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Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease in China. There is no specific drug approved for marketing at home and abroad. At present, some adjuvant drugs are mainly used to improve the progress of the disease. Being familiar with and mastering the pharmacokinetic characteristics is very important for the selection and use of drugs. According to the characteristics of drug absorption, distribution, metabolism and excretion, reasonable drugs are selected to improve the therapeutic effect and reduce adverse reactions. Therefore, this paper reviews the pharmacokinetics and clinical significance of drugs commonly used to improve nonalcoholic fatty liver disease in hope of providing basis for clinical medication.
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Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
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AIM: To study the inhibitory effect and mechanism of Jolkinolide B (JB) on the proliferation and metastasis of colon cancer HT-29 cells. METHODS: HT-29 cells were treated with different concentrations of JB, the cell proliferation rate was detected by MTT method, the cell clone formation rate was detected by plate cloning experiment, the cell cycle change was detected by flow cytometry, the cell migration ability was analyzed by wound healing assay, the cell invasion ability was studied by Transwell assay, E-cadherin, N-cadherin, vimentin, Snail1, Snail2, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression levels were detected by immunofluorescence and Western blotting, and p-PI3K, PI3K, p-Akt, Akt, NF-κB P65and p-NF-κB P65 protein expression levels were detected by Western blotting. HT-29 cells were treated with 100 μg/L IGF-1 and 100 μg/L IGF-1+20 μmol/L JB, respectively. The expression of PI3K/Akt/NF-κB pathway related proteins was detected by Western blotting. RESULTS: JB inhibited the proliferation of HT-29 cells in a concentration-dependent manner, with an IC
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BackgroundCOVID-19 has been deeply affecting peoples lives all over the world. It is significant for prevention and control to model the evolution effectively and efficiently. MethodsWe first propose the multi-chain Fudan-CCDC model which is based on the original Fudan-CCDC model to describe the revival of COVID-19 in some countries. Multi-chains are considered as the superposition of distinctive single chains. Parameter identification is carried out by minimizing the penalty function. ResultsFrom results of numerical simulations, the multi-chain model performs well on data fitting and reasonably interprets the revival phenomena. The band of {+/-}25% fluctuation of simulation results could contain most seemly unsteady increments. ConclusionThe multi-chain model has better performance on data fitting in revival situations compared with the single-chain model. It is predicted by the three-chain model with data by Apr 21 that the epidemic curve of Iran would level off on round May 10, and the final cumulative confirmed cases would be around 88820. The upper bound of the 95% confidence interval would be around 96000.
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BackgroundCOVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense world-wide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. MethodsWe propose the multi-chain Fudan-CCDC model based on the original single-chain model in [8] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify parameters of models by minimizing the penalty function. ResultsThe numerical simulation results exhibit the multichain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of {+/-}25% fluctuation from simulation results. It is predicted by multi-chain models that Singapore are experiencing a nonnegligible risk of explosive outbreak, thus stronger measures are urgently needed to contain the epidemic. ConclusionThe multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data in those countries where the single-chain model shows deviation from the data.
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COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately.
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In this paper, we estimate the reproductive number R0 of COVID-19 based on Wallinga and Lipsitch framework [11] and a novel statistical time delay dynamic system. We use the observed data reported in CCDCs paper to estimate distribution of the generation interval of the infection and apply the simulation results from the time delay dynamic system as well as released data from CCDC to fit the growth rate. The conclusion is: Based our Fudan-CCDC model, the growth rate r of COVID-19 is almost in [0.30, 0.32] which is larger than the growth rate 0.1 estimated by CCDC [9], and the reproductive number R0 of COVID-19 is estimated by 3.25 [≤] R0 [≤] 3.4 if we simply use R = 1 + r * Tc with Tc = 7.5, which is bigger than that of SARS. Some evolutions and predictions are listed.
