The new-generation proteasome inhibitor oprozomib increases the sensitivity of cervical cancer cells to cisplatin-induced apoptosis.

This study aimed to evaluate the anti-tumor effect of a new generation of protease inhibitor, oprozomib (OPZ), used alone and in combination with cisplatin, also called CDDP, on cervical cancer. Five different types of cervical cancer cell lines - HeLa, Caski, HeLa-CDDP, C33a, and SiHa - and one nontransformed cervical cell line - HaCaT -were treated with OPZ alone or in combination with cisplatin. The inhibitory effects of OPZ and cisplatin on the proliferation of cervical cancer cells were then analyzed using cytotoxicity tests, flow cytometry, and Western blotting. It was found that OPZ alone or in combination with cisplatin can reduce the proliferation of the five types of cancer cells by enhancing the lysis of caspase-3 and PARP and inducing cancer cell apoptosis. In the combined treatment, OPZ was found to inhibit the degradation of inhibitory factor κB alpha induced by cisplatin, thereby inhibiting the activation of NF-κB, which causes cisplatin resistance, and enhancing the sensitivity of the tumor cells to cisplatin. Moreover, OPZ promoted the phosphorylation of the apoptosis signaling pathway JNK that was activated by cisplatin, thereby inducing tumor cell apoptosis. These findings provide a theoretical basis for the clinical use of OPZ alone and in combination with cisplatin in the treatment of cervical cancer.

Insurance status and risk of suicide mortality among patients with cancer: a retrospective study based on the SEER database.

OBJECTIVE: Given that the presence of insurance may affect the risk of suicide mortality in cancer patients, we aimed to examine the association in a population-based study using the Surveillance, Epidemiologic, and End Results (SEER) database. STUDY DESIGN: A retrospective analysis of data from the SEER database. METHODS: We conducted a retrospective study using the SEER database. Hazard ratios (HRs), adjusted HRs (aHRs), and 95% confidence intervals (95% CIs) of suicide death were calculated using Cox proportional hazard models to evaluate the risk of suicide mortality among the cohorts. RESULTS: Multivariable analysis revealed that cancer patients without insurance had an increased risk of suicide death compared with patients with private insurance (aHR, 1.37; 95% CI, 1.01-1.72), whereas no significant result was observed in patients with any Medicaid (aHR, 1.10; 95% CI, 0.93-1.30; P = 0.27). In addition, the stratified analysis indicated that the risk of suicide death in patients in the uninsured and Medicaid groups presented with localized stage of disease (aHR, 1.32; 95% CI, 1.02, 1.69), White (aHR, 1.34; 95% CI, 1.05, 1.71), and American Indian/Alaska Native and Asian/Pacific Islander (aHR, 1.89; 95% CI, 1.08, 3.30) were greater than insured patients. CONCLUSION: Overall, our results indicated that insurance status was a statistically significant predictor of suicide death in patients with cancer. Healthcare providers should identify those patients at high risk of suicide and provide appropriate mental health and psychosocial oncology services in time.

[Endocervical adenocarcinomas classified by International Endocervical Adenocarcinoma Criteria and Classification: a clinicopathological and prognostic analysis of 286 cases].

