Objective To explore the effect of vitamin D receptor (VDR) in intestinal tumor development and the relationship between VDR and β-catenin signaling pathway. Methods The interaction of vitamin D receptor and β-catenin were detected by co-immunoprecipitation assay after human colonic carcinoma cells SW480 were treated with vitamin D in vitro for 4 hours. The expression of E-cadherin protein was detected by Western blot after treated for 24 hours. To compare APCmin/+VDR-/- and APCmin/+ mice in vivo, the expression of VDR,β-catenin and BrdU proteins in intestinal tumor were determined by immunohistochemistry. The expression of β-catenin protein in tumor and adjacency intestinal was further determined by Western blot. Results After SW480 cells were treated with vitamin D, vitamin D receptor and β-catenin protein showed binding, the expression of E-cadherin protein further increased (Gray value the control group 145.57±4.21,Gray value of the experimental group 109.35±3.56,t＝32.63,P＜0.05). Immunostaining and Western blot detection（Gray value 166.47±2.36） showed a marked increase of β-catenin level(Gray value 140.51±2.57) in APCmin/+VDR-/- tumor compared to APCmin/+ tumor(145.41±3.62,182.35±3.24,t＝2.65,4.36,P＜0.05). Conclusions The role of vitamin D suppressing intestinal tumor may be achieved through VDR affectingβ-catenin signaling pathway.

ObjectiveTo explore the relationship among 25-hydroxyvitamin D,serum calcium,calcium-sensing receptor,and breast cancer. Methods The expressions of calcium-sensing receptor (CaSR) in primary breast cancer,breast benign tumors,and normal breast tissue beside tumors were determined by immunohistochemistry S-P method as well as the concentration of serum 25 (OH) D and serum calcium in breast cancer and breast benign tumors by Enzyme-linked immunosorbent assay (ELISA),Tribromoarsenazo Ⅲ method.ResultsSerum 25 (OH) D level of breast cancer was significantly lower than the breast benign tumors [ (34.13 ± 14.14) nmol/L vs (50.29 ± 25.65 ) nmol/L,t =2.870,P =0.001 ].Serum level of 25 ( OH ) D in lymph node metastasis positive patient was lower than that in negative group [ (30.8 ± 9.71 ) nmol/L vs (43.7 ± 23.59) nmol/L,t =2.467,P =0.021 ].The positive expression of CaSR in breast cancer(88.9％ )was higher than breast benign tumors(60％,x2 =6.717,P ＜ 0.01 ) and normal breast tissue beside tumors (60％,x2 =5.628,P ＜ 0.05 ).ConclusionsConcentration of serum 25 (OH)D and expression of calcium-sensing receptor in the tissues may be associated with occurrence,development and prognosis of breast cancer.

Objective To observe the expression of tumor necrosis factor-α(TNF-α)in acute lung injury caused by paraquat(PQ)in rats,and investigate the mechanism of the rhubarb in respect of pmteetive effects.Method PQ intragastrically poisoning at the dose of 50 mg/kg made a model of the acute lung injury in Sprague-Dawley(SD)rats.Totally 144 adult healthy SD rats(72 female,72male)were randomly divided into control group (group A,n=24),poisoned group(group B,n=48),rhubarb treated group(group C,n=48)and the shaln poisoning group(group D,n=24).Rats of group B and group C were poisoned intmgastrically with PQ(50 mg/kg).and rats of group C and group D were intervened intragastrieally with 300 mg/(kg·d)of rhubarb in 15 min-utes.The white blood cells and total cells in bronchoalveolar lavage fluid(BALF)were counted by using a blood cell counting plate and the protein content of BALF was measured by using the way of Lowry in order to calculate the neutmphiks pereentage and lung permeability index.A small portion of left lung was stained with HE to observe the pathological changes and the expression oftumor necrosis factor-α in the rest of the left lung was observed with immunohistochemistry.The data were handled by the analysis of variance and NK method using SPSS 14.0.Re-suits Compared with group A,the lungs of rats mainly showed congestion,edema and leukocytes infiltration in group B,and fibrosis was found onlyt in a few rats.And the rate neutrophils percentage,protein content and lung permeability index in BALF increased(P＜0.01).The expression of TNF-α were obviously inereased at 12 hours after PQ poisoning,and immtmohistochemistry score (IHS)was higher,and peaked at 24 hours later(P＜0.05),then remained on a high level for a while and sluggishly declined.Compared with group B,the changes of above mentioned were alleviated obviously,and the expression of TNF-α delayed with the less magnitude of increasing an an obvious tendency of less expression.Compared with group B,delayed,lower increasing extent,obviously re-ducing tendency in group C with statistical difference in IHS(P＜0.05).Conclusions Rhubarb ameliorates a-cute lung injury caused by PQ poisoning in rats by means of inhibiting the expression of TNF-α in turn to alleviate inflammatory reaction.

