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Purpose@#Mixed-lineage leukemia protein 4 (MLL4/KMT2D) is a histone methyltransferase, and its mutation has been reported to be associated with a poor prognosis in many cancers, including lung cancer. We investigated the function of MLL4 in lung carcinogenesis. @*Materials and Methods@#RNA sequencing (RNA-seq) in A549 cells transfected with control siRNA or MLL4 siRNA was performed. Also, we used EdU incorporation assay, colony formation assays, growth curve analysis, transwell invasion assays, immunohistochemical staining, and in vivo bioluminescence assay to investigate the function of MLL4 in lung carcinogenesis. @*Results@#We found that MLL4 expression was downregulated in non–small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues and tended to decrease with disease stage progression. We analyzed the transcriptomes in control and MLL4- deficient cells using high-throughput RNA deep sequencing (RNA-seq) and identified a cohort of target genes, such as SOX2, ATF1, FOXP4, PIK3IP1, SIRT4, TENT5B, and LFNG, some of which are related to proliferation and metastasis. Our results showed that low expression of MLL4 promotes NSCLC cell proliferation and metastasis and is required for the maintenance of NSCLC stem cell properties. @*Conclusion@#Our findings identify an important role of MLL4 in lung carcinogenesis through transcriptional regulation of PIK3IP1, affecting the PI3K/AKT/SOX2 axis, and suggest that MLL4 could be a potential prognostic indicator and target for NSCLC therapy.
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Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.
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Objective:To investigate the efficacy and safety of programmed death-1 (PD1) inhibitor combined with transcatheter arterial chemoembolization (TACE) in the treatment of huge primary liver cancer.Methods:From June 2016 to December 2019, the clinical data of 31 patients with huge primary liver cancer enrolled in the Central Hospital of Lishui were retrospectively collected and analyzed. The tumor size ranged from 10.1 to 18.8 cm, with an average of (14.2±2.3) cm. The patients were divided into TACE group (TACE treatment, 18 cases) and combined group (one week after TACE, patients receiving a dose of 200 mg PD1 inhibitor administration every 21 days, 13 cases), according to whether patients receiving PD1 inhibitors. The patients were followed up. The disease control rate (DCR) were compared between the two groups using Mann-Whitney U test. The median overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method. Results:The DCR in combined group (53.8%, 7/13) was higher than that in TACE group (22.2%, 4/18), and the difference was statistically significant ( Z=-2.13, P=0.04). The median PFS (5.0 months) in combined group was longer than that in TACE group (3.0 months), the difference was statistically significant (χ2=4.39, P=0.04). The median OS (15 months) in combined group was longer than that in control group (9 months), and the difference was statistically significant (χ2=5.51, P=0.02). Conclusion:The combine PD1 inhibitors with TACE is an effective and safe therapy for huge primary liver cancer.
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ObjectiveTo investigate the clinical features of patients with different types of acute drug-induced liver injury (DILI) through a retrospective analysis. MethodsClinical data were collected from 790 patients who were diagnosed with acute DILI in Beijing YouAn Hospital and Beijing Tongren Hospital affiliated to Capital Medical University from December 2010 to March 2019, and according to the type of damaged target cell, the patients were divided into hepatocellular injury type group with 554 patients, cholestasis type group with 99 patients, and mixed type group with 137 patients. The patients were evaluated based on severity grade and score, clinical outcome, and Hy′s rule. An analysis of variance was used for comparison of normally distributed continuous data between three groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical data between three groups. The Kruskal-Wallis H test was used for comparison of ranked data between three groups, and the Mann-Whitney U test was used for comparison between two groups. ResultsMost of the patients were female in all three groups, and the hepatocellular injury type group had a significantly higher proportion of female patients than the cholestasis type group (70.8% vs 54.5%, P＜0.05), and the Cholestasis type group had a significantly lower proportion of female patients than the mixed type group(54.5% vs 54.7%, P＜0.05). There were 244 patients with grade 3 hepatocellular injury type DILI (244/554, 44.4%), 56 patients with grade 3 cholestasis type DILI (56/99, 56.6%), and 46 patients with grade 3 mixed type DILI (46/137, 33.6%), and there was a significant difference between the three groups (χ2=36.589, P＜0.05). Drugs inducing liver injury included traditional Chinese medicine, Western medicine, combination of traditional Chinese medicine and Western medicine, and other drugs, among which traditional Chinese medicine was the most common cause of liver injury. There was a significant difference in the outcome at discharge between the patients with different types (H=14.390, P=0.001). Compared with the cholestasis type group, the hepatocellular injury type group had a significantly higher cure rate and significantly lower uncured rate and mortality rate (all P＜0.05). Among the 554 patients with hepatocellular injury type DILI, 388 (70.0%) met Hy′s rule and 166 (300%) did not meet Hy′s rule, and there was a significant difference in clinical outcome between these two groups (U=38 372.0, P=0.033). ConclusionDILI is more common in women, and most patients have hepatocellular injury type DILI. Traditional Chinese medicine is the main cause of liver injury. There is a high proportion of patients with severe DILI among the patients with hepatocellular injury type or cholestasis type. DILI often has good prognosis with a relatively low mortality rate. Hy′s rule cannot predict the death of patients with acute DILI.
