Actins ; metabolism ; Angiomyolipoma ; pathology ; Carcinoma, Renal Cell ; pathology ; Diagnosis, Differential ; Epithelioid Cells ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; pathology ; Gastrointestinal Stromal Tumors ; pathology ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; Lung Neoplasms ; pathology ; Lymphangioleiomyomatosis ; pathology ; Male ; Melanoma ; pathology ; Melanoma-Specific Antigens ; metabolism ; Pancreatic Neoplasms ; pathology ; Perivascular Epithelioid Cell Neoplasms ; metabolism ; pathology ; Sarcoma, Clear Cell ; pathology ; Skin Neoplasms ; pathology ; Uterine Neoplasms ; pathology

Objective:To investigate the mechanism of PE_PGRS60 protein in the pathogenesis of Mycobacterium tuberculosis infection. Methods:The cloned and purified PE_PGRS60 protein from Mycobacterium tuberculosis was used to stimulate RAW264.7 cells. The expression of cyclooxygenase 2(COX2) mRNA and protein was detected by qRT-PCR and Western blot, respectively. The signal pathways that may regulate the expression of COX2 were screened, and the expression of inflammatory cytokines induced by PE_PGRS60 was detected by ELISA. The level of cell death was measured by lactate dehydrogenase(LDH) release test and flow cytometry PI staining. Western blot was used to detect the expression of COX2 in Peripheral blood mononuclear cell(PBMC) from active tuberculosis patients. Results:PE_PGRS60 protein was found to promote the expression of COX2 in RAW264.7 cells and activate the three major members of the mitogen-activated protein kinase(MAPK) family: extracellular regulated protein kinase(ERK), p38 and c-Jun N-terminal kinase(JNK). Interestingly, only JNK-IN-7, the inhibitor of JNK was observed to suppress the up-regulation expression of COX2 induced by PE_PGRS60. This up-regulated expression of COX2 was also found in PBMCs from active tuberculosis patients. The COX2 inhibitor celecoxib can effectively block the expression of the inflammatory factors IL-1β, TNF-α and IL-6 induced by PE_PGRS60 and promote macrophage death.Conclusions:PE_PGRS60 can promote macrophages to release inflammatory factors by activating JNK/COX2 signal axis. Some macrophages still die under the protection of COX2.

Objective To evaluate 99tcm-DTPA nuclear dynamic imaging in distinguishing the renal occupied disease.Methods A total of 164 in-patients with renal occupied disease who underwent surgery were included.According to the pathological diagnosis,119 patients had malignant tumors,and 45 patients had benign diseases.All patients’ imaging was retrospectively analyzed.Application of 99Tcm-DTPA nuclear dynamic imaging in renal occupied disease was compared with ultrasonography (US),computed tomography (CT),magnetic resonance imaging (MRI),intravenous pyelogram (IVP),and positron emission tomography (PET)-CT.Results The accuracy rates of different imaging methods in distinguishing between renal malignant and benign disease were 99Tcm-DTPA (84 ％,45 ％),US (72 ％,64 ％),CT ( 91％,92 ％),MRI (50 ％,67 ％),IVP (50 ％, 17 ％), respectively.The diagnostic accuracy rate of PET-CT for malignant tumors was 67 ％.The accuracy rates of 99Tcm-DTPA in distinguishing different phases of renal cell carcinoma were statistically significant (x 2 =83.4, P ＜ 0.01), while the accuracy rates in distinguishing renal cyst from renal angiomyolipoma were not statistically different.With the greater diameter, the diagnostic accordance rate is higher (x 2 =16.05,P ＜ 0.05).Conclusion 99Tcm-DTPA could be used not only to evaluate the renal function quantificationally,but also be helpful to distinguish renal malignant tumor from benign disease.

