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{L-End}Objective To analyze the effects of night shift work and overweight/obesity on blood pressure of workers in chemical fiber industry. {L-End}Methods A total of 1 004 workers of a chemical fiber factory were selected as the study subjects using convenient sampling method, and their blood pressure and body mass index were measured. Multiple linear regression model was used to analyze the relationship between night shift work and blood pressure, and multiple logistic regression was used to assess the independent impact and combined impact of night shifts and overweight/obesity on the risk of hypertension. {L-End}Results Compared with the non-night shift workers, the prevalence of hypertension in night shift workers was increased (5.3% vs 13.0%, P<0.05), with elevated systolic and diastolic blood pressure (both P<0.05). The results of multiple linear regression analysis showed that the systolic blood pressure and diastolic blood pressure of the night shift workers were higher than those of the non-night shift workers (both P<0.05), and the systolic blood pressure and diastolic blood pressure of overweight/obesity workers were higher than those of non-overweight/obesity workers (both P<0.01). The results of multiple logistic regression analysis showed that the risk of hypertension in night shift workers and overweight/obesity workers was higher than that in non-night shift workers and non-overweight/obesity workers [odds ratio (OR) and 95% confidence interval (CI) were 2.49 (1.04-5.99) and 2.65 (1.77-3.95), both P<0.05]. Night shift work and overweight/obesity showed a synergistic effect on blood pressure of workers. Compared to non-overweight/obesity non-night shift workers, overweight/obesity night shift workers had a higher risk of hypertension (OR=4.93, 95%CI: 1.70-14.29, P<0.01). {L-End}Conclusion Night shift work could lead to elevated blood pressure in workers in the chemical fiber industry, which is a potential risk factor for hypertension. The synergistic effect of night shift work and overweight/obesity may contribute to the increased risk of hypertension.
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Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1highCD11b+ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8+ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1highCD11b+ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1highCD11b+ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
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Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn2+ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn2+, we constructed a TDN-MnO2 complex and found that it displayed a much higher efficacy than TDN plus Mn2+ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO2. These findings provide new therapeutic opportunities for cancer therapy.
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Purpose@#This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). @*Materials and Methods@#From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). @*Results@#Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. @*Conclusion@#Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.
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<p><b>OBJECTIVE</b>To investigate the effect of aloin on apoptosis of human gastric cancer cells and explore the molecular mechanism.</p><p><b>METHODS</b>Gastric cancer MKN-28 and HGC-27 cells were cultured routinely in 1640 medium supplemented with 10% fetal bovine serum and 10% non-essential amino acids (for HGC-27 cells) and treated with different concentrations of aloin for different durations. The cell viability, cell nuclear morphology, and apoptotic rate of the cells were detected using CCK-8 assay, DAPI staining and AnnexinV-FITC/PI, respectively; Western blotting was used to detect the expression levels of PARP, procaspase 3 and the phosphorylation of p38, ERK and JNK. The cells were treated with specific inhibitors of p38, ERK and JNK, and the inhibitory effects on these pathways were detected with Western blotting; DAPI staining was used to detect the effects of inhibitors on apoptosis of gastric cancer cells.</p><p><b>RESULTS</b>Aloin dose-dependently inhibited the viability and induced apoptosis of HGC-27 and MKN-28 cells. Alion treatment obvious enhanced the phosphorylation of p38 and JNK but decreased ERK phosphorylation in the cells. Blocking ERK activation with the ERK inhibitor obviously enhanced aloin-induced cell apoptosis, where inhibiting p38 and JNK activation partly reversed alion-induced apoptosis in the cells.</p><p><b>CONCLUSIONS</b>Aloin induces apoptosis of human gastric cancer cells by activating p38 and JNK signaling pathways and inhibiting ERK signaling pathway.</p>
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Objective To investigate the molecular background of the New Delhi-metallo-1 (NDM-1)-producing Morganella morganii.Methods Two carbapenem-resistant M.morganii named 1 and 2 were isolated in the Second Hospital of Jiaxing,Zhejiang on October 4th and 29th,respectively.Antimicrobial susceptibility was determined by agar dilution method.Pulsed-field gel electrophoresis (PFGE) was performed to analyse the homololgy of isolates.Amplification with specific primers,DNA sequencing,conjugation experiments and genetic environment analysis were conducted to investigate the molecular mechanisms of resistance.Results The two M.morganii isolates were resistant to carbapenem and fluoroquinolones,while susceptible to aztreonam.PFGE analysis indicated that the two isolates were distinguishable.Amplification and DNA sequencing confirmed the coexistence of blaNDM-1,blasHv-12,qnrS1 and aac(6')-Ib-cr in both isolates.Transconjugants were detected with blaNDM.1 and qnrS1 simultaneously.Genetic environment analysis demonstrated that the blaNDM-1-bleMBL-trpF-dsbC-cutA1 structure was in consistence with those from known blaNDM-1-carrying Klebsiella pneumoniae.Conclusion The blaNDM-1 in M.morganii isolates possiblely obtained from K.pneumoniae through translatable plasmids.
