupropion and nicotine replacement therapy plus mecamylamine have a higher probability of being the best smoking cessation in.

Varenicline and related interventions on smoking cessation: A systematic review and network meta-analysis.

BACKGROUND: Based on randomized controlled trials, a network meta-analysis was conducted to compare treatment effects across varenicline and related smoking interventions. METHODS: English databases were screened for randomized controlled trials reporting the effect of varenicline as treatment for smoking. The risk of bias in included trials was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and the GRADE approach was used to assess the evidence credibility on the tobacco treatment effects of different interventions. RESULTS: Thirty-four studies involving 26,130 smokers were included in the network meta-analysis. Varenicline and 11 other interventions were reported, yielding 66 pairs of comparisons. Network meta-analysis showed that varenicline monotherapy or its combination with other interventions were superior in achieving smoking cessation compared to bupropion, nicotine replacement therapy, counselling, and placebo. Furthermore, compared to the varenicline, evident abstinence superiority was found in varenicline + bupropion (odds ratio = 1.49, 95% confidence interval [1.02, 2.18]). Finally, the surface under the cumulative ranking curve value indicated that varenicline + bupropion has the highest probability to become the best intervention. CONCLUSIONS: Varenicline monotherapy increased the odds of smoking cessation further than bupropion monotherapy, nicotine replacement therapy, counselling, and placebo, while varenicline combined with other interventions may even achieve a better abstinence effect. More credible evidence has been reported indicating that the combination of varenicline and bupropion is a superior treatment for smoking.

Effects of different interventions on smoking cessation in chronic obstructive pulmonary disease patients: A systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVES: Smoking is responsible for 9 out of 10 deaths related to chronic obstructive pulmonary disease, and this number can be reduced by quitting smoking. In this study, the effect of different interventions on smoking cessation of patients with chronic obstructive pulmonary disease was assessed through a network meta-analysis. METHODS: Eight databases were searched to obtain randomized controlled trials involving different interventions for smoking cessation in chronic obstructive pulmonary disease patients. The Cochrane Handbook tool was employed to assess the risk bias of included studies. Network meta-analysis was performed using STATA software. RESULTS: A total of 23 studies involving 13,480 patients were included. Eight studies were rated as having a high risk of bias, seven studies had a low risk, and in eight studies, the risk was unclear. All studies employed 13 different interventions, including eight monotherapies and five combination therapies. Network meta-analysis showed that a combination of behavioral therapy and pharmacotherapy was superior in achieving patients' smoking cessation compared to monotherapy. Moreover, varenicline was more helpful for smoking cessation than other single interventions. The final surface under the cumulative ranking curve value indicated that cognitive behavior therapy combined with bupropion achieved the best smoking cessation effect. CONCLUSIONS: The obtained results indicate that a combination of behavioral therapy and pharmacotherapy is most powerful in helping chronic obstructive pulmonary disease patients to quit smoking. Researchers should focus more on the safety of pharmacotherapeutic interventions. Moreover, more high-quality trials investigating the stability of evidence levels of different interventions on abstinence must be conducted.

Transdermal delivery of flurbiprofen from polyoxypropylene-polyoxyethylene block copolymer stabilized reduced graphene oxide to manage pain in spondylitis: In vitro and in vivo studies.

Ankylosing spondylitis is an inflammatory arthritic disease affecting the spine and large joints, causing severe pain. Flurbiprofen is widely used as an oral formulation (tablet dosage form) to control pain in spondylitis; however, owing to its short half-life (3.9 h), need for frequent dosing (four times daily), and abdominal discomfort, patient compliance remains extremely poor. In the present study, a flurbiprofen-loaded reduced graphene oxide transdermal (non-invasive) hydrogel was developed to improve drug permeation and achieve sustained drug release for pain management. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of polyoxypropylene-polyoxyethylene block copolymer stabilized reduced graphene oxide. Transmission electron microscopy images presented flat, wrinkled nanosheets of reduced graphene oxide. The developed hydrogel showed desirable viscosity, pH, drug content, adhesiveness, hardness, and cohesiveness (texture profile) for transdermal application. The ex vivo permeability studies revealed the ability of the reduced graphene oxide hydrogel to increase drug permeation and release (sustained-release) for up to 72 h owing to strong π-π interactions, as well as π-sigma and π-hydrogen bonds between flurbiprofen and reduced graphene oxide. In the rat model, in vivo pharmacokinetic parameters confirmed the improved relative bioavailability of reduced graphene oxide hydrogel when compared with the control hydrogel (without reduced graphene oxide) and marketed transdermal patch. The analgesic and anti-inflammatory assessments in rat models confirmed the ability of the flurbiprofen-reduced graphene oxide hydrogel to manage pain in various diseases, such as ankylosing spondylitis, to substitute tablets and parenteral injections, compared with the marketed transdermal patch.