Objective To evaluate the clinical outcome and the acute toxicity in nasopharyngeal carcinoma (NPC) treated with tomotherapy followed by the anti-EGFR monoclonal antibody.Methods Between March 2008 and November 2009,34 newly diagnosed NPC patients were treated with helical tomotherapy combined with nimotuzumab or cetuximab.All the patients underwent tomotherapy at the dose of 70 Gy/33F for the gross tumor volume (pGTVns) and positive lymphnodes (GTVnd) ,and 60 Gy/33F for the high risk clinical target volume (PTV1),and 56 Gy/33 F for the low risk clinical target volume (PTV2),respectively.17 patients in group N were given weekly injection of 200 mg for 6-7 times and 17 patients in group C were given initial dosage 400 mg/m2 followed by subsequent weekly dosage of 250 mg/m2 for 6-7 times.Acute lesions were evaluated with the RTOG/EORTC criteria.Result The median follow-up time was 22 months.The effective rates (CR + PR) in 3,6 and 12 months were 14/17,12/17,12/17 in group N and 15/17,14/17,14/17 in group C.The 1 year survival rate was 15/17 in group Nand 17/17 in group C.Nimotuzumab had less acute mucositis reaction (u = 2.25,P < 0.05),weight loss(t=2.56,P=0.02) and rash (u=4.36,P＜0.01) compared with cetuximab.Conclusions Helical tomotherapy combined with nimotuzumab or cetuximab was effective and made no difference in the shortterm efficacy and 1 year survival rate for the patients with NPC.Nimotuzumab has less acute reaction than cetuximab.More studies should be done to prove long-term effects.

OBJECTIVE: To analyze the clinical features and prognosis in patients with primary Sjögren's syndrome (pSS) and autoimmune liver diseases (ALD). METHODS: A retrospective analysis of clinical manifestation and prognosis was performed in patients with ALD or without ALD during the three years (February 2014 to December 2017). RESULTS: Totally, 203 patients with pSS were included in this study, 68 patients had ALD (31 patients with autoimmune hepatitis, 37 patients with primary biliary cholangitis), while 135 patients did not have ALD. There were no differences between the two groups regarding age, gender, clinical manifestations, such as dry mouth, dry eyes, pain, fatigue, lymphadenopathy, glandular swelling, cutaneous involvement, lung involvement, and renal involvement, and the incidence rate of other autoimmune diseases, such as autoimmune thyroid disease, rheumatoid arthritis, and vasculitis. There were also no differences in the titer of antinuclear antibody (ANA), the positive rates of anti-Sjögren's syndrome A antibody (SSA), SSA52, and anti-Sjögren's syndrome B antibody (SSB), and at the levels of erythrocyte sedimentation rate and C-reactive protein between the two groups. Most importantly, the pSS patients with ALD had a shorter disease course, a higher positive rate of anti-mitochondrial M2 antibody (AMA-M2) and anti-centromere antibody, a higher level of IgG and IgM, a lower level of complement 3, and a decreased number of blood cells. They also had a higher level of liver related serum index, such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase and total bilirubin, direct bilirubin, indirect bilirubin, a higher incidence rate of liver cirrhosis, an increased death incident (the mortality was 13.24% in the pSS patients with ALD, while 2.96% in the controls, P=0.013), and a worse prognosis. Binary Logistic regression analysis revealed that liver cirrhosis, the EULAR Sjögren's syndrome disease activity index (ESSDAI) scores and the level of total bilirubin were the prognostic factors of mortality in the pSS patients with ALD. The survival curve was estimated by the Kaplan-Meier method. It demonstrated that the pSS patients with ALD had a lower survival rate when compared with the controls. CONCLUSION The patients with both pSS and ALD will suffer from a more severe disease and a higher death incident. We should pay more attention to these patients and provide a better symptomatic treatment for them during clinical practice.
Hepatitis, Autoimmune/epidemiology* ; Humans ; Liver Cirrhosis, Biliary ; Prognosis ; Retrospective Studies ; Sjogren's Syndrome/epidemiology*

OBJECTIVE: To compare the clinical features and follow-up results of systemic lupus erythematosus (SLE) between boys and girls. METHODS: A retrospective analysis was performed for the clinical data of 79 children (18 boys and 61 girls), aged ≤14 years, who were diagnosed with SLE from 2008 to 2018. The boys and the girls were compared in terms of initial and major clinical symptoms, injury of organs/systems, related laboratory markers, and follow-up results. RESULTS: As for the initial and non-initial symptoms, fever had the highest incidence rate in the boys, while facial erythema had the highest incidence rate in the girls. The boys tended to develop renal injury and hematological damage (P<0.05), with a significantly higher incidence rate of proteinuria than the girls (P<0.05), while the girls tended to develop joint pain (P<0.05). There were high abnormal rates (>80%) of anti-nuclear antibody, dsDNA, complement C3, and erythrocyte sedimentation rate in both boys and girls (P>0.05). The boys had a significantly higher disease activity than the girls at the first visit and in year 9 of follow-up (P<0.05). A one-month to ten-year follow-up showed that among the boys, 3 were lost to follow-up, 1 died, 7 were well controlled but required oral administration of large doses of hormones or immunosuppression, 2 progressed to chronic renal failure, and 1 developed lupus encephalopathy. Among the girls, 3 were lost to follow-up; 5 died; 34 were well controlled, among whom 5 were maintained on oral prednisone acetate with a dose of <10 mg, 1 was withdrawn from the drug for 1 year, and 2 were withdrawn from the drug for 2 years; 4 developed lupus encephalopathy; 1 developed depression and anxiety and had suicidal tendency in the 7th year after disease onset; 2 experienced impaired vision, blurred vision, and chloropsia; 1 developed a vascular necrosis of both femoral heads in the 3rd year of hormone administration. CONCLUSIONS There are differences in clinical features, several laboratory markers, and prognosis between boys and girls with SLE. Boys tend to have a high severity at disease onset, develop renal injury and hematological damage, and have poor long-term prognosis, while girls tend to have joint involvement.