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Objective:To investigate the efficacy and safety of short-term transcatheter arterial chemoembolization （TACE）-radiofrequency ablation （RFA） sequential therapy for advanced hepatocellular carcinoma (HCC).Methods:The clinical data of 117 patients with advanced HCC enrolled in the Central Hospital of Lishui from March 2010 to January 2019 were retrospectively analyzed. All patients received TACE and RFA sequential therapy. The patients were divided into 2 groups including short interval group (interval≤7 d, 61 cases) and long interval group (interval>7 d, 56 cases) according to interval between TACE and RFA. The difference of response rate was analyzed by Wilcoxon test. Kaplan-Meier survival curve was used to calculate the overall survival (OS) time and progression free survival (PFS) time.The risk factors of TACE-RFA sequential therapy were tested using Cox multivariate analysis. The complications in the two groups were compared using χ 2 test. Results:The response rate in the short interval group (72.1%, 43/61) was significantly higher than that in the long interval group (41.1%，23/56) with significant difference ( Z=-2.50, P=0.01). The median PFS in the short interval group (14.9 months) was longer than that in the long interval group (9.1 months). The difference of PFS survival curve between the 2 groups was statistically significant (χ2 =5.90, P=0.01).The median OS in the short interval group (34.7 months) was longer than that in the long interval group (20.3 months). The difference of OS survival curve between the 2 groups was statistically significant (χ2 =6.60, P=0.01). Cox multivariate analysis showed that tumor size [hazard ratio (HR)=2.42, P<0.01], cirrhosis (HR=2.04, P<0.01), interval (HR=0.44, P<0.01), aspartate aminotransferase (HR=1.71, P=0.03) were the independent risk factors for advanced HCC.There were no significant differences in the complication incidence between the 2 groups ( P>0.05). Conclusion:Short-term interval TACE-RFA sequential therapy as a protective factor is efficient and safe for advanced HCC treatment.
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Objective:To investigate the trait of exosomes serected by mesenchymal stem cells derived form orofacial bone(OMMSCs-Exo) and the communication between the exosomes and macrophages.Methods:OMMSCs were isolated from orthognathic surgical sites and cultured by limited dilution.Their cell surface markers were characterized by flow cytometry.the rate of colony formation and the differentiation potential of OMMSCs were evaluated.Exosomes were prepaired from the culture supernatants of OMMSCs(P4-P6).Transmission electron microscopy(TEM) and western blot were used to identify the exosomes.The expression of miRNAs associated with immunity such as miR-223 and miR-let-7c were determined by Real-time RT-PCR.Human peripheral blood mononuclear cells(PBMCs) were isolated from health donor and co-cultured with OMMSCs-Exo.After co-cultured for 24 h,the communication between exosomes and macrophages was tested using a confocal microscope.Results:Human OMMSCs were proved to have the characteristics of mesenchymal stem cells.The diameter of OMMSCs-Exo ranged from 40 to 160 nm.The OMMSCs-Exo expressed CD63 and CD81 and contained miRNAs associated with immune regulation such as miR223 and miR-let-7c.OMMSCs-Exo could be uptaken by macrophages.After co-culture of OMMSCs-Exo with marcrophages for 72 h,miR223 expression in macrophages increased.Conclusion:OMMSCs-Exo has the potential of immune regulation.
