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Wei Wang,1,* Qiang Li,2,* Ge Huang,3 Bing-yao Lin,1 Dongzi Lin,1 Yan Ma,1 Zhao Zhang,4 Tao Chen,1 Jie Zhou1 1Department of Laboratory, Foshan Fourth People’s Hospital, Foshan, 528000, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510000, People’s Republic of China; 3Intensive Care Unit, Foshan Fourth People’s Hospital, Foshan, 528000, People’s Republic of China; 4Research and Development Centre, South China Institute of Biomedicine, Guangdonglongsee Biomedical Co., Ltd, Guangzhou, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhao ZhangResearch and Development Centre, South China Institute of© Biomedicine, Guangdonglongsee Biomedical Co., Ltd, 5/F Building A, No. 83 Ruihe Road, Huangpu District, Guangzhou, 510535, People’s Republic of ChinaEmail zhangzhao0402@163.comGe HuangIntensive Care Unit, Foshan Fourth People’s Hospital, No. 106, Jinlan Road, Foshan, 528000, People’s Republic of ChinaEmail Lang.x.c.d@sina.comPurpose: The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation.Patients and Methods: Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC−MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC).Results: A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC.Conclusion: A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC.Keywords: tandem mass tag, proteomic analysis, hepatocellular carcinoma, histological differentiation, diagnosis, prognosis

The anisotropic deformation behavior and forming limit of hot-rolled Al/Mg/Al three-layered composite sheets have been investigated in detail. Uniaxial tensile tests were conducted on composite sheets at 0°, 45°, and 90° to the rolling direction. The results show that the properties of the hot-rolled 5052/AZ31/5052 three-layered composite sheet with fine grain distribution and diffusion layer of 18.71 μm were anisotropic and showed temperature dependence. The 0° direction showed the highest n value and the 90° direction the lowest. The highest Lankford parameter was found in the 45° direction, with the maximum $$ \bar{r} $$ value and minimum absolute value of $$ \Delta r $$ at 230°C. Moreover, hemispherical punch tests revealed that the composite sheet exhibited better formability at 230°C than 170°C, especially in the biaxial stress state. In the equibiaxial tensile stress state, significant anisotropy of the thickness distribution and different fracture appearance were also observed.

Background This preclinical study in sheep sought to demonstrate the initial safety and feasibility of a novel transcatheter mitral valve system (Mi-thos valve) composed of a self-expanding frame and a bovine pericardial tissue bioprosthesis. Methods The valve was implanted in 26 sheep using a transapical approach for short- and long-term evaluation. The technical feasibility, safety, durability, and valve function were evaluated during and 6 months after the procedure using intracardiac and transthoracic echocardiography, multisliced computed tomography, histological analysis, and electron microscopy. Results The success rate of valve implantation was 100%, and the immediate survival rate after surgery was 84%. Five animals died within 90 min after the development of the prosthetic valve due to an acute left ventricular outflow tract obstruction (n = 2) and sudden intraoperative ventricular fibrillation (n = 3). Twelve animals died within 1 month due to acute left heart dysfunction. Mild (n = 5) and moderate (n = 2) paravalvular leakage occurred in seven animals, and two moderate PVL animals died of chronic heart failure within three months. Multimodality imaging studies of the remaining seven animals showed excellent function and alignment of the valves, with no coronary artery obstruction, no left ventricular outflow tract obstruction, no severe transvalvular gradients and no paravalvular leakage. Macroscopic evaluation demonstrated stable, secure positioning of the valve, with full endothelialization of the valve leaflets without injury to the ventricular or atrial walls. Histological and electron microscopic examinations at six months showed no obvious macro- or microcalcification in the leaflets. Conclusions Preclinical studies indicate that transcatheter implantation of the Mi-thos valve is technically safe and feasible. The durability, functionality, and lack of leaflet calcification were all verified in animal experiments. The information from these preclinical studies will be applied to patient selection criteria and the first-in-human studies.