BACKGROUNDHelical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the changes in the target volume and organs at risk (OARs) of patients with nasopharyngeal carcinoma (NPC) during helical tomotherapy.

METHODSForty-three patients with NPC and treated via HT from March 2008 to January 2010 were reviewed retrospectively. Repeated CT scanning and plan adaptation were conducted at the 20th fraction during radiotherapy. The volumetric differences between the two scans were evaluated for nasopharyngeal tumor and retro-pharyngeal lymph nodes (GTVnx), neck lymph nodes (GTVnd), and parotid glands, as well as the axial diameter of the head.

RESULTSThe median interval between the two scans was 25 days (23 - 28 days). The volumetric decrease in GTVnx was 30.1% (median, 29.8%) and in GTVnd 41.6% (median, 45.9%). The variation in the GTVnd volume was correlated with the weight loss of the patient. The volume of the left parotid gland decreased by 35.5% (median, 33.4%) and of the right parotid glands decreased by 36.8% (median, 33.5%). The axial diameter of the head decreased by 9.39% (median, 9.1%).

CONCLUSIONSThe target volume and OARs of patients with NPC varied considerably during HT. These changes may have potential dosimetric effects on the target volume and/or OARs and influence the clinical outcome. Repeated CT scanning and replanning during the HT for NPC patients with a large target volume or an obvious weight loss are recommended.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma ; Child ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; radiotherapy ; Organs at Risk ; Radiotherapy, Intensity-Modulated ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the role of endoplasmic reticulum stress (ERS) in alcoholic liver disease (ALD)-related hepatocyte apoptosis.

METHODSA rat model of ALD was established by continuous intragastric administration of ethanol. At 4, 8, 12, and 16 weeks later, randomly selected rats were sacrificed for serum and liver sample collection. Serum levels of total homocysteine (tHcy) were examined by chemiluminescence analysis. Cystathionine beta-synthase (CBS) activity in liver tissue was measured by chromatometry. The mRNA and protein expressions of ERS-related factors, glucose-regulated protein (GRP)-78, calpain 2 and caspase-12, were analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Hepatocyte apoptosis was detected by the TdT-mediated dUTP nick end labeling assay.

RESULTSAt 16 weeks, the ALD rats' livers exhibited diffuse microvesicular adipose degeneration and fibrosis in the liver sinus and portal septa. As the duration of ethanol administration extended, the tHcy levels gradually increased (P less than 0.01), CBS activity decreased (P less than 0.01), gene expression levels of GRP-78, calpain 2, and caspase-12 were up-regulated (P less than 0.01), and protein expression levels of GRP-78 and calpain 2 were gradually increased. However, the protein level of procaspase-12 was found to decrease with increased duration of ethanol administration. Finally, the hepatocyte apoptosis index showed an increasing trend over time (P less than 0.01).

CONCLUSIONIn our experimental ALD rat model, hepatic apoptosis was detected with increasing frequency over the duration of ALD. Increased apoptosis was likely due to decreased CBS activity causing hyperhomocysteinemia, which further induced ERS and activated the calpain 2 and caspase-12 signaling pathway. These ethanol-induced molecular changes may provoke hepatic apoptosis and subsequently promote the pathogenic processes of alcoholic liver disease.

Animals ; Apoptosis ; Calpain ; metabolism ; Endoplasmic Reticulum Stress ; HSP70 Heat-Shock Proteins ; metabolism ; Hepatocytes ; metabolism ; pathology ; Liver ; pathology ; Liver Diseases, Alcoholic ; metabolism ; pathology ; Male ; Membrane Proteins ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo explore the reversal effect of multidrug resistance of Curcuma Wenyujin (CW) and its possible mechanism by establishing Vincristine-resistant gastric cancer SGC-7901 cells (SGC-7901/VCR) induced subcutaneous transplanted tumor in nude mice.

