Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis / 中华医学杂志(英文版)

BACKGROUND@#Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms.@*METHODS@#Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); β-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer.@*RESULTS@#MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; β-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer.@*CONCLUSION@#MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Research progress of immunotherapies on correction of immunoparalysis in sepsis / 药学实践杂志

Immunoparalysis is the main cause of death in patients with intermediate and terminal sepsis. The correction of immunoparalysis is an important direction of sepsis treatment. In the pathological process of sepsis, a variety of factors contribute to the imbalanced secretion of cytokines, weakened function of antigen-presenting cells, apoptosis and depletion of lymphocytes, and ultimately lead to immunoparalysis, secondary infection, and even patient deaths. Cytokines such as GM-CSF, IFN-γ, IL-7, and IL-15, immune checkpoint-related therapies such as PD-1/PD-L1 antibodies, CTLA-4 antibodies, TIM-3 antibodies, and LAG-3 antibodies, and immunoreactive substances such as thymosin α1 and immunoglobulin might be beneficial to correct the immune paralysis of patients. the progress of immunotherapy to correct immune paralysis in sepsis were reviewed in this article.

Research progress of anti-sepsis treatment using traditional Chinese medicine / 药学实践杂志

Sepsis is life-threatening with complex pathogenesis. It is a big problem in the medical field. Clinically, antibiotics, hormones and mechanical ventilation are the main treatments. There is a lack of specific therapeutic drugs. The treatment effect is not good. In recent years, more and more progress has been made in the treatment of sepsis with traditional Chinese medicine. This article reviews the etiology, pathogenesis and treatment strategies of sepsis. It focuses on four therapies, including clearing away heat and detoxification, clearing the interior, activating blood circulation and removing blood stasis, and strengthening the foundation. We further discuss the advantages and disadvantages of traditional Chinese medicine in the treatment of sepsis, in order to provide reference for the clinical treatment of sepsis.

Effect of miR-524-5p on Epithelial-mesenchymal Transition in Esophageal Cancer Cells by Regulating HEG1 Expression / 肿瘤防治研究

Objective To investigate the mechanism and the effect of miR-524-5p regulating HEG1 expression on the proliferation and epithelial-mesenchymal transition of esophageal cancer cells. Methods The expression levels of miR-524-5p and HEG1 mRNA in esophageal cancer cells and normal esophageal epithelial cells were detected by qRT-PCR. KYSE30 cells were divided into miR-524-5p mimic group, miR-524-5p NC group, miR-524-5p mimic+pcDNA3.1 group, and miR-524-5p mimic+pcDNA3.1-HEG1 group. Non-transfected cells were set as the normal control group (group Control). CCK-8 method was applied to detect the proliferation ability of KYSE30 cells. Western blot analysis was conducted to detect the expression of proteins related to EMT, invasion, and migration and the HEG1 protein. Scratch and Transwell assays were applied to detect the migration and invasion abilities of KYSE30 cells. A dual-luciferase reporter gene was used to examine the targeting relationship between miR-524-5p and HEG1. Results miR-524-5p was lowly expressed in four esophageal cancer cell lines, namely, TE-1, KYSE30, KYSE150, and NEC (P < 0.05). KYSE30 cells with the lowest expression level were selected for subsequent experiments. HEG1 mRNA was highly expressed in four esophageal cancer cell lines (P < 0.05). The GEPIA database showed that HEG1 was highly expressed in esophageal cancer tumor tissues (P < 0.05). KYSE30 cells in the miR-524-5p mimic group had lower proliferation ability, colony formation number, mesenchymal marker protein expression, and migration and invasion abilities and upregulated epithelial marker protein E-cadherin level than cells in the miR-524-5p NC group (P < 0.05). The miR-524-5p mimic+pcDNA3.1-HEG1 group significantly reversed the inhibitory effect of overexpression of miR-524-5p on the proliferation, epithelial–mesenchymal transformation, invasion, and metastasis of KYSE30 cells (P < 0.05). The luciferase activity of cells in the miR-524-5p mimic and WT-HEG1 co-transfection groups was lower than that in the miR-524-5p NC and WT-HEG1 co-transfection groups (P < 0.05). Conclusion miR-524-5p is lowly expressed in EC cells and tissues. The overexpression of miR-524-5p can negatively regulate the expression of HEG1 in esophageal cancer cell line (KYSE30 cells) and reduce the proliferation, EMT process, and invasion and migration abilities of KYSE30 cells.

Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid / 药物分析学报

Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

Genotypes and epidemiological characteristics of Noroviruses in Shenzhen during the winter of 2017 / 中华微生物学和免疫学杂志

Objective To study the genotypes, epidemiological characteristics and homology of Noroviruses (NoV) circulating in Shenzhen in the winter of 2017. Methods RT-PCR was performed using Nov-specific primers after extracting viral genome from 313 fecal samples. Positive RT-PCR products were then sequenced. Phylogenetic trees were constructed based upon the gene sequences of isolated and reference NoV strains using Mega 4. 1 and Clustal W software. Results There were 26 NoV-positive samples and all belonged to G Ⅱ. 4 subtype. These strains shared high homologies with G Ⅱ. 4 ( KY407156), G Ⅱ. 4 (KY580757) and GⅡ. 4 (KX372682). Phylogenetic analysis also suggested that 88. 46％ of them had a lower homology with the NoV strains isolated in the same area in recent years and 46. 15％ were different from the epidemic strains in other provinces of China. Conclusion NoV GⅡ. 4 was the epidemic strain in Shenzhen during the winter of 2017. More attention should be paid to it from the local public health authori-ties considering its owned characteristics in epidemic and homology.

Expression of Oct4 and Sox2 and their clinical significance in tongue squamous cell carcinoma / 中华口腔医学杂志

Objective@#To investigate Oct4 and Sox2 protein expression in tongue squamous cell carcinoma (TSCC) and the relationships between the expressions of Oct4 and Sox2 and clinical pathological characteristics and survival of patients.@*Methods@#The paraffin imbedded tissue specimens of 51 patients with histologically confirmed TSCC were included. Immunohistochemistry was employed to detect the protein expression of Oct4 and Sox2 in 51 TSCC tissue samples. The protein expression levels of Oct4 and Sox2 and their relationships with both clinicopathological features and survival of patients with TSCC were evaluated.@*Results@#In 51 TSCC cases,positive expressions of Oct4 and Sox2 were mainly located in the nucleus of tumor cells. The expression of Oct4 was strongly positive in 27 cases (53%), weakly positive in 16 (31%) and negative in 8 (16%), whereas that of Sox2 was strongly positive in 25 cases (49%), weakly positive in 22 (43%) and negative in 4 (8%). Oct4 and Sox2 expression levels were significantly correlated with the histological grade of TSCC (P=0.004, P=0.006, respectively), not correlated with age, gender, T stage, tobacco smoking and alcohol consumption status (P>0.05), but Oct4 expression level was significantly associated with lymph node metastasis (P=0.001). Sox2 expression level was not associated with lymph node metastasis (P>0.05). The expression of Sox2 was significantly correlated with Oct4 (P<0.001). Oct4 and Sox2 expression was associated with poor overall survival of patients with TSCC (P=0.001, P=0.002, respectively), cases with higher Oct4 and Sox2 expression had the poorest overall survival (P<0.001). Sox2 expression and lymph node metastasis were independent prognostic factors of overall survival in patients with TSCC (P=0.02, P=0.001, respectively).@*Conclusions@#Sox2 had independent prognostic effects on overall survival, suggesting that Sox2 expression may be an usefull indicator for predicting the prognosis of patients with TSCC.

The key points in inquiry training under different scenes in diagnostics / 中华医学教育探索杂志

Inquiry is the main method of history taking. The training should not be limited to the medical inpatients inquiry. Different training scenes should be taken. The outpatient history inquiry needs a similar clinic room and set time limit, and focuses on key point history inquiry as well as document writing. Some principles in emergency inquiry are introduced, such as SAMPLE principle. The key points of inquiry of different patients including elderly patients, child patients, traumatic patients and drug addiction patients are also introduced. Through the combination of theory and practice mode, the group discussion and role-play, different scenes design and standardized patients application, reasonable design of teaching hours and content distribution, as well as feedback in time, optimal teaching effect can be finally achieved.

Effect of dronedarone on HCN channel mRNA and protein expression in neonatal rat ventricular myocytes / 重庆医学

Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.

Current status and influencing factors of enteral feeding intolerance in patients with severe acute pancreatitis / 中华护理杂志

Objective To explore the occurrence of enteral feeding intolerance and its influencing factors in patients with severe acute pancreatitis. Methods A retrospective analysis of severe acute pancreatitis patients undergoing enteral nutrition therapy admitted to a tertiary hospital from October 2012 to October 2015 was performed. The occurrence of enteral feeding intolerance was analyzed,and its influencing factors were evaluated by single factor analysis and multivariate logistic regression analysis. Results There were 54 patients suffered from enteral feeding intolerance among 92 patients. The results of single factor analysis and multivariate regression analysis showed that higher APACHE II score,intra-abdominal pressure and central venous pressure were independent risk factors of feeding intolerance,while adding dietary fiber was a protective factor. Conclusion Severe acute pancreatitis patients with higher APACHE II score,intra-abdominal pressure and central venous pressure can aggravate the risk of feeding intolerance,while adding dietary fiber is beneficial for reducing the incidence.