Objectives: To investigate the clinicopathological and prognostic significance of International Endocervical Adenocarcinoma Criteria and Classification (IECC) in classifying endocervical adenocarcinomas among Chinese women. Methods: A total of 286 endocervical adenocarcinomas diagnosed from January 2013 to December 2019 at the Women's Hospital, Zhejiang University School of Medicine were identified and included. The cases were reviewed and reclassified based on IECC. The histological types were correlated with p16 immunostaining, human papilloma virus (HPV) mRNA status, the clinicopathological parameters including the International Federation of Gynecologic Oncology (FIGO) stage, and clinical follow-up data. Results: The patients aged from 19 to 77 (median 47) years. There were 223 patients at FIGO stage Ⅰ, 22 at stage Ⅱ, 38 at stage Ⅲ and 3 at stage Ⅳ. The IECC types included 213 (74.5%) HPV-related adenocarcinomas (HPVA), 60 (21%) non-HPV-related adenocarcinomas (NHPVA), and 13 (4.5%) adenocarcinomas, no other specified (NOS). The major histological subtypes in HPVA and NHPVA were common type (n=156, 54.5%) and gastric type (GAC, n=46, 15.9%), respectively. The p16 positive rates in HPVA, NHPVA and adenocarcinoma, NOS were 92% (173/188), 26.6% (17/64) and 61.5% (8/13), respectively, and those of HPV mRNA hybridization in situ were 89.4% (144/161), 0/18 and 7/13, respectively. Compared to HPVA, NHPVA was more frequently associated with older age, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression (P<0.05). Univariate survival analysis showed that age (>47 years), NHPVA, GAC, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression were indicators for a poorer overall survival and tumor recurrence (P<0.05). Mucinous HPVA showed worse clinical outcomes compared to usual-type HPVA (P<0.01). Multivariate survival analysis demonstrated that FIGO stage Ⅱ-Ⅳ, NHPVA and aberrant p53 expression were independent indicators for poor overall survival while FIGO stage Ⅱ-Ⅳ and GAC were independently associated with tumor recurrence (P<0.05). Conclusions: The two broad IECC categories, HPVA and NHPVA, not only provide morphological links to the etiology (HPV infection), but also have significant clinicopathological and prognostic relevance.

[Analysis of clinicopathological features of clear cell tumor of the lung].

Objective: To analyze the clinicopathological features of clear cell tumor of the lung (CCTL). Methods: A total of 9 cases were collected from August 2008 to August 2019 in the Department of Pathology of the First Medical Center of PLA General Hospital and Hainan Hospital of PLA General Hospital. Their clinical data, pathological characteristics, immunohistochemical staining and special staining results were summarized and analyzed. Results: There were 3 males and 6 females, aged from 28 to 70 years (average 52.2 years). All tumors were located in the peripheral part of the lung, and were solitary in 8 cases, and multiple (24 nodules) in 1 case. The lesion was round or oval, with clear boundary. The diameter of the nodule was 0.5-5.5 cm. Histologically, the tumor cells were oval, short fusiform or polygonal, with obvious nucleoli. The tumor cells were mostly distributed in sheet around thin-walled vessels, and there was hyaline degeneration around the blood vessels. Neither necrosis nor mitosis could be seen. Immunohistochemical staining showed tumor cells were diffusely positive for Vimentin, and CD34, Melan-A, specific monoclonal antibody against melanoma (HMB45) and S-100 were positive with different degrees. Broad spectrum cytokeratin (CK), epithelial membrane antigen (EMA), smooth muscle actin (SMA), desmin, CD10, paired box gene 8 (PAX-8) or myomodulatory protein (Myo-D1) were all negative. The positive index of the proliferating cell nuclear antigen (Ki-67) was low. Schiff dyeing with periodate (PAS) staining was positive, PAS staining of glycogen digested by amylase (d-PAS) staining was negative. All the tumors in the nine cases were resected and patients were followed up for 5-137 months. Except 1 case was lost for follow-up, the other 8 cases survived without recurrence or metastasis of the disease. Conclusions: CCTL is a rare benign tumor, most of which are single, few of which can be multiple; histopathological characteristics and immunohistochemical staining are helpful for diagnosis and differentiated diagnosis. After complete resection, the prognosis was good. However, when histological features indicating malignancy, intense follow-up should be considered.

[Pathological diagnosis of lung cancer based on deep transfer learning].

Objective: To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning. Methods: The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set. Results: The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model. Conclusions: The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.

[Long-term outcome of patients with hypertrophic obstructive cardiomyopathy post percutaneous transluminal septal ablation].

