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Both hypertension and type 2 diabetes are attributable to premature death, cardiovascular and kidney diseases with largely overlapping population. Followed the GRADE approach, this expert consensus aimed to reduce the cardiovascular and kidney death and disability due to hypertension and minimize the treatment burden in adults with type 2 diabetes. Through online survey and discussion, a multidisciplinary team comprehensively prioritized seven key guideline questions. Informed by the evidence synthesis and online discussion, the team developed 12 recommendations under the GRADE Evidence-to-decision (EtD) framework. The recommendations covered the screening of hypertension in adults diagnosed with type 2 diabetes but not hypertension and the monitoring, lifestyle interventions, and medications in those diagnosed with type 2 diabetes and hypertension., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

To investigate the clinical characteristics of patients with membranous nephropathy (MN) and the therapeutic efficacy of Sodium Dimercaptosulphonate (DMPS), as well as the relationship between mercury (Hg) exposure and MN, we investigated the clinical manifestations and treatment outcomes of six patients with MN and searched the China National Knowledge Internet (CNKI), PubMed, Web Of Science, and Embase databases for relevant studies on Hg exposure and MN published from the inception of the databases to April 2024. Data analysis was performed using SPSS 26.0 and Stata 16.0. We found that (1) the clinical symptoms of MN patients were mainly characterized by proteinuria, edema, hypoproteinemia, and hyperlipidemia. Comparative analysis before and after DMPS treatment showed a decrease in 24-h urinary Hg, 24-h urinary protein, and total cholesterol levels, as well as an increase in serum albumin levels (p < 0.05). (2) Two MN patients received DMPS for sole Hg detoxification treatment, whereas four patients received Hg detoxification combined with hormone therapy, and all patients showed significant improvement in symptoms after treatment. (3) Among the 564 articles, four met the inclusion criteria. The results showed that Hg exposure increased the incidence of MN by 5.74 times (95% confidence interval [CI] = 2.57, 12.83). The clinical symptoms of MN patients are mostly manifested as proteinuria, edema, hypoproteinemia, and hyperlipidemia. DMPS Hg detoxification treatment is effective for Hg-induced MN. Hg exposure can increase the prevalence of MN, therefore making it necessary to take prudent measures to reduce the risk of Hg exposure., (© 2024 John Wiley & Sons Ltd.)

Callicarpa nudiflora Hook (C. nudiflora) is an anti-inflammatory, antimicrobial, antioxidant, and hemostatic ethnomedicine. To date, little has been reported regarding the activity of C. nudiflora against ulcerative colitis (UC). In this study, we investigated the effect of a flavonoid extract of C. nudiflora on Dextran Sulfate Sodium (DSS)-induced ulcerative colitis in mice. Mice in the treatment group (CNLF+DSS group) and drug-only (CNLF group) groups were administered 400 mg/kg of flavonoid extract of C. nudiflora leaf (CNLF), and drinking water containing 2.5 % DSS was given to the model and treatment groups. The symptoms of colitis were detected, relevant indicators were verified, intestinal barrier function was assessed, and the contents of the cecum were analyzed for intestinal microorganisms. The results showed that CNLF significantly alleviated the clinical symptoms and histological morphology of colitis in mice, inhibited the increase in pro-inflammatory factors (TNF-α, IL-6, IL-1β, and IFN-γ), and increased the level of IL-10. The expression of NF-κB and MAPK inflammatory signal pathway-related proteins (p-p65, p-p38, p-ERK, p-JNK) was regulated. The expression of tight junction proteins (ZO-1, OCLDN, and CLDN1) was increased, while the content of D-LA, DAO, and LPS was decreased. In addition, 16S rRNA sequencing showed that CNLF restored the gut microbial composition, and increased the relative abundance of Prevotellaceae, Intestinimonas butyriciproducens, and Barnesiella&#95;intestinihominis. In conclusion, CNLF alleviated colitis by suppressing inflammation levels, improving intestinal barrier integrity, and modulating the intestinal microbiota, and therefore has promising future applications in the treatment of UC., Competing Interests: Declaration of competing interest All co-authors have seen and agreed with the contents of the manuscript and there is no conflict of interest to report., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs., Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678., Findings: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29)., Interpretation: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective., Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University., Competing Interests: Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pleurocidin is an antimicrobial peptide derived from the mucous membranes of the skin or intestinal secretions of Pseudopleuronectes americanus that has antimicrobial and immunomodulatory activities. Ulcerative colitis is recognized as a widespread human disease that may be influenced by environmental and genetic factors. Evidence emphasizes the critical role of the gut microbiota in UC. Synthetic Pleurocidin was analyzed by a combination of liquid chromatography and mass spectrometry. Pleurocidin pharmacological effects were evaluated by DAI score, colon histological score, cytokine levels, and tight junction protein expression in mice. The preliminary molecular mechanism was explored by the levels of key proteins in the NF-κB and MAPK inflammatory signaling pathways in colon tissues. The main analytical methods such as immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blot were used. We then used 16S rRNA gene sequences to characterize the gut microbiota. Firstly, our study demonstrated that rectal injection of Pleurocidin at 5 mg/kg body weight alleviated clinical symptoms and colonic histopathological changes in UC mice caused by DSS. Secondly, Pleurocidin altered the abnormal levels of inflammatory and immune-related cytokines in serum, modulated the significant down-regulation of tight junction proteins, and inhibited the expression of NF-κB and MAPK inflammatory signaling pathway-related proteins. Finally, Pleurocidin can regulate gut microbiota, increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. In conclusion, Pleurocidin alleviates UC symptoms in mice, and its effects on the gut microbiome may be potential pathways. It is providing a promising therapeutic option for UC., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemoselective protein modification plays extremely important roles in various biological, medical, and pharmaceutical investigations. Mimicking the mechanism of the chemoselective reaction between natural azaphilones and primary amines, this work successfully simplified the azaphilone scaffold into much simpler 3-acyl-4-pyranones. Examinations confirmed that these slim-size mimics perfectly kept the unique reactivity for selective conjugation with the primary amines including lysine residues of peptides and proteins. The newly developed pyranone tool presents remarkably increased aqueous solubility and compatible second-order rate constant by comparison with the original azaphilone. Additional advantages also include the ease of biorthogonal combinative use with a copper-catalyzed azide-alkyne Click reaction, which was conveniently applied to decorate lysozyme with neutral-, positive- and negative-charged functionalities in parallel. Moderate-degree modification of lysozyme with positively charged quaternary ammoniums was revealed to increase the enzymatic activities.

Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ulcerative colitis (UC) is a kind of inflammatory bowel disease (IBD) that often recurs and is difficult to cure, and no drugs with few side effects are available to treat this disease. LfcinB is a small molecular peptide obtained by the hydrolysis of bovine lactoferrin in the digestive tract of animals. It has strong antibacterial and anti-inflammatory activities. However, direct evidence that LfcinB improves the condition of colitis in mice is rarely reported. In this study, UC was induced in mice by adding 2.5% dextran sulfate (DSS) to drinking water and LfcinB was orally administered. The results showed that oral administration of LfcinB improved colonic tissue damage and inflammatory cell infiltration, increased the expression of tight junction proteins, and down-regulated the phosphorylation of proteins related to the NF-κB/MAPK inflammatory signalling pathway in mice. It also significantly suppressed the relative abundance of potentially pathogenic bacteria ( Bacteroides, Barnesiella and Escherichia ) in the intestinal flora. In conclusion, oral administration of LfcinB significantly alleviated DSS-induced UC. This may be related to the regulation of inflammatory signalling pathways and gut microbial composition by LfcinB.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that cannot be completely cured by current treatments. C. nudiflora Hook has antibacterial, anti-inflammatory, and hemostatic biological functions; however, the therapeutic role of C. nudiflora Hook or its extracts in IBD remains poorly understood. In this study, we extracted and purified three fractions of C. nudiflora Hook polysaccharides by hydroalcohol precipitation method, which were named as CNLP-1, CNLP-2 and CNLP-3, respectively. CNLP-2, the main component of the polysaccharides of C. nudiflora Hook is an pyranose type acidic polysaccharide composed of Fuc, Rha, Ara, Gal, Glc, Xyl, Man, Gal-UA and Glc-UA, with an Mn of 15.624 kDa; Mw of 31.375 kDa. CNLP-2 was found to have a smooth lamellar structure as observed by scanning electron microscopy. To investigate the effect of CNLP-2 (abbreviated to CNLP) on dextran sodium sulfate (DSS)-induced UC mice and its mechanism of action, we treated DSS-induced UC mice by administering CNLP at a dose of 100 mg/kg every other day. The results of the study showed that CNLP alleviated the clinical symptoms such as body weight (BW) loss, pathological damage, and systemic inflammation. The mechanism may be through the regulation of intestinal flora and its metabolism, which in turn affects the expression of NF-κB/MAPK pathway-related proteins through the metabolites of intestinal flora to further alleviate inflammation and ultimately improve the intestinal barrier function in UC mice. In conclusion, CNLP has great potential for the treatment of IBD., Competing Interests: Declaration of competing interest The authors declare no competing financial and non-financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

