Succinate dehydrogenase-deficient renal cell carcinoma:a clinicopathological, ultrastructural and molecular analysis / 中华病理学杂志

Objective: To investigate the clinicopathological features, immunophenotype, ultrastructure, genetic alterations and prognosis of succinate dehydrogenase-deficient renal cell carcinoma (SDH RCC). Methods: A total of 11 SDH RCCs, diagnosed from 2010 to 2019, were selected from the Department of Pathology of Nanjing Jingling Hospital, Nanjing University School of Medicine for clinicopathologic, immunohistochemical (IHC), ultrastructural investigation and follow-up. The molecular features of seven cases were analyzed by the panel-targeted DNA next generation sequencing (NGS). Results: There were seven males and four females, with ages ranging from 24 to 62 years (mean 41.4 years, median 41 years). Microscopically, SDH RCC was mainly composed of solid and tubular structures with local cystic change. Four cases showed nested or trabecular structure distributed in a loose hypocellular connective tissue or around scar, similar to oncocytoma. The neoplastic cells demonstrated flocculent eosinophilic cytoplasm with typical intracytoplasmic vacuoles. Immunohistochemically, eight cases were negative for SDHB; three cases showed focal and weak expression, whereas normal renal tubular and vascular endothelial cells demonstrated strong cytoplasmic staining. NGS of DNA targeted-panel detected pathogenic mutations of SDHB gene in seven cases (including three cases with equivocal IHC expression of SDHB), without any mutations in other SDH related genes. There were four cases of SDHB missense mutation, one case of frameshift mutation, one case of splicing mutation, and one case of acquired stop codon mutation. Conclusions: SDH RCC is a distinct variant of RCCs with genetic tendency or with hereditary cancer syndrome. NGS is recommended to detect the related gene mutations for a definitive diagnosis. The patients should be closely followed up.

Gallbladder Paraganglioma Associated with SDHD Mutation: a Potential Pitfall on ¹⁸F-FDOPA PET Imaging / 대한핵의학회잡지

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on ⁶⁸Ga-DOTATATE PET/CTand retrospectively on ¹⁸F-FDOPA PET/CT but was nonavid on ¹⁸F-FDG PET/CT. Biochemical work-up including plasma catecholamines, metanephrines, and chromogranin A levels were found to be within normal limits. This lesion was surgically resected and was confirmed to be a paraganglioma (PGL) originating from the gallbladder wall on histopathology. Pheochromocytoma (PHEO) and PGL are rare tumors of the autonomic nervous system. Succinate dehydrogenase subunit D (SDHD) pathogenic variants of the succinate dehydrogenase complex are usually involved in parasympathetic, extra-adrenal, multifocal head, and neck PGLs. We report an unusual location of PGL in the gallbladder associated with SDHD mutation which could present as a potential pitfall on ¹⁸F-FDOPA PET/CT as its normal excretion occurs through biliary system and gallbladder. This case highlights the superiority of ⁶⁸Ga-DOTATATE in comparison to ¹⁸F-FDOPA and ¹⁸F-FDG in the detection of SDHD-related parasympathetic PGL.ClinicalTrials.gov Identifier: NCT00004847.

Germline gene testing of the RET, VHL, SDHD and SDHB genes in patients with pheochromocytoma/paraganglioma / 北京大学学报(医学版)

