Antigen Presentation and Proteome Study of Exosomes Secreted by Co-Culture of Macrophages and Talaromyces marneffei.

It is known that intracellular pathogens interact and react with the cellular immune system through exosomes produced by macrophages. This study aimed to determine whether co-culture of macrophages and Talaromyces marneffei induces exosomes and leads to immune responses. T. marneffei was incubated to collect conidia, co-cultured with human macrophages, which then induced exosomes. In cellular experiments, after extraction and purification, the exosomes were then observed by electron microscopy and detected by flow cytometry and mass spectrometry. In animal experiments, flow cytometry and enzyme-linked immunosorbent assay were used to examine whether exosomes were antigenpresenting. The results showed that purified exosomes produced a pro-inflammatory response and stimulated production of TNF-α in non-fungal-treated macrophages. Protein mass spectrometry analysis of exosomes also indicated their potential ability to activate the internal immune response system and the pro-inflammatory response. Translation and ribosomes were the most abundant GO terms in proteins, and the most relevant KEGG pathway was the biosynthesis of secondary metabolites. Furthermore, in vivo experiments revealed that exosomes induced activation of lymphocytes and increased expression of TNF-α and IL-12 in the lung, mediastinum, and spleen area. In conclusion, exosomes can be released by co-culture of T. marneffei and macrophages, having antigen-presenting functions, promoting macrophage inflammation, and initiating adaptive immune responses. These processes are inextricably linked to the translation of secondary metabolites, ribosomes and biosynthesis.

[Analysis of clinical features and etiological diagnostic indices of reproductive age women with hyperandrogenism].

Objective: To investigate the clinical features and the value of different diagnostic indices for etiology in reproductive age women with hyperandrogenism. Methods: The medical records of 96 reproductive age women with hyperandrogenism in the multi-disciplinary team of Peking University First Hospital from January 2020 to April 2021 were collected. The patients were divided into four groups based on final diagnosis: congenital adrenal hyperplasia (CAH) (n=8), polycystic ovary syndrome (PCOS) (n=67), idiopathic hyperandrogenism (n=13) and other specific diseases (n=8), respectively. The indices related to androgens in different groups were compared, and then their efficiency for diagnosis of CAH and PCOS were analyzed with receiver operator characteristic curve (ROC curve). Results: A total of 96 patients with hyperandrogenism were recruited, with the age of 19-45 (29±6) years old. Overall, 4.2% (4/96) of the patients were with single clinical hyperandrogenism, 56.3% (54/96) were with single laboratory hyperandrogenaemia and 39.6% (38/96) were with both. The breakdown into laboratory hyperandrogenaemia subtypes was as follows: only T elevation 22.8% (21/92), only A2 elevation 7.6% (7/92), none DHEAS elevation, only FAI elevation 5.4% (5/92) and elevation of more than one of the androgen indices mentioned above accounted for 64.1% (59/92). In the reasons of consultation, simple irregular menstruation (36.0%, 32/89) or accompanied by clinical hyperandrogenism with or without infertility (36.0%, 32/89) were the most common. As for primary visiting departments, Obstetrics and Gynecology accounted for 53.2% (51/96), and then Endocrinology as 39.5% (38/96). The 17-OHP level of CAH, PCOS and idiopathic hyperandrogenism group was 20.0 (8.2, 33.1), 1.1 (0.8, 1.4), 0.9 (0.8, 1.3) ng/ml, respectively. The androstenedione level in these groups was 6.3 (4.6, 8.7), 3.8 (2.9, 4.8) and 3.2 (2.7, 3.7) ng/ml, respectively. The 17-OHP and androstenedione levels of CAH group were significantly higher than that in PCOS or idiopathic hyperandrogenism group (all P<0.05). The ratio of LH and FSH in these three groups was 0.8(0.5, 1.0), 1.3(0.6, 1.9) and 0.6(0.3, 0.7), respectively. The ratio of LH and FSH was significantly higher in PCOS than that in idiopathic hyperandrogenism group (P=0.024), but yet there was no significant difference compared with CAH group (P>0.05). The AUC of ROC curve of 17-OHP for CAH diagnosis was 0.94, followed by androstenedione 0.83, whereas LH/FSH for PCOS diagnosis was only 0.63. Conclusions: Among the reasons of consultation in reproductive age women who visited our multi-disciplinary team for female hyperandrogenism, simple irregular menstruation or accompanied by clinical hyperandrogenism with or without infertility are the most common. PCOS accounts for the majority of different androgen excess disorders. 17-OHP is the most valuable parameter for the diagnosis of CAH and secondly androstenedione.

Radio-sensitizing effects of microRNA-27a elevation in lung cancer cells by inhibiting ZEB1 expression and activating DNA damage repair pathway.

