Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal

Progress of Clinical Research on Individualized Precision Treatment of Helicobacter pylori Infection / 胃肠病学

Helicobacter pylori (Hp) can cause a variety of gastric diseases and has a high infection rate. With the widespread use of antibiotics and the influence of geographical, strain and host differences, the failure rate of Hp eradication and reinfection rate are increasing. Therefore, there is a need for individualized precision treatment of refractory Hp infection. This article reviewed the progress of clinical research on individualized precision treatment of Hp infection.

A Single-arm Study on Minocycline Combined With Metronidazole, Rabeprazole, and Bismuth Potassium Citrate for Eradication of Helicobacter pylori Infection / 胃肠病学

Background: Antibiotic resistance of Helicobacter pylori (Hp) is an important cause of failure of eradication treatment, the latest national and international consensus have recommended a quadruple regimen based on the use of amoxicillin or tetracycline as the first-line treatment for Hp eradication. Minocycline is a semi-synthetic tetracycline easily available clinically and has a low secondary resistance rate, and can be used in penicillin-allergic patients. Aims: To investigate the efficacy and safety of regimen with minocycline combined with metronidazole, rabeprazole and bismuth potassium citrate for eradication of Hp infection. Methods: Patients with Hp infection from August 2020 to January 2021 at Jiangqiao Hospital in Jiading District having the primary treatment for Hp eradication were selected. All the enrolled patients received rabeprazole enteric-coated tablets 10 mg bid + minocycline capsules 100 mg bid + metronidazole tablets 400 mg tid + bismuth potassium citrate capsules 220 mg bid for 14 days. Symptoms and adverse reactions during treatment were recorded. The eradication of Hp was determined by

Myeloid-specific targeting of Notch ameliorates murine renal fibrosis via reduced infiltration and activation of bone marrow-derived macrophage

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.

Expression of MiR-455-5p in epithelial ovarian cancer and its target gene function / 实用肿瘤学杂志

Objective The aim of this study was to investigate the expression of miR-455-5p in epithelial ovarian cancer and its effect on the development of epithelial ovarian cancer. Methods The miRNA expression data of normal ovarian epithelial tis-sues and epithelial ovarian cancer tissues GSE83693 were downloaded from the GEO database. Differential expression analysis was used to obtain differential expression data of miRNAs in epithelial ovarian cancer. The expression of miR-455 -5p was analyzed whether there is difference expression between normal ovarian epithelium and epithelial ovary cancer tissues; qRT-PCR was used to verify the differential expression prediction results; bio-informatics software was used to analyze the KEGG pathway enrichment and GO gene function annotation of miR-455-5p target genes,and to explore the disorders of dyregulated miR-455-5p in the devel-opment of epithelial ovarian cancer. Results A total of 101 cases of differentially expressed miRNAs were screened,34 cases were up-regulated and 67 cases were down-regulated. Among them,miR-455-5p was down-regulated significantly(P<0. 01),and the different fulds were -2. 9019. The results of qRT-PCR showed that the expression of miR-455-5p in epithelial ovarian cancer cells(SKOV-3,OVCAR-3 and A2780)was significantly lower than that in normal ovarian epithelial cells(IOSE-80),and the dif-ferential expression was statistically significant(P<0. 05). The results of KEGG pathway enrichment analysis showed that miR-455-5p regulated target genes mainly involved in five pathways,including TGF-β signaling pathway,Hippo signaling pathway,ECM-receptor interaction,transcriptional dysregulation pathway in cancer,and chronic granule cellular leukemia,which were associated with tumors. GO functional annotation analysis showed that the target genes regulated by miR-455-5p in the above pathway was mainly involved in protein phosphorylation,promoted cell proliferation and migration,inhibited apoptosis,promoted epithelial-mesenchymal transition,regulated transcription and regulated cell cycle,etc. ,which associated with tumorigenesis. Conclusion The expression of miR-455-5p is down-regulated in epithelial ovarian cancer. The miR-455-5p target genes are involved in the pathogenesis and function of epithelial ovarian cancer,and are associated with the development of epithelial ovarian cancer.