OBJECTIVE@#To analyze the germline variations of genes RET, VHL, SDHD and SDHB in patients with pheochromocytoma and/or paraganglioma and to evaluate variations of these genes in Chinese patients.@*METHODS@#Patients who were treated in Peking University First Hospital from September 2012 to March 2014 and diagnosed with pheochromocytoma and/or paraganglioma by pathologists were included in this study. Twelve patients were included in total, of whom 11 had pheochromocytoma, and 1 had paraganglioma. Deoxyribonucleic acid (DNA) was extracted from the leukocytes of peripheral blood of the patients. The exons 10, 11, 13-16 of the RET gene, and all exons of VHL, SDHB and SDHD genes and their nearby introns (±20 bp) were amplified with polymerase chain reactions, and the products were sent to a biotechnology company for sequencing. The sequencing results were compared with wildtype sequences of these genes to identify variations. One of the patients was diagnosed with multiple endocrine neoplasia type 2A. A family analysis was performed in his kindred, and his family members received genetic tests for the related variations.@*RESULTS@#Three patients were found to have germline gene variations. A c.136C>T (p.R46X) variation of the SDHB gene was found in a patient with malignant pheochromocytoma. A c.1901G>A (C634Y) variation, as well as c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were found in a patient with multiple endocrine neoplasia type 2A. After a family analysis, five family members of this patient were found to have the same variations. c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were also found in a clinical sporadic patient without evidence of malignancy. A patient with congenital single ventricle malformation and pheochromocytoma was included in this study, and no variation with clinical significance was found in the four genes of this patient.@*CONCLUSION@#25% (3/12) patients with pheochromocytoma or paraganglioma were found to have missense or nonsense germline gene variations in this study, including the c.136C>T (p.R46X) variation of the SDHB gene, the c.1901G>A (C634Y) variation of the RET gene, and c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene. The former two variations have already been confirmed to be pathogenic. The existence of these variations in Chinese patients with pheochromocytoma and/or paraganglioma was validated in this study, which supports the conclusion that genetic testing is necessary to be generally performed in patients with pheochromocytoma and/or paraganglioma.

Effects of soybean isoflavones on the energy metabolism of swimming mice / 中国应用生理学杂志

OBJECTIVE@#To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice.@*METHODS@#Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured.@*RESULTS@#Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(<0.05).@*CONCLUSIONS@#Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.

Sunitinib in the therapy of malignant paragangliomas: report on the efficacy in a SDHB mutation carrier and review of the literature

SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.

Update on Gastrointestinal Stromal Tumors for Radiologists

The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

Effects of hydrogen sulfide on contraction capacity of diaphragm from type 1 diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats.
@*METHODS@#Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. 8 weeks later, the diaphragm contractility was assessed by isolated draphragm strips perfusion. The peak twitch tension (Pt), maximum tetanic tension (Po) and maximal rates of contraction/relaxation (±dT/dtmax) were determined. The alterations in diaphragm ultrastructure were observed under electron microscopy. The diaphragm weight/body weight (DW/BW) was measured. The activities of succinic dehydrogenase (SDH), lactate dehydrogenase (LDH) and sarcoplasmic reticulum Ca2+ ATPase (SERCA) were analyzed by spectrophotometric method. The mRNA levels of SERCA and prospholamban (PLB) in diaphragm were detected by RT-PCR.
@*RESULTS@#Compared with the NC group, there was no significant change in all measured index in the NaHS group (P>0.05), while Pt, Po and ±dT/dtmax were significantly decreased in the DM group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the diaphragm. The DW/BW ratio and the activities of SDH, LDH and SERCA were decreased. The SERCA mRNA was decreased, while PLB mRNA was increased. Compared with the DM group, the diaphragm contractility and ultrastructure damage were improved in the DM+NaHS group. The DW/BW ratio and the activities of SDH, LDH and SERCA were increased. The SERCA mRNA was increased, while PLB mRNA was decreased (all P<0.05).
@*CONCLUSION@#H(2)S can enhance the contraction capacity of diaphragm in type 1 diabetic rats, which is involved in regulating the activities of biological enzymes and the gene expressions of calcium regulatory proteins.

Protective effect of diosgenin on chondrocytes mediated by JAK2/STAT3 signaling pathway in mice with osteoarthritis / 浙江大学学报·医学版

