Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

The Role of Pharmacists in Perioperative Antibiotic Application in a Hospital of Traditional Chinese Medicine (TCM)

Objective: To determine adherence to Chinese guidelines for perioperative antibiotic use in our hospital of TCM and discuss the role of pharmacists on antibiotic management. Methods: 2844 operative cases between May 2011 and December 2011 in our hospital were investigated by pharmacists and relative data were collected, including demographic data, type of surgery, wound classification (clean and clean contaminated) and parameters of antibiotic application (antibiotic choice, route, dose, time of first dose, time of operative re-dosing and duration of prophylaxis). The rationality of antibiotic administration in these cases was respectively evaluated based on Chinese guidelines for perioperative antibiotic use. Results: After intervention of pharmacists, perioperative antibiotic application in our hospital was obviously improved from May to December of 2011: the rates of antibiotic application in operative cases and antibiotic prophylaxis in clean operation were both decreased. However, there was no significant improvement for the rate of rationality. In detail, TCM surgery was well compliant with the guidelines: the rate of antibiotic application was less than 30%, regimen of antibiotic prophylaxis and therapy was reasonable;in the breast ward, antibiotic application was improved after pharmacists’ intervention: the rate of antibiotic prophylaxis in clean operation significantly decreased from 100% to 30%;however, in the anorectal ward, some troubles were resolved while other new problems came out;in other ward such as general surgery and orthopedics, old problems still existed. Conclusions: Protocol violations were frequent to perioperative antibiotic application in our hospital due to considerable over prescription. Intervention was effective but not enough. Further educational strategies are essential for reducing costs and antibiotic resistance rates.

High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic postischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord

Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.

Causal Association Between Tea Consumption and Gout:A Mendelian Randomization Study

Objective Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited.We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization(MR).Methods Genome-wide association studies in UK Biobank included 349376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day.Summary statistics from the Chronic Kidney Disease Genetics consortium included 13179 cases and 750634 controls for gout.Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk.The inverse-variance weighted(IVW)method was used for primary analysis,and sensitivity analyses were also conducted to validate the potential causal effect.Results In this study,the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method(OR:0.90;95%CI:0.82–0.98).Similar results were found in weighted median methods(OR:0.88;95%CI:0.78–1.00),while no significant associations were found in MR-Egger(OR:0.89;95%CI:0.71–1.11),weighted mode(OR:0.80;95%CI:0.65–0.99),and simple mode(OR:1.01;95%CI:0.75–1.36).In addition,no evidence of pleiotropy was detected by MR-Egger regression(P=0.95)or MR-PRESSO analysis(P=0.07).Conclusion This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia

Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.

Fixation of Calcaneal Tuberosity Beavis II Fracture in Elderly Patients Using Locking Plate Combined with Tension Screw

Background:Calcaneus is the largest bone of foot and the main load-bearing structure of heel.The incidence of simple calcaneal tubercle avulsion fracture is low,accounting for about 1%to 3%of all calcaneal fractures.Beavis II fracture has large bone fracture,obvious displacement,obvious soft tissue irritation,and often leads to skin necrosis.It needs surgical treatment,reduction and fixation as soon as possible.Although open reduction and tension screw internal fixation is used for Beavis II calcaneal tubercle fracture,but the failure rate is more common.Methods:This study retrospectively analyzed the surgical treatment of calcaneal tubercle Beavis II fracture over 55 years old in our hospital from January 2013 to January 2019.The patients were treated with tension screw combined with locking plate,and followed up and analyzed.Results:12 patients in this group were followed up for 12 to 36 months(mean 20 months).After operation,the fracture healed smoothly in all patients,the healing time was 8 to 12 weeks(mean 10.7 weeks),and there were no complications such as poor incision healing,fracture displacement,internal fixation loosening,fracture and so on.When the patients were followed up 18 weeks after operation,the AOFAS score was 47 to 100,with an average of 91.1,of which 8 cases were excellent,3 good and 1 poor,with an excellent and good rate of 91.7%.Conclusion:Our hospital has been treated with tension screw combined with locking plate,fixed firmly,can early functional exercise,achieved good results.