Objective To investigate the expression and clinical significance of CXCR3/CXCL10in human cancer.Methods CXCR3 and CXCL10 were detected in 60 paraffinic tissues of patients with primary breast cancer,20 of mammary fibroma and 20 of mastopathy by immunohistochemistry S-P method and two stage method.Results The expression of CXCR3 (40/60,66.7％ ) and CXCL10 (45/60,75％)in breast cancer was higher than that in mastopathy [CXCR3(8/20,40％ )x2 =4.44,P =0.035 ;CXCL10( 10/20,50％ )x2 =4.36,P =0.037)].The expression of CXCR3 was related to status of axillary lymph node metastasis,clinical stage and the expression of HER-2 (x2 =4.15,P =0.042; x2 =7.74,P =0.021 ;x2 =4.27,P =0.039).The expression of CXCR3 had positive relationship to the number axillary lymph node metastasis( rs =0.375,P =0.003 ),clinical stage ( rs =0.451,P =0.000).Conclusions CXCR3 may be related to the progression and metastasis of breast cancer,and it may be used as a marker of breast cancer prognosis.

To study the clinical and pathological characteristics and prognostic factors of primary breast diffuse large B-cell lymphoma (PBDLBCL). Methods: Clinical and pathological data of 62 patients with PBDLBCL from January 2006 to December 2016 were retrospectively analyzed. The Kaplan-Meier method was used for univariate analysis and the Cox regression model for multivari-ate analysis. Results: The 62 patients analyzed included women aged 26-71 years, with a median age of 47 years. Patients were fol-lowed up from 6 to 105 months; the 3-year overall survival (OS) rate was 71.0%, and 5-year OS rate was 51.0%. The univariate analysis showed statistically significant differences in the clinical stage, lactic acid dehydrogenase level, International Prognostic Index score, Myc/Bcl-2 protein expression, and chemotherapy regimen at 3 and 5 years associated with OS rates. The multivariate analysis showed that Myc/Bcl-2 protein expression was an independent prognostic factor of OS. Conclusions: Comprehensive treatment with chemo-therapy and radiotherapy is appropriate for PBDLBCL. Myc/Bcl-2 protein expression is an independent adverse prognostic factor for PB-DLBCL.

Objective To explore relationship between the change of serum N terminal brain natriuretic peptide (NT-proBNP) , central venous oxygen saturation (SCVO2 ) and venous-arterial partial pressure of carbon dioxide [P(v-a)CO2 ] levels and prognosis in elderly patients with septic shock .Methods 94 cases of elderly patients with septic shock ,treated from March 2015 to July 2016 in Intensive Care Unit (ICU) of our hospital ,were chosen as the observation group A ,another 80 cases of nonsevere sepsis patients were chosen as the observation group B ,and a total of 56 patients healthy volunteers with the physical examination at the same peri-od of time in our hospital as normal control group .The serum NT-proBNP level was detected by electrochemiluminescence immuno-assay ,and PvCO2 ,PaCO2 and SCVO2 levels were detected by blood gas analyzer .records of patients with central venous blood car-bon dioxide .The NT-proBNP and P (v-a) CO2 levels in the serum of the three groups were compared between the groups of pa-tients in the observation group (SCVO2 ) .Logistic regression analysis was used to analyze the prognostic factors in elderly patients with septic shock ,and the receiver operating characteristic curve (ROC) was used to analyze the predictive value of NT-proBNP ,P (v-a)SCVO2 and SCVO2 levels .Results The serum NT-proBNP level of the observation group A was higher than that in the the observation group B and the control group (P<0 .05) .The SCVO2 level of the A group was lower than that in the B group ,and the P(v-a)CO2 level of the A group was higher than that in the B group ,the difference was statistically significant (P<0 .05) .The age , NT-proBNP ,P(v-a)CO2 ,lactic acid level and APACHE II score in the death group were higher than those in the survival group , and the difference was statistically significant (P< 0 .05) .SCVO2 level in the death group was lower than that in the survival group ,and the difference was statistically significant (P<0 .05) .Logistic multivariate regression analysis showed that NT-proBNP , P(v-a)CO2 and SCVO2 levels were the risk factors for the prognosis of elderly patients with septic shock .ROC curve showed AUC and the sensitivity of P(v-a)CO2 were higher than those of NT-proBNP ,SCVO2 .Conclusion The levels of serum NT-proBNP ,SC-VO2 and P(v-a)CO2 are related to the prognosis of elderly patients with septic shock ,and P(v-a)CO2 has a high value in the prog-nosis of the patients with septic shock ,and has a good clinical value .