Objective: To evaluate the long-term outcome of patients with hypertrophic obstructive cardiomyopathy(HOCM) after percutaneous transluminal septal ablation(PTSMA). Methods: HOCM patients who underwent PTSMA and surgical myectomy at the Chest Hospital of Shanghai Jiao Tong University from April 2001 to February 2019 were included in this retrospective analysis. Patients were divided into PTSMA group and surgical myectomy group. In addition, patients undergoing PTSMA were further divided into HOCM-PTSMA non-survivor group and HOCM-PTSMA survivor group. The general clinical information, procedural/surgical information and complications during hospitalization were compared between groups. Multivariate Cox regression model was used to analyze the independent risk factors for all-cause death in HOCM patients after PTSMA. Results: A total of 104 patients with HOCM who underwent PTSMA were enrolled. Mean age of the patients was (54±15) years old, including 41 females (38.7%). The follow-up time was 37.5(14.3, 76.8) months. At the last follow-up, 12 patients died (HOCM-PTSMA non-survivor group) and 92 were alive(HOCM-PTSMA survivor group). The proportion of patients with NYHA function class Ⅲ/Ⅳ was higher(P=0.036), and the posterior wall of the left ventricle was thicker(P=0.006) in the HOCM-PTSMA non-survivor group than in the HOCM-PTSMA survivor group. The immediate success rate of PTSMA in this cohort was 66%(70/104). The amount of absolute alcohol during the operation in the HOCM-PTSMA non-survivor group was (2.9±0.8) ml, which tended to be higher as compared to that in the HOCM-PTSMA survivor group((2.4±1.0)ml, P=0.056). Kaplan-Meier survival curve analysis showed that patients with HOCM who underwent PTSMA had an all-cause mortality-free survival rate of 90.1%, 78.3%, and 56.9% at 5, 10 and 15 years, and a HOCM-free survival rate of 91.3%, 79.4% and 57.7% at 5, 10 and 15 years, respectively. Multivariate Cox regression analysis showed that age≥ 65 years was an independent risk factor for all-cause death after PTSMA in patients with HOCM (HR=2.697, 95%CI 1.292-18.977, P=0.020). There were 32 patients in the surgical myectomy group. The proportion of patients with NYHA function class Ⅲ/Ⅳ was higher than that in the PTSMA group(P<0.001), while age, gender, and major comorbidities(atrial fibrillation, coronary heart disease, hypertension, and diabetes) as well as the left atrium dimension were all similar between the two groups(all P>0.05). Patients in the surgical myectomy group were followed up for 38.0(17.6, 64.2)months, and no deaths occurred during the follow-up period. Kaplan-Meier survival curve analysis showed that there were no statistically significant differences in all-cause-free and HOCM-free survival rates between patients in PTSMA group and surgical myectomy group(P=0.089 and 0.110, respectively). Conclusion: PTSMA is safe and effective for the treatment of patients with HOCM, and the long-term survival rate of patients after PTSMA is similar as patients undergoing classical surgical myectomy surgery.

[The predictive value of epicardial adipose tissue and inflammatory factors for in-stent restenosis].

Objective: To investigate the predictive value of epicardial adipose tissue volume (EATV) and inflammatory factors on in-stent restenosis (ISR) after percutaneous coronary implantation (PCI) in patients with coronary heart disease (CAD). Methods: A total of 407 patients with CAD who were treated with drug-eluting stents in TEDA international cardiovascular disease hospital were enrolled from November 2016 to October 2017. Levels of inflammatory cytokines such as high sensitive c-reactive protein (Hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) were detected. EATV was measured preoperatively by multi-sliced CT. Patients were divided into ISR group (n=52) and N-ISR group (n=355) according to ISR occurred within 1 year after procedure. The relationship between EATV and inflammatory factors and ISR after PCI was analyzed. Results: The differences between ISR group (n=52) and N-ISR group (n=355) were statistically significant in terms of diabetes history, IL-6, TNF-α, EATV ((150±36) cm(3)vs(120±40) cm(3),P=0.001)), bifurcation lesions, stent length and Gensini score (P<0.05). Multivariate Logistic regression analysis results showed that diabetes history,bifurcation lesions, TNF-α, EATV, and Gensini score were risk factors for in-stent restenosis.The area under the ROC curve (AUC) of EATV, TNF-α, and IL-6 in patients with CAD after PCI was 0.712, 0.752 and 0.675 (95%CI 0.648-0.776, 0.686-0.819, 0.584-0.766, respectively, all P<0.001), with a sensitivity of 86.5%, 67.3% and 69.2%, a specificity of 53.8%, 74.4% and 70.1% and a cut-off value of 116.61 cm(3),138.40 µg/L and 126.4 µg/L, respectively. Conclusion: EATV, TNF-α, and IL-6 have certain predictive values for in-stent restenosis, and can be used as clinical indicators to predict in-stent restenosis.

