Mechanism of Chaishao Liujunzi Tang in Treatment of Ulcerative Colitis Through TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and curative effect of Chaishao Liujunzi Tang （CSLJZT） on colonic mucosal injury induced by dextran sulfate sodium （DSS） in mice with ulcerative colitis （UC） and its mechanism. MethodFifty Balb/c male mice were randomly divided into normal group， model group， CSLJZT low-dose group， CSLJZT high-dose group， and sulfasalazine group. Except for the normal group， other groups were given 2.5% DSS freely for 7 d， and were given drug intervention after successful modeling for 7 d. Bodyweight， feces， and other general physiological statuses of mice were recorded every day， and disease activity index （DAI） scores were calculated.The colon length was measured， and stained by hematoxylin-eosin （HE） staining to observe the morphological changes of the colon.The enzyme-linked immunosorbent assay （ELISA） was used to determine the content of interleukin-1β （IL-1β）， myeloperoxidase （MPO）， and superoxide dismutase （SOD） in the serum. Western blot was used to determine the protein expression levels of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， nuclear factor kappa B （NF-κB）， inhibitor-kappa binding protein （IκB）， Caspase-1， and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in the colon tissues. ResultAs compared with the normal group， mice in the model group had significantly decreased body weight （P<0.01）， severe diarrhea and hematochezia， and significantly increased DAI score （P<0.01）. As compared with the model group， the decreasing trend of body weight was significantly alleviated in the CSLJZT groups （P<0.01）， diarrhea and hematochezia were significantly improved， DAI score was significantly decreased （P<0.01）， and colon length increased （P<0.05）. HE staining showed that the pathological damage of colon tissue was significantly improved and the inflammatory cell infiltration was reduced in the CSLJZT groups as compared with the model group. As compared with the normal group， the serum levels of IL-1β and MPO were significantly higher （P<0.01） and SOD levels were significantly lower （P<0.01） of mice in the model group.Compared with the model group， the treated group reduced the serum IL-1β and MPO levels （P<0.01）， and raised the SOD level （P<0.01）. The results of Western blot showed that as compared with the normal group， the expression levels of TLR4， MyD88， NF-κB， Ccaspase-1， and NLRP3 proteins were significantly increased （P<0.01）， whereas the expression level of IκB protein was significantly decreased （P<0.01） in the colonic tissue of mice in the model group. As compared with the model group， the expression levels of TLR4， MyD88， NF-κB， Caspase-1， and NLRP3 proteins were decreased （P<0.01）， whereas the expression level of IκB protein was increased （P<0.01） in the colonic tissue of mice in the CSLJZT groups. ConclusionCSLJZT improves the inflammatory injury of the colon tissue in DSS-induced UC mice through TLR4/MyD88/NF-κB signaling pathway.