Heterotopic Ossification after Arthroscopic Elbow Release.

OBJECTIVES: To evaluate the incidence and risk factors of heterotopic ossification (HO) after arthroscopic elbow release. METHODS: The present study included 101 elbows, with arthroscopic release performed on 98 patients over the 5-year period from November 2011 to December 2015. Patients were divided into three groups: group 1, with elbow arthritis, including 46 elbows in 43 patients; group 2, with posttraumatic extrinsic elbow stiffness (without intraarticular adhesion), including 23 elbows in 23 patients; and group 3, with intrinsic contractures (with intraarticular adhesion), including 32 elbows in 32 patients. Arthroscopic elbow release was performed under general anesthesia. For intrinsic stiffness, a radiofrequency device was applied to release intraarticular scar tissue and create work space, which was rarely necessary in groups 1 and 2. In the postoperative period, X-rays and CT scans were assessed at follow up to determine if there was HO formation, which was diagnosed when new calcifications were identified. The functional recovery was evaluated by comparing the range of motion (ROM) and pain relief preoperativley and postoperatively in each group. Other complications were also assessed postoperatively. RESULTS: The patients' mean age was 38.6 years (range, 12-66), with 57 males and 41 females. Mean follow-up was 21 months (range, 4-56). The active ROM and Mayo elbow performance index (MEPS) were improved from 93° ± 8.3° to 126° ± 12.4° (P < 0.05) and 71.4 ± 7.6 to 91.3 ± 8.7 (P < 0.001) in group 1, 66° ± 10.3° to 121° ± 10.7° (P < 0.005) and 65.6 ± 9.2 to 93.5 ± 11.2 (P < 0.05) in group 2, and 46° ± 6.7° to 91° ± 11.1° (P < 0.001) and 52.3 ± 6.4 to 80.6 ± 9.4 (P < 0.005) in group 3. HO developed in 25/101 cases (25%) and 4 patients with severe cases underwent repeat surgery. Those in group 1 were primarily arthritis patients; there were 3 out 46 cases with minor HO evident on X-ray. In group 2, 1/23 had minor HO. In group 3, 21/32 patients had HO; 4 cases were considered severe, 4 were considered moderate, and 13 were considered minor. The average flexion-extension arc was improved by 47° at the last follow up. Other postoperative complications included 8 cases of prolonged drainage from portal sites, 17 transient nerve palsies, 1 permanent radial nerve injury, and 1 patient who developed delayed-onset ulnar neuritis. This patient was fully recovered 5 months after surgery. CONCLUSIONS: The high incidence of HO formation after arthroscopic elbow release may relate to improper application of a radiofrequency device. Minimizing thermal injury from these radiofrequency devices could reduce HO formation and improve postoperative functional recovery.

C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation.

Numerous factors have been claimed to play important roles in colorectal cancer (CRC) tumorigenesis, including myeloid-derived suppressor cells (MDSCs) and other immune cells, cytokines, and chemokines; however, the precise mechanisms of colorectal tumorigenesis remain elusive, and there is a lack of effective preventive treatments. Here, we investigated the role of complement system, a key regulator of immune surveillance and homeostasis, in colorectal tumorigenesis. Methods: The prototypical CRC model was induced by combined administration of azoxymethane (AOM)/ dextran sulfate sodium (DSS) in Wild-type (WT), C3-, C5-, C5ar1-, and C5ar2-deficient mice. Using flow cytometry, immunohistochemical staining and multiplex bead assay, we profiled the immune cells, cytokines and chemokines. Bone marrow transplantation was employed to determine the contribution of immune cells in colorectal tumorigenesis. Further, we used C5aR1 antagonist PMX205 to investigate the protective role in colorectal tumorigenesis. Results: Complement was extensively activated in inflamed tissues of AOM/DSS-induced murine CRC model, leading to multifaceted consequences. The deficiency of complement C5 or especially C5ar1, but not C3 almost completely prevented CRC tumorigenesis. C5a/C5aR1 signaling recruited MDSCs into the inflamed colorectum to impair CD8+ T cells, and modulated the production of critical cytokines and chemokines, thus initiating CRC. Moreover, the C5aR1 antagonist PMX205 strongly impeded colorectal tumorigenesis. Bone marrow transplantation further revealed that C5aR1 expression by immune cells was critical for colorectal tumorigenesis. Conclusion: Our study identifies C5a/C5aR1 signaling as a vital immunomodulatory program in CRC tumorigenesis and suggests a feasible preventive strategy.