Background: Alternate level of care (ALC) patients are those who reside in acute hospital beds but can be managed in non-hospital settings. They contribute to high occupancy levels in Canadian hospitals. Between 2017-18, Ontario spent 1.1 billion dollars on hospitalized patients waiting for alternate level of care (ALC) beds. To improve value for care, Ontario Ministry of Health (MOHLTC) invested into reintegration units which are designed to transfer ALC patients out of hospital and transition them back into the community or long-term care (LTC). Given today’s healthcare budget pressures, it is unclear if reactivation units are feasible. In 2018, the MOHLTC funded a reintegration unit, Pine Villa with an operational partner, Sunnybrook Hospital and community service providers (SPRINT Senior Care, LOFT) in Toronto, Ontario. The objective was to determine averted costs for ALC-patients and impact on Sunnybrook patient flow-through if ALC-patient Pine Villa transfers occurred on the day of ALC readiness. Methods: Retrospective, observational analysis of Sunnybrook ALC-patients discharged to Pine Villa between January 9, 2018 to February 4, 2019. From the healthcare payer’s perspective (MOHTLC), cost analysis was modelled for ALC patients designated for 1) LTC and 2) home with supports. Avoided costs at time of ALC readiness were determined by case-costing. Averted hospital ALC days were established. Results: If ALC patients were transferred to Pine Villa at time of ALC readiness for LTC, the healthcare system could have averted 5.4 million dollars from Sunnybrook. If the patients were transferred for home, 2.3 million dollars could have been averted. Both models increased acute Sunnybrook Hospital capacity by 34 beds. Conclusion: There is a business case supporting reintegration units if ALC-patients are discharged from the hospital on the day of ALC-readiness.

As part of our continuous studies on dietary supplements for diabetes, 1 new phenolic diterpene, 7-butoxyrosmanol (1), and 3 known ones (2-4) were isolated from Rosmarinus officinalis. The new structure was elucidated based on comprehensive spectroscopic methods, including multiple nuclear magnetic resonance techniques, mass spectrometry, and x-ray diffraction analysis. In addition, compound 1 showed moderate activity against pancreatic lipase with an IC50 value of 46.2 μM.

Telmesteine, a useful agent for respiratory tract disorders, has been reported to be a critical active ingredient in topical compositions for dermatitis. The present study was designed to elucidate the in vitro and in vivo anti-inflammatory properties of telmesteine. LPS-induced NO production in RAW264.7 cells was significantly decreased after telmesteine treatment. TPA-induced skin inflammation as assessed by skin edema and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) was significantly decreased after telmesteine topical treatment. Further analysis results demonstrated that the anti-inflammation properties of telmesteine were associated with its ability to inhibit activation of nuclear factor kappa-κB (NF-κB) by blocking phosphoinositide 3-kinase/protein kinase B (PI3K/Akt)/IκB kinase (IKK) activities.

Background TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apoptosis. Thus, reagents that potentiate TRAIL-induced cytotoxicity are needed. Herein, we investigated whether shikonin, a natural compound from the root of Lithospermum erythrorhizon, can sensitize TRAIL-resistant cells to TRAIL-induced cytotoxicity. Results The viability of A549 cells, which were resistant to TRAIL, was significantly decreased after treatment with TRAIL followed by shikonin. The underlying mechanisms by which shikonin sensitizes cells to TRAIL-induced cytotoxicity were also examined. Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid. Conclusions In conclusion, the results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.

We describe a case of generalized cutis laxa (CL) in a 7-year-old female child. At 2 months of age, she was found to have a hoarse voice, and at 3 years, she was much smaller than her peers. Her aging face and short stature caught our attention, and the treatment of the patient was accepted by our hospital. She underwent a thorough examination. X-ray of the wrist bone showed a markedly delayed bone age, and thyroid function tests revealed significantly elevated free triiodothyronine 3 and free thyroxine 4 levels, but thyrotropin was within the normal range. Thyroid dysfunction and CL can be associated with lagged growth and development. Whether her abnormal development was due to thyroid dysfunction or CL could not be ascertained. CL is possibly more complex than it has been supposed so far, and is therefore worth to be further studied.

Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identified mono-substituted resveratrol-ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.

At present, big data environment in electric power field develops. Our platform has a poor efficiency of data analysis and the main bottleneck is disk I/O time of fetch operations. In order to address the problem, we use the characteristics that several tasks usually execute on the same data sets simultaneously, and propose a Loop Query method based on Fetch operations sharing (LQF). It lets all the operations on the data set to process each record circularly, which largely improves the efficiency of data analysis. We also present a Data Placement algorithm with low Transmission cost (DPT). It extends the queries to the cloud environment and reduces the result transmission cost of fetch operations. Last extensive experiments show that the proposed LQF algorithm performs 75.4% better than the benchmark solution when the number of tasks is large, and the DPT algorithm has on average 47.6% less execution time than random placement method.

Psechrus kunmingensis Yin, Wang & Zhang, 1985 was first described from the female only. The first illustration of the male appeared without any text description and lacked other critical information. For this study, we collected fresh specimens of this species from diverse localities around Yunnan Province, China. Here, the male is described in detail for the first time and a supplementary description of the female is given. Based on the largest collection of P. kunmingensis specimens ever assembled, we found a remarkably high level of morphological variation in this species.

Objective To compare the effects of carbamyl-β -methylcholine chloride (CMCC) administered by intra-acupuncture point injection (IAI), intramuscular injection (IMI), and intravenous injection (IVI), and to analyze the mechanisms. Methods In the IAI group, CMCC was injected into the Zusanli acupoint (ST 36) immediately after 30-min stimulation by electro-acupuncture (EA) at the acupoints, and into the femoral vein and skeletal muscle in IVI and IMI groups, respectively. Intragastric pressure was detected. The plasma concentration of CMCC was measured at various times. Results The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups. In the IAI group, this effect was significantly stronger than that in the IMI group at 2 min and 15 min, but not significantly different between the two groups at 5 min and 30 min. Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min, but higher than that in the IMI group. The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5, 15 and 30 min, indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group. There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups. Conclusion The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI, which correlated with the blood concentration of CMCC.

It is debatable whether high-flexion (HF) total knee arthroplasty (TKA) designs will improve postoperative flexion and function or will diminish the need for manipulation under anaesthesia (MUA). We retrospectively analysed range of motion (ROM), flexion, Knee Society Score (KSS), and rate of MUA in a consecutive group of patients who underwent TKA with a conventional posterior stabilised (PS) insert or an HF insert using identical surgical technique, implant design, and postoperative care. Fifty TKAs with a standard PS insert were matched for patient's age, gender, preoperative ROM, and KSS with 50 TKA performed with an HF insert. The patient's ROM and KSS were evaluated at six weeks, four months, and one year postoperatively. The outcome variables (flexion, ROM, KSS, and manipulation rate) in both groups were compared using the generalised estimating equations method. A second analysis of patients with preoperative flexion ≥120° was performed. The ROM, flexion, and patient-reported KSS was similar in both groups at each time period. The rate of MUA was also similar. Patients with a preoperative ROM of at least 120° showed similar results. Our study found that one year after surgery, patients who underwent TKA with a PS or an HF insert achieved similar flexion, ROM, and function.

To take into account the couple stress effects, a modified Reynolds equation is derived for dynamically loaded journal bearings with the consideration of the elasticity of the liner. The numerical results show that the influence of couple stresses on the bearing characteristics is significant. Compared with Newtonian lubricants, lubricants with couple stresses increase the fluid film pressure, as a result enhance the load-carrying capacity and reduce the friction coefficient. However, since the elasticity of the liner weakens the couple stress effect, elastic liners yield a reduction in the load-carrying capacity and an increase in the friction coefficient. The elastic deformation of the bearing liner should be considered in an accurate performance evaluation of the journal bearing.