PR39 is an antimicrobial peptide (AMP) with a variety of biological functions, including antimicrobial, wound healing, leukocyte chemotaxis, angiogenesis, and immunomodulation; however, its therapeutic efficacy in colitis (IBD) has rarely been reported. For this reason, the present study aimed to investigate the therapeutic effect of PR39 on IBD and its underlying mechanisms. In this experiment, a mouse model of ulcerative colitis (UC) was induced with 3 % dextran sulfate (DSS) and administered by rectal injection of PR39. The results of the study showed that 5 mg/kg of PR39 was able to ameliorate the clinical manifestations of DSS-induced UC mice by improving the clinical symptoms, colonic tissue damage, up-regulating the expression of tight junction proteins, and alleviating the systemic inflammation in mice in various ways. The mechanism of action may involve inhibition of the phosphorylation level of proteins related to the NF-κB/MAPK signaling pathway and modulation of the relative abundance of potentially pathogenic (Bacteroides, Pseudoflavonifractor, Barnesiella, and Oscillibacter) and potentially beneficial bacteria (Candidatus&#95;Saccharibacteria, Desulfovibrio, Saccharibacteria) in the intestinal flora. The results enriched the biological functions of PR-39 and also suggested that PR-39 may be able to be used as a novel drug for the treatment of IBD., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lead is one of the heavy metals that is toxic and widely distributed in the environment, and children are more sensitive to the toxic effects of lead because the blood-brain barrier and immune system are not yet well developed. The objective of the study was to investigate the clinical characteristics of lead poisoning in children aged 0∼6 years in a hospital in Guangxi, and to provide scientific basis for the prevention and treatment of lead poisoning. We collected and analyzed the clinical data of 32 children with lead poisoning admitted to a hospital in Guangxi from 2010 to 2018. The results showed that most of the 32 cases presented with hyperactivity, irritability, poor appetite, abdominal pain, diarrhea, or constipation. The hemoglobin (HGB), mean corpusular volume (MCV), mean corpuscular hemoglobin (MCH), and hematocrit (HCT) of the lead-poisoned children were all decreased to different degrees and were below normal acceptable levels. Urinary β 2 -microglobulin was increased. Blood lead levels (BLL) decreased significantly after intravenous injection of the lead chelator, calcium disodium edetate (CaNa 2 -EDTA). In addition, HGB returned to normal levels, while MCV, MCH, and HCT increased but remained below normal levels. Urinary β 2 -microglobulin was reduced to normal levels. Therefore, in this cohort of children, the high-risk factors for lead poisoning are mainly Chinese medicines, such as baby powder. In conclusion, lead poisoning caused neurological damage and behavioral changes in children and decreased erythrocyte parameters, leading to digestive symptoms and renal impairment, which can be attenuated by CaNa 2 -EDTA treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study was conducted to investigate the beneficial effect of purple sweet potato anthocyanins (PSPA) on growth performance, oxidative status, immune response, intestinal morphology, and intestinal flora homeostasis in heat-stressed Wenchang chickens. A total of 100 Wenchang chickens (50-day-old) were randomly assigned to 5 groups, including the thermoneutral environment (TN) group (26°C); high-temperature stressed (HS) group (33°C ± 1°C); low-dose PSPA treatment (L&#95;HS) group (8 mg/kg body weight, 33°C ± 1°C); medium-dose PSPA treatment (M&#95;HS) group and high-dose PSPA treatment (H&#95;HS) group (16 mg/kg and 32 mg/kg body weight, respectively, 33°C ± 1°C). The results showed that PSPA reversed the adverse effects of heat stress on growth performance, meat quality, and carcass characteristics. And the effect was associated with the concentration of PSPA partially. Heat stress increased the serum lipids of Wenchang chickens. LDL-C, TG, TC, and FFA in the serum were significantly decreased, and HDL-C and LPS in the serum were increased by PSPA treatment. The digestive enzymes in duodenal chyme were significantly (P < 0.05) increased by PSPA treatment. And PSPA treatment significantly (P < 0.05) enhanced the redox status by improving antioxidant parameters (GSH-Px and SOD) and decreasing the MDA level in the serum and liver. Moreover, the level of inflammatory cytokines was significantly (P < 0.05) regulated by PSPA treatment compared to the HS group. The villus length and goblet cell numbers after PSPA treatment were significantly higher than HS group. Furthermore, PSPA also played protection on the intestine structure by decreasing the level of D-LA and DAO. 16S rRNA sequencing revealed the microbial composition was altered by PSPA, and Acetanaerobacterium and Oscillibacter were dominant in the H&#95;HS group. Microbial functional prediction indicated that function pathways based on KEGG and metacyc database were regulated by PSPA, and intestinal flora correlated with metabolic function significantly. The spearman correlation analysis showed that Saccharibacteria and Clostridium&#95;IV correlated with the serum lipids, antioxidant, and inflammatory cytokines. Collectively, these findings suggest that PSPA has a positive effect against heat stress in poultry., (Copyright © 2023. Published by Elsevier Inc.)