To investigate the effect of diosgenin (Dgn) on chondrocytes and its relation to JAK2/STAT3 signaling pathway in mice with osteoarthritis (OA).Fifteen male C57BL/6 mice were randomly divided into three groups:control group, OA group and OA+Dgn group. After 4 weeks of treatment, the histopathological changes of cartilage tissue were observed by toluidine blue staining under light microscopy and the ultrastructure of chondrocytes was observed under electron microscopy. The primarily cultured chondrocytes of OA mice were randomly divided into 4 groups:(1) OA group, (2) Dgn group, (3) Dgn+AG490 group, (4) AG490 group. The expression of p-JAK2, p-STAT3, Bax, succinate dehydrogenase (SDH) and cytochrome c oxidase (COX) were detected by Western blotting, and superoxide dismutase (SOD) was detected using colorimetric method.The morphological observation showed that the chondrocytes of OA group presented considerable pathological changes, while the chondrocytes in OA+Dgn group maintained intact membrane. Electron microscopy observation found obvious injury in cartilage tissues of OA group, while that in OA+Dgn group remained smooth. Compared with OA group, the expressions of p-JAK2 and p-STAT3 in chondrocytes of Dgn group were increased (all<0.05), and the expressions of Bax protein, SDH, COX and SOD were decreased (all<0.05). While compared with Dgn group, the expressions of p-JAK2, p-STAT3, SDH, COX and SOD in chondrocytes of Dgn+AG490 group were decreased (all<0.05), and the expression of Bax protein was increased (<0.05).Diosgenin can inhibit apoptosis and increase mitochondrial oxidative stress capacity of chondrocytes in mice with osteoarthritis, which is closely related to the activation of JAK2/STAT3 signaling pathway.

The influence of the aerobic endurance training on the skeletal muscular mitochondria function and PI3K-Akt protein expression / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To determine the role of phosphatidylinositol 3-kinase--protein kinase B (PI3K-Akt) signaling pathway in the pro- tective effect of aerobic endurance training on the skeletal muscular mitochondria.</p><p><b>METHODS</b>Thirty-six rats were randomly divided into three groups( n = 12): control group, aerobic endurance training group and one-time exhaustive group. After the intervention, the quadriceps femoris muscle sample was obtained to detect the mitochondrial membrane potential( MMP), the activities of succinate dehydrogenase (SDH) and cy- tochrome coxidase (COX), and the protein levels of p-PI3K and p-Akt.</p><p><b>RESULTS</b>Compared with the control group, the levels of mitochondrial membrane potential, the activities of succinate dehydrogenase and cytochrome coxidase, and the protein levels of p-PI3K and p-Akt were all significantly decreased in the one-time exhaustive group (P < 0.05). However, all the above was partially reversed in the endurance training group (P < 0.05), and there was no obvious difference with the control group (P > 0.05).</p><p><b>CONCLUSION</b>Aerobic endurance training plays an important role in the protective effect on the skeletal muscular mitochondria, the mechanism may be related to activation PI3K-Akt signaling pathway.</p>

Effect of occupational exposure to toluene diisocyanate on workers' health / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.</p><p><b>METHODS</b>A total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.</p><p><b>RESULTS</b>The exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.</p><p><b>CONCLUSION</b>TDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.</p>