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ObjectiveTo explore the clinical application of ultrasound-guided radiofrequency thermocoagulaion in brachial plexus block.MethodsC5-C7 brachial plexus block was performed by 6-13 MHz high-frequency ultrasound probe in 65 patients with cervical spondylotic radiculopathy. Visual analogue scale (VAS) score were compared before and after treatment.ResultsThe brachial plexus was showed clearly in 62 patients; however, 3 patients had to be confi rmed by nerve stimulation positioning. The percentage of successful rate is 100%. There was no operation related nerve injury and other complications. The VAS score of preoperation and 1st, 4th and 12nd week after treatment was 8.67±0.76, 3.58±0.62, 2.46±0.2 and 1.77±0.28, respectively. There were significantly difference between before and after treatment (t=58.71, 6.23, 107.72, allP<0.01).ConclusionThe brachial plexus block using radiofrequency thermocoagulaion combined with ultrasound guidance is a safe and radiation-free treatment and warrants to be promoted in clinical practices.
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AIM:To evaluate the safety and feasibility of using vascular endothelial growth factor (VEGF) in the establishment of Walker-256 transplanted liver cancer model .METHODS: SD rats ( n =45) were divided into 3 groups:via the caudal vein, the rats in normal saline (NS) group were injected with 0.9%sodium chloride (0.1 mL/d), the rats in 20 mg/L VEGF group were injected with 20 mg/L VEGF (0.1 mL/d), and the rats in 40 mg/L VEGF group were injected with 40 mg/L VEGF (0.1 mL/d).All the injection began 1 week before transplantation of liver cancer , and stopped on the day the cancer model was established .Prepared tumor tissue was transplanted into the subcapsular space of the liver.Three days, 1 week and 2 weeks after the transplantation, magnetic resonance imaging (MRI) was performed for analyzing the tumor growth and the characteristics .The overall survival of the rats was also recorded .RESULTS:Success-ful establishment of Walker-256 transplanted liver cancer model was achieved .Among 45 rats, 1 rat died 1 d after implan-ting the tumor both in NS group and 20 mg/L VEGF group, while 3 rats died in 40 mg/L VEGF group 1 week after building the model, mainly because of the progression of tumors .Three days after modeling,the numbers of the rats in which the tumor was positively detected by MRI in 3 groups were 0, 7 and 10, respectively;1 week after modeling, those were 3, 13 and 13, respectively;2 weeks after modeling,those were 12, 13 and 10, respectively.Between NS group and 20 mg/L VEGF group, the statistical significance existed in the number of the rats in which the tumor was positively detected by MRI after 3 d of implanting, so did the NS group and 40 mg/L VEGF group.No statistical significance in the overall survival time between NS group and 20 mg/L VEGF group (P>0.05) was observed, but the significance existed between 40 mg/L VEGF group and NS group (P<0.01).CfONCLUSION:The application of VEGF at dose of 20 mg/L and 0.1 mL/d shortens the time to establish the transplanted liver cancer model without influence on the overall survival , which is a safe, feasible and efficient way, and is more suitable for anti-VEGF drug investigation.