The aim of this study was to evaluate the contribution of mitochondrial DNA (mtDNA) mutations in oxidative phosphorylation (OXPHOS) deficiency. The complete mitochondrial genomes of 41 families with OXPHOS deficiency were screened for mutations. Mitochondrial functional analysis was then performed in primary and cybrid cells containing candidate mutations identified during the screening. A novel mitochondrial NADH dehydrogenase 5 (ND5) m.12955A > G mutation was identified in a patient with exercise intolerance and developmental delay. A biochemical analysis revealed deficiencies in the activity of complex I (NADH:quinone oxidoreductase) and IV (cytochrome c oxidase) of this patient. Defects in complexes I and IV were confirmed in transmitochondrial cybrid cells containing the m.12955A > G mutation, suggesting that this mutation impairs complex I assembly, resulting in reduced stability of complex IV. Further functional investigations revealed that mitochondria with the m.12955A > G mutation exhibited lower OXPHOS coupling respiration and adenosine triphosphate (ATP) generation. In addition, the cytotoxic effects, determined as reactive oxygen species (ROS) and lactate levels in the present study, increased in the cells carrying a higher m.12955A > G mutant load. In conclusion, we identified m.12955A > G as a mitochondrial disease-related mutation. Therefore, screening of m.12955A > G is advised for the diagnosis of patients with mitochondrial disease.

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China, and prenatal diagnosis has not been performed so far. In this report, 8 patients (4 girls and 4 boys) with MSUD from 8 unrelated Chinese families were diagnosed at the age of 9 days to 1 year and 8 months. The diagnosis was confirmed by serum BCAAs and genetic analyses. Among the 8 patients, only one was detected by newborn screening. The remaining 7 patients were admitted because of neurological disorders and underwent selective screening. Significantly elevated BCAAs were observed in 7 patients. One patient was diagnosed by post-mortem study. 12 mutations were found in the BCKDHA, BCKDHB and DBT genes. 11 of these mutations were novel: c.178G > T, c.491T > C, c.740A > G, c.1214_1219dupCCAACC and IVS6+1delG in BCKDHA; c.482T > G, c.508C > T, c.767A > G, c.768C > G and IVS4,-2A > C in BCKDHB; and c.1A > G in DBT. Only one mutation, c.659C > T in the BCKDHA gene, had been previously reported. 7 patients were treated by dietary intervention and symptomatic therapy. 6 of them showed clinical improvement. The mother of one patient who died from MSUD underwent amniocentesis during her second pregnancy. The BCAAs level in her amniotic fluid was normal. Only one heterozygous mutation, IVS4,-2A > C in the BCKDHB gene, was detected in the cultured amniocytes. The results revealed that the fetus was not affected by MSUD. Normal development and the blood BCAAs profile confirmed the prenatal diagnosis after birth. Thus, we identified eleven novel mutations associated with MSUD in the Chinese population. Prenatal diagnosis of MSUD was successfully performed on one fetus by genetic analysis of the cultured amniocytes.

The aim of our study is to investigate the effects of ovarian steroid hormones on focal adhesion kinase (FAK) expression in ESCs and whether there is alteration in women with endometriosis. FAK expression was assessed by western blotting analysis. Elevated expression of FAK was seen in the cultured ESCs treated with estrogen (P < 0.05). Expression of FAK protein was not changed in ESCs after treated by progesterone or treated by estrogen and progesterone. The level of up-regulation by estrogen in endometriosis is significantly higher than that from women without endometriosis (P < 0.05). FAK expression in endometrial stromal cells from endometriosis was more sensitive to estrogen, which might contribute to the pathogenesis and progress of endometriosis.

Objective Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare mitochondrial fatty acid β-oxidation disorder. We aimed to explore the clinical, biochemical, and genetic findings, treatments and outcomes in eight Chinese VLCADD patients. Methods Eight patients from six unrelated Chinese families with symptomatic VLCADD were diagnosed in the past 4 years. The clinical features and ACADVL gene mutations were analyzed. Results One patient underwent newborn screening and has been treated timely, she hardly had any symptoms. The remaining seven patients were found because of edema, diarrhea, coma, liver damage and psychomotor retardation. Seven patients had fatty liver. Five had myopathy. All patients had elevated blood tetradecanoylcarnitine. Nine heterozygous mutations of the ACADVL gene were found. Three (c.1102C > T, c.1795G > A and IVS10, +6T > A) were novel. Seven patients completely recovered after treatment. One patient died before diagnosis due to cardiomyopathy. His mother underwent amniocentesis for prenatal diagnosis. The fetus had the same gene mutation of the proband and markedly elevated tetradecanoylcarnitine in amniotic fluid. The boy has been treated after birth and he is healthy now. Conclusions Dietary treatment usually leads to good outcomes to VLCADD patients. Amniocytes ACADVL mutations and amniotic fluid tetradecanoylcarnitine analysis are useful for the prenatal diagnosis.

