Single-Stage Surgical Procedure for Patients with Primary Esophageal and Lung Cancers.

BACKGROUND: The aim of this study was to evaluate the safety and feasibility of simultaneous surgery for patients with primary esophageal and lung cancers. METHODS: Patients with primary esophageal and lung cancers who underwent simultaneous surgical procedures between January 2016 and January 2022 were retrospectively analyzed. The data of patients who underwent esophagectomy and lobectomy (group EL) were compared with those of patients who underwent esophagectomy and sublobar resection (group ES). RESULTS: A total of 21 patients were included with an average age of 64.62 ± 5.24 years. Group EL contained 8 patients and group ES contained 13 patients. All procedures were completed uneventfully with a mean operative time of 251.19 ± 66.93 minutes. Pulmonary complications occurred in six (28.57%) patients. Other complications included anastomotic leakage in 1 patient, pleural effusion requiring drainage in 8 patients, atrial fibrillation in 2 patients, and incision infection in 1 patient. All patients were followed up for 30.23 ± 21.82 months. During the follow-up period, nine patients had a recurrence of cancer and died of tumor progression, and one patient died of a tracheothoracogastric fistula. Complications and mortality in group EL did not increase when compared to those in group ES. CONCLUSION: It is safe and feasible to perform a single-stage surgical procedure for patients with primary esophageal and lung cancers. Simultaneous esophagectomy and lobectomy did not increase postoperative complications or mortality compared with esophagectomy and sublobar resection.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Study on incidence and disease burden of foreign body in eyes in 1990 and 2019 of China / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the incidence and disease burden of foreign body in eyes in 1990 and 2019 of China.METHODS: Using the global burden of disease database in 2019, the incidence and disability adjusted life years(DALY)of foreign body in eyes in 1990 and 2019 of China were analyzed among the total population and different age groups of China.RESULTS: In 2019, the number of cases of foreign body in eyes in China was 11.2535 million, and the incidence was 79.12/10 000. The number and incidence of foreign body in eyes in 2019 decreased 12.87% and 27.49% respectively compared with those in 1990. In 2019, the DALY of foreign body in eyes in China was 181 200 person-years, and the DALY of foreign body in eyes in 2019 increased by 6.14% compared with 1990. In 2019, the age groups with the highest number of cases, incidence and DALY were all 20-54 years old, which were 8 012 600, 103.97/10 000 and 102 500 person-years, respectively. From 1990 to 2019, the incidence of foreign body in eyes in China showed a decreasing trend, average annual percentage change(AAPC)=-1.2%(95%CI: -1.8～-0.7, P<0.05), and DALY rate also showed a decreasing trend, AAPC=-0.6%(95%CI:-2.1～0, P<0.05). From 1990 to 2019, the incidence and DALY rate of foreign body in eyes in China and the World showed a downward trend. In 2019, the incidence and DALY rate of foreign body in eyes in China were significantly higher than those in the World and regions with different sociodemographic index(SDI).CONCLUSION: Although the incidence and DALY rates of foreign body in eyes in China have been decreasing in recent years, China has a large population base and the burden of foreign body in eyes is still large in the World. Active preventive measures should be taken to reduce the disease burden of foreign body in eyes.

MEOX1 suppresses the progression of lung cancer cells by inhibiting the cell-cycle checkpoint gene CCNB1.

The previous study has shown that transcriptional factor MEOX1 could promote proliferation and sphere formation ability of non-small cell lung cancer (NSCLC) cells, however, we found that MEOX1 mRNA was lowly expressed in lung cancer tissues compared to that in normal adjacent tissues, and MEOX1 mRNA expression was positively correlated with the survival of lung cancer patients, especially in lung adenocarcinoma patients. Functional experiments using in vitro and in vivo experiments revealed that stable overexpression of MEOX1 significantly suppressed the proliferation ability, promoted cell cycle arrest in G2 phase, and apoptotic ability of NSCLC cells. Additionally, it was identified that MEOX1 and CCNB1 mRNA expression exhibited a negative correlation in different lung cancer tissues. Mechanistically, we indicated that MEOX1 bound to the transcriptional initiation site of CCNB1 and thus suppressed CCNB1 expression. Notably, CCNB1 overexpression rescued the inhibition of MEOX1 overexpression on NSCLC progression. This study deciphers a novel MEOX1/CCNB1 axis suppressing NSCLC progression.