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UL48 plays essential role in replication of MDV genome and interacts with UL36 as well as other MDV tegument proteins.To investigate the interaction between UL48 and UL36 during MDV oncogenisis,antibody against UL48 was prepared and characterized in current study.UL48 gene was amplified from MDV-Ⅰ genome and then subcloned into pTYB1 and pGEX-4T3 vectors for UL48 expression with induction of IPTG in BL21(DE3) E..coli cells.Chitin-sepharose and Glutathion-sepharose were,respectively,used to purify fusion protein intein-UL48 and GST-UL48.Four subcutaneous injections of intein-UL48 fusion protein were done on the lower back and the thigh of rabbit and then other three injections with an interval 10 days.The titer of antibody was measured by the sandwich ELISA with UL48 protein isolated from GST-UL48 after cleavage of thrombin.Western blot was carried out for specificity analysis of antibody against UL48 protein.The results suggested that UL48 antibody was succesfully prepared,and its titer was 1 ∶ 512 000.
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Objective:To explore the relation between parental cohesion,peer acceptance and the loneliness of left-behind children,and furthermore explore the mediation role of self-esteem.Methods:Totally 427 left-behind children in Hubei Province (275 males,152 females) were surveyed,and the Parental Cohesion Scale (PCS),Peer Nomination (PN),Self-Esteem Scale (SES) and Children Loneliness Scale (CLS) were used to assess parental cohesion,peer acceptance,self-esteem and loneliness respectively.The relation between parental cohesion,peer acceptance andthe loneliness of left-behind children,and the mediation role of self-esteem wereanalyzed.Results:The CLS scores in left-behind children were negatively correlated with the scores of PCS,PN,and SES (r =-0.31,-0.37,-0.50,P ＜ 0.01),the SES scoresplayed a mediation role in the relation between PN scores and CLS scores (95 ％ CI:-7.02--0.01),and between PCS scores and CLS scores (95 ％ CI:-0.18--0.09).Furthermore,the unique effect of the PN scores on the CLS scores (sr2 =0.10) was higher than that of PCS scores (sr2 =0.06).Conclusion:The current research indicates that the loneliness,parental cohesion,peer acceptance and self-esteem of the left behind children have a close relationship.Furthermore,it suggests that self-esteem may play partial mediating effects between parental cohesion,peer acceptance and the loneliness of left-behind children.
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Objective To evaluate the feasibility, safety, and efficacy of Y-shaped jogged stent in patients with malignant hilar biliary obstruction. Methods During the period of January 2010 to June 2015,We retrospectively reviewed 98 cases of malignant hilar biliary obstruction who were received implantation of biliary tract stent. 17 consecutive patients who were treated with Y-shaped jogged stent were identified (group A) during January 2012 to June 2015. Group A was carefully matched according to patients' age, sex, type of tumor, stage, type of biliary obstruction, level of bilirubin at diagnosis, presence of metastasis and treatment, and 17 patients who were underwent unilateral stent placement alone with PTCD were chosen as control group (group B). Patients' baseline characteristics, stenting strategy, complications, stent patency time and survival rates were analyzed, and continuous variables of the two groups were compared using Student's t-test. Categorical variables were analyzed using the Fisher exact test. Results Y-shaped jogged stent implantation group and control groups were closely matched in terms of patients' age, sex, type of tumor, stage, type of biliary obstruction, level of bilirubin at diagnosis, presence of metastasis and treatment ( P>0.05). The bilirubin decreased rate in the two groups was 88.2%and 53.0%respectively (P<0.05). The median time of stent patency after stent implantation was(7.3 ± 1.0)months and(5.7 ± 0.9) months respectively (χ2=4.04,P=0.044), and the median survival time was(9.1 ± 1.5)months and(7.2 ± 1.1)months (χ2=4.60,P=0.032), with significant difference according to Kaplan-Meier analysis. There were no severe complications such as massive hemorrhage, perforation, biliary fistula and severe pancreatitis, which were associated with stent implantation. Conclusions The application of Y-shaped jogged stent is safe, feasible and effective in patients with malignant hilar biliary obstruction. It can relieve the clinical symptoms of biliary obstruction effectively with prolongation of stent patency time and survival rate significantly.
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To review the literatures on the treatment of sleep disorder with acupuncture and moxibustion in China in recent years. we believed that combined acupuncture and medicine, acupuncture and auricular acupuncture had obvious advantages in the treatment of sleep disorder after stroke.
