Objective To investigate the relationship between thyroid nodules with calcification and thyroid carcinoma and its significance in the screening of thyroid carcinoma in high risk group.Methods The clinical data of 1771 patient undergoing surgery for thyroid nodules from March, 2006 to March, 2009 in Huashan Hospital, Fudan University were retrospectively analyzed. Results Among 1771 patients, 500 were finally identified as having malignant tumors. Incidence of calcification in thyroid carcinoma was 68. 4%, and that in benign thyroid nodules was 27.0% ( χ2 = 259. 5, P ＜ 0. 05 ). The specificity of microcalcification for the diagnosis of carcinoma was 89. 4%, and its positive predictive value was 66. 3% ( χ2 = 368.6, P ＜ 0. 01 ). The incidence of thyroid carcinoma in patients ＜ 45 years was 39.2%, while that in patients ≥ 45 years was 22.9% ( χ2 = 51.12, P ＜ 0. 05 ). The incidence of carcinoma in patients of single thyroid nodule was 31.7% and that in those with multiple nodules was 26. 4% (χ2 =4. 766,P ＜ 0. 05). Metastasis was pathologically diagnosed in 26. 8% of lymph nodes found by preoperative ultrasonography. Conclusions The specificity of thyroid nodule calcification, especially microcalcification is high for the diagnosis of thyroid carcinoma. High-risk index for carcinoma includes thyroid nodules with microcalcification, ＜ 45 years old and single thyroid nodule.

Aim To investigate the effects of classic calcium antagonists verapamil(Ver),nifedipine(Nif),diltiazem(Dil)and the novel calcium antagonist N-n-butyl haloperidol iodide(F2)which was synthesized by our lab by regulating Ca2+-independent phospholipase A2(iPLA2)on hypoxia/reoxygenation(H/R)injury of cardiac microvascular endothelial cells(CMECs)and the mechanisms.Methods The CMECs were isolated from SD neonatal rats.The H/R model was established,then cells were treated with different concentrations of calcium antagonists and F2.The content of LDH in the cell supernatant was measured by colorimetric method.The levels of IL-6 and AA in cell supernatant were measured by ELISA;and late-stage apoptosis was measured by TUNEL.The mRNA and protein expression levels of iPLA2 in CMECs were examined by real time-PCR and Western blot analysis.Results Calcium antagonists except Dil decreased the generation of LDH,IL-6 and AA in a dose-dependent manner(P<0.05),and reduced the apoptosis(P<0.05).F2 and Ver decreased the mRNA and protein expression of iPLA2 in a dose-dependent manner,while there were no such effects for Nif and Dil.Conclusions Calcium antagonists except Dil have protective effects against H/R injury.F2 and Ver protect CMECs against H/R injury partly through iPLA2.

Aim To investigate the effect of N-n-butyl haloperidol iodide(F2) on mitochondria-dependent apoptotic pathway of H9c2 cardiac myocytes during hypoxia/reoxygenation(H/R) injury.Methods The H/R models of H9c2 cardiac myocytes were established.The H9c2 cardiac myocytes were randomly divided into five groups: control group(C group), hypoxia/reoxygenation group(H/R group), F2 low concentration group(L), F2 medium concentration group(M), F2 high concentration group(H).Apoptotic rate was evaluated by flow cytometry(FCM).The levels of Cyto C, Bcl-2, Bax were observed by Western blot.Caspase-3 activity was measured with colorimetry.Results Compared with H/R group, F2 low, medium and high concentrations group could significantly decrease apoptosis rate and increase the ratio of Bcl-2 to Bax proteins and inhibit the release of Cyto C into the cytosolic fraction, and decrease caspase-3 activity.Conclusion F2 can protect H9c2 cardiac myocytes against H/R-induced injury through interfering in mitochondria-dependent pathway.

Objective To explore the diagnosis and treatment of primary small bowel tumors. Methods The clinical data of 58 cases of primary small bowel tumors were retrospectively analyzed. Results Fifty-eight cases of primary small intestinal tumors were comfirmed by operation and/or pathology .Of them,19 suffered from benign tumors and 39 from malignant tumors.The main clinical manifestations of small bowel tumors were abdominal pain, abdominal mass, ileu and upper gastrointestinal hemorrhage.Twenty cases were diagnosed before the operation,and the misdiagnosis rate was 65.5%.All the 19 benign small intestinal tumors underwent local intestinal resection.In 39 malignant cases,18 underwent radical excision of the tumors, 6 received palliative excision and 5 underwent intestinal bypass operation. One patient died after the operation.The 1,3,5 -year survival rate of malignant tumors was 57.1%,28.6%and 9.5% respectively. Conclusions Primary small bowel tumor is uncommon and easy to be misdiagnosed.So attention must be paid to this disease.Endoscopy, X-ray ,BUS, CT and capsule endoscopy are the ideal diagnostic methods for small intestinal tumors .