Background: Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia., Methods: Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence., Results: Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s)., Conclusions: In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objective: To analyze the case characteristics of Chronic obstructive pulmonary disease caused by occupational irritant chemicals (OI-COPD). To provide basis for revising its diagnostic criteria. Methods: From June to December 2021, we investigated the information of OI-COPD patients confirmed by Shandong Institute of Occupational Health and Prevention of Occupational Diseases, Guangxi Zhuang Autonomous Region Institute of Occupational Disease Prevention and Control, Qingdao Central Hospital affiliated to Qingdao University and other diagnostic institutions in the past five years, a total of 41 cases. The basic information of OI-COPD cases, occupational risk factors exposure information, medical history, smoking history and clinical symptoms were analyzed retrospectively. The measurement data were tested for normal distribution, which was described by x ± s , and compared between groups by t test; Those who do not conform to the normal distribution are described by the median [ M ( Q (1), Q (3)) ] and analyzed by nonparametric test; The counting data were expressed in frequency and rate (% ), and the comparison between groups was tested. Results: Of the 41 cases, 33 were male and 8 were female. The age of the patient diagnosed with OI-COPD was (49.5±10.3) years old, and the minimum age was 30 years old; Among them, 8 patients had a definite long-term smoking history (more than 5 years) ; The exposure duration of occupational risk factors was (18.6±10.3) years, of which 3 patients had exposure duration of less than 5 years; The occupational risk factors leading to OI-COPD include acids and acid-forming compounds, bases, aldehydes, nitrogen oxides, chlorine and its compounds, etc. The exposure level of occupational risk factors is related to the degree of COPD airflow restriction (χ(2)=6.17, P <0.05). 18 patients with diagnosis age <50 years old were diagnosed as early-onset COPD. The incidence of respiratory symptoms in the early diagnosis COPD group was lower than that in the non-early diagnosis COPD group, and the FEV1% pred was significantly higher than that in the non-early diagnosis COPD group. The difference was statistically significant ( P <0.01 ) . Conclusion: The exposure level of occupational risk factors may be the risk factor affecting the degree of COPD airflow restriction. With the increase of the exposure level of COPD patients, the proportion of respiratory symptoms will also increase accordingly.

Objective: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options., Design: Systematic review and network meta-analysis., Data Sources: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022., Eligibility Criteria for Selecting Studies: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach., Results: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes)., Conclusions: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes., Systematic Review Registration: PROSPERO CRD42022325948., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from Sichuan Science and Technology Bureau and West China Hospital, Sichuan University for the submitted work; QS, KNo, POV, AAg, TA, RS, QH, QF, ZQ, FY, XZ, XC, YJ, LG, YM, QinY, AAs, CZ, JPL, KNu, SRC, SG, YG, XL, QiuY, HZ, XA, ZC, XL, SH, YC, HT, and GHG received no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. ES reported personal fees from Oxford Diabetes Trials Unit, Bayer, Berlin Chemie, Boehringer Ingelheim, Menarini, Merck Serono, EXCEMED, Novartis, Novo Nordisk, and Sanofi. LR reported grants or contracts from Swedish Heart Lung Foundation, Stockholm County Council, Erling Perssons Foundation, and Boehringer-Ingelheim, and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer AG, Boehringer Ingelheim, and Novo Nordisk. FCB reported grants or contracts from National Institutes of Health, and consulting fees from Gilead Sciences. RAM reported grants or contracts from Boehringer Ingelheim. OS reported payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott Diagnostics, Lilly Deutschland, Boehringer Ingelheim, Bayer, Mannkind, and Lifescan and is a founder and CEO of Sciarc GmbH. NM reported grants or contracts from Boehringer Ingelheim, Merck, Novo Nordisk, Deutsche Forschungsgesellschaft (German Research Foundation; TRR 219), and consulting fees from Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, and AstraZeneca. SL received the fund from the Sichuan Science and Technology Programme and West China Hospital of Sichuan University., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Acid sphingomyelinase (ASM), which regulates sphingolipid metabolism and lipid signaling, has been considered as a new potential target for the treatment of atherosclerosis. In this study, a series of benzene-heterocyclic-based ASM inhibitors were rationally designed, synthesized, and screened for the first time. As a result, some compounds showed favorable inhibitory activity against recombinant human ASM. The detailed SARs are also discussed. Compound 4i revealed good pharmacokinetic data and in vivo inhibitory activity against ASM by reducing the level of ceramide in mice plasma and liver. Pharmacodynamic studies confirmed that 4i could lessen lipid plaques in the aortic arch and aorta and reduce plasma ceramide concentration and Ox-LDL levels. Moreover, 4i was found to significantly decrease LPS-induced and Ox-LDL-induced cell inflammation by regulating the levels of ceramide and sphingomyelin. Overall, this study preliminarily demonstrates that ASM may be an effective target against atherosclerosis for the first time.