A prediction of in vivo mechanical stresses in blood vessels using thermal expansion method and its application to hypertension and vascular stenosis

Mechanical stimuli play critical roles in cardiovascular diseases,in which in vivo stresses in blood vessels present a great challenge to predict.Based on the structural-thermal coupled finite element method,we propose a thermal expansion method to estimate stresses in multi-layer blood vessels under healthy and pathological conditions.The proposed method provides a relatively simple and convenient means to predict reliable in vivo mechanical stresses with accurate residual stress.The method is first verified with the opening-up process and the pressure-radius responses for single and multi-layer vessel models.It is then applied to study the stress variation in a human carotid artery at different hypertension stages and in a plaque of vascular stenosis.Our results show that specific or optimal residual stresses exist for different blood pressures,which helps form a homogeneous stress distribution across vessel walls.High elastic shear stress is identified on the shoulder of the plaque,which contributes to the tearing effect in plaque rupture.The present study indicates that the proposed numerical method is a capable and efficient in vivo stress evaluation of patient-specific blood vessels for clinical purposes.

Protein corona mediated liposomal drug delivery for bacterial infection management

Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections.However,the inevitable formation of protein corona on the liposomal surface can heavily impact in vivo performance.A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development.Here,the critical role of protein corona in mediating liposome-bacteria interactions was elucidated.Adsorption of negatively charged protein on cationic liposome weakened electrostatic attractionenhanced liposomal binding to the bacteria.Cumulative complement deposition on anionic liposome composed of phosphatidylglycerol(DSPG s Lip)contributed to a superior binding affinity of DSPG s Lip to planktonic bacteria and biofilms,which was exploited to enhance bacteria-targeted drug delivery.In both S.aureus-related osteomyelitis and pneumonia mice models,DSPG s Lip was demonstrated as a promising antibiotic nanocarrier for managing MRSA infection,indicating the benefits of lipid composition-based protein corona modulation in liposomal antibiotic delivery for bacterial infection treatment.

sPLA2-IB Level Correlates with Hyperlipidemia and the Prognosis of Idiopathic Membranous Nephropathy

Summary:Recent studies suggested that serum secretory phospholipase A2 group IB(sPLA2-IB)was increased in idiopathic membranous nephropathy(IMN).However,the interference of high lipemia on the sPL.A2-IB levels was not taken into account in these studies.The present study aimed to investigate the correlation between sPLA2-IB and lipemia,and the clinical merit of sPLA2-IB in the prediction of prognosis of IMN patients.A total of 64 IMN patients,39 immunoglobulin A nephropathy(IgAN)patients and 64 healthy controls were included in the study.The levels of serum sPLA2-IB,lipemia and proteinuria were measured.Fifty IMN patients were followed up for 6 months.Pathologic stages were made for all IgAN and IMN patients.The results showed that the levels of serum sPLA2-IB,cholesterol and low-density lipoprotein cholesterol(LDL-C)were significantly higher,and the levels of albumin and high-density lipoprotein cholesterol(HDL-C)were significantly lower in IMN patients than in healthy controls and IgAN patients.Serum sPLA2-IB levels were also found to be higher in IgAN patients than in heathy controls,but the association of serum sPLA2-IB levels with proteinuria,cholesterol and albumin was only shown in IMN patients.Antibody against M-type receptor for secretory phospholipase A2(PLA2R1)was positive in 813%IMN patients.Glomerular sPLA2-IB deposition,podocyte fused processes,and density deposition on thickened basement membrane were seen in IMN patients,but not in IgAN patients.IMN patients with lower sPLA2-IB and proteinuria levels were found to have better outcome after the 6-month follow-up.In IMN patients,sPLA2-IB levels were significantly increased in both serum and renal tissue.In conclusion,serum sPLA2-IB was closely correlated with proteinuria,albumin and cholesterol,and IMN patients with lower sPLA2-IB levels were more likely to achieve a better outcome.

Unraveling GLUT-mediated transcytosis pathway of glycosylated nanodisks

Glucose transporter(GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines.However,the transcytosis process remains elusive.Glycopeptide-modified nanodisks(Gly-A7R-NDs),which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports,were utilized to better understand the whole transcytosis process.Gly-A7R-NDs internalized brain capillary endothelial cells mainly via GLUT-mediated/clathrin dependent endocytosis and macropinocytosis.The intracellular Gly-A7R-NDs remained intact,and the main excretion route of Gly-A7R-NDs was lysosomal exocytosis.Glycosylation of nanomedicine was crucial in GLUT-mediated transcytosis,while morphology did not affect the efficiency.This study highlights the pivotal roles of lysosomal exocytosis in the process of GLUT-mediated transcytosis,providing a new impetus to development of brain targeting drug delivery by accelerating lysosomal exocytosis.