Spine surgeon specialty differences in single-level percutaneous kyphoplasty.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a procedure performed by a spine surgeon who undergoes either orthopedic or neurosurgical training. The relationship between short-term adverse outcomes and spine specialty is presently unknown. To compare short-term adverse outcomes of single-level PKP when performed by neurosurgeons and orthopedic surgeons in order to develop more concretely preventive strategies for patients under consideration for single-level PKP. METHODS: We evaluated patients who underwent single-level PKP from 2012 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). We used univariate analysis and multivariate logistic regression to assess the association between spine surgeon specialty and short-term adverse events, including postoperative complication and unplanned readmission, and to identify different independent risk predictors between two specialties. RESULTS: Of 2248 patients who underwent single-level PKP procedure, 1229 patients (54.7%) had their operations completed by a neurosurgeon. There were no significant differences in the development of the majority of postoperative complications and the occurrence of unplanned readmission between the neurosurgical cohort (NC) and the orthopedic cohort (OC). A difference in the postoperative blood transfusion rate (0.7% NS vs. 1.7% OC, P = 0.039) was noted and may due to the differences in comorbidities between patients. Multivariate regression analysis revealed different independent predictors of postoperative adverse events for the two spine specialties. CONCLUSIONS: By comparing a large range of demographic feature, preoperative comorbidities, and intraoperative factors, we find that short-term adverse events in single-level PKP patients does not affect by spine surgeon specialty, except that the OC had higher postoperative blood transfusion rate. In addition, the different perioperative predictors of postoperative complications and unplanned readmissions were identified between the two specialties. These findings can lead to better evidence-based patient counseling and provide valuable information for medical evaluation and potentially devise methods to reduce patients' risk.

Intra-articular Osteotomy for Malunited Proximal Interphalangeal Joint Fracture.

BACKGROUND: Intra-articular malunion of the proximal interphalangeal joint is challenging. Multiple treatment options vary from arthrodesis to different types of osteotomy procedures. The aim of this study was to evaluate the effectiveness of intra-articular osteotomy in treating malunited proximal interphalangeal (PIP) joint fractures. MATERIALS AND METHODS: Fifty-nine consecutive patients with chronic PIP joint fractures were presented to us from May 2007 to December 2017. Sixteen joints of 15 patients were malunited PIP fracture without severe cartilage damage and underwent intra-articular osteotomy. The average interval from injury to operation was 4 (1-48) months. The mean duration of follow-up was 9 (2-43) months. Radiographic evidence of bone healing, joint alignment, range of motion of PIP, and distal interphalangeal joints were documented and assessed. RESULT: Fifteen patients underwent intra-articular osteotomy. The average age was 32 (15-54) years. Fourteen of them were males. Fractures affect 9 middle phalangeal bases and 7 proximal phalangeal heads. Bony union was obtained in all patients by 6 to 10 weeks after surgery. Pain was relieved in 14 patients and the deformity was corrected in 12 joints of 11 patients. The average arc of motion for involved PIP joints was improved from 30.3 (10.0-39.1) degrees to 68.4 (7.2-75.6) degrees. One patient arose painful degenerative arthritis after surgery. Ten patients were satisfied or very satisfied. CONCLUSIONS: For malunited PIP joint fracture without severe cartilage damage, intra-articular osteotomy provides predictable functional recovery and minimal donor site sacrifice.

Inhibition of Complement Retards Ankylosing Spondylitis Progression.

Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-ß1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-ß1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy.

The membrane complement regulatory protein CD59 promotes tumor growth and predicts poor prognosis in breast cancer.

Breast cancer is the most prevalent type of cancer among women. CD59, a membrane complement regulatory protein, has been demonstrated to be overexpressed in most solid tumors, where it facilitates tumor cell escape from complement surveillance. However, the role of CD59 in breast cancer growth and clinical prognosis is not fully revealed. To investigate the role of CD59 in breast cancer growth and prognostic significance, we knocked down CD59 in a breast cancer cell line that is highly metastatic to the lungs, MDA-MB­231-HM. Cell growth was measured in vitro and in vivo using a xenograft model. In addition, clinical data on a cohort of 120 patients with or without lung metastasis was analyzed based on CD59 expression, which was detected by immunohistochemistry. Knockdown of CD59 significantly inhibited MDA-MB­231-HM cell growth both in vitro and in vivo. An analysis of clinical data on 120 patients revealed that patients with CD59 overexpression may have a worse prognosis. CD59 may therefore be a prognostic biomarker for poor outcome in breast cancer patients.

Association of STAT4 rs7574865 polymorphism with susceptibility to inflammatory bowel disease: A systematic review and meta-analysis.