Vitamin D 3 (VD 3 ) is an indispensable micronutrient in livestock and poultry feed. Its function in antioxidant stress has been reported. We investigate whether the addition of different concentrations of VD 3 to the diet affects the production performance, slaughter performance, meat quality, organ index, and gut injury on the diquat (DQ)-induced model of oxidative stress in Wenchang chickens. Four hundred and eighty one-day-old chickens were randomly divided into six groups: control (basal diet), 4000 VD (basal diet + VD 3 4000 IU per kg feed intake), 1000 VD+DI (DQ, basal diet + VD 3 1000 IU per kg feed intake), 2000 VD+DI (DQ, basal diet + VD 3 2000 IU per kg feed intake), and 4000 VD+DI (DQ, basal diet + VD 3 4000 IU per kg feed intake). The results showed that the addition of VD 3 to the diet promoted DQ-induced weight loss and reduced ADFI, slaughter rate, splenic index, and pH after 1 h and 24 h in the leg muscles. VD 3 decreased the increase in content of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) among proinflammatory cytokines ( p < 0.05) and increased the reduction in anti-inflammatory cytokines content of interleukin-10 (IL-10) ( p < 0.05) induced by DQ. In addition, liver and kidney injury biomarkers and the intestinal permeability index in serum were disordered after treatment with DQ ( p < 0.05). VD 3 perfected the increase of D-lactic acid (D-LA), diamine oxidase (DAO), total cholesterol (T-CHO), creatinine (CR), blood urea nitrogen (BUN), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) content, aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) activity ( p < 0.05); it increased the decrease of albumin (ALB) content ( p < 0.05). Meanwhile, VD 3 regulated the intestinal morphology and intestinal barrier. Moreover, DQ induced a decrease in total antioxidant capacity and antioxidant enzyme activity in the serum, liver, and jejunum ( p < 0.05), and an increase in malonaldehyde (MDA) content ( p < 0.05). However, the addition of different levels of VD 3 could alleviate the above phenomenon of oxidative stress in Wenchang chickens to different degrees. Thus, this research suggested that the addition of VD 3 can relieve the DQ-induced oxidative stress of Wenchang chickens, and the level of VD 3 acquisition is positively correlated with the remission effect.

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection impairs intestinal barrier function, causing intestinal inflammation and enteric dysbacteriosis. The human cathelicidin LL-37 can regulate excessive inflammatory responses, barrier function, and balance the intestinal microbial community; however, little is known about its effects on inflammation, intestinal barrier function, and microbiota disorders in EHEC O157:H7-infected mice. In this study, we investigated the protective effect of LL-37 against EHEC O157:H7 infection and elucidated the underlying mechanism using a mouse model. LL-37 treatment was found to inhibit body weight loss, restore edema and destruction of the intestinal villi, and significantly reduce epithelial apoptosis (P < 0.05) in EHEC O157:H7-infected mice. Furthermore, inflammatory infiltration of macrophages and neutrophils into the jejunum and colon was significantly decreased (P < 0.05). LL-37 significantly downregulated the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) (P < 0.05) and upregulated the anti-inflammatory cytokine (IL-10) during EHEC O157:H7 infection. LL-37 increased the expression of tight junction proteins (ZO-1, ZO-2, claudin-1, and occludin), which are associated with intestinal barrier function, and had a positive effect on EHEC O157:H7-induced microbial disorders, particularly in terms of the inflammation-related microbiota. LL-37 also significantly decreased the E. coli load in the liver and spleen (P < 0.01) and restored the structure of the liver and kidney. Taken together, LL-37 conferred protection in a EHEC O157:H7-induced mouse model by reducing intestinal inflammation, enhancing intestinal barrier function, and restoring the balance of the intestinal microbiota, which indicates the therapeutic potential of LL-37 against pathogen infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Cardiac rehabilitation, which combines cardiology and preventive medicine, is an important part of treatment for cardiovascular diseases. Systematically, cardiac rehabilitation, including simultaneously inhibiting endothelial injury and promoting endothelial repair, is beneficial for physical and mental recovery and reduces the risks of recurrence and death in patients with cardiovascular diseases. Cardiac rehabilitation has developed rapidly in the last 50 years. A preliminary system for cardiac rehabilitation has been developed in China. The present article mainly focuses on the progress of cardiac rehabilitation from the aspects of goals, measures, and modes of research in the current scenario., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2022 Wei Wei et al.)