Mechanism of Chaishao Liujunzi Tang in Treatment of Ulcerative Colitis Through TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and curative effect of Chaishao Liujunzi Tang （CSLJZT） on colonic mucosal injury induced by dextran sulfate sodium （DSS） in mice with ulcerative colitis （UC） and its mechanism. MethodFifty Balb/c male mice were randomly divided into normal group， model group， CSLJZT low-dose group， CSLJZT high-dose group， and sulfasalazine group. Except for the normal group， other groups were given 2.5% DSS freely for 7 d， and were given drug intervention after successful modeling for 7 d. Bodyweight， feces， and other general physiological statuses of mice were recorded every day， and disease activity index （DAI） scores were calculated.The colon length was measured， and stained by hematoxylin-eosin （HE） staining to observe the morphological changes of the colon.The enzyme-linked immunosorbent assay （ELISA） was used to determine the content of interleukin-1β （IL-1β）， myeloperoxidase （MPO）， and superoxide dismutase （SOD） in the serum. Western blot was used to determine the protein expression levels of Toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， nuclear factor kappa B （NF-κB）， inhibitor-kappa binding protein （IκB）， Caspase-1， and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in the colon tissues. ResultAs compared with the normal group， mice in the model group had significantly decreased body weight （P<0.01）， severe diarrhea and hematochezia， and significantly increased DAI score （P<0.01）. As compared with the model group， the decreasing trend of body weight was significantly alleviated in the CSLJZT groups （P<0.01）， diarrhea and hematochezia were significantly improved， DAI score was significantly decreased （P<0.01）， and colon length increased （P<0.05）. HE staining showed that the pathological damage of colon tissue was significantly improved and the inflammatory cell infiltration was reduced in the CSLJZT groups as compared with the model group. As compared with the normal group， the serum levels of IL-1β and MPO were significantly higher （P<0.01） and SOD levels were significantly lower （P<0.01） of mice in the model group.Compared with the model group， the treated group reduced the serum IL-1β and MPO levels （P<0.01）， and raised the SOD level （P<0.01）. The results of Western blot showed that as compared with the normal group， the expression levels of TLR4， MyD88， NF-κB， Ccaspase-1， and NLRP3 proteins were significantly increased （P<0.01）， whereas the expression level of IκB protein was significantly decreased （P<0.01） in the colonic tissue of mice in the model group. As compared with the model group， the expression levels of TLR4， MyD88， NF-κB， Caspase-1， and NLRP3 proteins were decreased （P<0.01）， whereas the expression level of IκB protein was increased （P<0.01） in the colonic tissue of mice in the CSLJZT groups. ConclusionCSLJZT improves the inflammatory injury of the colon tissue in DSS-induced UC mice through TLR4/MyD88/NF-κB signaling pathway.

Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine / 中华肿瘤杂志

Objective@#To determine the clinical benefits of internal mammary sentinel lymph node biopsy (IM-SLNB) acquired by breast cancer patients with clinically positive axillary lymph node (ALN), and further optimize the IM-SLNB indications.@*Methods@#All primary breast cancer patients with clinically positive ALN from February 2014 to September 2017 were prospectively recruited in this study. IM-SLNB was performed under the guidance of the modified injection technique. The success rate and visualization rate of IM-SLNB, metastatic rate of internal mammary sentinel lymph node (IMSLN) and its related factors were analyzed, and the clinical benefits were accessed according to the current guidelines.@*Results@#Among 126 patients, all of 94 patients (74.6%) who showed internal mammary drainage successfully underwent IM-SLNB. The incidence of internal mammary artery bleeding and pleural lesion were 4.3%(4/94) and 9.6%(9/94), respectively. The metastatic rate of IMSLN was 38.3% (36/94), which was significantly associated with the number of positive ALN (P<0.001) and tumor size (P=0.024). The lymph node staging of 94 patients who underwent IM-SLNB was more accurate. Among them, 36 cases with positive IMSLN underwent internal mammary radiotherapy (IMRT), while the other 58 cases with negative IMSLN avoided radiotherapy.@*Conclusions@#IM-SLNB should be routinely performed in patients with positive ALN. IM-SLNB can provide more accurate staging and guide tailored IMRT to benefit more breast cancer patients.

Application of pathological three-dimensional reconstruction in margins assessment and radiotherapy adjustment of breast-conserving surgery / 国际肿瘤学杂志