OBJECTIVE: Association of Signal transducers and activators of transcription-4 (STAT4) gene polymorphism with susceptibility to inflammatory bowel disease have been investigated in a number of epidemiological studies, but the results are inclusive. The aim of this meta-analysis was to more precisely estimate the relationship. METHODS: The databases of Pubmed and CBM updated to October, 2014 were retrieved. Random- or fixed-effect model was used to estimate odd radio (OR) and corresponding 95% confidence interval (95%CI) on the basis of heterogeneity. RESULTS: Seven articles containing 2196 Crohn's disease (CD) cases, 1588 ulcerative colitis (UC) cases and 4126 controls were identified. We detected a significant association between STAT4 rs7574865 polymorphism and IBD susceptibility in overall population (GG vs. GT+TT, OR=0.855, 95% CI=0.760-0.962, P=0.009), but not in Caucasian and Asian population, respectively. No association was detected between rs7574865 polymorphism and CD susceptibility in overall, Asian and Caucasian population, respectively. Interestingly, a significant association was detected between rs7574865 with UC susceptibility in overall population (G vs. T, OR=0.881, 95% CI=0.798-0.972, P=0.012; GG vs. GT+TT, OR=0.788, 95% CI=0.679-0.914, P=0.002; GG vs. TT, OR=0.683, 95% CI=0.498-0.937, P=0.018) and Caucasians (GG vs. GT+TT, OR=0.833, 95% CI=0.701-0.990, P=0.038; GG+GT vs. TT, OR=0.667, 95% CI=0.456-0.975, P=0.037; GG vs. TT, OR=0.636, 95% CI=0.433-0.934, P=0.021), respectively, and a possible association was found in Asian population (GG vs. GT+TT, OR=0.709, 95% CI=0.503-0.998, P=0.049). CONCLUSIONS: STAT4 rs7574865 gene is IBD risk factor, and this gene polymorphism is associated with UC susceptibility, especially in Caucasians. To confirm these findings, further studies with more sample size are required for a definitive conclusion.

Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults.

Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45-60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day(-1) in men and 10 g day(-1) in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: "Traditional Chinese", "Animal food", "Grains-vegetables" and "High-salt" dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the "Animal food" pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063-1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the "Grains-vegetables" pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618-0.977, p < 0.05). However, the "traditional Chinese" and "high-salt" dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the "Animal food" dietary pattern was associated with an increased risk of NAFLD.

Modified partial pedicle subtraction osteotomy for the correction of post-traumatic thoracolumbar kyphosis.

BACKGROUND CONTEXT: Pedicle subtraction osteotomy (PSO) is the most commonly recommended technique for the correction of local post-traumatic thoracolumbar deformity; however, the surgical results are not always satisfactory because the possibly damaged upper disc is preserved, and all the posterior elements are resected. PURPOSE: The aim was to compare the results of standard PSO and modified PSO in the treatment of post-traumatic thoracolumbar kyphosis. STUDY DESIGN: This was a retrospective multicenter comparative clinical study. PATIENT SAMPLE: A total of 86 patients were included in the final analysis. OUTCOME MEASURES: The outcome measures included local Cobb angle of the kyphosis, visual analog scale (VAS) score, and Oswestry disability index (ODI) score. METHODS: The upper disc was resected, and the inferior wall of the index pedicle and the lower facet joint were preserved in the modified PSO. Patients with focal kyphosis greater than 30° who were treated with one-level osteotomy, without the presence of spine neoplasm, infection, or previous surgery, were included. The measurements included the VAS score, ODI score, and preoperative and postoperative Cobb angles. RESULTS: Forty-two patients in the modified PSO group and 44 in the standard PSO group were included in the final analysis. The mean surgical time and blood loss were similar between the two groups. Both the VAS and ODI scores had improved significantly at the final follow-up in the two groups. The mean Cobb angle significantly improved from 39.6° to 5.6° in the modified PSO group and from 39.1° to 4.8° in the standard PSO group, with no significant difference between the two groups preoperatively or at the final follow-up. CONCLUSIONS: The modified PSO provides an alternative method with which to correct kyphotic deformity in patients with post-traumatic thoracolumbar kyphosis.

MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), one of the first found cancer-associated long noncoding RNAs (lncRNAs), involves in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of MALAT1 in osteosarcoma progression are still unknown up to now. Here, we investigated the role of MALAT1 in human osteosarcoma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, the MALAT1 messenger RNA (mRNA) was highly expressed in human osteosarcoma tissues, and its expression level was closely correlated with pulmonary metastasis. Then, we employed lentivirus-mediated knockdown of MALAT1 in U-2 OS and SaO2 to determine the role of MALAT1 in osteosarcoma cell lines. Lentivirus-mediated MALAT1 small interfering RNA (siRNA) could efficiently downregulated the expression level of MALAT1 in osteosarcoma cell lines. Knockdown of MALAT1 inhibited the proliferation and invasion of human osteosarcoma cell and suppressed its metastasis in vitro and vivo. At the same time, the proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 9 (MMP-9), phosphorylated PI3Kp85α, and Akt expressions were significantly inhibited in MALAT1-deleted cells. These findings indicated that MALAT1 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promoted proliferation and metastasis of osteosarcoma and could be regarded as a therapeutic target in human osteosarcoma.