The study aimed to describe a novel port design and simple surgical strategy for uniportal thoracoscopic right middle lobectomy. In this approach, a 3- to 4-cm incision was created at the sixth intercostal space posterior to the scapular line. The surgery was performed by serial division of the anterior oblique fissure, vein, bronchus, artery, and horizontal fissure. Based on our preliminary experience, this approach could provide an appropriate direction and angle for dissection and stapling, solving the challenge of conventional uniportal right middle lobectomy., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This retrospective study aimed to present our surgical experience in patients with benign tumour or trauma in spleen who underwent laparoscopic partial splenectomy (LPS) and to compare the results with those of patients who underwent an open partial splenectomy (OPS)., Methods: We analysed the medical data of patients who underwent LPS or OPS between January 2010 and January 2020., Results: In total, 41 patients were enrolled. Nine patients underwent open surgery, 32 patients underwent laparoscopic surgery. The proportion of patients with tumours in the upper pole in LPS group was more than patients in OPS group. No difference was observed in estimated blood loss, allogeneic transfusion, postoperative stay, pathology and complications between LPS and OPS groups. The operation time in the LPS group (137.5 ± 30.8 min) was longer than that in the OPS group (88.3 ± 30.1 min) for patients with splenic traumatic rupture (P = 0.019)., Conclusions: LPS is an effective and safe spleen-preserving surgery as OPS. The advantages are small trauma, light pain and quick recovery. It is suitable for patients with benign tumours or trauma confined to one side of the spleen., (© 2022 Royal Australasian College of Surgeons.)

Background: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs., Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678., Findings: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27)., Interpretation: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective., Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University., Competing Interests: Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Selenium is a trace element necessary for the growth of organisms. Moreover, selenium supplementation can improve the immunity and fertility of the body, as well as its ability to resist oxidation, tumors, heavy metals, and pathogenic microorganisms. However, owing to the duality of selenium, excessive selenium supplementation can cause certain toxic effects on the growth and development of the body and may even result in death in severe cases. At present, increasing attention is being paid to the development and utilization of selenium as a micronutrient, but its potential toxicity tends to be neglected. This study systematically reviews recent research on the toxicological effects of selenium, aiming to provide theoretical references for selenium toxicology-related research and theoretical support for the development of selenium-containing drugs, selenium-enriched dietary supplements, and selenium-enriched foods.

Objective: To analyse potential risk factors for postoperative pancreatic fistula (POPF)., Methods: A retrospective study on risk factors for POPF was conducted in patients undergoing laparoscopic pancreatoduodenectomy. Basic characteristics, and preoperative, intraoperative and postoperative patient data were collected and analysed., Results: A total of 268 patients were enrolled in this study, including 54 patients with POPF following surgery (POPF incidence, 20.15%). Univariate analysis indicated that patient's age, body mass index (BMI), preoperative bilirubin level, pancreas texture, and drainage fluid amylase level on day 1 following surgery were associated with POPF. Multiple logistic regression analysis indicated that preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25, and age ≥65 years were independent risk factors associated with POPF., Conclusions: For patients with preoperative bilirubin level ≥170 µmol/l, soft pancreas texture, BMI ≥25 and age ≥65 years, clinically relevant measures should be taken as early as possible for the prophylaxis of POPF.

Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis, and biological evaluation of hydroxamic acid-based direct inhibitors of ASM with the effort of validating their antidepressant effects in vivo . As a result, a series of novel ASM inhibitors were developed using a structure-based approach. Our studies demonstrated that the administration of 21b improved depression-like behaviors of rats. Importantly, this positive result was relevant to the inhibition of ASM and the increasing neurogenesis in hippocampus. To the best of our knowledge, this is the first time that direct inhibitors of ASM were developed to support the possibility of ASM as a potential therapeutic target for depression.