Antioxidating and energy metabolism improving effects of Qiangjing Decoction on oligospermia and asthenospermia: An experimental study / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of Qianjing Decoction in the treatment of oligoasthenospermia (OAS).</p><p><b>METHODS</b>We randomly divided 100 SPF male rats into five groups of equal number: normal, model, Huangjingzanyu, levocarnitine, and Qiangjing. OAS models were established in the animals followed by intragastrical administration of normal saline, ornidazole, Huangjingzanyu Capsules (200 mg per kg body weight per day), levocarnitine (100 mg per kg body weight per day), and Qianjing Decoction (10 g per kg body weight per day), respectively, qd, for 4 successive weeks. Then, we detected the concentration and motility of the epididymal sperm, obtained the contents of superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), lactate dehydrogenase (LDH), α-glucosidase, and fructose in the epididymis, and determined the mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and succinate dehydrogenase (SDH) in the epididymal tissue of the rats by real-time PCR.</p><p><b>RESULTS</b>The concentration and motility of the epididymal sperm in the model, Huangjingzanyu, levocarnitine, and Qianging groups were (35.34 ± 4.22) x 10(6)/ml and (40.04 ± 7.05)%, (48.12 ± 5.56) x 10(6)/ml and (62.46 ± 7.12)%, (47.14 ± 4.87) x 10(6)/ml and (63.23 ± 6.34)%, and (50.25 ± 5.08) x 10(6)/ml and (66.34 ± 7.58)%, respectively, all significantly lower than in the normal group ([53.05 ± 4.55] x 10(6)/ml and [70.20 ± 8.54]%) (P < 0.05), but remarkably higher in the Huangjingzanyu, levocarnitine, and Qiangjing groups than in the model rats (P < 0.05). Compared with the thinned epididymal lumen walls, decreased sperm count, and disorderly and loose arrangement of the lumens in the OAS models, the rats in the Huangjingzanyu, levocarnitine, and Qiangjing groups showed evidently thicker epididymal lumen walls, with the lumens full of sperm cells and arranged regularly and compactly, similar to those of the normal rats. The levels of SOD and GSH-Px were significantly lower but that of MDA markedly higher in the model rats ([84.12 ± 23.25], [10.56 ± 3.02], and [14.04 ± 2.06] nmol/mg) than in the normal group ([110.04 ± 19.56], [17.25 ± 3.56], and [8.87 ± 1.35] nmol/mg) (P < 0.05), while the former two indexes remarkably higher and the latter one significantly lower in the animals treated with Qiangjing Decoction ([120.56 ± 23.68], [16.34 ± 3.12], and [8.45 ± 1.56] nmol/mg), Huangjingzanyu Capsules ([115.34 ± 21.35], [15.23 ± 3.67], and [8.33 ± 1.54] nmol/mg), and levocarnitine ([116.67 ± 22.67], [15.35 ± 3.45], and [8.05 ± 1.78] nmol/mg) than in the models (P < 0.05). The levels of fructose, LDH and α-glucosidase were decreased markedly in the OAS models ([100.22 ± 12.12] mg/[ ml x g], [322 ± 46.13] U/[ ml x g], and [10.48 ± 2.33] U/[ml x g]) as compared with the normal rats ([128.12 ± 13.45] mg/[ml x g], [428 ± 35.12] U/[ml x g], and [15.34 ± 3.12] U/[ ml x g]) (P < 0.05), remarkably higher in the rats treated with Qiangjing ([130.23 ± 13.67] mg/[ml x g] [455 ± 51.50] U/[ml x g], and [18.56 ± 4.67] U/[ml x g]), Huangjingzanyu ([124.16 ± 14.02] mg/[ml x g], [ 419 ± 43.14] U/[ml x g], and [17.64 ± 4.08] U/[ml x g]), and levocarnitine ([123.34 ± 14.02] mg/[ml x g], [430 ± 31.80] U/ [ml x g], and [16.85 ± 5.55] U/[ml x g]) than in the models (P < 0.05). The Nrf2 mRNA expression was significantly reduced in the models as compared with the normal rats (P < 0.05) but remarkably increased in the Huangingzanyu, Qiangjing and levocarnitine groups as compared with the model and normal animals (P < 0.05). The SDH mRNA expression was significantly lower in the model than in the normal rats (P < 0.05) but markedly elevated in the Huangjingzanyu, Qiangjing and levocarnitine groups as compared with the model and normal animals (P < 0.05), remarkably higher in the Qiangjing than in the Huangjingzanyu group (P < 0.05).</p><p><b>CONCLUSION</b>Ornidazole induces OAS in rats, which is closely associated with excessive oxidation and energy metabolism dysfunction. Qiangjing Decoction can improve and even reverse ornidazole-induced OAS in rats as well as improve the ultrastructure of their testicular and epididymal tissues. Antioxidation and improvement of energy metabolism are probably the action mechanisms of Qiangjing Decoction in the treatment of OAS.</p>

Molecular mechanism of gastrointestinal stromal tumors and progress in drug research / 中华胃肠外科杂志

The functional mutation of c-kit and platelet-derived growth factor receptor α (PDGFRA) which encode proto-oncogene receptor tyrosine kinase are the crucial pathogeneses of gastrointestinal stromal tumors(GISTs). 80%-85% c-kit gene mutation including exon 11,exon 9,exon 13,exon 17 and 5%-10% PDGFRA gene mutation such as exon 18, exon 12 are examined in GISTs. Neither of c-kit or PDGFRA gene mutation are called wide type GISTs. The pathogeneses of wild type GISTs are not clear. The deficiency of succinate dehydrogenase B(SDHB)-related insulin-like growth factor 1(IGF-1R) activation, BRAF gene mutation and neurofibromatosis type 1 may be related to progression of wild type GISTs. More than half of metastatic GISTs patients receiving imatinib treatment can develop to c-kit secondary mutations, which are responsible for secondary resistance. However, the reasons of imatinib resistance in GISTs without c-kit secondary mutation need to be explored. At present, many clinical trials are ongoing to evaluate new drugs in GISTs treatment, including nilotinib, masitinib, pazopanib, dovitinib, ponatinib, dasatinib, crenolanib, linsitinib and immunotherapy, which may bring resistance GISTs treatment to new hope. Next generation sequencing (NGS) and liquid biopsy will be very important in GISTs research and clinical practice.