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Diabetic nephropathy is a microvascular complication in the advanced stage of diabetes. About 20%-40% of patients with diabetes will progress to diabetic nephropathy. And worldwide, diabetic nephropathy has become the leading cause of end-stage renal disease. Animal model is a useful tool to study the pathogenesis and treatment of diabetic nephropathy. Currently, the commonly used diabetic nephropathy models all simulate partial characteristics of human diabetic nephropathy in different degrees of pathophysiology. However, the research on diabetic nephropathy has not achieved considerable progress. The main obstacle is that there is no effective animal model that can fully simulate all the characteristics of human diabetic nephropathy. In this paper, the animal models of diabetic nephropathy were reviewed from the aspects of modeling mechanism, pathophysiology, their advantages and disadvantages.
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Recurrent laryngeal nerve (RLN) injury is a serious complication of thyroidectomy. Intraoperative neuro-monitoring(IONM) is a technology for identifying the integrity of nerves during operation by electrophysiological means, which included the intermitted IONM and the continuous IONM.This paper aims to compare the superiorities and defects of both IONM methods and summarize the current state and progress of IONM.
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Objective To obtain a non-invasive subclinical hypothyroidism ( SCH) mouse model, and to explore microRNAs profile related to lipid metabolism in the model mice. Methods C57BL/6 male mice (8 weeks) were treated with methimazole ( MMI, 0. 08 mg/kg BW/d) to construct SCH mouse model. MicroRNAs profiling analysis was performed by real-time quantitative polymerase chain reaction ( qRT-PCR) . Results Compared with the control group, the serum thyroid stimulating hormone ( TSH ) in subclinical hypothyroidism group increased significantly (P>0.01), while the serum free thyroxine(FT4) level did not show significant difference between the two groups (P>0. 05), which was in line with the diagnostic criteria of SCH. SCH mice was accompanied by dyslipidemia and liver lipid metabolism disorders. Four lipid metabolism related miRNAs, miR-33, miR-122, miR-199a-5p, and miR-375 in the liver of SCH mice were significantly decreased compared with those of control ( P>0. 05). Conclusion The noninvasive SCH model generated by MMI and miRNAs profile provide an animal model and a molecular basis for the study of SCH related lipid metabolism disorders.
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The protection of recurrent laryngeal nerve in thyroidectomy has been a research topic for clinicians. High-risk thyroidectomy is an operation with high rate of recurrent laryngeal nerve injury which including thyroid reoperation, giant goiter surgery, substernal goiter surgery, dorsal thyroid tumor surgey and thyroid malignancy surgery and so on. The application value of three kinds of laryngeal recurrent nerve protection techniques during high-risk thyroidectomy will be reviewed in this article, such as visualization alone, intraoperative nerve monitoring and continuous intraoperative nerve monitoring.
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Objective To explore the method and effect of orbital lateral fat replacement combined with orbicularis oculi muscle flap for correction of severe upper eyelid depression with multiple eyelid.Methods From January 2014 to January 2017,26 patients with severe upper eyelid sag with multiple eyelid were treated in Department of Plastic Surgery,Huai'an Second People's Hospital,including 18 cases of multiple physiological sag eyelid,improper operation on the formation of 8 cases of multiple eyelid eyelid sag.All the patients adopt outside orbital fat reset with the orbicularis muscle flap folded for the treatment.Results The follow-up time was 6 months to 1 year,with an average of 8.5 months.23 patients with upper eyelid sag with multiple eyelid were rectified,3 cases of upper eyelid depression associated with multiple eyelid depression alleviated,multiple eyelid disappeared,including 5 cases of preoperative patients with mild ptosis,and symptoms improved after surgery.Conclusions The orbital lateral fat replacement combined with orbicularis oculi muscle flap folding is a safe and effective treatment for upper eyelid depression with multiple eyelid.