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[ABSTRACT]AIM:ToobservehowfarnesoidXreceptor(FXR)functionedinconcanavalinA(ConA)-induced hepatitis (CIH) and the regulation of FXR-thyrotropin embryonic factor (TEF) pathway.METHODS:C57BL/6 mice were injected with Con A to induce hepatitis .The expression of FXR and TEF in the liver specimens was determined by qRT-PCR and Western blotting .The concentrations of serum ALT/AST and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the blood samples were tested after Con A injection .RESULTS:FXR was down-regulated in CIH mice .TEF was up-regula-ted when FXR was activated by chenodeoxycholic acid (CDCA).Activation of FXR reduced the levels of aminotransferases and inflammatory cytokines IFN-γ, TNF-α, IL-4 and IL-2 in the CIH mice induced by Con A injection .CONCLUSION:FXR activation attenuates CIH mouse liver injury and reduces inflammatory cytokines .FXR activation results in TEF up-regu-lation.The FXR-TEF pathway may play a protective role in autoimmune hepatitis .
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ObjectiveTo evaluate the clinical effect of post bladder sparing surgery intra-arterial chemotherapy combined with intravesical chemotherapy for the treatment of T1G3 bladder urothelial carcinoma.MethodsSeventy-four T1G3 bladder cancer patients were enrolled in this study.After bladder sparing surgery,22 patients received intra-arterial chemotherapy combined with intravesical chemotherapy,while the other 52 patients were treated with intravesical chemotherapy only.There was no significant difference between the 2 groups in sex,age,the size and number of bladder tumor and newly diagnosed cases (P ＞0.05).Twenty-two patients were treated with intra-arterial chemotherapy of piarubicin or epirubicin (40 -60 mg)+ cisplatin (60 -80 mg) 2 or 3 weeks after bladder sparing surgery,3 times as a cycle,repeat every 4 - 6 weeks.All the patients received the same protocol of intravesical chemotherapy.With a median follow-up of 32 months,effects of combination therapy group were compared with intravesical chemotherapy group in the aspects of tumor-specific death rates,recurrent rate,progressive rate,recurrent interval and the adverse reactions.ResultsThe tumor-specific death rates of combination therapy group and intravesical chemotherapy group were 0％ (0/22) and 13.5％ (7/52),respectively.There was no difference between the 2 groups (P =0.096).The recurrent rates were 13.6％ (3/22) and 46.2％ ( 24/52 ) ； The progressive rates were 0％ (0/22) and 21.2％ (11/52).There were significant differences between the 2 groups in recurrent rate (P =0.000) and progressive rate (P =0.048 ).The recurrent intervals of the 2 groups were 15 months and 6.5 months.During the interval of intra-arterial chemotherapy cycle,12 patients suffered 1 -2 degree nausea and vomit,2 patients suffered hypoleukemia,2 patients suffered neutropenia,4 patients'liver function was impaired and 1 patient's renal function was impaired.All the adverse reactions were minimal and reversible.ConclusionsIntra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing T1 G3 bladder cancer from recurrence and metastasis after bladder sparing surgery.The adverse reactions of this protocol were minimal and reversible.
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Objective To understand the clinical effect of conservative lapamscopic surgery with stripping corpus luteum for fallopian pregnancy to prevent persistent ectopic pregnancy.Methods From January 2005 to Augnst 2008.82 cases of fallopian pregnancy (6 cases for the second time) were performed conservative operatio through laparoscopic surgery with stripping corpus luteum.Seventy one cases underwent salpingostomy to remove the embryo, and other 11 cases were performed with extrusion of embryo sac at ampulla.The level of serum progesterone,β-HCG were measured before and after the therapy.All patients were followed up for one year.Results All patients'surgery had been successfully done through laparoscopie surgery.The duration of stripping corpus luteum was 5 to 10 minutes.The serum β-HCG(Mean±SD:(1213.51±118.84)U/L)and progesterone(Mean±SD:(3.25±2.44)nmol/L)arer operation were significantly lower than before the therapy(Mean±SD:(4267.86±983-56)U/L.(13.71±6.24)nmol/L,respectively)(P<0.01).The decrease of β-HCG value wag significantly correlated with the decreasing of progesterone(r=0.697,P<0.05).Only one patient had a persistent ectopic pregnancy.Fallopian examination through hysterosalpingography after 3 months was unobstructed in 71.1%(32/45 cases)and oh-strueted in 7 cases(15.6%).After one year ofthetherapytwo patients hadectopic pregnancy atthe same fallopian tube.Conclusions For females who have reproductive requirements with experience of fallopian pregnancy,conservative operation through laparoscopic surgery with stripping corpus luteum is safe and effective,and might have an important clinical effect to prevent postoperative persistent ectopic pregnancy.