[Atypical epithelioid trophoblastic lesions after a cesarean section with cyst and fistula formation:a clinicopathological analysis of 4 cases].

Objective: To elucidate the clinicopathologic characteristics of atypical epithelioid trophoblastic lesions with cyst and fistula formation after cesarean section. Methods: The clinical and pathological data of 4 cases of post-cesarean atypical epithelioid trophoblastic lesions with cyst and fistula formation diagnosed at Women's Hospital, School of Medicine, Zhejiang University during April 2007 to June 2018 were evaluated by hematoxylin and eosin stain and EnVision two-step immunohistochemical staining technique. Results: The age of the 4 patients ranged from 32 to 41 years, with a mean age of 36.5 years. Three patients recieved cystectomy and one underwent subtotal hysterectomy. Histologically, the lesions were well circumscribed and consisted of uniform cells of medium size, irregularly enlarged with hyperchromatic nuclei and 1 to 2 inconspicuous nucleoli embedded in abundant hyalinized matrix with fibrinoid material in the center. The cells exhibited immunohistochemical feature of chorionic-type intermediate trophoblastic cells (CK18+, p63+ and CD146-). All patients were alive without recurrence during follow-up of 1 to 40 months (mean=22 months). Conclusion: Atypical epithelioid trophoblastic lesion with cyst and fistula formation after cesarean section has unique histological features, and its biological behavior and prognosis are still unclear, which need further exploration.

Prevalence of pollen-induced allergic rhinitis with high pollen exposure in grasslands of northern China.

BACKGROUND: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. RESULTS: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions.

Histochemical distribution of four types of enzymes and mucous cells in the gastrointestinal tract of reared half-smooth tongue sole Cynoglossus semilaevis.

The histochemical distribution of acid phosphatase (ACP), alkaline phosphatase (ALP), non-specific esterase (NSE), peroxidase (POD) and mucous-cell types was evaluated in the gastrointestinal tract of the half-smooth tongue sole Cynoglossus semilaevis. The enzymes were detected in the entire stretch of the gastrointestinal tract. ACP activity was found in the supranuclear region of enterocytes and the lamina propria of the intestine, as well as the cytoplasm of epithelial cells of the stomach. The staining intensity of ACP in the anterior and posterior intestines was stronger than in the stomach. ALP activity was detected in the striated border of enterocytes and muscularis of the whole intestine, lamina propria and supranuclear cytoplasm of the enterocytes in the anterior intestine, as well as in the blood vessels of the stomach. The staining intensity for ALP in the anterior intestine was stronger than in the posterior segment and the latter was stronger than in the stomach. NSE activity was detected in the cytoplasm of the epithelial cells in the entire gastrointestinal tract, with the anterior intestine showing stronger intensity than the stomach. POD activity was located in the blood cells of the lamina propria of the gastrointestinal tract and the levels in the stomach were similar to the anterior and posterior intestines. Alcian blue (pH 2·5) periodic acid Schiff (AB-PAS) histochemical results revealed three types of mucous cells in the gastrointestinal tract. Type I cells (PAS+AB-) were observed among the gastric mucosa columnar cells in the stomach and enterocytes in the basal region of the villi and in the middle and top regions of the intestinal villi. Type II cells (PAS-AB+) and type III cells (PAS+AB+) were not detected in the stomach but were distributed ubiquitously among enterocytes in the middle and top regions of the intestinal villi.

[Effects of epicardial adipose tissue and inflammatory factors on left ventricular diastolic function in patients with coronary heart disease].