Objective: To investigate the epidemiological and spatio-temporal characteristics of influenza in Jiaxing City, Zhejiang Province, so as to provide insights into perfecting the prevention and control strategies of influenza. Methods: Data of influenza in Jiaxing City from 2019 to 2023 were collected from the Chinese Disease Prevention and Control Information System. Population data of the same period were collected from the Zhejiang Health Information Network Reporting System. The epidemiological characteristics of influenza were analyzed using descriptive analysis. Vector map information was collected from the Open Street Map, and the spatio-temporal clustering characteristics of influenza were analyzed using spatial autocorrelation and spatio-temporal scanning. Results: A total of 181 501 cases of influenza were reported in Jiaxing City from 2019 to 2023, with an average annual reported incidence of 653.93/105. The majority of cases were aged 5 to <15 years (59 785 cases, 32.94%). The majority of the occupations were students (78 239 cases, 43.11%) and pre-school children (33 715 cases, 18.58%). The county (city, district) with the highest reported incidence was Haining City (1 451.70/105), and the town (street) with the highest reported incidence was Chang'an Town (1 932.78/105). Spatial autocorrelation analysis showed that the incidence of influenza in Jiaxing City from 2019 to 2023 had positive spatial correlations (all Moran's I>0, all P<0.05), with a high-high clustering in the southern region. Spatio-temporal scanning analysis showed that there was a spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with the southern region being the primary-type clustering area and the period between November and January of the following year being the clustering time. Conclusion There was a significant spatio-temporal clustering of influenza in Jiaxing City from 2019 to 2023, with winter being the peak season and the southern region being the primary area.

Objective:To investigate the relationship between serum miR-501 and miR-195 levels and sensitivity to concurrent chemoradiotherapy in patients with locally advanced cervical cancer (LACC).Methods:Clinical data of 96 patients with LACC admitted to Nanyang Central Hospital from January 2020 to June 2022 were retrospectively analyzed and compared with those of 96 healthy subjects during physical examination in our hospital during the same period to compare the differences of serum miR-501 and miR-195 levels. Tumor status was reviewed at 6 months after concurrent chemoradiotherapy. Patients were divided into the sensitive and resistant groups according to the evaluation criteria of solid tumor efficacy. The relationship between serum miR-501 and miR-195 levels and the sensitivity to concurrent chemoradiotherapy in LACC patients was analyzed by univariate and multivariate analyses. The receiver operating characteristic (ROC) curve was also drawn to predict differential efficacy of concurrent chemoradiotherapy sensitivity in LACC patients. Multivariate analysis was conducted by binary logistic regression analysis. P<0.05 indicated statistically significant differences. Results:In LACC patients, serum miR-501 level was significantly higher, whereas serum miR-195 level was significantly lower than those in physical examination subjects (both P<0.05). Univariate analysis showed that serum miR-501 level at admission in the resistant group was significantly higher, whereas serum miR-195 level was significantly lower than those in the sensitive group (both P<0.05). Multivariate analysis showed that serum miR-501 and miR-195 levels were significantly correlated with the sensitivity to concurrent chemoradiotherapy in LACC patients. The area under the ROC curve (AUC) was 0.736 and 0.913, respectively. Conclusions:The higher the serum miR-501 level and the lower the serum miR-195 level before treatment, the higher the probability of resistance to concurrent chemoradiotherapy in LACC patients. Serum miR-501 and miR-195 levels of LACC patients before treatment have certain predictive value for the sensitivity to concurrent chemoradiotherapy.

Objective:To discuss the effect of the small ubiquitin-like modifier-specific protease 1(SENP-1)/hypoxia-inducible factor 1α(HIF-1α)pathway on chronic intermittent hypoxia(CIH)-induced vascular endothelial injury in the rats,and to clarify the related mechanism.Methods:The SD rats were randomly divided into control group and CIH group,and then the rats in each group were further divided into 2,4,and 6-week subgroups,and there were 8 rats in each subgroup.The rats in CIH group were exposed to CIH in a CIH chamber to induce CIH and create the obstructive sleep apnea hypopnea syndrome(OSAHS)models,while the rats in control group were exposed to normoxic conditions.The serum and thoracic aorta tissue of the rats in various groups were collected at each time point.HE staining was used to observe the thoracic aorta vascular injury of the rats in various groups;ELISA method was used to detect the levels of nitric oxide(NO),endothelin-1(ET-1),von Willebrand factor(vWF),and thrombomodulin(TM)in serum of the rats in various groups;Western blotting method was used to detect the expression levels of SENP-1,HIF-1α,and vascular endothelial growth factor A(VEGFA)proteins in thoracic aorta tissue of the rats in various groups.In vitro,the aortic endothelial cells(rAECs)of the rats were cultured and infected with SENP-1 shRNA adenovirus(sh-SENP-1)to construct the cell line with low expression of SENP-1.The CIH was used to induce the vascular endothelial cell injury,and the cells were divided into CIH group,CIH+sh-NC group,and CIH+sh-SENP-1 group;control group was set up separately.CCK-8 method was used to detect the proliferation activities of the cells in various groups;ELISA method was used to detect the activities of lactate dehydrogenase(LDH)in the supernatant and the levels of NO,ET-1,malondialdehyde(MDA),and activities of superoxide dismutase(SOD)in the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of SENP-1,HIF-1α,and VEGFA proteins in the cells in various groups.Results:With the extension of CIH induction time,compared with control group,the thoracic aorta endothelium in CIH group gradually became rough and significantly thickened,the level of serum NO of the rats in CIH group was decreased(P＜0.05),and the levels of serum ET-1,vWF,and TM,and the expression levels of SENP-1,HIF-1α,and VEGFA proteins in thoracic aorta tissue were increased(P＜0.05).Compared with control group,the proliferation activity of the cells in CIH group was decreased(P＜0.05),the LDH activity in the supernatant,the levels of ET-1,MDA,and the apoptotic rate in the cells were increased(P＜0.05),while the levels of NO and activity of SOD in the cells were decreased(P＜0.05),and the expression levels of SENP-1,HIF-1α,and VEGFA proteins in the cells were increased(P＜0.05).Compared with CIH group,the proliferation activity of cells in CIH+sh-SENP-1 group was increased(P＜0.05),the activity of LDH in the supernatant,the levels of ET-1,MDA,and the apoptotic rate of the cells were decreased(P＜0.05),while the level of NO and activity of SOD in the cells were increased(P＜0.05),and the expression levels of SENP-1,HIF-1α,and VEGFA proteins were decreased(P＜0.05).Conclusion:The SENP-1/HIF-1α pathway is highly activated in the thoracic aorta injury tissue of the rats induced by CIH.Silencing SENP-1 expression can reduce CIH-induced vascular endothelial cell injury,and its mechanism may be related to downregulating the activation level of SENP-1/HIF-1α pathway.