Clinicopathologic features of succinate dehydrogenase-deficient gastrointestinal stromal tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate clinicopathologic features of succinate dehydrogenase-deficient gastrointestinal stromal tumors (SDH-deficient GIST).</p><p><b>METHODS</b>Immunohistochemical EnVision technique was used to assess the expression of succinate dehydrogenase subunit B (SDHB) in 192 cases of GIST. Cases of SDH-deficient GIST were further evaluated for the presence of CKIT exons 9, 11, 13 and 17 mutations and PDGFRA exons 12 and 18 mutations with clinical followed-up data.</p><p><b>RESULTS</b>Seven of the 192 cases showed SDHB-deficiency (3.6%, 7/192). The patients ranged in age from 35 to 84 years (median=56 years; mean=60 years). Four were male and three were female. Six tumors involved stomach and one involved mesentery. Histopathologic features of SDHB-deficient GIST included four cases of mixed-cell type and three of epithelioid cell type. The tumors commonly involved muscularis propria of the stomach as multiple nodules, creating a plexiform pattern. The tumors had high cellularity with cytoplasmic vacuolization. Five cases developed lymph node metastases including one also metastasizing to liver and pancreas. Two cases showed no evidence of metastasis. None of the 7 cases of the SDHB-deficient GIST had CKIT exons 9, 11, 13 and 17 mutations and PDGFRA exons 12 and 18 mutations. Three of the seven SDHB-deficient GIST cases had followed-up data: two did not recur and one died after 24 months of surgery of unknown cause.</p><p><b>CONCLUSION</b>SDHB-deficient GIST has characteristic clinicopathologic features with wide-type CKIT gene and a favorable prognosis.</p>

Low expression of succinate dehydrogenase subunit B in locally recurrent nasopharyngeal carcinoma and implication for prognosis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the expression of succinate dehydrogenase subunit B (SDHB) in the tissues of locally recurrent nasopharyngeal carcinoma (rNPC) and the correlation with the clinicopathological factors and prognosis of rNPC.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expression of SDHB in the tissues of primary and locally recurrent nasopharyngeal carcinoma. The relationship between SDHB expression and clinicopathological features was analyzed using the Chi-square test, and Kaplan-Meier method and Log-rank test were used for survival analysis. The independent prognostic factors of rNPC were analyzed by Cox regression model.</p><p><b>RESULTS</b>Low SDHB expression was showed in 76.5% (39/51) of the patients with rNPC, significantly higher than 57.1% (24/42) of primary nasopharyngeal carcinoma (χ(2) = 4.098, P < 0.05). Low expression of SDHB strongly was correlated with T classification, clinical stage and cranial nerve palsy. Patients with low SDHB expression had a shorter survival time and a lower 3 or 5 year survival rate compared to the patients with high SDHB expression. Multivariate analysis showed that low SDHB expression was an independent predictor for overall survival of patients with rNPC (P < 0.05).</p><p><b>CONCLUSION</b>The low SDHB expression is an independent indicator for poor prognosis of rNPC and may play an important role in the recurrence of rNPC.</p>