METHODSFirst we identified the resistance of SGC-7901/VCR by using methyl thiazolyl tetrazolium (MTT). The SGC-7901/VCR induced subcutaneous transplanted tumor model was established in 50 BALB/c nude mice by tissue block method. After 2 -3 weeks 36 mice with similar tumor size were selected and divided into 6 groups by random digit table, i.e., the model group, the Vincristine (VCR) group, the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group, 6 in each group. Normal saline was intraperitoneally injected to mice in the model group at 10 mL/kg, once per 2 days. VCR was intraperitoneally injected to mice in the VCR group at 0.28 mg/kg once per 2 days. CW at 1.4 and 2.8 g/kg was administered to mice in the low and high dose CW groups by gastrogavage, 0.2 mL each time, once daily. CW at 1.4 and 2.8 g/kg was administered by gastrogavage and VCR was intraperitoneally injected at 0.28 mg/kg, once per 2 days to mice in the low dose CW combined VCR group and the high dose CW combined VCR group. All medication lasted for 14 days. The tumor growth was observed. The inhibition rate was calculated. Meanwhile, the positioning and expression of P-glycoprotein (P-gp) were detected by immunohistochemistry and Western blot.

RESULTSSGC-7901/VCR had strong resistance to VCR, Adramycin (ADM), fluorouracil (5-FU), and Cisplatin (DDP), especially to VCR. Proliferation activities of SGC-7901/VCR were significantly enhanced after drug elution. The tumor volume gradually increased as time went by. The tumor volume was the minimum in the high dose CW combined VCR group. The tumor volume was obviously reduced in the high dose CW combined VCR group with obviously reduced with increased inhibition rate of 51.56%, when compared with that of the model group and the VCR group (P < 0.05). Western blot test showed that, when compared with the model group, the gray level of P-gp in the VCR group increased (P < 0.05), and the relative expression of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group significantly decreased (P < 0.05). Compared with the VCR group, the gray level of the P-gp decreased in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05). Results of immunohistochemistry showed that, when compared with the model group, expression scores of P-gp in the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group decreased with statistical difference (P < 0.05). Compared with the VCR group, expression scores of P-gp were obviously lowered in the low dose CW group, the high dose CW group, the low dose CW combined VCR group, and the high dose CW combined VCR group (P < 0.05).

CONCLUSIONSCW could reverse the drug resistance of SGC-7901/VCR subcutaneous transplanted tumor. And its mechanism might be related to down-regulating the expression of P-gp, suggesting that CW could be used as a kind of multidrug resistance reversal agent based on P-gp.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Cell Line, Tumor ; Cisplatin ; therapeutic use ; Curcuma ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluorouracil ; therapeutic use ; Guanylate Cyclase ; Mice ; Mice, Nude ; Receptors, Cytoplasmic and Nuclear ; Soluble Guanylyl Cyclase ; Stomach Neoplasms ; Vincristine ; therapeutic use

OBJECTIVETo observe the effect of angiotensin II (Ang II) on expression of gap junction channel protein connexin 43 (Cx43) in the proliferation process of vascular smooth muscle cells (VSMCs) during the early stage of arteriosclerosis.

METHODSThirty-two adult male rabbits were randomly divided into 4 groups. Rabbits in Group A were fed common diet while others in Groups B, C, and D were fed high-cholesterol diet. Losartan (10 mg/(kg.d)) and ramipril (0.5 mg/(kg.d)) were added in the diet of Groups C and D, respectively. The animals were sacrificed after 8 weeks and abdominal aortas were removed and dissected. The expression of Cx43 was assayed using RT-PCR and Western Blotting analysis.

RESULTSCx43 was increased markedly in both protein and mRNA level in Groups B, C, and D fed high-cholesterol diet compared with that in control group (P<0.01). Cx43 level in losartan or ramipril treated groups was higher than that in control group (P<0.01, P<0.05), but lower than that in high-cholesterol diet groups (P<0.05, P<0.01).

CONCLUSIONCx43 level was upregulated in VSMCs during early atherosclerosis. Losartan and ramipril can inhibit the expression of Cx43.

Angiotensin II ; physiology ; Animals ; Arteriosclerosis ; metabolism ; Body Weight ; Cholesterol ; blood ; Connexin 43 ; analysis ; genetics ; Losartan ; pharmacology ; Male ; Muscle, Smooth, Vascular ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; RNA, Messenger ; analysis ; Rabbits ; Ramipril ; pharmacology