Primary involvement of the larynx in non-Hodgkin's lymphoma (NHL) is rare. Early symptoms are non-specific and thus, it is difficult to diagnose. In the present study, the case of a 52 year-old male with hoarseness due to diffuse T-cell lymphoma as the first manifestation of precursor T-cell acute lymphoblastic leukemia is presented. Subsequent to treatment with three cycles of the etoposide and cytosine arabinoside (EA) and one cycle of the EA+L-asp chemotherapy regimens, the patient achieved complete remission. A series of consolidation therapy courses were performed subsequently. At present, the patient remains disease-free, indicating that the treatment was effective. Primary involvement of the larynx in NHL is rare. Symptoms in the early stage are subtle and non-specific and thus, diagnosis is difficult to establish. This type of tumor requires special diagnostic and therapeutic attention.

BackgroundThere are few widely accepted criteria other than caseation, which has low sensitivity, for differentiating intestinal tuberculosis (ITB) and Crohn's disease (CD).ObjectiveWe performed a meta-analysis to evaluate the use of confluent granulomas and ulcers lined by epithelioid histiocytes as histological methods for differentiating ITB and CD, compared with that of caseation.MethodsWe searched PubMed, Medline, Embase, Web of Science, the Cochrane Library and Chinese Biomedicine Database for all relevant studies on the histological differentiation of ITB and CD. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Study quality and heterogeneity were assessed. Meta-regression analysis and sensitivity analyses were performed.ResultsTen randomized trials involving 316 ITB and 376 CD patients were included. The results showed that analysis of caseation showed an overall weighted area under the curve (AUC) of 0.9966, overall sensitivity and specificity were 0.21 and 1.00, respectively, with a positive likelihood ratio (+LR) of 10.79, negative likelihood ratio(-LR) of 0.82 and DOR of 13.74. Confluent granulomas had a lower overall weighted AUC of 0.9381, sensitivity and specificity were 0.38 and 0.99, respectively, with a +LR of 16.29, -LR of 0.65 and DOR of 26.52. Overall weighted AUC for ulcers lined by epithelioid histiocytes was 0.9017, sensitivity and specificity were 0.41 and 0.94, respectively, with a +LR of 6.46, -LR of 0.54 and DOR of 13.17. Significant heterogeneity was noted for the studies. Meta-regression analysis showed that study source, publication year, size, design and quality did not affect heterogeneity.ConclusionConfluent granulomas and ulcers lined by epithelioid histiocytes are helpful in distinguishing ITB from CD, which may provide a new method, other than caseating granulomas and acid-fast bacilli, to differentiate ITB and CD in mucosal biopsies.

To investigate the renal microvascular injury in acute aristolochic acid nephropathy (AAN) and the protective effects of prostaglandin E1 (PGE1) in acute AAN.Female Sprague-Dawley rats were randomly divided into three groups. The rats in PGE1 group received Caulis Aristolochia manshuriensis (CAM) decoction by gavage for 5 days, and PGE1 was given by vena caudalis before gavage. The rats in model group were gavaged with CAM for 5 days, and the same dose of 0.9% physiologic saline was given by vena caudalis. The rats in control group only received an equal daily volume of saline solution by gavage. Animals were killed at days 3, 5, and 7. Blood urea nitrogen (BUN), serum creatinine, and urinary protein were monitored before killing. Microvascular density was determined by JG12 immunostaining. The expression of angiogenic factor was assessed by vascular endothelial growth factor (VEGF). Tubulointerstitial hypoxia was assessed by hypoxia-inducible factor-1α (HIF-1α) expression.CAM induced a significant decrease in VEGF expression and microvascular density in the kidney tissue, accompanied by a significant increase in HIF-1α, which reduced renal function and increased 24-h urinary protein excretion rates. PGE1 lessened the capillary loss, relieved hypoxia, and protected renal function. No significant pathological changes were found in control rats.The renal microvascular injury in acute AAN is severe. PGE1 can significantly ameliorate the renal microvascular injury, relieve hypoxia, and protect renal function.