Objective To reconstruct the original three-dimensional conformation of tumor resection tissue through the study of breast-conserving surgery excision specimens for part-mount sub-serial section and pathological three-dimensional (3D) reconstruction,to establish a new margin assessment model,and to guide tumor bed delineation individually for radiotherapy.Methods From February 2016 to February 2017,thirtythree eligible breast cancer patients underwent breast-conserving surgery in Breast Cancer Center of Shandong Cancer Hospital were recruited.The excision specimens were prepared with part-mount sub-serial section,and residual tumors were microscopically outlined,scanned and registered by Photoshop software.The 3D model of residual tumors was reconstructed with 3D-DOCTOR software to evaluate margin status and record pathological type,tumor length and 3D negative margin distance.The gross tumor volume (GTV) was delineated based on clips placed in the lumpectomy cavity.CTV1 and CTV2 were defined by adding uniform 1.00 cm and 1.50 cm margin based on GTV respectively.CTV3 and CTV4 were defined by adding 1.00 cm and 1.50 cm margin based on 3D boundary of excision tumor respectively,and compared the volume differences of CTV1 and CTV3,CTV2 and CTV4.Results Based on the marginal assessment results of 3D pathological reconstruction,the rates of false negatives during the intraoperative rapid pathological examination and postoperative routine pathological margin evaluation were 6.7％ (2/30) and 3.4％ (1/29) respectively.The pathological type of pathological large slice and routine pathological examination was consistent with rate of 93.9％ (31/33).The M(QR) tumor lengths of routine pathological and pathological 3D reconstruction were 1.90 (1.50-2.40) cm and 2.00 (1.60-2.70) cm respectively,with statistical difference between the two groups (Z =-2.438,P =0.015).The M(QR) volumes for CTV1,CTV2,CTV3,CTV4 were 70.76 (49.84-78.07)cm3,110.11 (83.38-126.17) cm3,23.85 (16.46-31.49)cm3 and 38.74 (30.47-50.58) cm3 respectively.There were statistical differences between CTV1 and CTV3,CTV2 and CTV4 (Z =-4.372,P ＜0.001;Z =-4.372,P ＜0.001).Conclusion The application of pathological 3D reconstruction technology can largely compensate for the shortcomings of the traditional margin assessment model,make the decisions of adjuvant treatment after breast-conserving surgery more accurate,and guide the tumor bed delineation individually for radiotherapy.

Application of enhanced recovery after surgery in the treatment of common bile duct stones / 中国基层医药

Objective To explore the effect and safety of enhanced recovery after surgery (ERAS) in the surgical treatment of common bile duct stones.Methods According to random number table,48 patients with common bile duct stones were randomly divided into the ERAS group and the control group.The patients of the control group received the traditional perioperative management and laparotomy exploration of common bile duct.The patients of the ERAS group received the ERAS perioperative management and laparoscopic exploration of common bile duct.The preoperative and postoperative level of C reactive protein (CRP),time to out-of-bed activity,time to food taking,time to anal exsufflation,postoperative hospital stay,hospitalization cost and postoperative complications between the two groups were compared.Results Compared with the control group,the ERAS group had lower levels of CRP on the postoperative 1 day and 3 days[d1:(102.6±13.5) mg/L vs.(81.3±17.3)mg/L;d3:(71.8±15.3)mg/L vs.(41.2±11.2)mg/L,t=2.553,3.287,all P<0.05],had shorter time to out-of-bed activity[(3.2±1.8)d vs.(0.9±0.4)d],time to food taking[(4.3±1.9)d vs.(1.8±1.2)d] and time to anal exsufflation[(2.5±0.7)d vs.(1.2±0.3)d],and had shorter operative hospital stay[(7.3±3.2)d vs.(3.8±1.4)d]and less hospitalization cost[(7 200±800)RMB vs.(5 900±700)RMB] (t=5.561,4.319,3.765,2.351,1.671,all P<0.05).The incidence rate of postoperative complications of the ERAS group decreased markedly (61.91% vs.18.52%,x2=25.82,P<0.05).Conclusion ERAS management in the surgical treatment of common bile duct stones is safe and effective,which can enhance the recovery of the patients.