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Objective Study cisplatin intraperitoneal hot perfusion chemotherapy for colorectal cancer effect a radical cure the prognosis of the patients and the influence of immune function.Methods120 patients who underwent radical resection of colorectal cancer patients, divided into observation group and control group, 60 cases in each group.The observation group were treated with cisplatin in postoperative continuous hyperthermic perfusion chemotherapy (chemotherapy for 200mg/m2 solution to cisplatin and injected with 1L), once a week, continuous treatment three weeks.The control group was treated with mFOLFOX6 intravenous chemotherapy (oxaliplatin 100mg/m2 fluorouracil leucovorin 400mg/m2, 400mg/m2), once every two weeks, 12 times of treatment.After the treatment, observation and analysis of two groups of patients before and after treatment of tumor markers (CEA, cancer antigen 19-9, cancer antigen 242), immune function (CD3+ cells, CD4+ cells, CD8+ cells, CD4+ cell ratio/CD8+ cell natural killer cells), quality of life, and the incidence of recurrence and metastasis.ResultsAfter treatment, the quality of life of patients in the observation group the total effective rate was 91.67%, significantly higher than the control group 70.00% (P<0.05), the recurrence rate is 8.33%, the metastasis rate of 10.00% was significantly higher than the control group 28.33% and 25.00% (P<0.05).The observation group of patients with carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 242 level respectively (3.4±1.1)% and (17.5±7.1)% and (4.7±1.9)% was significantly lower than the control group (10.2±2.8)% and (30.1±10.3)% and (20.3±4.5)% (P<0.05), the observation of immune function effect is improved significantly better than the control group, significant differences (P<0.05).ConclusionChemotherapy after radical resection of colorectal cancer patients using cisplatin intraperitoneal hyperthermic perfusion, can significantly reduce the recurrence rate and metastasis rate, improve immune function, reduce the level of tumor markers, so as to improve the quality of life of patients.
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Objective To investigate the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in gastric mucosa of patients with hepatogenic ulcer,and to analysis the relationship between them and the incidence of complications and disease progression in patients.Methods During July 2014 to May 2016,133 cases of patients with hepatocir rhosis and portal hypertension associated with gastric or duodenal ulcer were selected as study object.Marginal tissue of ulcer were collected,and normal mucosa tissue were collected as control group.Reverse transcription-polymerase chain reaction(RT-PCR) detect the expression of VEGF mRNA and bFGF mRNA in 133 cases of normal gastric mucosa and 133 cases of marginal tissue of ulcer,including 52 cases of gastric ulcer activity period(GA),45 cases of gastric ulcer healing period(GH) and 36 cases of gastric ulcer scar period(GS).Spearman correlation coefficient analysis the correlation between the expression of VEGF mRNA and bFGF mRNA and complication rate.Results The expression of VEGF mRNA and bFGF mRNA in ulcer marginal tissues was significantly higher than that in normal mucosa tissues,the difference was statistically significant(P＜0.05).The expression of VEGF mRNA in GH and GS of patients was significantly higher than that in GA patients,the difference was statistically significant (P＜0.05),the expression of bFGF mRNA in GS of patients was significantly higher than that of GA patients,the difference was statistically significant(P＜0.05).Spearman correlation analysis showed VEGF mRNA and bFGF mRNA was negatively correlated with incidence rate of ulcer complications (rs=-0.672,-0.508,P＜0.05).Conclusion bFGF mRNA and VEGF mRNA may play an important role in the repair of hepatogenic ulcer.It is a potential clinical marker.