Molecular Mediators of Estrogen Reduction-induced Otolith Shedding

Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.

Effect of simvastatin on expression of IL17,HMGB1 and TLR4 in LN kidney tissues of rats

Objective:To observe the intervention influence and effect of simvastatin on the expression of interleukin 17(L117),high mobility group protein 1(HMGB1)and TLR4 path in Lupus nephritis(LN)rats.Methods:A total of 28 BSXSB male mice with LN(16 weeks)were randomlv divided into observation group and the comparison group,observation group was given 6 mg·kg^(-1)·d^(-1)simvastatin in 0.1%PBS lavage for 4 weeks.the comparison group was not given any trestment.Blood urea nitrogen(BUN)level and urine trace albumin(Scr)level of two groups were determined.The expression of IL17.HMGB1 and TLR4 protein was detected using immune histochemical method,and the kidney histological damage was observed.Results:BNU,LI17.HMGB1,TLR4protein and HMGB1 mRNA in observation group was significantly lower than that in control group(P<0.05):There was no statistical difference of Scr level between two goups(P<0.05).Histological observation showed glomerular lesions integral of observation group was obviously lower than that of control group.Conclusions:Simvastatin can reduce the expression of IL17.HMGB1 and TLR4 protein in LN mice,thereby can inhibit the autoimmune response as a potential treatment function of LN.

Optimal Threshold of Stimulated Serum Thyroglobulin Level for ^(18)F-FDG PET/CT imaging in Patients with Thyroid Cancer

This study was to explore the optimal threshold of thyroid-stimulating hormone(TSH)-stimulated serum thyroglobulin(s-Tg) for patients who were to receive18F-fluorodeoxyglucose(18F-FDG) PET/CT scan owing to clinical suspicion of differentiated thyroid cancer(DTC) recurrence but negative post-therapeutic 131I whole-body scan(131I-WBS). A total of 60 qualified patients underwent PET/CT scanning from October 2010 to July 2014. The receiver operating characteristic(ROC) curve analyses showed that s-Tg levels over 49 μg/L led to the highest diagnostic accuracy of PET/CT to detect recurrence, with a sensitivity of 89.5% and a specificity of 90.9%. Besides, bivariate correlation analysis showed positive correlation between s-Tg levels and the maximum standardized uptake values(SUVmax) of18F-FDG in patients with positive PET/CT scanning, suggesting a significant influence of TSH both on Tg release and uptake of18F-FDG. So, positive PET/CT imaging is expected when patients have negative 131I-WBS but s-Tg levels over 49 μg/L.

Novel conservative treatment for peritoneal dialysis-related hydrothorax:Two case reports

BACKGROUND Peritoneal dialysis (PD) is an important renal replacement therapy for patientswith end-stage renal disease. PD-related hydrothorax is a rare but seriouscomplication in PD patients, produced by the movement of peritoneal dialysatethrough pleuroperitoneal fistulas. In previous reports, patients with hydrothoraxsecondary to PD were usually recommended to discontinue PD and transfer tohemodialysis (HD). Herein, we describe another method of managing thiscomplication—with an adjusted PD prescription and continuous drainage ofpleural effusion, patients could continue PD without recurrence of hydrothorax.CASE SUMMARY In this report, we present the medical records of 2 patients with hydrothoraxsecondary to PD. We recommended intermittent PD with continuous drainage ofpleural effusion. A type 18Ga soft catheter was placed to drain pleural effusion.Ultrasound-guided thoracentesis was performed, and the soft catheter was placedin the pleural cavity for a long period (3 mo and 2 mo, respectively). The pleuralcatheter was removed when no fluid was drained from the pleural cavity. Afterseveral months, pleuroperitoneal fistulas were closed in both patients and PD wascontinued. These patients did not transfer to HD, had no recurrence ofhydrothorax and were still treated with PD after 1 year.CONCLUSION These 2 case reports show that continuous drainage of pleural effusion with an18Ga soft catheter is a useful method for hydrothorax secondary to PD.