Deep chemical identification of phytoecdysteroids in Achyranthes bidentata Blume by UHPLC coupled with linear ion trap-Orbitrap mass spectrometry and targeted isolation / 中国天然药物

Achyranthes bidentata Blume is widely used as a traditional Chinese medicine with the effects of nourishing the liver and kidneys and strengthening muscles and bones. In this work, a rapid and simple strategy was developed for characterizing phytoecdysteroids by ultra-high-performance liquid chromatography coupled with liner ion trap-Orbitrap mass spectrometry using electrospray ionization in the negative mode. As a result, 47 phytoecdysteroids were unambiguously or tentatively characterized. Among them, seven known compounds were identified according to the reference standards along with molecular formula, retention time and fragmentation patterns, while others were mostly potential new compounds. Through targeted isolation, the structures of three new compounds were determined by NMR spectra, which were consistent with LC-MS characterization. The present study provides an efficient method to deeply characterize phytoecdysteroids.

A novel modified Nuss procedure without plate turnover for treatment of adult recurrent pectus excavatum / 中国胸心血管外科临床杂志

@#Objective    To summarize the experience of treating adult recurrent pectus excavatum without plate turnover. Methods    Twenty-seven patients with recurrent pectus excavatum treated by thoracoscopy-assisted placement without plate turnover from 2010 to 2019 in our hospital were enrolled. There were 23 males and 4 females with the age of 3-29 (12.81±7.79) years at the first operation, and 18-29 (21.74±3.56) years at this operation. Incision of 2-3 cm at bilateral axillary midline of the deepest point of pectus excavatum was made, and an auxiliary incision under xiphoid process was adopted according to the intraoperative situation. Results    All patients underwent thoracoscopy-assisted correction of pectus excavatum without bar turnover, and subxiphoid incision was performed in 11 patients. Twenty-five patients had one bar placed, and two patients required two bars. The operation time was 28-45 (33.00±6.44) min. Postoperative Haller index (2.95±0.40) was improved compared with preoperation (4.63±1.03). The postoperative hospital stay was 4-6 (4.00±0.32) day. All patients were followed up for 1-8 years. Complications included poor wound healing in 1 patient, and steel wire fracture and displacement in 1 patient. There was no plate rotation or bar displacement. Fourteen patients removed the bar 29-84 (40.36±13.93) months after the placement. Haller index was improved to 2.43-3.61 (2.86±0.35) during removal of steel plate. Untill June 2020, there was no recurrence of pectus excavatum. Conclusion    The treatment of adult recurrent pectus excavatum without plate turnover is satisfactory, and the protection of intercostal muscle and firm fixation is the key to ensure the success of operation and long-term effects.

Clinicopathological study of BCOR rearrangement in high grade endometrial stromal sarcoma / 中华病理学杂志

Objective@#To investigate clinicopathological, cytogenetic features and differential diagnoses of high grade endometrial stromal sarcoma (HGESS) with BCOR gene rearrangement.@*Methods@#Five cases of HGESS with BCOR rearrangement were collected from consultant files (2016-2018) at Fudan University Shanghai Cancer Center. Interphase FISH was performed using a dual color break-apart probe. The clinical data, histologic features and immunohistochemical findings were reviewed.@*Results@#All 5 cases occurred in adult women with a median age of 48 (range, 45-55) years. Abdominal pain and abnormal vaginal bleeding were the most common symptoms. Microscopically, the tumors showed mainly tongue-like and/or intersecting myometrial invasion. Stromal myxoid matrix and/or collagen plaques were prominent in all the cases. Most tumors consisted of uniform, haphazard fascicles of short spindle cells with mild to moderate nuclear atypia. Mitotic figures and necrosis were easily identified. Significant nuclear pleomorphism was not seen. Most tumors were rich in thick-walled small vessels. Prominent perivascular tumor cell whorling seen in conventional low-grade endometrial stromal sarcoma was not seen. All tumors expressed CD10 with only focal or absent desmin, SMA and/or h-caldesmon staining. ER or PR expression was seen in 4 tumors and 1 tumor showed both marker expression. Diffuse cyclin D1 was present in 2 tumors. BCOR immunoreactivity was present with strong staining in 3 cases and moderate staining in 1 case respectively. Ki-67 index ranged from 10% to 30%. Fluorescence in situ hybridization confirmed chromosomal aberration of BCOR gene in all tumors, that were previously diagnosed as myxoid leiomyosarcoma (2 cases), spindle cell uterine sarcoma (2 cases) and low-grade endometrial stromal sarcoma (1 case). Limited follow-up information revealed that 3/5 patients developed tumor recurrence, metastasis or death within one year.@*Conclusion@#BCOR rearranged HGESS has distinct morphological features and aggressive clinical behavior. In the presence of significant overlapping morphologic features between BCOR rearranged HGESS and other myxoid uterine mesenchymal tumors, especially myxoid leiomyosarcoma, molecular analysis is essential for accurate diagnoses.

Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features / 中华病理学杂志

Objective@#To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features.@*Methods@#Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed.@*Results@#BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033).@*Conclusion@#BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.

A new steel bar used in minimally invasive surgery for pectus carinatum / 中华胸心血管外科杂志

Objective To introduce the application experience of a new steel bar used in minimally invasive surgery for pectus carinatum.Methods From January to October 2018, Cardiothoracic Surgery Department of Shanghai Xinhua Hospital performed a minimally invasive surgery for 25 cases of patients with pectus carinatum used a new type of steel bar.All 25 pa-tients were male, aged 10 -17 years, with an average age of(13.80 ±1.66)years.The application experience of the new bar in pectus carinatum minimally invasive surgery was summarized .Results All operations were successfully completed .The op-eration time was 35-100 min, averaged(73.44 ±17.49)min, postoperative hospital stay was 3 -6 days, averaged(3.68 ± 0.85)days.Postoperative complications included 5 cases of pneumothorax(the lung compression was about 2％ -10％, not necessary for surgical intervention).One case occured wound healing delay 1 month after operation, and healed after no surger-cal treatment.The other patients recovered smoothly.Conclusion The new steel bar is convenient to use, greatly reduces the difficulty of the pectus carinatum surgery procedure , also reduced surgical trauma and complications , has a good application prospect.

Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing endogenous RNA for the treatment of diabetic wounds.

Diabetic wounds, one of the most enervating complications of diabetes mellitus, affect millions of people worldwide annually. Vascular insufficiency, caused by hyperglycemia, is one of the primary causes and categories of diabetic impaired wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly decreased in diabetes and may be crucial in triggering angiogenesis, has attracted increasing interest. The possible relationship between the decrease of LncRNA-H19 and the impairment of angiogenesis in diabetes could involve impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19 delivery is feasible. In this study, we investigated the possibility of using high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective nano-drug delivery system for LncRNA, and studied the function of EMNVs with a high content of LncRNA-H19 (H19EMNVs). The results, which were exciting, showed that H19EMNVs had a strong ability to neutralize the regeneration-inhibiting effect of hyperglycemia, and could remarkably accelerate the healing processes of chronic wounds. Our results suggest that bioengineered EMNVs can serve as a powerful instrument to effectively deliver LncRNA and will be an extremely promising multifunctional drug delivery system in the immediate future.

miR-26 Induces Apoptosis and Inhibits Autophagy in Non-small Cell Lung Cancer Cells by Suppressing TGF-ß1-JNK Signaling Pathway.

Non-small cell lung cancer (NSCLC) is one of the causes of cancer mortality worldwide. The role of miR-26 in the development and progression of NSCLC remains largely unknown. In this study we found an abnormal expression of miR-26 in human NSCLC tissues. It was found that miR-26 mimics induced cell apoptosis and promoted caspase-3, 9 activities in human NSCLC cells. The miR-26 inhibitor enhanced the expression of the light chain 3 (LC3) protein and the autophagy related genes in NSCLC cells. Moreover, miR-26 regulated apoptosis and autophagy by inhibiting TGF-ß expression in a JNK dependent manner. In addition, miR-26 mimics induced cell apoptosis, was involved in the endoplasmic reticulum stress (ERS) signaling pathway. Down-regulation of the ERS, inhibited apoptosis which was induced by miR-26 mimics in NSCLC cells. In in vivo studies, TUNEL staining revealed that the number of TUNEL positive cells of the tumor tissue in the miR-26 treatment group, were significantly increased in comparison with the control group, while the number of TUNEL positive cells in the tumor tissue were remarkably decreased in the groups treated with miR-26, combined with the TGF-ß1 inhibitor or JNK inhibitor. Additionally, the immunoreactivity of TGF-ß1 in the cells treated with the miR-26 inhibitor, decreased in comparison to the control group. Our results indicated that miR-26 induced apoptosis and inhibited autophagy in human NSCLC cells through the TGF-ß1-JNK signaling pathway, suggesting that miR-26 could be a potential novel target for the treatment of NSCLC.