Cleft lip and cleft palate in Jangxi province: A case-control study on familial occurrence of 1 967 cases / 实用口腔医学杂志

Objective:To assess whether familial occurrence has an influence on the morphological characteristics of patients with nonsyndromic cleft lip and/or palate (NsCL/P).Methods:A case-control analysis was performed on the morphological characteristics of familial group and sporadic group,using medical records of 1967 patients with NsCL/P treated in the Affiliated Stomatological Hospital of Nanchang University from 2002 to 2014.Results:164 (8.34％) cases presented a positive history of cleft in their families.The cleft types,the positive familial rate of cleft lip only (CLO),cleft lip and alveolar ridge(CLA),cleft lip and palate (CLP) and cleft palate only (CPO) were 8.11％,8.54％,6.19％ and 9.65％ respectively.A positive family history of NsCL/P was associated with 0.66 times risk of CPO (P =0.036,OR =0.66,95％ CI 0.44-0.98) compared to those of CLO,CLA and CLP.In familial group of CLP,the lateral incidence of male patients was different from that of female patients (P ＜ 0.001).There was no significant difference between familial group and sporadic group on birth weights,parental child-bearing age and clinical manifestations of patients.Conclusion:Familial occurrence might have an influence on cleft type,laterality and gender of the patients with NSCL/P.

Simple bone cyst of the jaw: a retrospective study of 11 cases / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study described the clinical, surgical, and radiographic findings of simple bone cysts.</p><p><b>METHODS</b>A retrospective study was conducted for patients diagnosed with simple bone cysts in the Department of Oral and Maxillofacial Surgery of the Affiliated Stomatological Hospital of Nanchang University from March 2005 to March 2015. Clinical, radio-graphic, surgical, and follow-up data were gathered. Results were statistically analyzed by central tendency and dispersionusing SPSS 20.0 software.</p><p><b>RESULTS</b>Eleven cases of simple bone cysts were collected, including three male and eight female patients. Ten cases (90.9%) were asymptomatic and one case developed symptoms of swelling. All of the cases had no history of trauma in the affected area, and all were solitary; ten cases (90.9%) were unilocular, and one (9.1%) was multilocular.The shape of each lesion could be assigned to four categories: cone (3 cases), round (2 cases), oval (4 cases), and irregular (2 cases). The treatment in 10 cases consisted of surgery to explore the cavity and curettage of the bone walls. During surgery,the bone cavity in seven cases (70%) was vacant, whereas serous fluid was found in two cases (20%) and serous-bloody fluid in one case (10%). Of the ten cases, three cases exhibited complete bone healing and seven cases showed new bone formation.</p><p><b>CONCLUSION</b>Simple bone cysts of the jaws are usually asymptomatic and appear incidentally on routine radiographies. The prevalence is higher in the mandible and young people. The patient usually has no history of trauma, and the bone cavity of lesion is mostly vacant. Curettage of the bone walls of the lesion is suggested for simple bone cysts. Systemic clinical and radiologic follow-up are necessary to ensure successful treatment.</p>

A new method to improve the success rate of establishing a canine model of atrial fibrillation induced by sympathetic stimulation / 中国比较医学杂志

Objective To develop a new method to expose the stellate ganglion to increase the success rate of establishing a dog model of atrial fibrillation indinced by sympathetic stimulation .Methods A total of 28 adult dogs were randomly divided into traditional group and improvement group , 14 dogs in each group .The stellate ganglions were separated by the two different methods , respectively , to establish a sympathetic stimulation induced atrial fibrillation model in all the dogs .Changes of vital signs , survival rate of the dogs and the voltage required to stimulate the stellate ganglion were recorded intraoperatively .Changes of cardiac electrophysiology were recorded before and after electric stimulation . The levels of released neurotransmitters were detected by immunohistochemistry . Results The survival rate of the improvement group was 100%(14/14), significantly higher than the 64.3%(9/14) of the traditional group (P<0.05). The operation time of the improvement group was 122.71 ±3.62 min, significantly shorter than the 269.44 ±8.79 min of the traditional group (P<0.05).The threshold voltage of the improvement group was significantly lower than that of the traditional group ( P<0.05) .Conclusions Our modified surgical procedure can effectively reduce the mortality of dogs , significantly shorten the operation time , and reduce the intraoperative blood loss , keeping a more intact stellate ganglion , and maintains a more stable voltage of electric stimulation , Therefore, it is a new method more suitable for establishment of a sympathetic stimulation induced atrial fibrillation model in dogs .