Inhibitory effect of Genipin on uncoupling protein-2 and energy metabolism of androgen-independent prostate cancer cells / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore whether the inhibitory effect of Genipin on uncoupling protein-2 (UCP-2) in mitochondria is involved in energy metabolism of androgen-independent PC3 prostate cancer cells.</p><p><b>METHODS</b>PC3 prostate cancer cells were cultured and treated with Genipin at the concentrations of 40, 80, and 160 μmol/L for 48 hours. Then the proliferation of the cells was detected by MTT assay, the expression of UCP-2 mRNA determined by RT-PCR, and the content of intracellular pyruvic acid (PA) and the activity of succinate dehydrogenase (SDH) in the mitochondria measured by visible spectrophotometry.</p><p><b>RESULTS</b>With the increased concentration of Genipin, the proliferative activity of the PC-3 cells, the expression level of UCP-2 mRNA, the content of intracellular PA and the activity of SDH in the cells were all decreased, namely, with the enhanced inhibitory effect of Genipin on UCP-2, a trend of reduction was observed in the proliferation of the cells, intracellular PA content, and SDH activity in the mitochondria.</p><p><b>CONCLUSION</b>Genipin is involved in the energy metabolism of androgen-independent PC3 prostate cancer cells by reducing the content of intracellular PA and the activity of SDH in the mitochondria, which may be associated with its inhibitory effect on UCP-2.</p>

Succinate dehydrogenase deficient gastrointestinal stromal tumor: a clinicopathologic analysis of eight cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumors (GISTs) as a unique tumor subtype.</p><p><b>METHODS</b>SDHB and SDHA immunohistochemistry was performed in 120 gastric GISTs, in addition to CD117, DOG-1, CD34, smooth muscle actin (SMA), desmin, S-100 protein, cytokeratin (CK) and Ki-67. Subset of the cases was further evaluated for the presence of mutations in CKIT exons 9, 11, 13 and 17 mutations and platelet derived growth factor receptor alpha(PDGFRA) exons 12 and 18.</p><p><b>RESULTS</b>Eight of 120 (6.6%) GIST cases were found SDH-deficient including 3 male and 5 female patients (median age of 36.2 years; ranging 16 to 65 years of age). The tumors involved antrum (6 cases), lesser curvature (1 case) and fundus (1 case). Macroscopically, the dominant tumor masses varied from 3 to 10 cm in diameter with a multinodular or plexiform pattern involving the gastric wall. Microscopically,tumor cells had predominantly epithelioid morphology, with occasional mixed spindle cell nodules. Lymphovascular invasion was identified in 5 cases. Immunohistochemistry for SDHB was negative in all 8 cases, and SDHA was negative in 5 cases. All 8 SDHB negative cases also expressed CD117, DOG-1 and CD34, but were negative for SMA, desmin, S-100 and CK. All 8 cases were found to have wild-type CKIT and PDGFRA genes. Available clinical follow-up were obtained in 7 cases, ranging from 2 to 60 months (median follow-up 23.3 months), and all patient were alive. Three cases were found to have liver metastases at their first diagnosis, and one developed omental and mesenteric metastases in 17 months.</p><p><b>CONCLUSIONS</b>SDH-deficient GIST is a distinct subtype of GIST, with a predilection to occur in young and female patients. Characteristic pathological findings include multinodular gastric wall involvement, epithelioid cell morphology, frequently lymphovascular invasion with occasional lymph node and liver metastases, but an overall indolent clinical behavior. Immunohistochemistry for SDHB is required for the diagnosis.</p>

Fiebre chikungunya en México: caso confirmado y apuntes para la respuesta epidemiológica / Chikungunya fever in Mexico: confirmed case and notes on the epidemiologic response

La fiebre chikungunya (CHIK) es una enfermedad viral transmitida al ser humano por el mismo vector del dengue, el mosquito Aedes. Además de fiebre y fuertes dolores articulares, produce otros síntomas como mialgias, cefalea, náuseas, cansancio y exantema. No tiene tratamiento específico; el manejo terapéutico de los pacientes se enfoca en el alivio de los síntomas. Históricamente se han reportado brotes de grandes proporciones; incluso desde 2010 se llegó a considerar como una potencial epidemia emergente. En 2013 se introdujo a las islas del Caribe y recientemente se ha reportado en el continente americano. En este trabajo se describe el primer caso confirmado de chikungunya en México, en el municipio de Tlajomulco de Zúñiga, Jalisco, en mayo de 2014, importado de la isla Antigua y Barbuda, en el Caribe, por una mujer de 39 años de edad.