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Objective To investigate the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in gastric mucosa of patients with hepatogenic ulcer,and to analysis the relationship between them and the incidence of complications and disease progression in patients.Methods During July 2014 to May 2016,133 cases of patients with hepatocir rhosis and portal hypertension associated with gastric or duodenal ulcer were selected as study object.Marginal tissue of ulcer were collected,and normal mucosa tissue were collected as control group.Reverse transcription-polymerase chain reaction(RT-PCR) detect the expression of VEGF mRNA and bFGF mRNA in 133 cases of normal gastric mucosa and 133 cases of marginal tissue of ulcer,including 52 cases of gastric ulcer activity period(GA),45 cases of gastric ulcer healing period(GH) and 36 cases of gastric ulcer scar period(GS).Spearman correlation coefficient analysis the correlation between the expression of VEGF mRNA and bFGF mRNA and complication rate.Results The expression of VEGF mRNA and bFGF mRNA in ulcer marginal tissues was significantly higher than that in normal mucosa tissues,the difference was statistically significant(P＜0.05).The expression of VEGF mRNA in GH and GS of patients was significantly higher than that in GA patients,the difference was statistically significant (P＜0.05),the expression of bFGF mRNA in GS of patients was significantly higher than that of GA patients,the difference was statistically significant(P＜0.05).Spearman correlation analysis showed VEGF mRNA and bFGF mRNA was negatively correlated with incidence rate of ulcer complications (rs=-0.672,-0.508,P＜0.05).Conclusion bFGF mRNA and VEGF mRNA may play an important role in the repair of hepatogenic ulcer.It is a potential clinical marker.
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Objective To investigate the postoperative complication and nursing experience of hand-assisted laparoscopic J-type ileal pouch-anal anastomosis (IPAA) in familial adenomatous polyposis (FAP). Methods A total of 36 patients with FAP who had undergone hand-assisted laparoscopic J-type ileal pouch- anal anastomosis (IPAA) were analyzed retrospectively. Results The postoperative complication included ileal pouch bleeding in 2 cases, urinary retention in 3 female patients, external hemorrhoids swelling in 3 cases, and anastomotic fistula in 2 cases. Six cases had ileum pouch inflammation during the postoperative follow- up. All the complications were relieved after conservative medical therapy. Conclusions IPAA operation puts forward high technical requirements with more postoperative complications. Therefore, it is important to strengthen nursing of the patients, reduce postoperative complication and increase quality of life of FAP.
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Objective To observe the effect of ligustrazine injection combined with chemotherapy on common immunological parameters in patients with advanced hepatocellular carcinoma.Methods Eighty cases diagnosed with advanced hepatocellular carcinoma from January 2013 to January 2015 in the hospital were randomly divided into observation group and control group, 40 patients in each group.The control group received only conventional treatment of chemotherapy and observation group received ligustrazine injection on the basis of control group.The levels of interleukin-1 (IL-1), IL-4 and transforming growth factor beta ( TGF-β) wwere compared based on the record between two groups pre-and post-treatment.Results There were no significant differences between two groups in IL-1,IL-4 and TGF-βlevels pre-treatment.After treatment, the IL-1, IL-4 and TGF-βlevels in observation group were lower than those in control group [(41.4 ±11.8)vs (76.0 ±12.2)ng/L,(118.5 ±39.9)vs(223.0 ±47.3)ng/L,(6.7 ±3.2)vs(11.7 ± 2.6)ng/mL, respectively, all P<0.05].Conclusion Ligustrazine injection combined with chemotherapy has an exact effect on improving the immunological parameters associated with advanced hepatocellular carcinoma without significantly increasing side effects, it is worthy of further research and application.
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Objective To explore the short-term efficacy and safety of edaravone combined with clopidogrel in treatment of acute cerebral infarction (ACI).Methods 120 cases of ACI were selected and they were randomly divided into the observation group(60 cases)and the control group according to the visiting order(60 cases).On the basis of routine treatment of ACI,the control group were treated with clopidogrel,and the observation group were added with edaravone combined with clopidogrel.All patients were treated continuously for 14 days.Patients' neural function,activities of daily living,and adverse reactions were evaluated before and after treatment.All patients were followed up for 1 year to record recurrence.Results After treatment,patients' limb movements,neural functions and language had varying degrees of recovery.Total efficiency was 93.33％ and 78.33％ respectively for the observation group and the control group.Grading of the neurologic impairment and life ability of the observation group were both better than the control group.The one-year recurrence rate was 5.77 ％ and 9.26％ for the observation group and the control group,and the difference had statistical significance (P ＜ 0.05).No obvious adverse reaction in the 2 groups was found.Conclusion The curative effect of edaravone combined with clopidogrel is remarkable in treating ACI,and it can remit patients' neurological deficit,improve their daily life ability,reduce the recurrence rate,and has high safety.