Objective: To investigate the effects ofepicardial adipose tissue volume (EATV) and inflammatory factors on left ventricular diastolic function in patients with coronary heart disease(CHD). Methods: The clinical data of patients with coronary heart disease receiving coronary artery intervention therapy from January 2014 to October 2015 in TEDA international cardiovascular hospital were preoperatively collected.We measured the indexes of EATV and left ventricular diastolic function. Results: The difference of age (F=7.76, P=0.01), IL-6 (F=14.34, P<0.01), Hs-CRP (F=4.08, P=0.04), adiponect-in (F=4.50, P=0.04) and EATV (F=71.29, P<0.01) between the diastolicdysfunction group (n=156) and the normal group (n=76) was statistically significant.Multivariate logistic regression analysis showed that EATV was a risk factor for left ventricular diastolic dysfunction in patients with coronary artery disease (P<0.05), OR=1.05, 95%CI (1.03-1.06). The AUC value of EATV in the diagnosis of left ventriculardiastolic function in patients with coronary heart disease was 0.79, 95%CI (0.73-0.85) P<0.01. Conclusions: EATV can be used as an independent risk factor for left ventricular diastolic dysfunction.It has some non-invasive diagnosis and predictive value, and it can be used as a new therapeutic target.

[Relationship between epicardial adipose tissue and clinical prognosis of patients with coronary heart disease after percutaneous coronary intervention].

Objective: To further evaluate the clinical value of epicardial adipose tissue volume (EATV) in predicting the prognosis of coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: From July 2013 to July 2016 in TEDA International Cardiovascular Disease Hospital, a total of 474 patients diagnosed with CHD were included in this study.According to the result of EATV, patients were divided into three groups, group A (EATV≤75 ml), group B (75 ml120.39 ml can be used as an independent risk factor for predicting the occurrence of MACE. Conclusion: The level of EATV is closely related to the occurrence of MACE events, and EATV>120.39 ml is an independent risk factor for MACE in patients with CHD after PCI.

[Clinicopathologic features and prognosis of adenoid cystic carcinoma of external auditory meatus].

Objective: To investigate clinicopathologic features and prognosis of adenoid cystic carcinoma (ACC) involving external auditory meatus. Methods: The clinical presentation and follow-up data of 63 patients with ACC of external auditory canal were collected from January 2006 to February 2017 at PLA General Hospital and Hainan Branch of PLA General Hospital. The clinicopathologic features and prognostic factors of external auditory canal ACC were analyzed. Results: (1) There were 28 males and 35 females and the average age of the first diagnosis was 48.9 years (22-81 years). The tumors showed cribriform pattern in 35 cases (15 cases of late stage), tubular pattern in 14 cases (8 cases of late stage), and solid pattern in 14 cases (9 cases of late stage). Cases with solid pattern was relatively more frequent than that of cribriform pattern and tubular pattern, but the difference was not statistically significant (P>0.05). (2) The average follow-up time was 62.4 months (2-228 months) in the 57 available cases. Among the 33 cases with recurrence, 18 cases had local recurrence and 15 cases had distant metastasis. The mean recurrence time was 40.6 months (2-204 months). Nine patients died of ACC: 2 cases in early stage (died at 48 and 102 months after the first treatment), 7 cases in late stage and 57 with (died at 9, 30, 32, 60, 72, 94 and 228 months). (3) Among the 37 patients with perineural invasion, there were 21 cases of cribriform pattern, 4 cases of tubular pattern and 12 cases of solid pattern; the number of cases in early stage and late stage were 15 and 22, respectively; and the differences were statistically significant (P<0.05). In addition, 31 cases had otalgia among the 37 patients with perineural invasion, where differences were not significant (P>0.05). (4) Thirty of 45 cases with tumor resection or partial resection of temporal bone had recurrence, whereas 3 of 12 cases of tumor combined with superficial lobectomy of parotid gland had recurrence. The difference was statistically significant (P<0.05). Postoperative adjuvant radiotherapy was given in 19 cases, including 7 cases of early stage (2 cases of recurrence), and 12 cases of late stage (8 cases of recurrence), among which there was no significant difference (P>0.05). Conclusions: ACC occurring in external auditory canal frequently recurs. Superficial parotid lobectomy at the first operation is necessary to prevent tumor recurrence. Postoperative adjuvant radiotherapy has certain curative effect on patients with early stage tumor, but it does not affect the recurrence rate. Patients at late stage are more prone to perineural invasion than those in early stage. In addition, cribriform and solid patterns are more common that tubular pattern, and there is no significant correlation between perineural invasion and otalgia.