Chikungunya fever (CHIK) is a viral disease transmitted to human beings by the same vector as dengue -the Aedes mosquito. Besides fever and severe pain in the joints, it produces other symptoms such as myalgias, headache, nausea, fatigue and exanthema. There is no specific treatment for it; the therapeutic management of patients focuses on symptom relief. Historically, outbreaks of large proportions have been reported; even since 2010 it was considered to be a potential emerging epidemic. In 2013 it was introduced into the islands of the Caribbean, and it has recently been reported in the American continent. This paper describes the first confirmed case of chikungunya in Mexico -in the municipality of Tlajomulco de Zúñiga, Jalisco, in May, 2014-, which was imported from the Caribbean island of Antigua and Barbuda by a 39 year-old woman.

The effects of Kangai injection on enzyme activities of macrophages in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of Kangai injection on the enzyme activities of macrophages and morphology of spleen and thymus from rats.</p><p><b>METHODS</b>Twenty four male SD rats were randomly divided into two groups (n = 12), normal control group and experimental group. The rats in experimental group were injected with Kangai injection at the dosage of 5 ml/kg x d for 30 days peritoneally and those in control group were injected with nomal saline at the same volume. The content of supermicro protein was assayed by BCA method, the activities of lactate dehydrogenase (LDH), glutathione peroxidase(GSH-Px), and inducible nitric oxide synthase (iNOS) from alveolar macrophages(AM) and peritoneal macrophages (PM) were detected biochemically. The activities of acid phosphatase (ACP), superoxide dismutase(SOD) and succinate dehydrogenase (SDH) from AM and PM were detected by ELISA. The morphology of spleen and thymus were observed by light microscopy.</p><p><b>RESULTS</b>The activities of LDH, GSH-Px and iNOS within AM and PM from experimental group were increased significantly compared with those of control group (P < 0.05). The activities of ACP, SOD and SDH in AM and PM from experimental group were also higher than those from control group (P < 0.05). Microscopically, there was thickening of peripheral arterial lymphatic sheath, enlargement of splenic lymphoid nodules with expended germinal center in the spleen of experimental group. There was no significant difference in the mophology of thymus between the two groups.</p><p><b>CONCLUSION</b>Kangai injection may improve immune function by activating macrophages.</p>

Study on discrimination mode of cold and hot properties of traditional Chinese medicines based on biological effects / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of cold or hot properties of traditional Chinese medicines (TCM) on biological effect indexes, and analyze the contribution of variables on cold or hot properties, in order to preliminarily establish the discrimination mode for the biological effects of cold or hot properties.</p><p><b>METHOD</b>Rats were randomly divided into the blank control group, cold TCM groups (Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix and Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex and Evodiae Fructus), and orally administered with 10 mL x kg(-1) of corresponding TCM water decoctions for 30 d, twice a day. Altogether 53 biological effect indexes correlated to cold or hot properties of traditional Chinese medicines were founded by searching literatures. The data warehouse were established by using data-mining software Clementine12.0. Data of the blank control group, cold TCM groups (Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, Sophorae Flavescentis Radix, Gentianae Radix) and hot TCM groups (Aconiti Lateralis Preparata Radix, Zingiberis Rhizoma, Alpiniae Officinarum Rhizoma, Zanthoxyli Pericarpium, Cinnamomi Cortex) were selected into a training set. C5.0 algorithm and C&R classification and regression algorithm were adopted to define the importance of variable, create the decision trees, and test hot or cold properties of Evodiae Fructus and Scutellariae Radix.</p><p><b>RESULT</b>According to C&R classification and regression algorithm, SDH activity of livers was the most important hot or cold property, with the significance closed to 30%. It was followed by triglyceride, liver Na' -K' -ATPase enzyme, muscle glycogen and platelet distribution width, with the accuracy up to 97.39% in models. C5.0 algorithm showed that liver SDH activity was the most important hot or cold property, with the significance closed to 40%. It was followed by triglyceride, GOT, muscle glycogen and liver Na(+)-K(+)-ATPase enzyme, with the accuracy up to 98.26% in models. The possibilities that Evodiae Fructus is in hot property and Scutellariae Radix is in cold property were 100. 00% and 77.78% by using both C&R classification and regression algorithm and C5.0 algorithm.</p><p><b>CONCLUSION</b>The SDH activity of liver is the most important biological effect index to distinguish cold and hot properties of TCMs. The discrimination pathway or mode of cold and hot properties is closely related to energy metabolism.</p>