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Objective To evaluate the feasibility and safety of hand-assisted laparoscopic one-stage operation for colorectal cancer with single hepatic metastasis.Methods The clinical data of 6 patients of colorectal cancer with single hepatic metastasis treated with hand-assisted laparoscopic one-stage operation between Aug 2009 and Mar 2010 were analyzed retrospectively.Result Procedures were completed successfully in all cases and there was no conversion to open surgery.The mean operation time was (183 ±45) min,the mean blood loss in operation was (165 ±70) ml,the mean time to intestinal function recovery was (69.4 ± 10.5) h,and the average length of stay was (9.5 ±3.2) d.There was no major intraoperative or postoperative complications.All the patients received chemotherapy and up to 30 months follow-up found good condition in all but one dying of widespread intraabdominal tumor metastasis.Conclusions Handassisted laparoscopic one-stage operation for colorectal cancer with hepatic metastasis is feasible and safe.
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Objective To assess the effectiveness and safety of non-insufflation intra-abdominal compression as a prehospital hemostatic technique in treatment of liver injury.Methods Twenty-nine male Wistar rats were enrolled and randomly assigned into four experimental groups:IAP0 group ( n =8 ),IAP5 group (n =8),IAP10 group (n =8) and IAP15 group (n =5).Then,the anticoagulated rat models of severe liver injury were established with different intra-abdominal pressures ( 0,5,10 and 15 mm Hg) by using a non-expansible insufflated gas bag.Once the mean artery pressure (MAP) was less than 95 mm Hg,Lactated Ringer' s solution was infused through the right jugular vein at speed of 3.3 ml · min-1 · kg-1 until MAP reached 100 mm Hg.Thirty minutes later,the animals were killed by intravenous injection of 0.2 ml saturated potassium chloride solution to measure the intraperitoneal total blood loss,liver weight,volume of infused solution and MAP.Results No death was observed in IAP0,lAP5 and IAP10 groups and four rats (4/5) died at 10-15 minutes following exposure to the 15 mm Hg intra-abdominal pressure in IAP15 group.Total blood loss was reduced to ( 54.20 ±11.30)ml/kg in IAP0 group,(43.98 ±9.2) ml/kg in IAP5 group,(32.49 ±7.40) ml/kg in IAP10group and (25.77 ± 14.16) ml/kg in IAP15group ( P ＜0.01 ).The infused volume of resuscitation solution was (31.06 ± 3.14) ml in IAP10 group,which was higher than (24.94 ±6.67) ml in IAP0 group,(23.06 ± 7.98) ml in IAP5 group and (16.50 ±7.27) ml in IAP15 group (P ＜0.05).Liver weight was ( 11.18 ± 1.45) g in IAP5 group,( 12.13 ± 0.96) g in IAP10 group and ( 11.41 ± 1.20) g in IAP15 group,which was significantly higher than (10.03 ±0.58) g in IAP0 group (P＜0.05).The MAP was (64.81 ± 19.65) mm Hg in IAP5 group and (65.80 ± 15.36) mm Hg in IAP10 group ( insignificant difference between groups,P ＞ 0.05 ),which was higher than (41.22 ± 10.00) mm Hg in IAP0 group and (44.50 ±28.60) mm Hg in IAP15 group (P ＜0.05).Conclusions Non-pneumatic intra-abdominal compression can effectively control bleeding in rat models of severe liver injury,while the adverse effect of intra-abdominal hypertension should be avoided.