[The impact of goal directed analgesia on mechanical ventilated patients's outcomes in intensive care unit: a clinical observational study].

To investigate the impact of goal directed analgesia on the outcome of patients with mechanical ventilation in intensive care unit.A total of 126 patients who needed mechanical ventilation were recruited.With a method of before and after paired comparison, they were divided into two group: (1) analgesia with empirical administration or control group; (2) goal directed analgesia based on critical-care pain observation tool (CPOT). Compared with the control group, after goal directed analgesia was applied, the consumption of midazolam significantly dropped from (368.47±27.41) mg to (151.27±29.31) mg(P<0.05), whereas the consumption of dexmedetomidine significantly increased from (623.62±20.91) µg to (812.34±22.57) µg(P<0.05). The median score of Richmond agitation-sedation scale increased from -3 to -1.The incidence of delirium significantly reduced from 23.81% to 17.46%(P<0.05). The mean ventilator duration was significantly shortened from (168.49±11.41) h to (142.38±13.24) h(P<0.05). ICU length of stay was significantly shortened from (23.64±9.26) d to (19.63±8.46) d(P<0.05). Due to the mild sedation, patients receiving goal directed analgesia report less delirium, less ventilation time and shorter ICU length of stay, suggesting that the general outcome is improved.

[Effect of endoplasmic reticulum stress in trophocytes on the pathogenesis of intrahepatic cholestasis of pregnancy].

Objective: To evaluate the effect of endoplasmic reticulum stress in trophocytes, in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty-one pregnant women who were hospitalized in Women's Hospital, School of Medicine, Zhejiang University from January to December 2015 were recruited. Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group. The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique. Electronic microscope was used to observe ultra-microstructure change of the endoplasmic reticulum in trophocytes and cell line Swan71. Reverse transcription (RT)-PCR and western blot were used to investigate the expression of GRP-78 mRNA and protein in Swan 71 cell. Results: (1) GRP-78 protein was mainly expressed in the cytoplasm of cytotrophoblasts and syncytiotrophoblasts. The protein expression of GRP-78 in placentas of the ICP group (13.2±2.4) was significantly higher than that in the control group (7.8±1.3, P<0.01). (2) The volume of endoplasmie reticulum did not increase and the microvilli developed well, with no swelling and no expansion of endoplasmic reticulum in the control group.In the ICP group, microvilli injury, endoplasmic reticulum edema were found; the volume of endoplasmic reticulum increased, with dilation, vacuolation and significant degranulation. After treated with 100 µmol/L cholyglycine for 24 hours, universal dilatation of the endoplasmic reticulum were seen in the Swan71 cells. (3) In Swan71 cells, cholylglycine displayed a concentration-dependent up-regulation on the expression of GRP-78. The expressions of GRP-78 mRNA in 0, 25, 50, 100 µmol/L cholylglycine experimental group were 1.01±0.17, 2.17±0.16, 5.47±0.36, 5.65±0.82, respectively. The expression of GRP-78 protein in 0, 25, 50, 100 µmol/L cholylglycine experimental group were 1.01±0.04, 1.17±0.15, 1.33±0.13, 1.73±0.13, respectively. The expression of GRP-78 mRNA and protein in 100 and 50 µmol/L cholylglycine experimental group were significantly higher than 0 µmol/L (all P<0.01). Conclusion: The obvious expansion of endoplasmic reticulum and the increased expression of GRP-78 in trophocytes indicated that endoplasmic reticulum stress of trophocytes may be involved in the pathogenesis of ICP.

[Characteristics of ERG, Fli-1, CD34, CD31 and Fâ §RAg expression in hepatic malignant vascular tumors].