AIM: To evaluate the effects of pentoxifylline therapy in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed, Medline, Google Scholar, Embase, Web of Science, the Cochrane Library and the Chinese Biomedicine Database for all relevant controlled trials of pentoxifylline in patients with NAFLD from 1997 to July 2013. Five studies (3 randomized, double-blind, placebo-controlled trials and 2 prospective cohort studies with concurrent controls) were included in this meta-analysis. Statistical analysis was performed using RevMan 5.0 software. RESULTS: Five randomized trials of 147 patients with NAFLD/nonalcoholic steatohepatitis (NASH) were included. The results showed that compared to placebo, pentoxifylline therapy resulted in a significant decrease in body weight (P = 0.04), alanine aminotransferase (P < 0.00001), aspartate transaminase (P = 0.0006), glucose (P = 0.0008) and tumor necrosis factor-α (P = 0.007), but did not significantly affect body mass index (P = 0.28), total cholesterol (P = 0.80), triglyceride (P = 0.98), alkaline phosphatase (P = 0.29), γ-glutamyl transferase (P = 0.39) and interleukin-6 (P = 0.38). With regard to histological changes, pentoxifylline only reduced the NAFLD activity score (P < 0.00001) and improved lobular inflammation (P < 0.0001). Improvements in steatosis grade (P = 0.11), ballooning (P = 0.10) and fibrosis (P = 0.50) were not obvious. CONCLUSION: Pentoxifylline therapy results in weight loss, improved liver function and histological changes in patients with NAFLD/NASH. Therefore, pentoxifylline may be a new treatment option for NAFLD.

To investigate the relationship between the gut-liver axis and nonalcoholic fatty liver disease (NAFLD), we performed a meta-analysis to evaluate the effects of probiotic therapy in NAFLD.We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library and Chinese Biomedicine Database for all relevant randomized controlled trials on probiotics in patients with NAFLD/nonalcoholic steatohepatitis (NASH). A statistical analysis was performed using RevMan 5.0 software.Four randomized trials involving 134 NAFLD/NASH patients were included. The results showed that probiotic therapy significantly decreased alanine aminotransferase (ALT), aspartate transaminase (AST), total-cholesterol (T-chol), high density lipoprotein (HDL), tumor necrosis factor (TNF)-α and homeostasis model assessment of insulin resistance (HOMA-IR) [ALT: weighted mean difference (WMD) -23.71, 95%CI: -33.46--13.95, P0.00001; AST: WMD -19.77, 95%CI: -32.55--7.00, P = 0.002; T-chol: WMD -0.28, 95%CI: -0.55--0.01, P = 0.04; HDL: WMD -0.09, 95%CI: -0.16-0.01, P = 0.03; TNF-α: WMD -0.32, 95%CI: -0.48--0.17, P0.0001; HOMA-IR: WMD -0.46, 95%CI: -0.73--0.19, P = 0.0008]. However, the use of probiotics was not associated with changes in body mass index (BMI), glucose (GLU) and low density lipoprotein (LDL) (BMI: WMD 0.05, 95%CI: -0.18-0.29, P = 0.64; GLU: WMD 0.05, 95%CI: -0.25-0.35, P = 0.76; LDL: WMD -0.38, 95%CI: -0.78-0.02, P = 0.06).Probiotic therapies can reduce liver aminotransferases, total-cholesterol, TNF-α and improve insulin resistance in NAFLD patients. Modulation of the gut microbiota represents a new treatment for NAFLD.