Clinicopathologic analysis of primary carcinoid of the ovary / 中华病理学杂志

Objective@#To describe the clinicopathologic features, diagnosis and differential diagnosis of ovarian carcinoid tumors.@*Methods@#A retrospective chart review was performed of all patients diagnosed with primary ovarian carcinoid tumors at Fudan University Shanghai Cancer Centre from 2007 to 2017.@*Results@#The histologic analysis of these carcinoid tumors revealed 3 were insular, 1 was trabecular, 1 was mucinous, and 10 were strumal. Histologic features of insular and trabecular carcinoid were similar to other parts of the neuroendocrine tumor. Strumal carcinoid was composed of thyroid tissue intimately admixed with carcinoid tumor, showing trabecular pattern. Mucinous carcinoid was resembles Krukenberg tumor. Most ovarian carcinoid tomours were diffusely positive with at least one neuroendocrine marker, especially synaptophysin (14/14) and CD56(9/10). The median follow-up time was 53 months, 1 patient with squamous-cell carcinoma of cervixrecur rence in vaginal after 37 months, and only 1 patient died of disease. The remaining patients were disease-free survival.@*Conclusions@#Primary carcinoid of the ovary is a very rare low grade malignant monodermal teratomas and somatic-type tumours arising from a dermoid. The diagnosis and differential diagnosis mainly relies on the histopathologic characteristics and the immuno-phenotype. Primary ovarian carcinoid almost always exhibit a benign clinical behavious except mucinous carcinoid.

Chemical constituents from root barks of Dictamnus dasycarpus and their cytotoxic activities / 中国中药杂志

Nineteen compounds, including kihadanin D (1), obacunone (2), kihadanin A (3), kihadanin B (4), kihadanin C (5), limonin (6), evodol (7), fraxinellone (8), furo[2,3-b]quinolin-4-ol (9), preskimmianine (10), ifflaiamine (11), dictamnol (12), naringenin (13), diosmetin (14), wogonin (15), scopoletin (16), cleomiscosin A (17), apocynin (18), and methyl pyroglutamate (19), were isolated from the methanol extract of the root barks of Dictamnus dasycarpus by using various column chromatographies. Their chemical structures were extensively determined on basis of UV, IR, NMR, MS, and CD spectroscopic data analyses. Among them, 1 is a new limonoid, 9 was isolated from plant kingdom for the first time, 11, 13-14 and 17-19 were obtained from the genus Dictamnnus for the first time. Cytotoxicities of compounds 1-18 were tested, and the results indicated that 1 exhibited cytotoxicities against three human cancer cell lines MDA-MB-231, A549 and HT29 with IC₅₈ values of 16.22, 21.72 and 31.06 μmol·L⁻¹, respectively.

Mass spectrometry guided strategy based on feature fragment ions for guided-separation on quinoline alkaloids from root barks of Dictamnus dasycarpus / 中国中药杂志

The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.

A triage strategy in advanced ovarian cancer management based on multiple predictive models for R0 resection: a prospective cohort study / 부인종양