The effects of hypertriglyceridemia on autophagy of acinar cells in acute necrotic pancreatitis rats / 中华胰腺病杂志

Objectives To observe the changes of autophagy of acinar cells in hypertriglyceridemia (HTG) associated acute necrotic pancreatitis(ANP) rats,and investigate the effects of HTG on autophagy and AP. Methods Forty SD rats were randomly divided into 4 groups using random number method, including control group,ANP group,hyperlipemia(HL) group,hyperlipidemia associated acute necrotizing pancreatitis (HANP) group. Control group and ANP group were fed with normal diet for 2 weeks,while the rats in HL and HANP group were fed with a high-fat diet for 2 weeks,and after the blood collection ANP and HANP rats were induced by 3.5% sodium taurocholate retrograde injection into the pancreaticobiliary duct to establish the ANP model. Rats in control group and HL group were intraperitoneally injected with equal volume of normal saline solution. ALL rats were sacrificed at 48 h after the model establishment. Serum triglyceride (TG), total cholesterol (TC) and serum amylase levels were measured; pancreatic tissue was histologically examined and scored; Transmission electron microscope were used to observe the intracellular ultrastructure changes and calculate the number of autophagosome and autophagic lysosome;the expressions of autophagy related proteins such as LC3,LC3Ⅱ, LC3Ⅰ, p62 and Lamp-2 were determined by Western-blot. Results After 2-week high fat diet, serum levels of TG and TC in HANP and HL groups were obviously higher than those in the control and ANP group;Serum amylase levels in HANP group and ANP group were higher than the control and HL group,and the differences were statistically significant (all P<0.05). Transmission electron microscope showed that the number of autophagosomes in ANP group was significantly higher than those in other three groups and the difference was statistically different(all P<0.05);and the autophagy activity in HANP group was impaired compared with ANP group. Compared with the control group, in ANP group the protein expressions of LC3 Ⅱ/Ⅰ ratio and p62 in pancreatic tissue were up-regulated (2.11 ± 0.03 vs 1.70 ± 0.08, 9 420 ± 624 vs 4 973 ± 577),but LAMP-2 was down-regulated(20 533 ± 578 vs 23 231 ± 1 155). Compared with ANP group,the proteins expression levels of LC3Ⅱ/Ⅰand p62 in HANP group was obviously decreased (20 533 ± 578 vs 23 231 ± 1 155), and the difference was statistically significant (all P<0.05). Conclusions Hypertriglyceridemia can worsen the pathology injury of AP,and the mechanism may be related to the decreased autophagy related proteins LC3Ⅱ/Ⅰ and p62 and decreased number of autophagosome.

Clinical research progress on tissue defect repairing with acellular dermal matrices / 国际生物医学工程杂志

Acellular dermal matrix(ADM) is a special biological material that contains only collagen,elastin and other extracellular matrix.ADMs are made by special methods of separating skin epidermis and dermis,and removing Laugerhans cells,vascular endothelial cells,fibrohlasts cells and major histocompatibility complex (MHC)within the dermis.ADM causes no graft rejection,and provides a good scaffold for tissue reconstruction,angiogenesis and implantation of host cells.The preparation process of ADM includes the separation of epidermis and dermis,decellularization,perforation and freeze-drying.According to the classification method,ADMs can be classified into allogeneic and xenogeneic ADM,patch and injection type ADM,as well as cross-linked and non-crosslinked ADM,which can meet various clinical requirements.ADM is widely used in surgical field,such as treatment of deep burn wounds,breast reconstruction after masteetomy,oral mucosa repair,abdominal wall hernia repair,and treatment of vocal cord paralysis.Due to the characteristics ADM,its application prospect is considerable.The research progress of ADM in recent years was summarized.

The risk factors of recurrent fracture in patients having received percutaneous vertebroplasty for vertebral compression fracture: recent progress in research / 介入放射学杂志

Along with the aging of population in China,more and more people suffer from osteoporosis.As a consequence,osteoporotic vertebral compression fracture has become one of the major clinical issues.More and more patients like to take percutaneous vertebroplasty (PVP) as the preferred treatment,thus,the number of patients who develop recurrent vertebral fracture after PVP is also increased.In recent years,more and more attention has been paid to the recurrent fractures after PVP for vertebral compression fractures by clinicians.In order to reduce the incidence of recurrent vertebral fracture after PVP,it is necessary to make the further and deep studies on the risk factors that cause recurrent vertebral fractures.This paper aims to make a comprehensive review about the risk factors that may cause recurrent vertebral fractures after PVP for osteoporotic vertebral compression fracture.