Objective: To investigate the expression of ERG, Fli-1, CD34, CD31 and factor Ⅷ-related antigen(FⅧRAg) in hepatic malignant vascular tumors. Methods: A retrospective analysis was conducted on 63 cases of primary hepatic malignant vascular tumors and 31 cases of hepatic other malignant spindle cell tumors collected during January 1986 to January 2014. EnVision method was used to detect the expression of ERG, Fli-1, CD34, CD31, FⅧRAg. Results: Sixty-three cases of malignant vascular tumors, including 24 cases of angiosarcoma, 38 cases of epithelioid hemangioendothelioma and 1 case of hepatic Kaposi's sarcoma. All of the cases were positive for ERG(100.0%, 63/63). Positive rate of Fli-1, CD34, CD31, FⅧRAg was 96.8% (61/63), 87.3% (55/63), 81.0% (51/63) and 41.3% (26/63), respectively. In other hepatic malignant spindle cell tumors, the positive rate of ERG, Fli-1, CD34, CD31 and FⅧRAg was 3.2% (1/31), 19.4% (6/31), 19.4% (6/31), 9.7%(3/31) and 3.2%(1/31), respectively.The sensitivity of ERG, Fli-1, CD34, CD31, FⅧRAg was 100.0%, 96.8%, 87.3%, 81.0% and 41.3%, respectively.The specificity was 96.8%, 80.6%, 80.6%, 90.3% and 96.8%, respectively. Conclusion: ERG is a more sensitive and specific diagnostic marker for hepatic malignant vascular tumors in comparison to Fli-1, CD34, CD31 and FⅧRAg.

[The comparison of liver inflammation and fibrosis between chronic HBV and HCV infection].

Objective: To explore the difference of liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection and chronic hepatitis C virus (HCV) infection, and to investigate the relationship between hepatic pathology and alanine aminotransferase (ALT). Methods: 57 patients with chronic HCV infection and 346 patients with chronic HBV infection who were hospitalized at Shengjing Hospital of China Medical University from January 2012 to September 2016 were enrolled. In chronic HBV infection, including 88 cases whose ALT were more than two times of upper limited of normal (ALT≥2×ULN) and 258 cases whose ALT were less than two times of upper limited of normal (ALT < 2×ULN).All the patients were underwent liver biopsy. Chronic HBV infection (ALT≥2×ULN and ALT < 2×ULN) and chronic HCV infection were compared respectively. Statistical analyses were performed using a Univariate χ²-test and Mann-Whitney U test for comparison. Correlations between variables were analyzed using Spearman's rank correlation. Results: In chronic HBV infection group, 169 cases (48.8%) had inflammation grade≥2 (G≥2), 98 cases (28.3%) had fibrosis stage≥2 (S≥2), 81 cases (23.4%) with G≥2 and S≥2.In the ALT < 2×ULN group, there were 109 cases (42.2%) with G≥2, 62 cases (24%) with S≥2, 49 cases (19%) with G≥2 and S≥2. In the ALT≥2×ULN group, 60 cases (68.2%) with G≥2, 35 cases (39.8%) with S≥2, 31 cases (35.2%) with G≥2 and S≥2. The grade of inflammation and fibrosis have significantly different between ALT≥2×ULN group and ALT < 2×ULN group (χ² = 17.66, χ² = 8.06, P < 0.01). In chronic HCV infection group, 47 cases (82.5%) with G≥2, 20 cases (35.1%) with S≥2, 20 cases (35.1%) with G≥2 and S≥2. ALT had no correlation with inflammation and fibrosis (P > 0.05). The grade of inflammation was significantly different between chronic HCV infection and chronic HBV infection whose ALT < 2×ULN (χ² = 30.19, P < 0.01) but the fibrosis have no difference (χ² = 2.96, P > 0.05). Compared with chronic HBV infection whose ALT≥2×ULN, both inflammation and fibrosis had no significantly different (χ² = 3.65, χ² = 0.32, P > 0.05 respectively). Conclusion: In chronic HBV infection whose ALT < 2×ULN, about 30%-40% liver tissue with significant necroinflammation and /or fibrosis. About 80% chronic HCV infection with significant necroinflammation, and the grade of inflammation has no correlation with ALT. The grade of inflammation has significantly different between chronic HCV infection group and chronic HBV infection group whose ALT < 2×ULN.