OBJECTIVE: To present the surgical outcomes of advanced epithelial ovarian cancer (AEOC) since the implementation of a personalized approach and to validate multiple predictive models for R0 resection. METHODS: Personalized strategies included: 1) Non-invasive model: preoperative clinico-radiological assessment according to Suidan criteria with a predictive score for all individuals. Patients with a score 0–2 were recommended for primary debulking surgery (PDS, group A), or otherwise were counseled on the choices of PDS, neoadjuvant chemotherapy (NAC, group B) or staging laparoscopy (S-LPS). 2) Minimally invasive model: S-LPS with a predictive index value (PIV) according to Fagotti. Individuals with a PIV < 8 underwent PDS (group C) or otherwise received NAC (group D). Intraoperative assessment (with Eisenkop, peritoneal cancer index [PCI], and Aletti scores) and surgical results were prospectively collected. RESULTS: Between September 2015 and August 2017, 161 pathologically confirmed epithelial ovarian cancer patients were included. A total of 52 (32.3%) patients had a predictive score of 0–2, and 109 (67.7%) patients had a score ≥ 3. Among these individuals, 41 (25.5%) patients received S-LPS. Finally, 110 (68.3%) patients underwent PDS (A+C), and 51 (31.7%) patients received NAC (B+D). The R0 resection rates in PDS and NAC patients were 56.4% and 60.8%, respectively. The area under the curve (AUC) of Suidan criteria was 0.548 for group (A+C). The AUC of Fagotti score was 0.702 for group C. The AUC of Eisenkop, PCI, and Aletti scores were 0.808, 0.797, and 0.524, respectively. CONCLUSION: The Suidan criteria were not effective in these AEOC patients. S-LPS was helpful in decision-making for PDS and should be endorsed in the future.

Reimplantation of an extruded osteoarticular segment of the femur: Case series and in vitro study in a rat model.

BACKGROUND: The treatment of open femur fractures with reimplantation of large extruded segments remains one of the most difficult clinical management scenarios. The situation is even complicated when the extruded segments contains a large osteoarticular segment and no consensus exist about the efficient sterilization. We successfully managed five cases of open femur fracture by reimplantation of a large osteoarticular segment. While the outcomes were favourable, we performed an in vitro investigation in a rat model to determine whether the bone segment preparation strategy was optimal. MATERIALS AND METHODS: After meticulous debridement and sterilization with povidone-iodine scrub/orthopaedic antibiotic solution, osteoarticular segments of the femur were reimplanted successfully in five patients with Gustilo-Anderson IIIa-IIIb fractures. Furthermore, in vitro study performed to assess the relative efficacy of various methods of sterilization employed osteoarticular segments of rat femurs. After contamination, osteoarticular segments were treated via one of the following protocols: (1) saline rinse; (2) povidone-iodine scrub and saline rinse; (3) povidone-iodine scrub and autoclaving; (4) povidone-iodine scrub and immersion in antibiotic solution; (5) povidone-iodine scrub and immersion in povidone-iodine solution; or (6) povidone-iodine scrub and gamma-irradiation. The osteoarticular segments were then cultured and finally evaluated for infection and morphological changes. RESULTS: At the mean 40 month follow-up, there were no infection in the patients and the fractures achieved completed union. For the basic research, only approaches involving povidone-iodine scrub with autoclaving or antibiotic solution immersion were 100% effective in eliminating bacterial growth. Furthermore, povidone-iodine scrub with antibiotic solution immersion preserved the articular surface morphology. CONCLUSION: Our study suggests that reimplantation of extruded osteoarticular segments of long bone may represent a feasible alternative to amputation. This is the first description of such a technique and its long-term outcomes in the clinical setting, which were corroborated with the outcomes of in vitro investigation in a rat model, concluding that contaminated extruded osteoarticular segments can be adequately sterilized for reimplantation by cleaning with povidone-iodine scrub followed by brief soaking in antibiotic solution. However, it remains unclear whether the antibacterial efficacy of different sterilizations noted in vitro is reflected in vivo, warranting further research.

Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes.

AIMS: GATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases. METHODS: Immunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a cohort of 1637 cases of primary invasive breast carcinoma. The association of GATA3 expression with different histological and surrogate intrinsic subtypes was assessed and compared with the expression of GCDFP15 and mammaglobin. RESULTS: The overall positivity of GATA3 across the various immunohistochemistry-based surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B-like, 68.50% for HER2 overexpression and 20.16% for triple negative breast cancers. GATA3 expression was positively correlated with estrogen receptor (ER)-positive (luminal subtypes) breast carcinomas. For luminal-like and HER2 overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15. CONCLUSIONS: GATA3 exhibits a relatively high sensitivity for breast carcinomas. It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2 overexpression subtypes. GATA3 expression is associated with breast carcinomas of luminal subtype and low histological grade.

Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway.