Pancreatic cancer is highly prevalent and exhibits a high incidence and mortality rate. Hypoxia contributes to tumorigenesis and the progression of pancreatic cancer. To the best of our knowledge, the role of microRNA (miR)-519 has not been investigated in hypoxia-induced pancreatic cancer progression. The purpose of the present study was to elucidate the mechanism underlying miR-519-mediated regulation of pancreatic cancer progression. Reverse transcription-quantitative PCR and western blotting were performed to investigate miR-519 and programmed death ligand 1 (PD-L1) mRNA and protein levels, respectively. Additionally, a Transwell assay was performed to examine the invasiveness of PANC-1 and SW1990 cells. Cells were subsequently stained with Annexin V to determine the apoptotic rate of cells. Furthermore, bioinformatics analysis and a dual-luciferase reporter assay were performed to confirm the direct association between miR-519 and PD-L1, and a xenograft experiment was conducted to test the role of miR-519 in vivo . The results revealed that the expression levels of miR-519 in pancreatic cancer cells were reduced following hypoxia treatment. Furthermore, transfection with miR-519 mimics inhibited PANC-1 and SW1990 cell invasiveness, and induced apoptosis under hypoxic conditions. PD-L1 was also identified as a downstream target of miR-519, and rescued the miR-519 mimic-attenuated tumorigenesis of pancreatic cancer cells under hypoxic conditions. Additionally, treatment with miR-519 mimics significantly suppressed the tumor growth of PANC-1 cells. The results of the present study indicated a novel mechanism of miR-519-mediated tumorigenesis in pancreatic cancer cells under hypoxic conditions. The conclusions may be crucial for the improvement of future pancreatic cancer treatment., (Copyright: © Nong et al.)

The sound absorption performance of porous ceramisite is determined by its pore structure, which is mainly governed by a foaming agent and heating rate during a foaming process. By tuning the heating rate and foaming agent concentration, ceramisite with different pore structures was prepared by using flyash, cement, quick lime, and plaster as raw materials as well as ammonium acetate as a low-temperature decomposition foaming agent in this work. The phase composition, microstructure, and sound absorption performance of the prepared porous ceramisite were investigated. Results demonstrate that the apparent porosity and the pore diameter increased with the increase of foaming agent concentration, accompanied with the broadening of the pore diameter distribution. The apparent porosity is positively correlated with heating rate until the temperature is higher than 20 °C·min -1 , while the pore diameter is negatively correlated. The pore diameter distribution becomes narrow as a function of the heating rate. The sound absorption performance is positively correlated with the apparent porosity. An optimal pore diameter might exist, meaning diameter sizes that are larger or smaller than the optimal diameter are not conducive to the optimization of the sound absorption performance of the overall frequency band. It was determined that the curing time was not a key factor for optimizing the pore structure., Competing Interests: The authors declare no conflict of interest.

Purpose: The necessity to cease anticoagulation before photoselective vaporization (PVP) surgery remains nonconsensual. We aimed at assessing the efficacy and safety of PVP among high-risk benign prostate hyperplasia (BPH) patients on or off anticoagulation., Methods: We systematically searched Pubmed, Embase, and Cochrane Library Central Register of Controlled Trials (CENTRAL). 2299 patients from 11 studies were eventually included. Newcastle-Ottawa Scale (NOS) was employed to assess the quality and risk of bias of each study. All statistical analyses were conducted with Review Manager v.5.3 software., Results: Ten parameters (operation time, laser time, blood transfusion, urethral stricture, urinary tract infection, reoperation, dysuria, capsule perforation, catheterization time, and re-catheterization) from patients on or off anticoagulant therapy were collected. The patients without anticoagulants performed better at catheterization time [MD - 0.54, 95% CI (- 0.82, - 0.26), P = 0.96, I 2  = 0] with a reduction of 0.54 day than those on anticoagulants. Significant statistical difference was not observed from other parameters. Subgroup analysis, grouped by the power output of PVP systems (80 W, 120 W and 180 W), consistently showed no statistical significant difference except at catheterization time in the 180-W PVP subgroup., Conclusion: PVP, a safe and effective option for high-risk BPH patients, work comparably regardless of anticoagulant therapy, despite non-anticoagulant patients have shorter catheterization time. It is implied that the use of anticoagulants might be unnecessary to stop for high-risk BPH patients undergoing PVP for the sake of safety, which certainly requires further investigations to confirm.