Percutaneous bone cement fusion for the stress fracture of vertebral body adjacent to pseudoarthrosis in patients with ankylosing spondylitis: preliminary results in 4 cases / 介入放射学杂志

Objective To assess the clinical value of percutaneous bone cement fusion in treating stress fracture of vertebral body that is adjacent to pseudoarthrosis in patients with ankylosing spondylitis.Methods The clinical data of 4 ankylosing spondylitis patients with stress fracture of vertebral body adjacent to pseudoarthrosis,which was treated with percutaneous bone cement fusion,were retrospectively analyzed.Bone cement fusion through injection of bone cement was performed for 4 vertebral segments.Visual analogue scale (VAS) of pain and Oswesty disability index (ODI) were determined before and after operation,the results were compared,and the improvements of pain and daily activity were evaluated.Results The operation was successfully accomplished in all the 4 patients.The mean used amount of bone cement for each vertebral segment was 14.5 ml.Small amount of bone cement extravasation was observed in one patient,but no severe clinical complication occurred.The mean VAS score decreased from preoperative 9 points to postoperative 3.5 points;ODI score decreased from preoperative 43.8 points to postoperative 14.5 points.After the treatment,the pain was obviously relieved and the daily activity was markedly improved.Conclusion For the treatment of stress fracture of vertebral body that is adjacent to pseudoarthrosis in patients with ankylosing spondylitis,percutaneous bone cement fusion is minimally-invasive,safe and effective.

The relationship between the cystic fluid characteristics of symptomatic sacral canal cyst and the interventional therapeutic prognosis / 介入放射学杂志

Objective To investigate the relationship between the cystic fluid characteristics of symptomatic sacral canal cyst and the interventional therapeutic prognosis.Methods A total of 114 patients with symptomatic sacral canal cyst were enrolled in this study.Clinically,all patients complained of discomfort at lumbosacral area.Among the 114 patients,86 were primary sacral canal cyst and 28 were recurrent sacral canal cyst.Under DSA guidance,percutaneous puncturing of the cyst was performed,2-5 ml cerebrospinal fluid (CSF) was aspirated and sent for laboratory tests.Then a small amount of nonionic contrast agent was injected into the cyst to determine whether the cyst was communicated with the subarachnoid space or not.Finally,double-needle method was used to aspirate the cyst fluid.Results Radiography showed that communication between the cyst and subarachnoid space was detected in 66 patients (group A),while no communication between the cyst and subarachnoid space was observed in 48 patients (group B).In patients with primary symptomatic sacral canal cyst,the differences in the sugar and chloride levels of CSF between group A and group B were statistically significant.In patients with recurrent symptomatic sacral canal cyst,the differences in the sugar,protein and chloride levels of CSF between group A and group B were also statistically significant.Statistically significant correlation existed between the single or multiple CSF changes and the interventional therapeutic prognosis.Conclusion Sacral canal cysts can be classified into two types:cyst-subarachnoid space communicating type and cyst-subarachnoid space non-communicating type.The characteristics of CSF in patients with primary symptomatic sacral canal cyst are different from those in patients with recurrent symptomatic sacral canal cyst.Multiple CSF changes,the increased sugar level and decreased chloride level in CSF are well correlated with the interventional therapeutic prognosis.

Ovarian clear cell carcinoma derived from endometriotic cyst: a clinicopathological analysis of 54 cases / 中华妇产科杂志

Objective To clarify the clinicopathological features of ovarian clear cell carcinoma derived from endometriotic cyst (EC-OCCC).Methods Totally 54 cases of EC-OCCC were recruited in the current retrospective study.The relation between ages, clinical symptoms and signs, surgical and pathological stages, serum CA125, findings of ultrasound, treatments and the sites of tumors, macro-and micro-features and expression of immunostainings were analyzed.Results (1) Clinical features: the ages of patients were (50±6) years old (range 31-62 years old).Pelvic mass was the major complaint of 50 patients (93％, 50/54).Forty-five cases belonged to International federation of Gynecology and Obstetrics (FIGO) stage Ⅰ, 4 cases were stage Ⅱ and another 5 cases were stage Ⅲ.Serum CA125 was elevated in 21 cases (54％, 21/39) before therapy.Doppler ultrasound showed 46 cases (85％, 46/54) had solid masses in pelvis.(2) Pathological findings: 52 cases (96％, 52/54) had their tumor unilaterally, and 2 cases (4％, 2/54) occurred bilaterally.The maximal diameters of endometriotic cyst (EC) ranged from 1.5 to 23.0 cm and maximal diameters of ovarian clear cell carcinoma (OCCC) components were from 0.5 to 12.0 cm.Fifty-one cases (94％, 51/54) had their tumor within EC, which showed focally irregular protrudings, grey-white papillae or solid nodules attached to the cyst wall.Three cases (6％, 3/54) appeared as irregular thickened wall of the cysts, ranged from 1.5 to 6.0 cm in the maximal length, with the microscopic features of EC and OCCC and the transitional areas between the 2 morphologies.All cases expressed cytokeratin (CK) 7 and pan-CK AE1/AE3, 17 cases (33％, 17/51) expressed ER and 5 cases (10％, 5/51) expressed PR.TP53 showed mutational phenotype in 19 cases (36％, 19/53).Sixteen cases (30％, 16/54) combined with uterine adenomyosis and 25 cases (46％, 25/54) with endometriosis at other sites.(3) Survival survey: during the period of 39.1 months follow-up, 3 cases relapsed and 2 cases died.(4) There was a significant difference of serum CA125 between patients of early-and advanced-stages (P=0.049).There were no differences identified in ages, diameters of EC and OCCC, the expression level of ER, PR and TP53, the co-existence of adenomyosis and endometrosis, as well as ultrasonic findings (P＞0.05).Conclusion EC-OCCC could be recognized in early stage by symptoms and ultrasound due to accompanied endometriotic cysts, resulting in relatively good prognosis.