Accuracy of MRI for predicting shrinkage modes of primary breast tumor following neoadjuvant chemotherapy with three-dimensional reconstruction technique / 中国癌症杂志

Background and purpose:The most clearly recognized benefit of neoadjuvant chemotherapy (NAC) is that it can increase the proportion of patients who can be treated with breast-conserving therapy (BCT). However, the shrinkage modes of the primary breast tumor after NAC have been conifrmed as a predictor of BCT rate and prognosis. This study is to evaluate the accuracy of MRI predicting the shrinkage mode of the primary breast tumor after NAC with three-dimensional reconstruction technique.Methods:Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. Breast specimens were prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by PHOTOSHOP software. The 3D model of residual tumors was reconstructed with 3D-DOCTOR software based on pathology and MRI imaging characteristics to evaluate the shrinkage mode. We devided the pathological shrinkage modes into surgical pCR (no residual tumors), solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions. Further, the clinical-pathological shrinkage modes were divided into 2 categories: distinct shrinkage mode (DSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC) and non-distinct shrinkage mode (NDSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).Results:The surgical pCR, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions were observed in 23, 17, 5, 9, 7 and 18, 3, 13, 20, 7 patients by MRI and pathology, respectively (P=0.001). The accuracy, sensitivity and speciifcity of MRI for predicting pathological shrinkage modes were 86.2%, 65.6% and 91.4%, respectively. The DSM was observed in 36 (59.0%) patients by pathology, and 38 (62.3%) patients by MRI. Two methods had a high consistency in clinical-pathological shrinkage modes (κ=0.863,P=0.000). The accuracy, sensitivity and speciifcity of MRI for predicting clinical-pathological shrinkage modes were 91.0%, 64.0% and 94.8%, respectively. There was not a statistic difference in prediction between DSM and NDSM by MRI (P>0.05). Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.928 (P=0.000) for MRI to predict the clinical-pathological shrinkage mode.Conclusion:Three-dimensional MRI reconstruction after NAC could simulate and predict spatial location of residual tumors, and can be helpful in selecting patients who received BCT after NAC with tumor downstaging.

Validation study of the modified injection technique for internal mammary sentinel lymph node biopsy in breast cancer / 中华内分泌外科杂志

Objective To verify the accuracy of the modified technique for internal mammary sentinel lymph node biopsy ( IM-SLNB) in breast cancer .Methods In the validation study , the radiotracer was injected with the modified technique , and fluorescence tracer was injected into the peritumoral breast tissue .The radioac-tive IM-SLN was identified by preoperative lymphoscintigraphy and γprobe.The radioactive IM-SLN received bi-opsy during operation .The status of the fluorescence tracer was identified by the fluorescence imaging system . Results A total of 162 patients were enrolled from Sep .2013 to Dec.2014.IM-SLNB was performed in 110 pa-tients.The radiotracer and the fluorescence tracer were identified in the same IM-SLN in 94 cases, and the con-cordance rate was 85.5%(Case-base, Spearman coefficient correlation 0.823, P<0.001).Conclusion Dif-ferent tracers injected into the different sites of the intra-parenchyma can reach the same IM-SLN, proving the ac-curacy of the modified technique and the hypothesis of IM-SLN lymphatic drainage pattern ( IM-SLN receives not only the lymphatic drainage from the primary tumor area but the entire breast parenchyma ) .

Internal mammary sentinel lymph node biopsy in breast cancer pa-tients with clinically positive axillary lymph nodes / 中国肿瘤临床

Objective:This study was conducted to evaluate the roles of internal mammary sentinel lymph node biopsy (IM-SL-NB) in the treatment of breast cancer patients with clinically positive axillary lymph nodes. Methods:This study is a one-armed clini-cal research conducted from June 2013 to October 2014. A total of 64 breast cancer patients from Shandong Cancer Hospital with clini-cally positive axillary lymph nodes were enrolled in the study. All patients underwent axillary lymph node dissection. Meanwhile, IM-SLNB was performed in all patients using the new injection method of radiotracer. Results:Among the 64 enrolled patients, the visual-ization rate of internal mammary lymph node was 59.4%(38/64). For the 38 patients who were subjected to visualization of the internal mammary node, the detection rate was 100%(38/38), and the incidence of complications was 7.9%(3/38). The metastasis rate of inter-nal mammary lymph node was 21.1%(8/38). Patients with upper inner quadrant tumors and metastasis of more axillary lymph nodes had a significantly higher chance of developing sentinel lymph node metastasis (P<0.001 and P=0.017, respectively) than the other pa-tients. The clinical benefit rate of the above mentioned treatment was 59.4%. Among the patients, 12.5%(8/64) received extra internal mammary radiotherapy, whereas 46.9%(30/64) patients avoided the unnecessary internal mammary radiotherapy. Conclusion:IM-SL-NB should be performed in breast cancer patients with clinically positive axillary lymph nodes because IM-SLNB could provide the ac-curate indication of radiation to the internal mammary area, especially for the patients with upper inner quadrant tumors and those with a suspiciously high level of axillary lymph node metastasis.

Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in breast cancer with three-dimensional reconstruction technique / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy (NAC) with three-dimensional (3D) reconstruction technique.</p><p><b>METHODS</b>This was a prospective study. The data of 61 patients with pathologically proven solitary invasive ductal carcinoma (IIA-IIIC) who had received 6 to 8 cycles of NAC from July 2010 to August 2013 was analyzed. All the patients were female, aging from 31 to 70 years with a median of 49 years. Breast specimen after surgery was prepared with part-mount sub-serial section, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of pathological and MRI residual tumors was reconstructed with 3D-DOCTOR software. The longest diameter, maximum cross-section area and volume of the residual tumors determined using 3D MRI were compared with 3D pathological findings, and the associations between MRI and pathology were analyzed by Spearman rank correlation and Bland-Altman analysis.</p><p><b>RESULTS</b>The longest diameter, maximum cross-section area and volume of the residual tumors after NAC measured by MRI and pathology was highly correlated (r=0.942, 0.941, 0.903, all P=0.00). MRI appears to underestimate pathology in the longest diameter, maximum cross-section area, but slightly overestimate in volume, and two methods had a good consistence (MD=0.3 cm, 95% CI: -1.43 to 1.9 cm; MD=1.39 cm², 95% CI: -9.55 to 12.34 cm²; MD=-0.433 cm³, 95% CI: -7.065 to 6.199 cm³).</p><p><b>CONCLUSION</b>3D MRI reconstruction after NAC could accurately detects the residual tumors after neoadjuvant chemotherapy, and contribute to select patients who received breast conserving therapy after NAC with tumor downstaging.</p>

The characteristics of polysomnographic values and synchronous blood pressure in patients of obstructive sleep apnea with hypertension / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the differences of sleep respiratory parameters recorded by PSG and synchronous blood pressure measured by ambulatory blood pressure monitor between obstructive sleep apnea (OSA) patients with hypertension (HT) and simple OSA and simple HT; To determine the characteristics of sleep respiratory parameters and blood pressure changes in patient with OSA accompanied HT.@*METHOD@#We chose the patients who were diagnosed simple HT (n=45) and simple OSA (n=50) and OSA with HT (n=56), Compared the sleep respiratory parameters and blood pressure changes between the three groups. Meanwhile the correlations about the sleep respiratory parameters and synchronization blood pressure were analyzed.@*RESULT@#Compared with simple HT and simple OSA, OSA with HT has higher apnea hyponea Index (AHI) (P<0. 001), oxygen desaturation index (ODI), awake index (AI), wake after sleep onset (WASO) and the proportion of non-rapid eyemovement sleepl (N1) in total sleep time(TST), has lower mean arterial oxygen saturation (MSaO2), lowest arterial saturation oxygen (LSaO2), the proportion of slow wave sleep (SWS) and rapid eyemovement sleep (REM) in TST (P<0. 05). There were positive correlations between the systolic/diastolic blood pressure (SBP/ DBP) and AHI, ODI, AI, WASO and N1/TST (P<0. 05). Compared with simple OSA, the mean day systolic blood pressure (dMSP), mean night systolic blood pressure (nMSP), mean day diastolic blood pressure (dMDP), mean night diastolic blood pressure (nMDP) and mean night diastolic blood pressure (nMDP) were significantly decre- sed, meanwhile the difference between the average systolic/diastolic blood pressure day and night were significantly increased after continuous positive airway pressure (CPAP) treatment. OSA with HT has higher There were negative correlations between the SBP/DBP and MSaO2, LSaO2 (P<0. 05). Blood pressure mainly changed in the later sleep stage when the REM phase was increased. Blood pressure changes were characteristic of increasing DBP and decreasing SaO2.@*CONCLUSION@#There are significant differences between simple OSA and OSA with HT in the sleep respiratory parameters, which are closely related with changes of blood pressure in sleep stage; AHI is the high risk factor of the OSA with HT. PSG is a effective factor in estimating the OSA accompanied HT course of development and prognosis.