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Objective To evaluate the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating hepatocellular carcinoma (HCC) under liver capsular. Methods Forty three patients with 62 lesions of HCC under liver capsular received TACE followed by CT?guided percutaneous RFA after 1 to 2 weeks were analyzed retrospectively. The subjects were observed and follow?up imaging with enhanced MRI was performed to evaluate the therapeutic efficacy after combined treatment. The patients were followed up for 10 to 69 months. The patients with residual lesions received a second RFA, the patients with recurrence or new lesions received another TACE combined with RFA. The overall survival rates, median survival time and median time to progression were calculated by using Kaplan?Meier. Results A total of 55 TACE and 68 ablations were performed in 43 patients with 62 lesions. The procedure was successfully accomplished in all patients. The complete ablation rate after the first ablation was 90.3%(56/62). The 1, 3, 5?year overall survival rates were 95.3%, 78.1%and 43.9%, the median survival time was 58 months and the median time to progression was 32 months. Conclution For the treatment of hepatocellular carcinoma under liver capsular, TACE combined with RFA is safe and effective.
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Objective To investigate the reasons and the methods of prevention and cure for serious complications of radiofrequency ablations in the treatments of hepatocellular carcinomas. Methods A total of 410 patients with BCLC at A or B stage of hepatocellular carcinomas in our hospital were enrolled between November 2014 and June 2009. These patients underwent a total of 504 times radiofrequency ablations for the treatments of liver lesions. This retrospective study analysed the reasons and the strategies of prevention and cure for the serious complications. Results In the patients with a total of 504 times radiofrequency ablations, 2 patients had massive hemorrhage caused by puncture injuries, 2 patients had the tumors which were close to the liver capsules and 1 patient had bile peritonitis caused by the injury of thermal ablation on the gallbladder. The maximum diameter of tumor was 5 cm. That tumor was close to the gallbladder. 2 patients had needle tract metastases caused by incompletely needle path ablations. 1 of the 2 patients had a tumor near the liver capsule, and the other patient had un-enough temperature for needle path ablation. Tumor outbreaks were happened in 2 patients. 1 of the 2 patients had a tumor which was located in the liver capsule and close to the portal vein. The other patient had a 12 cm diameter tumor with rich blood supplement. 2 patients had liver abscesses. 1 of the 2 patients had a tumor near the ascending colon, and the other patient had diabetes. 1 patient had colonic perforation caused by thermal ablation. The tumor in that patient was located in the right hepatic lobe segment and adjacent to the ascending colon. The incidence of serious complications was 1.98% (10/504). Conclusions The incidence of the serious complications of radiofrequency ablations for the treatments of hepatocellular carcinomas is relatively low. The main reasons for the serious complications were direct injuries caused by punctures, heat radiation injuries, tumors adjacent to large blood vessels, gallbladders and intestines, tumors with abundant blood supplement, needle paths fail to cross normal liver tissues, low scores of liver function, weak immune system and diabetes. The key points for avoiding and reducing the serious complications are preoperative evaluations of patients' basic situations, choices of appropriate puncture channels and control ranges of ablations when tumors are close to important blood vessels, intestines and gallbladders.
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Objective To explore the MRI features of pelvic endometriosis outside the ovary.Methods 13 patients with pelvic endometriosis outside the ovary were imaged.Their clinical and imaging data were reviewed retrospectively.All cases were con-firmed by pathology.An enhanced MR using T1 WI sequence both in sagittal and transverse position was performed after T2 WI fat-suppression sequence and T1 WI sequence.Our MRI study was focused on the distribution of lesions locating in the deep pelvic cavity and abdominal wall,and the features of MRI signals .Results 13 lesions were found,in which 4 lesions located in the rectouterine pouch of Douglas,2 cases the bladder wall,2 cases the unilateral cystic inlet of ureter,1 case the anal canal wall,and 4 cases the ab-dominal wall.10(10/13)lesions were shown as solid nodules while 3(3/13)lesions as cyst-solid ones.All lesions showed moderate-ly heterogeneous enhancement.Conclusion Pelvic endometriosis outside the ovary mainly shows solid or cyst-solid lesions that lo-cates in the urinary,uterus,rectal wall and spaces around them.MR images show a higher value for the detection of the lesions out-side the ovary.