[摘 要] 目的：用组织代谢组学方法，探讨甲状腺乳头状癌（papillary thyroid carcinoma, PTC）组织及癌旁组织的代谢差异，寻找PTC的潜在生物标志物，探索PTC的发病机制与治疗策略。方法：收集2018年10月至2020年2月期间湖南省人民医院乳甲外科手术切除的40例PTC患者的癌组织及癌旁组织标本。利用HPLC-MS技术平台对PTC组织及癌旁组织样本的差异性代谢物进行多维统计分析，寻找与PTC相关的异常代谢通路。结果：经PCA、PLS-DA、OPLS-DA分析得知癌组织和癌旁组织的代谢轮廓具有显著性差异。经OPLS-Loading plot分析，结合VIP>1、FC>2，且P<0.05，筛选出76个潜在差异性代谢物。其中亮氨酸、2-褪黑素、香草酸等33种代谢物在PTC组织中表达上调；3-葡萄糖苷、甘油磷脂、磷脂酰胆碱、乳糖等43代谢物在PTC癌组织中表达下调。寻找到与差异性代谢物相关的13条异常代谢通路，如半胱氨酸与蛋氨酸代谢、与甘油磷脂代谢、嘧啶代谢、半乳糖代谢以及丙氨酸、天冬氨酸和谷氨酸代谢、柠檬酸循环等，这些代谢通路可能参与PTC代谢的病理生理过程。ROC曲线下面积大于0.9的差异性代谢物有5种，分别是庚二酸、糖醇、辛二酸、乳糖和L-丝氨酸。结论：PTC组织中半乳糖代谢和氨基酸代谢发生改变，PTC组织细胞中存在沃伯格效应(Warburg effect)。庚二酸、糖醇、辛二酸、乳糖、L-丝氨酸五种差异性代谢物可以用来区分PTC患者与正常人。

Objective:To observe the application effect of the multi-disciplinary team (MDT) process and program supported by WeChat group in the perioperative period of secondary hyperparathyroidism (SHPT) .Methods:A total of 80 SHPT patients who were hospitalized in Hunan Provincial People’s Hospital and Qidong County People’s Hospital from Jul. 2017 to Oct. 2019 were selected and divided into MDT group (40 cases) and control group (40 cases) according to the principle of complete randomization. In MDT group, there were 21 females and 19 males, aged (48.80±9.08) years old, ranging from 26 to 74 years; in the control group, there were 23 females and 17 males, aged (47.90±8.89) years old, ranging from 24 to 74 years. The control group were given a conventional treatment plan, and the MDT group were implemented with the WeChat MDT process on this basis. The perioperative preparation time, operation time, intraoperative blood loss, postoperative extubation time, and continuous full parathyroid were compared between the two groups. The levels of intact parathyroid hormone (iPTH) and blood calcium and phosphorus were compared with the postoperative complications and patient satisfaction in the two groups. The data in this study were analyzed using SPSS 23.0 statistical software.Results:The preoperative preparation time (4.35±1.12) d, operation time (130.00±32.58) min, intraoperative blood loss (15.75±7.89) ml, and postoperative extubation time (3.80±0.82) d in the MDT group were significantly lower than the preoperative preparation time of the control group (6.86±1.85) d, operation time (162.57±41.65) min, intraoperative blood loss (60.75±11.5) ml, postoperative extubation time (5.97±1.25) d ( P<0.05) 1 week after operation, the iPTH (20.86±1.52) pg/ml and blood calcium level (2.23±0.24) mmol/L of the MDT group were significantly lower than those of the control group (103.47±8.27) pg/ml and blood calcium level (2.87±0.21) mmol/L ( P<0.05) , meanwhile the blood phosphorus level of the MDT group (1.52±0.56) mmol/L was significantly higher than the blood phosphorus level of the control group (1.18±0.25) mmol/L ( P<0.05) . The number of complications in the MDT group (20 cases) was significantly lower than the number of complications in the control group (48 cases) ( P<0.05) ; and the satisfaction of treatment in the MDT group (100.00%) was significantly better than that of the control group (80.00%) ( P<0.05) . Conclusion:The WeChat MDT diagnosis and treatment process and treatment plan are safe and effective, which can effectively shorten the operation time, reduce the operation risk, reduce postoperative complications, and increase patient satisfaction. It can be further promoted in the clinic.