Establishment of nomograms to predict shrinkage modes of primary breast tumor after neoadj uvant chemotherapy / 吉林大学学报(医学版)

Objective To explore the clinical variables associated with the shrinkage modes of primary breast tumor in women after neoadj uvant chemotherapy (NAC ), and to develop a nomogram for predicting non-concentric shrinkage mode(NCSM).Methods Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC)were recruited. Breast specimen was prepared with PMSS, and residual tumors were microscopically outlined,scanned and registered by Photoshop CS 5 software.The 3D model of residual tumors was reconstructed with 3D-DOCTOR 4.0 software to evaluate the shrinkage mode.17 factors such as age and body mass index and menopausal status were chosen as independent variables,and the clinic-pathologic shrinkage mode was considered as dependent variable. A Logistic regression model was used to construct the nomogram. Results Primary tumor stage,lymph node down-staging, PR and mammographic malignant calcification before NAC were independent predictors of clinic-pathologic shrinkage mode (β:1.538,OR:4.656,95%CI:1.414-15.328,P=0.011;β:1.555,OR:4.735, 95%CI:1.082-20.722,P=0.039;β:-1.707, OR:0.181, 95%CI:0.044-0.741,P = 0.017;β:- 1.405, OR:3.808, 95% CI:0.06 - 0.998,P = 0.048, respectively ). The nomogram predicting the risk of NCSM showed a good concordance index(0.869),and its conformity of mean absolute error was 0.039. Conclusion Based on the clinicopathological findings of primary breast tumor, a nomogram to predict shrinkage modes after NAC in breast carcinoma patients is constructed.The statistical tool is helpful for individually selecting the patients who can be treated with BCT after NAC.

Risk factors for sentinel lymph node metastasis and validation study of the MSKCC nomogram in breast cancer patients / 中华内分泌外科杂志

ObjectiveTo evaluate the risk factors for sentinel lymph node(SLN)metastasis,and assess the value of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting SLN metastasis in breast cancer patients.Methods A sentinel lymph node biopsy(SLNB) database containing 1227 consecutive breast cancer patients(412 patients with a positive SLN)was retrospectively analyzed.The value of MSKCC nomogram was predicted by drawing the trend line and calculating the area under the curve(AUC) of receiver-operator characteristic(ROC). Meanwhile,the risk factors of SLN metastasis were evaluated. Results Tumor size,tumor location,histological grade,lymphovascular invasion,mulifocality,ER and PR status were correlated with SLN metastasis( all P ＜ 0.05 ).All the above factors but tumor location were significant independent predictors for SLN metastasis(all P ＜ 0.01 ).The MSKCC nomogram presented AUC value of 0.730 for ROC.Patients with predictive values lower than 16％ had the frequency of 0.9％ for SLN metastasis while patients with predictive values higher than 70％ had the frequency of 96.2％.ConclusionsThe risk factors of SLN metastasis in our study are consistent with those in MSKCC nomogram.MSKCC nomogram is a useful tool in predicting the probability of SLN metastasis for breast cancer patients.Axillary surgery can be avoided in patients with the predictive values lower than 16％,axillary lymph node dissection could be done in patients with the predictive values higher than 70％,and other patients should still undergo SLNB.