Cellular response to fludarabine treatment in combination with different ionizing radiation in renal carcinoma 786-O cells / 中华放射肿瘤学杂志

Objective To investigate DNA double-strand breaks and radiosensitization in renal carcinoma 786-O cells induced by fludarabine (FA) combined with different ionizing radiations.Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation.Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle.The neutral comet assay was used to detect DNA double-strand breaks.The colony-forming assay was used to evaluate the effects of different treatments on cell survival.Comparison between groups was made by one-way analysis of variance or Dunnet' s t test.Results Compared with FA alone or irradiation alone,FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX (P=0.007,0.001);FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase (P=0.000,0.000);the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage (P=0.020,0.060);FA significantly reduced the colony-forming rate after irradiation (P=0.000,0.030;0.001,0.040).Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties.Particularly,FA substantially enhances the cell death induced by heavy ion beam irradiation.

Dermoid cyst in the floor of the mouth with tongue fistula: a case report / 华西口腔医学杂志

Dermoid cysts in the floor of the mouth with tongue fistula are unusual lesions. This study reported a case of dermoid cyst in the floor of the mouth with tongue fistula, analyzed the causes of such formation, and discussed the appropriate diagnosis and treatment methods by reviewing relevant literature.

Eruption of impacted permanent teeth associated with cystic lesions of the jaws after fenestrating decom-pression in adolescents / 实用口腔医学杂志

Objective:To investigate the eruption of cystic lesion associated impacted permanent teeth(CAIPT)of the jaws after fe-nestrating decompression in adolescents and to analyze the related factors that affect the eruption of CAIPT.Methods:32 cases of CAIPT were examined restrospectively by panoramic radiographs.The subjects were divided into erupted group(n =22),and nonerupt-ed group(n =10).Patient age,angulation of the CAIPT,the cusp depth,eruption space and the level of dental root formation meas-ured on intial panoramic radiograph,were subjected to statistical analysis.Results:The eruption of the impacted mandibular molar was significantly related to the cusp depth,level of dental root formation and the patient's age(P 0.05).Conclusion:The patient's age,angulation of impacted permanent teeth,cusp depth,eruption space,level of dental root formation should be considered in the management of CAIPT.

Non-coding RNA and pancreatic cancer / 中南大学学报(医学版)

Non-coding RNA could regulate gene expression, involved in epigenetic modification, and participate in the cell differentiation, proliferation, apoptosis, and other life activities. Noncoding RNA also plays a crucial role in cancer occurrence, cancer cell invasion and distant metastases. Through mediating genome hyper-methylation, transcriptional regulation, regulation of transposable sequences, maintenance of genomic imprinting and DNA damage repair, noncoding RNA could regulate the growth and apoptosis of pancreatic cancer cells. Understanding the molecular mechanism of non-coding RNA in the development process of pancreatic cancer has important theoretical and practical value in the diagnosis, treatment and prognosis.

case of long-term survival after curative resection for synchronous solitary adrenal metastasis from rectal cancer

Clinically curable adrenal metastasis is rare. We report a case of synchronous solitary adrenal metastasis from rectal cancer in a 51-year-old man who underwent curative resection. A right adrenal mass was found by ultrasonography during his routine physical examination and this was confirmed by computed tomography [CT]. His serum carcinoembryonic antigen [CEA] level was found elevated, and colonoscopy revealed a rectal tumor located 10cm from anal verge. A simultaneous laparoscopic right adrenalectomy and anterior resection for rectal carcinoma was performed. Histopathological examination revealed well-differentiated rectal adenocarcinoma with adrenal metastasis. The patient is still alive and free from disease 6 years after the surgery. A review in the literature showed that synchronous solitary adrenal metastasis from colorectal carcinoma is very rare. Surgical resection and for selected patients, laparoscopic procedure may provide survival benefit and potential surgical cure for a solitary metastasis

Expression of angiogenic factors in myocardial tissue of diabetic rats / 中国病理生理杂志

AIM:To observe the expression of angiogenesis factors in the myocardial tissue of streptozotocin-induced diabetic rats .METHODS:The diabetic rat model was induced by intraperitoneal injection of streptozotocin .After 12 weeks, the cardiac function was measured by MPA cardiac function analysis system .The myocardial collagen volume fraction ( CVF) was assessed by Masson staining .The capillary vessels was quantified as the ratio of capillary to myocyte (C/M) using CD31 immunostaining.The expression levels of vascular endothelial growth factor (VEGF), angiopoietin ( Ang)-1, endostatin and Ang-2 were observed by Western blotting .RESULTS:Compared with normal control group , the left ventricular end-diastolic pressure (LVEDP) was evidently increased (P0.05).CONCLUSION:Im-balances between the angiogenic factors (VEGF and Ang-1) and anti-angiogenic factors (endostatin) may play an impor-tant role in the pathogenesis of diabetic cardiomyopathy .

Carcinoma ex pleomorphic adenoma occurring in the sublingual gland: a case report / 华西口腔医学杂志

Carcinoma ex pleomorphic adenoma occurring in the sublingual gland is extremely rare. In this report, a case of adenoid cystic carcinoma ex pleomorphic adenoma of the sublingual gland was presented.