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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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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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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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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 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 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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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.
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In order to prepare and apply the polyvinyl alcohol/drug-loaded chitosan microspheres composite wound dressing, we first prepared chitosan microspheres by emulsion cross-linking method, and then added chitosan microspheres into the reactants during the acetalization of polyvinyl alcohol and formaldehyde. We further studied the morphology, water absorption, swelling degree, mechanical properties and in vitro release of the sponge with different amount of chitosan microspheres. The results showed that polyvinyl alcohol/drug-loaded chitosan composite sponge has porous structure with connectionism. Increasing the amount of chitosan microspheres would make the apertures smaller, so that the water absorption and the swelling of sponge decreased, but the tensile strength and compressive strength increased. With the increase of the amount of chitosan microspheres, the drug absorption of cefradine and the release rate increase, and the release time become longer. With the results of toxicity grade of 0 to 1, this type of composite sponge is non-toxic and meets the requirement of biocompatibility. The observation of rabbit nasal cavity after surgical operation suggested that polyvinyl acetal sponge modified with the chitosan has antiphlogistic, hemostatic and non-adherent characteristic, and can promote the healing and recovering of the nasalmucosa. After using this composite material, best growing surroundings for patients' granulation tissue were provided. Exposed bone and tendon were covered well with granulation tissue.
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Animals , Female , Male , Rabbits , Bandages , Chitosan , Chemistry , Drug Carriers , Chemistry , Microspheres , Nasal Cavity , Wounds and Injuries , Polyvinyl Alcohol , Chemistry , Wound Healing , Wounds and Injuries , Pathology , TherapeuticsABSTRACT
BACKGROUND: Microspheric injectable scaffold has a perspective in cartilage tissue engineering; however, it is still limited by in vivo hard forming and microsphere transmigration.OBJECTIVE: To investigate the feasibility of self-assembly scaffolds by attaching negatively charged calcium alginate microspheres and positively charged chitosan microspheres by electrostatic force. METHODS: The calcium alginate and chitosan microspheres were prepared by emulsion-internal gelation and spray drying technique, respectively. The characterizations of the microspheres were determined by means of scanning electron microscopy, optical microscopy and zeta potential analysis methods. Self-assembly scaffolds were fabricated by mixing the aqueous suspensions of the microspheres with oppositely charged surfaces. The phenomenon of electrostatic attachment was characterized by optical microscopy and scanning electron microscopy, and the elastic compress modulus of the scaffolds was also investigated.RESULTS AND CONCLUSION: The average diameter of the calcium alginate microspheres was 52.5 μm, and the chitosan one was 4.1 μm, respectively. The zeta-potential of the calcium alginate microspheres was 23.5 mv, and the chitosan one was +9.8 mv, respectively. The microspheres were spherical and smooth. The small size chitosan microspheres could attach to the surface of the calcium alginate microspheres and anchor the calcium alginate microspheres together. The elastic compress modulus increased with the increase of solid content of the microspheres, but decreased with the increase of the ionic strength. The elastic compress modulus increased firstly and then decreased with the increase of the mass ratio of m (CHI):m (ALG), and it showed the highest elastic compress modulus when m (CHI):m (ALG) was 2:1. The positively charged chitosan microspheres could attach to the negatively calcium alginate microspheres to form a self-assembly scaffold.
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Objective To explore the effect of soup of promoting blood circulation and promoting pregnant on the ovulation function of sterility caused by endometriosis.Methods 60 cases of endometriosis had been randomly divided into treatment group(30 cases)and control group(30 cases),the treatment group treated by the traditional Chinese drug and the control group treated by nemestran.Results After 6 menstrual cycles,the pregnant rate in the test was 50.O%and the control,33.3%.There was no significant difference between two groups(P＞0.05).The diameter of ovarian follicle and the number of mature ovarian went up,there were significant difference in combination with the fro and post-treatment(P＜0.01).The incidence of premature lutionization follicle syndrome(LUFS)caused by ovarian cracking tend tO get down,there were significant difference in combination with the fro and post treatment(P＜0.05).Conclusion The soup of promoting blood circulation and promoting pregnant has effect of improving the growth of ovarian follicle,increasing ovulation and making the chance of pregnancy.
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Objective To study the clinical the rapeutic efficacy of reformed-fallopian tube recanalization (RFTR) with Chinese traditional medicines for treatment of infertility resulted from fallopian tube obstruction.Methods 80 patients of infertile women with fallopian tube obstruction were randomly divided in to the treated group( n = 40, treated with RFTR combined with Chinese traditional medicines) and the control group( n = 40,treated with RFTR alone). All cases were followed up for 6 to 12 months. The efficacy rate,pregnancy rate,ectopic pregnancy rate and the re-adhension rate were recorded in both groups. Results The efficacy rate of treated group and the control group were 72.5 % and 57.5 % respectively, with statistical significance( P < 0.05 ). The pregnancy rates of the two groups were 52.5 % and 30.0 % respectively. The ectopie pregnancy rate of the two groups were 5 % and 7.5 % respectively. Conclusion RFTR with Chinese traditional medicines therapy is an effective method to treat in fertility resulted from fallopian tube obstruction.
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OBJECTIVE: To provide reference for rational use of drugs. METHODS: 200 ADR cases induced by TCM injection from Huizhou were analyzed retrospectively. RESULTS: Of total 200 ADR cases, 133 cases were male, which was significantly higher than females in 67 cases(P
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<p><b>BACKGROUND</b>The expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 increases significantly in lung cancer tissues. The aim of this study is to investigate the expression of hnRNP B1 in exfoliative cells in the sputum of patients with lung cancer and its sensitivity and specificity in diagnosis of lung cancer.</p><p><b>METHODS</b>The expression of hnRNP B1 in sputum was detected by immunohistochemistry (IHC) using anti-hnRNP B1 monoclonal antibody in 70 patients with lung cancer and 30 normal subjects (control group).</p><p><b>RESULTS</b>The results of sputum exfoliative cytology were 27 positive in 70 samples diagnosed with lung cancer, whose sensitivity and specificity were 38.6% and 100.0% respectively. The results of sputum immunohistochemistry were 50 positive in 70 samples, with 23 positive in 29 squamous cell carcinoma and 17 positive in 26 adenocarcinoma and 10 positive in 15 small cell lung carcinoma. Sputum IHC of hnRNP B1 gave a sensitivity of 71.4% and specificity of 93.3%. Sputum IHC of hnRNP B1 was more sensitive than sputum exfoliative cytology (P < 0.05).</p><p><b>CONCLUSIONS</b>hnRNP B1 overexpresses in sputum exfoliative cells and its sensitivity is better than sputum exfoliative cytology in diagnosis of lung cancer.</p>