The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.

BACKGROUNDVon Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.

METHODSAn epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.

RESULTSA five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.

CONCLUSIONSThe results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.

Adolescent ; Adult ; Asian Continental Ancestry Group ; China ; Female ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Retrospective Studies ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; Young Adult ; von Hippel-Lindau Disease ; diagnosis ; genetics

ObjectiveTo investigate the clinical features of hepatic follicular dentritic cell sarcoma (FDCS).MethodsClinical data of a patient with hepatic FDCS treated in Cancer Hospital Affiliated to Zhengzhou University in 2004 were retrospectively analyzed. The informed consent of the patient was obtained and the local ethical committee approval had been received. The patient, female, 49-year-old, was admitted to the hospital for the complaint of abdominal pain for 1 month . A 12 cm×12 cm in diameter, hard, poor activity tumor was found below xiphoid by physical examination. Abdominal tenderness was positive and laboratory examinations were essentially normal. CT scan showed a 20 cm in diameter solid lesion in the left lobe of liver. The tumor was observed irregularly enhanced in the arterial phase by enhanced CT scan. The enhancement faded away in the delayed phase, and the tumor revealed a low-density lesion. The initial diagnosis was primary liver cancer.ResultsAfter an active preoperative preparation, the patient underwent left lobectomy under endotracheal general anesthesia on August 31, 2004. A tough tumor measuring 23 cm×20 cm in diameter was found in the left lobe of liver during the surgery. Nodule foci were found beside the tumor and no obvious metastasis was found within the abdomen, pelvic cavity and peritonium. Postoperative pathological examination indicated inlfammatory pseudotumor FDCS and Immunohistochemistry indicated positive CD21, CD23, CD35 and vimentin (VIM). Tumor recurrence and matastasis were observed in the liver, abdomen cavity and chest wall etc. repeatedly and was resected during 2006 to 2014. The patient is currently in stable condition and no recurrence or metastasis was observed during regular follow-up till submission date. ConclusionsHepatic FDCS is a very rare disease. The diagnosis relies on the results of pathological examination. Surgical resection is a reliable treatment and the prognosis is favorable.

Objective To explore the value of various diffusion parameters obtained from monoexponential, biexponential and stretched exponential diffusion-weighted imaging models in assessing hepatic fibrosis in chronic hepatitis B(CHB). Methods A total of 52 patients who were diagnosed hepatitis B by the markers of hepatitis and were confirmed by liver biopsy pathology were prospectively recruited between June 2014 and May 2016 in People's Hospital of Henan Province. Concomitantly, 30 healthy volunteers who had no history of hepatitis B and liver dysfunction were enrolled in the control group. All patients underwent multi-b values DWI on a 3.0 T MRI unit. ADC was calculated by using the monoexponential model. True diffusion coefficient(Dt),pseudo diffusion coefficient(Dp)and fraction of perfusion(f)were calculated by using the biexponential model.Distributed diffusion coefficient(DDC)and water molecular diffusion heterogeneity index(α)were calculated by using the stretched exponential model. Liver biopsy specimens were staged according to the degree of hepatic fibrosis (S0 to S4). The Kruskal-Wallis test was employed for the comparison of each parameter among the control group and the fibrosis stage groups. The Mann-Whitney U test was adopted to compare each parameter between fibrosis stage≤S1and≥S2,between≤S2 and≥S3.Spearman rank correlation coefficients were obtained to assess the correlation of the parameters with the fibrosis stages.ROC analysis was used to evaluate the performance of various parameters in predicting stage≥S2 and≥S3.Results The hepatic fibrosis stage distributions were as follows:1 cases with S0,9 cases with S1,22 cases with S2,11 cases with S3,9 cases with S4.ADC,Dt,f and DDC values all showed significant difference among the control group and groups S1,S2,S3,S4(all P<0.05), while Dp and α values showed no significant difference(P>0.05). Dt, DDC and ADC showed a moderate negative correlation with the fibrosis stage(r=-0.630,-0.603 and-0.464,respectively,all P<0.01),and f showed a mild negative correlation with the fibrosis stage(r=-0.379,P<0.05),while Dp and α values showed no correlation with the fibrosis stages(all P>0.05).The ADC, Dt, f and DDC values all showed significant difference between stage≥S2 and≤S1,between stage≥S3 and≤S2(all P<0.05),and the parameter values of the former were greater than those of the latter. While Dp and α values showed no significant difference among both groups(all P>0.05).The AUCs of ADC,Dt,f and DDC values for detecting fibrosis stage ≥S2 were 0.738,0.835,0.740 and 0.831, and the AUCs of ADC, Dt, f and DDC values for detecting fibrosis stage≥S3 were 0.716, 0.811, 0.672 and 0.798. Conclusion The Dt derived from biexponential and DDC derived from stretched exponential DWI could be useful for the staging of hepatic fibrosis in CHB.

OBJECTIVETo observe the effectiveness and safety of electrothermal acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in the cancerous patients of phlegm-stasis interaction in cisplatin-containing chemotherapy.

METHODSSixty cases of phlegm-stasis interaction in cisplatin-containing chemotherapy were randomized into a trial group and a control group, 30 cases in each one. In the control group, the intravenous drip of granisetron hydrochloride injection was adopted, 3 mg before and after cisplatin-containing chemotherapy 30 min, continuously for 3 days. 43 to 45℃ electrothermal acupuncture at zusanli(ST 36) for 30 min was used on the basis of the treatment as the control group in the trial group,once a day for 3 days. CINV, anti-nausea effects, Karnofsky score, the syndrome score of phlegm-stasis interaction, and relevant indices of safety were observed on the 1st and 7th days of cisplatin-containing chemotherapy separately.

RESULTS1.Regarding CINV and anti-nausea effect, CINV did not occur before chemotherapy in the patients of the two groups. On the 1st and 7th days of chemotherapy, CINV in the trial group were milder than those in the control group (both<0.05).The anti-nausea effects in the trail group were better than those of the control group.2.Regarding Karnofsky score and the syndrome score of phlegm-stasis interaction, the improvements on the 7th days of chemotherapy in the trial group were better than those in the control group, indicating the significant differences (both<0.05). 3.Regarding the safety indies, there was no adverse reaction during the treatment in the two groups.

CONCLUSIONSThe electrothermal acupuncture effectively relieves CINV, and improves self-care dbility and the symptoms of phlegm-stasis interaction.