Objective:To investigate the synergistic antitumor effect of pyrotinib in combination with 5-fluorouracil(5-Fu)on human epidermal growth factor receptor 2(HER2)positive breast cancer cells and its underlying molecular mechanism. Methods:HER2 positive breast cancer cells were screened by Western blotting.HER2 positive SKBR-3 and BT474 cells were treated with pyrotinib and 5-Fu individually or in combination for the following experiments.MTT assay was used to assess the effect of different drugs on the proliferation of the treated cells,and the combination index(CI)values were calculated using Combidrug software.Colony formation assay was used to evaluate the effect of different drugs on the colony-forming ability of the treated cells.FCM assay was used to analyze the effect of different drugs on the apoptosis rate and cell cycle of the treated cells.Western blotting was used to examine the effect of different drugs on the expression levels of proteins in the proliferation-and apoptosis-related signaling pathways.SKBR-3-cell-based tumor xenograft model was established using BALB/c nude mice.After treatment with pyrotinib and 5-Fu individually or in combination,the growth profiles of the xenograft tumors were recorded and the expression levels of proteins in the proliferation-and apoptosis-related signaling pathways were examined in the tumor tissues. Results:HER2 positive breast cancer cell lines SKBR-3 and BT474 were selected for further experiments after screening.The proliferation SKBR-3 and BT474 cells could be inhibited after treatment with pyrotinib and 5-Fu individually or in combination(all P＜0.05).Compared with pyrotinib or 5-Fu single drug treatment,pyrotinib in combination with 5-Fu had higher inhibition rate on the proliferation of SKBR-3 and BT474 cells with a Cl value of＜1,indicating the synergistic effect of pyrotinib and 5-Fu.In addition,in contrast to pyrotinib or 5-Fu single drug treatment,there was a further decrease in the number of colonies formed,increase in apoptosis rate,and increase in the percentage of G0/G,cells in SKBR-3 and BT474 cells after treatment with pyrotinib in combination with 5-Fu(all P＜0.01).Animal experiment results showed that the growth rate of xenograft tumors in mice treated with pyrotinib in combination with 5-Fu was significantly slower than that of the single-drug treated mice(P＜0.05).Western blotting analysis showed that the expression levels of HER2,HER4,AKT and phosphorylated ERK were significantly decreased after treatment with pyrotinib in combination with 5-Fu both in vitro and in vivo(all P＜0.01),indicative of the blockage of proliferation-related signaling pathways.Meanwhile,analysis of the apoptosis-related proteins revealed a decrease in the expression levels of caspase 3,poly ADP-ribose polymerase(PARP),and Bcl-2(all P＜0.01),while an increase in the expression levels of cleaved-caspase 3,cleaved-PARP,and p21(all P＜0.01). Conclusion:Pyrotinib and 5-Fu had synergistical antitumor effect on HER2 positive breast cancer cells,and the underlying mechanism may be related to the blockage of proliferation-associated signaling pathways and the induction of apoptosis and cell cycle arrest.

OBJECTIVE： To investigate the effects of total flavonoids of Jasminum nudiflorum （TFJN） on pancreatic islet function in type 2 diabetes mellitus （T2DM） model mice and its possible mechanism. METHODS： Totally 10 Kunming mice were included in blank group and given normal diet. Other 75 mice were included in model group and given high-lipid and high-glucose diet for 4 weeks combined with streptozotocin once via sublingual vein to induce T2DM model. After modeling， the mice were randomly divided into model group， metformin hydrochloride group （positive control， 350 mg/kg）， TFJN low-dose， medium-dose and high-dose groups （100， 200， 400 mg/kg， by crude drug）， with 10 mice in each group. Blank group and model group were given constant volume of normal saline intragastrically； administration groups were given relevant medicine intragastrically； once a day， for consecutive 6 weeks. The level of fasting dynamic blood glucose was measured after modeling （before medication） and 2， 4， 6 weeks after medication. The histomorphological characteristics of pancreatic tissue were observed by HE staining. The contents of serum insulin （INS）， insulin cell antibody （IAA）， TNF-α， IL-1β， IL-6， IL-18， CRP， leptin （LP） and adiponectin （ADPN） were measured by ELISA. RESULTS： Compared with blank group， islet atrophy， blurred boundary， insufficient cytoplasm and smaller volume of pancreatic tissue were observed in model group. The fasting dynamic blood glucose level （at different time points after medication）， the contents of IAA， TNF-α， IL-1β， IL-6， IL-18， CRP and LP were increased significantly， while the contents of INS and ADPN were decreased significantly （P＜0.01）. Compared with model group， above symptoms of pancreatic tissue in administration groups were relieved， and the fasting dynamic blood glucose level （2， 4， 6 weeks after administration in metform in hydrochloride group， 4， 6 weeks after administration in TFJN groups）， the contents of IAA， TNF-α， IL-1β， IL-6， IL-18， CRP and LP were decreased signifi- cantly， while the contents of INS and ADPN were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： TFJN can repair the damaged pancreas of mice with T2DM， reduce the level of blood glucose， and improve the sensitivity of the body to insulin， the mechanism of which may be associated with reducing the secretion of inflammatory factors.