Acid sphingomyelinase (ASM) has been shown to be involved in many physiological processes, emerging to be a promising drug target. In this study, we constructed a ligand-based pharmacophore model of ASM inhibitors and applied this model to optimize the lead compound α-mangostin, a known inhibitor of ASM. 23 compounds were designed and evaluated in vitro for ASM inhibition, of these, 10 compounds were found to be more potent than α-mangostin. This high hit ratio confirmed that the presented model is very effective and practical. The most potent hit, 1c, was found to selectively and competitively inhibit the enzyme and inhibit the generation of ceramide in a dose-dependent manner. Furthermore, 1c showed favorable anti-apoptosis and anti-inflammatory activity. Interactions with key residues and the Zn 2+ cofactor of 1c were found by docking simulation. These results provide promising leads and important guidance for further development of efficient ASM inhibitors and drug candidates., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: This study aimed to evaluate the effect of exosomes produced by human-induced pluripotent stem cell-derived mesenchymal stromal cells (hiPSC-MSCs-Exo) on hepatic ischemia-reperfusion (I/R) injury., Methods: Exosomes were isolated and concentrated from conditioned medium using ultracentrifugation and ultrafiltration. hiPSC-MSCs-Exo were injected systemically via the inferior vena cava in a rat model of 70% warm hepatic I/R injury, and the therapeutic effect was evaluated. The serum levels of transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were measured using an automatic analyzer. The expression of inflammatory factors was measured using enzyme-linked immunosorbent assay (ELISA). Histological changes indicated changes in pathology and inflammatory infiltration in liver tissue. Apoptosis of hepatic cells in liver tissue was measured using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining along with apoptotic markers., Results: hiPSCs were efficiently induced into hiPSC-MSCs with typical MSC characteristics. hiPSC-MSCs-Exo had diameters ranging from 50 to 60 nm and expressed exosomal markers (CD9, CD63 and CD81). Hepatocyte necrosis and sinusoidal congestion were markedly suppressed with a lower Suzuki score after hiPSC-MSCs-Exo administration. The levels of the hepatocyte injury markers AST and ALT were significantly lower in the treated group than in the control group. Inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and high mobility group box 1 (HMGB1), were significantly reduced after administration of hiPSC-MSCs-Exo, which suggests that the exosomes have a role in suppressing the inflammatory response. Additionally, in liver tissues from the experimental group, the levels of apoptotic markers, such as caspase-3 and bax, were significantly lower and the levels of oxidative markers, such as glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were significantly higher than in the control group. These data point to an anti-apoptotic, anti-oxidative stress response role for hiPSC-MSCs-Exo., Conclusions: Our results demonstrated that hiPSC-MSCs-Exo alleviate hepatic I/R injury, possibly via suppression of inflammatory responses, attenuation of the oxidative stress response and inhibition of apoptosis., (Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

SUMOylation is a dynamic process which can be reversed by a family of sentrin/SUMO-specific protease (SENPs). Recently, SENP1, a member of SENPs family was shown to have a pro-oncogenic role in many types of cancer. Here, we showed that SENP1 was upregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues. Moreover, clinical data showed that SENP1 was positively associated with lymph node metastasis and TNM stage. Furthermore, knockdown of SENP1 by SENP1-siRNA inhibited pancreatic cancer cell proliferation, migration, and invasion, suggesting that SENP1 played an important role in PDAC progression and metastasis. Mechanistically, silencing of SENP1 results in downregulation of MMP-9, which is pivotal for PDAC cell growth and migration. Taken together, these results suggest that SENP1 may serve as a potential novel diagnostic and therapeutic target of PDAC.

The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.

Background: microRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein., Methods: Quantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC., Results: miR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212., Conclusion: These data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.

Background: The dysregulation of oncogenes and tumor suppressor genes plays an important role in many cancers, including hepatocellular carcinoma (HCC), which is one of the most common cancers in the world. In a previous microarray experiment, we found that DLGAP5 is overexpressed in HCCs. However, whether the up-regulation of DLGAP5 contributes to hepatocarcinogenesis remains unclear., Methodology/principal Findings: In this study, we showed that DLGAP5 was significantly up-regulated in 76.4% (168 of 220) of the analyzed HCC specimens when compared with adjacent liver tissue. DLGAP5 overexpression was evident in 25% (22 of 88) of the HCC specimens without AFP expression, suggesting that DLGAP5 may be a novel biomarker for HCC pathogenesis. The silencing of DLGAP5 gene expression by RNA interference significantly suppressed cell growth, migration and colony formation in vitro. The expression level of DLGAP5 was also found to be related to the methylation level of its promoter in the HCC specimens., Conclusions/significance: Taken together, these data suggest that the expression of DLGAP5 is regulated by methylation and that the up-regulation of DLGAP5 contributes to HCC tumorigenesis by promoting cell proliferation.

The WHO recommends antiretroviral therapy (ART) for most HIV-infected tuberculosis patients. To assess the impact of ART on tuberculosis case-fatality rates in Cambodia, we compared treatment outcomes of patients newly diagnosed with tuberculosis in 2004 (before implementation of ART clinics) with outcomes of patients diagnosed in 2005 (after these clinics opened). In 2004, 37% of HIV-infected tuberculosis patients died during TB treatment compared with 5% of HIV-uninfected tuberculosis patients. In 2005, 18% of HIV-infected tuberculosis patients died compared with 5% of HIV-uninfected tuberculosis patients. The case-fatality rate for HIV-associated tuberculosis decreased from 2004 to 2005, coincident with the introduction of ART.