An excess of glucocorticoids (GCs) is reported to be one of the most common causes of osteonecrosis of the femoral head (ONFH). In addition, GCs can induce bone cell apoptosis through modulating endoplasmic reticulum (ER) stress. Among the three main signal pathways in ER stress, the PERK (protein kinase RNA-like ER kinase)/CHOP (CCAAT-enhancer-binding protein homologous protein) pathway has been considered to be closely associated with apoptosis. Platelet-rich plasma (PRP) has been referred to as a concentration of growth factors and the exosomes derived from PRP (PRP-Exos) have a similar effect to their parent material. The enriched growth factors can be encapsulated into PRP-Exos and activate Akt and Erk pathways to promote angiogenesis. Activation of the Akt pathway may promote the expression of anti-apoptotic proteins like Bcl-2, while CHOP can inhibit B-cell lymphoma 2 (Bcl-2) expression to increase the level of cleaved caspase-3 and lead to cell death. Consequently, we hypothesized that PRP-Exos prevent apoptosis induced by glucocorticoid-associated ER stress in rat ONFH via the Akt/Bad/Bcl-2 signal pathway. To verify this hypothesis, a dexamethasone (DEX)-treated in vitro cell model and methylprednisolone (MPS)-treated in vivo rat model were adopted. Characterization of PRP-Exos, and effects of PRP-Exos on proliferation, apoptosis, angiogenesis, and osteogenesis of cells treated with GCs in vitro and in vivo were examined. Furthermore, the mechanism by which PRP-Exos rescue the GC-induced apoptosis through the Akt/Bad/Bcl-2 pathway was also investigated. The results indicate that PRP-Exos have the capability to prevent GC-induced apoptosis in a rat model of ONFH by promoting Bcl-2 expression via the Akt/Bad/Bcl-2 signal pathway under ER stress.

Values of JAZF1 gene rearrangement detected by fluorescence in-situ hybridization in diagnosis of endometrial stromal tumours / 中华病理学杂志

Objective@#To investigate the role of JAZF1 gene rearrangement in the diagnosis and differential diagnosis of endometrial stromal sarcomas by fluorescence in situ hybridization (FISH).@*Methods@#JAZF1 gene rearrangement was analyzed by FISH in 129 cases of ESS diagnosed from January 2008 to December 2016 including 105 cases of low-grade endometrial stromal sarcoma (LG-ESS), 21 cases of high-grade endometrial stromal sarcoma (HG-ESS) and 3 cases of undifferentiated uterine sarcoma (UUS). Sixteen cases of the related tumours in uterus were also collected as control group. The results were compared with our previous studies of JAZF1/JJAZ1 fusion gene in ESS by RT-PCR.@*Results@#Detection of JAZF1 gene rearrangement by FISH was successfully analyzed in 144 cases. JAZF1 gene alteration was detected in 63 cases, all of which were LG-ESS, with an overall positivity of 60.6% (63/104), while no JAZF1 gene rearrangement was found in all other cases. JAZF1 gene rearrangement was present in LG-ESS with classic histology (69.3%, 52/75), smooth muscle differentiation (2/10), sex cord-like differentiation (4/5), fibromyxoid change (1/5), clear cell change (0/1), skeletal muscle differentiation (0/1), and schwannoma-like palisading pattern (0/1). The different components in all the cases of LG-ESS with variant histology had the clonal origin, with or without JAZF1 gene alteration. Compared to the results of JAZF1/JJAZ1 fusion gene by RT-PCR, the positive rate of JAZF1 gene rearrangement in LG-ESS by FISH (61.9%, 26/42) was significantly higher than that of RT-PCR (30.0%, 12/40; P<0.01).@*Conclusions@#JAZF1 gene rearrangement is present only in LG-ESS, but not in HG-ESS, UUS or other related tumours in uterus. The frequency of JAZF1 gene rearrangement varies between classic LG-ESS and different morphologic variants. It is frequently, but not consistently, present in classic LG-ESS and less often positive in variant cases. The results of JAZF1 gene alterations in LG-ESS with different morphologic variants support the contention that the endometrial stromal and their variant morphologic components have the same clonal origin. Detection of JAZF1 gene rearrangement by FISH is very useful for the diagnosis and differential diagnosis of ESS.