[Effect of quorum sensing system on the infection of MRSA and the intervention of erythromycin on it].

Objective: To investigate the destructive effects of erythromycin on biofilm of MRSA and find the effect of erythromycin on QS related factors. Methods: Tested the MBC of erythromycin on MRSA.Established the model of biofilm.Erythromycin was added into the medium when bacteria were inoculated for 24 h. Tested the biofilm and collected the supernatant or serum of rat at 6, 12, 24, 48, 72 h and 7 d after adding erythromycin to detect the concentration of autoinducing peptides (AIP). Results: The MBC of the erythromycin on standard strains of MRSA was 256 g/L.There is a decreasing tendency of biofilm in a short time after adding erythromycin or TSB and then gradually increase until to a steady state. Biofilm of experimental group(1.348, 1.236, 1.667)were significantly less than the control group(1.789, 1.712, 2.349, P<0.05)at 12, 24, 48 h. Adding erythromycin to the mature biofilm, there was a significant decrease of biofilm.Adding erythromycin within 3 hours after inoculating bacteria, there was no bacterial growth or biofilm formation. The development trend of AIP was similar with biofilm and AIP happened earlier than biofilm.With the intervention of erythromycin, AIP of experimental group(0.891 5, 0.853 9, 0.792 4)were significantly less than the control group(1.023 7, 1.061 6, 1.034 7, P<0.05)at 6, 24, 48 h. Conclusion: Adding erythromycin timely before biofilm formation, then bacteria were killed effectively.Erythromycin was able to destroy biofilm. Biofilm was inhibited by AIP obviously.To some extent, erythromycin can inhibit the synthesis or secretion of AIP.

[Clinicopathologic characteristics of thyroid-like follicular carcinoma of the kidney: an analysis of five cases and review of literature].

Objective: To study the clinicopathologic features of thyroid-like follicular renal cell carcinoma. Methods: Clinical data were collected in 5 cases of thyroid-like follicular renal cell carcinoma. HE staining and immunohistochemistry were carried out in surgically-removed specimen to analyze the clinical and pathological features with review of the literatures. Results: The patients aged 20-55 years, with one male and four females; the tumor occurred in the left kidney in three cases and right kidney in two cases. One case had a history of thyroid papillary carcinoma 3 years ago, and the patient had left flank pain, macroscopic haematuria for 2 weeks. The rest four cases had no consciousness of clinical symptoms and signs, without history of thyroid gland surgery; the physical examination found a mass in the kidney and normal thyroid glands. Three patients underwent radical nephrectomy, and the other two patients underwent tumor partial nephrectomy. The tumors were 2-4 cm in size. They showed a solitary nodular mass of well circumscribed with taupe and gray on cut surface. Microscopically, most of tumor cells arranged in thyroid follicular pattern in different sizes, with papillary configuration in a small portion, in four cases; the follicular structure was intermixed with the papillary each half in one case. A large amount of thyroid colloid was deposited within follicule-like structure or papillary axis, lined by simple columnar cells or cubic cells, with obvious atypia, ground-glass nuclei, nuclear groove and rare mitosis. Immunohistochemical staining showed tumor cells were positive for PAX8, and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin (Tg). One of five patients presented with lymph node metastases (4/4) of renal hilum the same time in the diagnosis. Five cases were followed up for 5-84 months after operation, and no tumor progression was found. Conclusions: Thyroid-like follicular renal cell carcinoma is primary renal epithelial malignant tumor. The diagnosis mainly depends on its characteristics of histological appearance, namely similar to the histological morphology of well-differentiated thyroid follicular carcinoma and papillary carcinoma, and the metastasis from the thyroid papillary or follicular carcinoma must be excluded. On the premise of clinical history, immunohistochemical markers TTF1 and Tg have certain value in the differential diagnosis.