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Objective To assess the clinical value of transcatheter arterial chemoembolization (TACE) together with radiofrequency ablation (RFA) and sorafenib in treating recurrent hepatocellular carcinoma (HCC) after surgery.Methods A total of 40 patients with recurrent HCC after surgery, who were encountered at authors' hospital during the period from December 2009 to May 2014, were collected. The patients were divided into the study group (n=20) receiving TACE combined with RFA and sorafenib and the control group (n=20) receiving TACE plus RFA. Within 7-10 days after TACE, RFA was carried out. In the study group, oral sorafenib therapy (400 mg, two times everyday) started at 4 days after TACE. Withdrawal of sorafenib would be ordered if drug resistance occurred. Each patient underwent TACE combined with RFA not less than two times. Results The median survival time of the study group and the control group was 31.0 months and 24.8 months respectively, and statistically significant difference existed between the two groups (P0.05). The progression free survival (PFS) time of the study group and the control group was 6.8 months and 5.7 months respectively, the difference between the two groups was statistically significant (P<0.05). Conclusion TACE combined with RFA and sorafenib can prolong the overall survival time and the progression free survival time of patients with recurrent HCC after surgery.
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One hundred kinds of excellent books on basic medicine were selected from Wanfang Data Knowledge Platform to develop a books-papers citation database.Their academic levels of the selected books were evaluated by PageRank algorithm.The chapters and sections of the books were divided into 4 parts according to their PageRank value and the distribution characteristics of their citation frequencies to study the PageRank and the top 20 cited chapters and sections of the books.The advantages and disadvantages of PageRank algorithm in book evaluation were described.
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Objective To evaluate the short-term efficacy, safety and effectiveness of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with radioactive 125I seed implantation in treating advanced non-small-cell lung cancer (NSCLC). Methods A total of 48 patients with inoperable and EGFR mutation-positive advance NSCLC were included in this study. The patients were divided into study group (n = 26) and control group (n = 22). Patients in the study group were treated with EGFR-TKIs combined with radioactive 125I seed implantation; while patients in the control group only received EGFR-TKIs treatment, which was kept on until the disease progressed. The clinical efficacy, and the incidence of side effect as well as the survival rate were determined, and the results were compared between the two groups. Results Local disease control rate of the study group and the control group was 92.3% and 68.2%respectively, the difference was statistically significant (P= 0.033), while the effective rate was 76.9% and 54.5%respectively, the difference was not significant (P=0.101). Progression-free survival (PFS) time of the study group and the control group was 14.1 months and 9.7 months respectively (P< 0.05). The one-year survival rate of the study group and the control group was 80.8%and 63.6%respectively (P<0.05), and the median survival time was 26.9 months and 17.1 months respectively (P < 0.05). The major complication caused by radioactive 125I seed implantation was pneumothorax. Conclusion For EGFR mutation-positive advance NSCLC, EGFR-TKIs together with radioactive 125I seed implantation is a safe and effective treatment.Its short-term efficacy is superior to pure EGFR-TKIs therapy. At present, this combination therapy is a new alternative for the treatment of EGFR mutation-positive advance NSCLC.
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Objective:A method that is based on microfluidic cell chip technology was developed for the first time to analyze CD14+monocyte myeloperoxidase (MPO) expression in myelomonocytic leukemia (M4) patients. CD14+monocyte MPO expression in M4 patients was preliminarily discussed. Methods:a. The chip was prepared by using polydimethylsiloxane as the host material and by secondary foam molding. b. A total of 48 clinically diagnosed M4 patients and 52 patients with normal myelogram were included as the test and control groups, respectively. c. A method based on the microfluidic cell chip approach was established to detect CD14+mono-cytes and to determine the positive rate and degree of MPO expression in the cells. d. The microfluidic cell chip technique was used to compare CD14+monocyte MPO expression in M4 patients with that in the control. Results:a. The designed microfluidic single cell analysis chip allowed the entry of granulocytes into the corresponding microfluidic channels. Thus, blood cells were separated. Numer-ous ghost corpuscles surrounded the separated white blood cells (WBCs). WBC morphology did not show obvious changes. b. The posi-tive rate of MPO expression and the activity of CD14+monocytes in the bone marrow of M4 patients were significantly higher than those in the bone marrow of the control (P<0.05). Conclusion:A method based on microfluidic single cell technology was developed for the first time to analyze the MPO expression in CD14+monocytes. CD14+monocyte MPO activity in M4 patients was significantly higher than in the control. CD14+monocyte MPO activity can be used as an auxiliary examination marker for clinical diagnosis.