The minute ventilation recovery time used as a predictor of weaning in patients with chronic obstructive pulmonary disease / 中华急诊医学杂志

Objective To explore the value of minute ventilation recovery time (VERT) as a weaning predictor in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD).Methods A prospective study was performed from March 2008 to July 2012.Fifty-two COPD patients under mechanical ventilation for more than 48 hours in our RICU tolerated a spontaneous breathing trial (SBT) and were ready for planned extubation.After SBT,these patients were placed back on their pre-SBT ventilator settings for up to 25 minutes,during which VERT was obtained.VERT was defined as the time for minute ventilation to return to baseline measured before SBT.Respiratory rate,tidal volume,minute ventilation and respiratory rate/tidal volume ratio were also obtained before SBT and just after SBT.Arterial blood gas data were measured and recorded before weaning.According to the weaning outcome,the patients were classified as successful group (40 cases) or failed group (12 cases).VERT and other quantitative variables were compared using t test.A multiple logistic regression was performed to explore possible factors associated with the weaning outcome.The sensitivity and specificity of VERT for predictive capacity in weaning were assessed using ROC cure.Results VERT and respiratory rate after SBT were significantly different between two groups.Multiple logistic regression revealed that VERT was the only predictor associated with weaning outcome (b =0.282,P ＜0.001).The area under ROC curve for VERT was 0.957 (95％ CI:O.907-1.008).With a cut-off value of 10.5 minutes,the sensitivity and specificity of VERT for predicting weaning failure were 1.0 and 0.85,respectively.Conclusions VERT may be a new predictor for extubation and determination of mechanical ventilation weaning in patients with COPD.VERT is a variable to be easily measured thereby being conveniently used in clinical practice.

In vitro effect of erlotinib on the growth of pancreatic cancer cell line BxPC3 and its mechanism / 中华胰腺病杂志

Objective To investigate the effect and possible mechanism of erlotinib,an epidermal growth factor recceptor inhibitor,on human pancreatic cancer cell lines BxPC3 in vitro.Methods Methyhhiazolyhetrazolium(MTT)assay was used to detected the proliferation of BxPC3 after exposure to erlotinib,apoptosis and cell cycle changes were studied by flow eytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling assay(TUNEL).The expressions of bcl-2 mRNA,bax mRNA,bcl-xL mRNA and bak mRNA were determined by reverse transcriptase polymerase chain reaction(RT-PCR). Results Edotinib inhibited BxPC3 cells growth in a dose and time dependent manner in vitro.The cell viabilities in erlotinib 1 μmol/L and 100 μmol/L groups 72 h later were(90.25 ±2.62)%and(40.75 ±2.98)%,and the difference was statistically significant(P<0.01).The cell viability in edotinib 50 μmol/L groups 24 h and 96 h after BxPC3 exposure were(74.0±4.08)%and(49.50 ±1.29)%,and the difference was statistically significant(P<0.01).Cell apoptosis rate in erlotinib 50 μmol/L group was(11.0 μ1.1)%,which was significantly higher than(6.2 ±1.1)%in control group(P<0.01).G_0/G_1 cell accounted for (73.4±1.3)%of all the cells,which was significantly higher than(63.3 ±1.O)%in control group.With transmission electron microscope,the morphology of BxPC3 ceils showed typical apoptosis and apoptotic body. The expressions of bcl-2 mRNA,bel-xl mRNA were down-regulated,while the expression of bax mRNA was slightly up-regulated,and the expression of bak mRNA was not affected.Conclusions The growth of BxPC3 cells could be suppressed by erlotinib and possible mechanisms involved blocking cell cycle,up-regulating apoptosis proteins and down-regulating apoptosis inhibitor proteins.