The correlation between different ABO blood group gene loci and the pathogenesis and prognosis of acute myocardial infarction

Objective: To assess the effect of different ABO blood group gene locus on severity and prognosis of acute myocardial infarction (AMI). Methods: 100 patients with AMI diagnosed in our hospital from June 2018 to June 2019 were selected as the myocardial infarction group. At the same time, 100 healthy patients with physical examination results in our hospital were selected as the control group. Single-nucleotide polymorphisms of peripheral blood ABO gene loci rs505922, rs579459, rs643434, rs651007, and rs8176743 were detected. The differences of ABO blood group gene loci in different groups were compared. The correlation between the distribution of ABO blood group gene loci and the incidence and prognosis of patients with AMI was analyzed. Results: 98 cases were included in the myocardial infarction group and 99 cases were included in the control group. Compared with the control group, the genotypes of rs643434 and rs651007 locus in the myocardial infarction group were statistically significant (P<0.05). Analysis under different genetic models , compared with the control group, the myocardial infarction group had a significant difference in the rs643434 gene dominant mode, rs651007 dominant mode and recessive mode (P<0.05). The dominant mode of rs643434 was correlated with Gensini score and TIMI grade. The dominant mode of rs651007 was correlated with Gensini score, TIMI grade and troponin.The recessive mode of rs651007 was correlated with Gensini score, and the differences were statistically significant (P < 0.05). The dominant mode of rs643434 was related to the occurrence of MACE, and the difference was statistically significant (P < 0.05).Conclusion: Different genetic models of ABO blood group genes rs643434 and rs651007 may be related to the condition and prognosis of AMI.

Clinical Pathological Analysis in 104 Ductal Breast Cancer Cases

Ductal breast cancer is a clinically heterogeneous disease;we investigate the correlation between tumor size, comedo necrosis, number of cell mitoses and axillary lymph node metastasis in ductal breast cancer. In this study, 104 ductal breast cancer specimens were collected and divided into 3 groups: T1 group (tumor size ≤ 2 cm), T2 group (2 5.0 cm). Among those specimens, 95 cases were diagnosed with invasive ducted carcinoma, and 9 cases were ductal carcinoma in-situ (DCIS). Results show that T3 group has a higher rate of axillary lymph node metastasis than T2 group and T1 group;T2 group has a higher rate of lymph node metastasis than T1 group. The patients with the number of cell mitoses (≥10) were also has a higher rate of axillary lymph node metastasis (P = 0.0139) than the patients with the number of cell mitoses (<10). No significance was found between comedo necrosis lesions and axillary lymph node metastasis, though the frequency of comedo necrosis lesions in patients with axillary lymph node metastasis was higher than those in non-metastatic patients. It is concluded that the tumor size and the number of cell mitoses were risk factors for axillary lymph node involvement in ductal breast cancer.

Role of Osteopontin in the Carcinogenesis and Metastasis of Colorectal Cancer

Colorectal cancer (CRC) is one of the most malignant tumors in both sexes among all types of tumors worldwide. Up to now, no precise biomarker has been capable of accurately predicting the prognosis for patients with CRC. Therefore, it is essential for us to find a new biomarker to predict the prognosis, overall survival, and disease-free survival of patients with CRC, especially for those patients who have a distant metastasis. There is a growing concern over the issues that osteopontin (OPN), a multifunction phosphorylated protein, has been identified in recent years among multiple tumors types, including CRC. There is increasing evidence showing that high expression of OPN is related to the proliferation, invasion and metastasis of CRC. OPN could support malignant formation by inducing tumor angiogenesis;aggravating the degradation of extracellular matrix;promoting chemo taxis, adhesion, and metastasis of tumors and affecting tumor immunity and apoptosis based on various complex mechanisms. More intensive studies are required in the future to clarify the roles of OPN and its related genes, relevant receptors, protein structure, biological features, and complex molecular mechanisms in colorectal carcinogenesis, as well as to develop beneficial agents for the clinical treatment of CRC to improve patient prognosis.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments

BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

Uremic clearance granule combined with Alprostadil in the treatment of chronic renal failure: A systematic review and meta-analysis

Objective: To evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stata 15.0. Results: Nine articles involving 726 patients were enrolled in this study. Meta-analysis showed that the total effective rate [OR = 3.68 (2.44, 5.55), P < 0.001], Scr [SMD =-2.34 (-3.49,-1.19), P < 0.001], BUN [SMD =-1.80 (-2.73,-0.87), P < 0.001], Ccr [SMD = 0.71 (0.44, 0.97), P < 0.001] were better in the experimental group. But there were no significant difference in UA, CysC, 24h-Upro and incidence of adverse reactions (all P > 0.05) between two groups. No serious adverse reactions were found. Conclusions: The effect of the integrated medicine on CRF was better than Alprostadil alone. Uremic clearance granule is safe and has no obvious adverse reactions.