Objective : To investigate the effects and mechanism of small ubiquitin-like modifier ( SUMO) specific proteinase-1 (SENP-1) on chronic intermittent hypoxia ( CIH) induced myocardial injury in rats． Methods : 32 male SD rats were randomly divided into : control group，CIH group，negative control adeno-associated virus interven- tion group (AAV-shNC) and SENP-1 shRNA adeno-associated virus intervention group (AAV-shSENP-1) ，with 8 rats in each group．After 6 weeks of CIH induction，echocardiography was performed．The levels of cardiac troponin I (cTNI) ，creatine kinase MB isoenzyme ( CKMB) ，myoglobin (Mb) ，lactate dehydrogenase (LDH) in serum and malondialdehyde (MDA) ，uperoxide dismutases ( SOD) ，glutathione ( GSH) ，interleukin( IL) -1 β , IL-6 and tumor necrosis factor-α(TNF-α) in myocardial tissue were detected by ELISA．The pathological changes of myocardial tis- sue was observed by HE staining．The reactive oxygen species ( ROS) level in myocardial tissue was detected by DCFH-DA fluorescence probe labeling．The small ubiquitin-like modifier (SUMO) level of hypoxia inducible factor- 1 α (HIF-1 α) protein in myocardial tissue was detected by kit．The mRNA and protein levels of SENP-1 and HIF- 1 α in myocardial tissue were detected by qRT-PCR and Western blot. Results : Compared with the control group， the pathological damage of myocardial tissue in CIH group was serious，the levels of left ventricular end diastolic diameter (LVEDD) ，left ventricular end systolic dimension (LVESD) and serum cTNI，CKMB，Mb and LDH signif- icantly increased (P＜0. 05) ，and the levels of ROS，MDA，IL-1 β , IL-6，TNF-α and the mRNA and protein levels of SENP-1 and HIF-1α in myocardial tissue also significantly increased (P ＜0. 05 ) ，while the levels of LVEF， LVFS，serum GSH and SOD significantly decreased (P ＜0. 05) ，and the SUMOylates level of HIF-1α protein in myocardial tissue also significantly decreased (P ＜0. 05 ) ．Compared with CIH group，AAV-shSENP-1 group had less myocardial pathological damage，the levels of LVEDD，LVESD and serum cTNI，CKMB，Mb and LDH signifi- cantly decreased (P＜0. 05) ，and the levels of ROS，MDA，IL-1 β, IL-6，TNF-α and the mRNA and protein levels of SENP-1 and HIF-1α in myocardial tissue also significantly decreased (P＜0. 05) ，the levels of LVEF，LVFS，serum GSH and SOD significantly increased (P＜0. 05) ，and the SUMOylates level of HIF-1α protein in myocardial tissue also significantly decreased (P＜0. 05) ． Conclusion Inhibition of SENP-1 expression can alleviate CIH induced myocarditis and oxidative stress in rats，improve myocardial injury and cardiac dysfunction，and its mechanism may be related to the improvement of HIF-1α SUMOylates level，thus inhibiting HIF-1α expression.

OBJECTIVETo evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.

METHODSTwenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.

RESULTSThe twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.

CONCLUSIONSCombination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.

Adenocarcinoma ; drug therapy ; metabolism ; secondary ; surgery ; Adult ; Aged ; Anorexia ; chemically induced ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Esophagogastric Junction ; Fatigue ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Receptor, ErbB-2 ; metabolism ; Remission Induction ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; metabolism ; secondary ; surgery ; Survival Rate ; Trastuzumab