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alterations on liver hemodynamics on IR injury following administration of medication.
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Objective To investigate the role of alprostadil on hepatic perfusion after transarterial chemoembolization(TACE) for hepatocellular carcinoma. Methods Sixty-four consecutive patients with HCC were randomized to either treatment with PGE_1 after TACE (treatment group, 32 cases) or no additional treatment after TACE (control group, 32 cases). In PGE_1 group, Lipo-PGE_1 was administered intravenously once a day for total of seven days, once after completion of TACE. The dosage of Lipo-PGE_1 was 0.4μg/kg and rote 0.05 μg·kg~(-1)·min~(-1). In control group, regular TACE was used. All patients underwent hepatic CT perfusion within 1 week before TACE and 4 weeks after TACE. The parameters of hepatic perfusion, including hepatic arterial perfusion value (HAP), portal vein perfusion value (PVP), total liver perfusion value (TLP) , and hepatic arterial perfusion index (HPI) were measured and compared. Chi-Square test was used for comparison of CT perfusion parameters in different stage, and t test was used for comparison of each CT porfusion parameter between two groups. Results In control group, HAP of pre-TACE, 4 weeks after first TACE, and 4 weeks after second TACE was (0.18±0.08), (0.22±0.09), (0.32±0.10) ml·min~(-1)·ml~(-1), respectively. Likewise, PVP was (1.11±0.31)、(0.82±0.27)、(0.59±0.25) ml·min~(-1)·ml~(-1), respectively, and TLP was (1.29±0.33), (1.04±0.28), (0.91±0.24) ml·min~(-1)·ml~(-1), respectively, and HPI was (14.31±6.36)%, (21.37±9.07)%, (36.67±13.42)%, respectively. The perfusion parameters at different stages of TACE were statistically different (F=19.71,27.47,14.75,41.41, P<0.05). In PGE1 group, HAP before TACE, after first TACE, and after second TACE was (0.17±0.08), (0.20±0.08), (0.26±0.08) ml·min~(-1)·mi~(-1) respectively, and PVP was (1.09±0.36), (1.03±0.40), (0.91±0.41) ml·min~(-1)·ml~(-1), respectively, and TLP was (1.26±0.38), (1.23±0.40), (1.17±0.44) ml·min~(-1)·ml~(-1) respectively, and HPI was (14.04±6.71)%, (17.26±7.86)%, (23.93±8.96)%, respectively. The difference of HAP and HPI at different stage of TACE was significant (F = 10.78, 13.05, P < 0.05), but there was no significant difference both PVP and TLP (F = 1.73,0.39, P > 0.05). The difference of PVP and TLP between the control and PGE1 group was significant after first TACE(t = -2.37, -2.14, P <0.05)and second TACE (t = 2.55, - 4.49, P < 0.05) In addition, after the second TACE, the HAP and HPI were also significantly different (t = - 3.41,5.09, P < 0.05). Conclusions PVP and TLP decrease while HAP and HPI increase after TACE. Lipo-PGE1 improves hepatic peffusion after TACE, exerting its greatest effect by increasing portal vein perfusion. Consequently, treatment with Lipo-PGE1 appears to increase liver tissue perfusion and thereby alleviate injury induced by TACE.
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AIM: To explore the effect and mechanism of preoperative transarterial chemoembolization on nephroblastoma.METHODS: Comparative analysis of clinical and pathological features in 39 children with Wilms’ tumor was conducted. TUNEL assay was used to detect the apoptosis of tumor in two groups with or without preoperative interventional treatment. The expressions of P53, Bcl-2 and Bax proteins were detected by immunochemical methods. The patients were followed-up for more than 2 years.RESULTS: The extent of neoplastic cell necrosis and degeneration, interstital fiber tissue hyperplasia of tumor and the number of infiltrating lymphocytes were observed, which were higher in interventional group than those in simple excision group (P