MicroRNAs (miRNAs or miRs) exert either as tumor-inhibiting or oncogenic roles in tumorigenesis of lung cancer. In the present study, we identified a novel microRNA (miR)-27a as being involved in the radiosensitivity of lung cancer cells. Therefore, we sought to characterize its potential underlying mechanism in lung cancer cell sensitivity to radiotherapy. To this end, A549 and H460 cells irradiated with 8 Gy irradiation (IR) were used as a cell model. RT-qPCR exhibited that the expression of miR-27a increased, whereas ZEB1 was poorly expressed in A549 and H460 cells exposed to IR. As reflected by dual-luciferase reporter gene assay, miR-27a could target and inversely modulate ZEB1 expression. Gain- and loss-of-function experiments exhibited that miR-27 inhibition promoted proliferation of IR-treated A549 and H460 cells and reduced the sensitivity of A549 and H460 cells to radiotherapy, which was rescued by silencing of ZEB1. Further, miR-27a inhibition disrupted the homologous recombination (HR)-mediated DNA repair, evidenced by reduced ATM, pCHK2 and Rad51 levels. Collectively, miR-27a activates HR-mediated DNA repair by inhibiting ZEB1 expression to enhance the radiosensitivity of lung cancer cells, highlighting a therapeutic target for lung cancer radiosensitivity.

[Single-center experience of robot-assisted laparoscopic nephron-sparing surgery for giant renal hamartoma].

The clinical data of 22 patients with giant renal hamartoma in Zhejiang Provincial People's Hospital who underwent robot-assisted laparoscopic nephron-sparing surgery from October 2014 to January 2020 were retrospectively analyzed. All the patients successfully completed the operation. The operation time and renal artery occlusion time was (179±34) min and (19.8±2.5) min, respectively. The intraoperative blood loss was (117±62) ml, and the postoperative hospital stay was (9.0±1.5) d. All cases were confirmed as renal angiomyolipoma by postoperative pathology. No urine leakage, postoperative bleeding and other complications occurred. Postoperative telephone follow-up was performed for 6 to 52 months, and no tumor recurrence on the surgical side was reported.

[Current status of hyperkalemia in dialysis patients in China].

Objective: To investigate the prevalence and associated factors of hyperkalemia in dialysis patients. Methods: Patients underwent hemodialysis (HD) and peritoneal dialysis (PD) from multi-center databases were recruited from January 2017 to December 2019, and those aged ≥18 years and with dialysis duration ≥3 months were included to analyze the prevalence and related factors of hyperkalemia. Results: A total of 12 364 patients were enrolled in the study, and 6 836 cases were men. The average age of the patients was (51±15) years. Among these patients, 4 230 cases underwent HD while 8 134 received PD. Hyperkalemia was detected in 20.7% (2 554/12 364) of the patients while hypokalemia was found in 17.0%(2 102/12 364) of the patients. Multivariate logistic regression showed that HD (OR=2.25, 95%CI: 1.54-3.30), diabetes mellitus (DM) (OR=1.65, 95%CI: 1.17-2.32), high body mass index (BMI) (OR=1.06, 95%CI: 1.03-1.09), high levels of serum albumin (OR=1.04, 95%CI: 1.01-1.07) and phosphorus (OR=3.12, 95%CI: 2.44-4.00), low levels of serum bicarbonate (OR=0.89, 95%CI: 0.87-0.92), triglycerides (OR=0.76, 95%CI: 0.68-0.85) and creatinine (OR=0.95, 95%CI: 0.90-0.99), usage of angiotensin converting enzyme inhibitor/Angiotensin Ⅱ receptor antagonist (ACEI/ARB, OR=1.38, 95%CI: 1.11-1.72) and beta-blocker (OR=1.32, 95%CI: 1.07-1.64) were associated with hyperkalemia. Conclusions: Hyperkalemia occurred in 20.7% of the dialysis patients. HD, DM, high BMI, high levels of serum albumin and phosphorus, low levels of serum bicarbonate, triglycerides and creatinine, use of ACEI/ARB were associated with hyperkalemia.

EFFECT OF PUERARIN ON THE PROLIFERATION AND DIFFERENTIATION OF OSTEOBLASTS AND THE EXPRESSION OF TYPE I COLLAGEN mRNA IN A HIGH-GLUCOSE ENVIRONMENT.

OBJECTIVE: To investigate the effect of puerarin (Pue) on the proliferation and differentiation of osteoblasts and the expression of type I collagen(Coll I) mRNA in a high-glucose (HG) environment, and to provide evidence for the clinical treatment of diabetic osteoporosis(DOP). SUBJECTS AND METHODS: The proliferation of osteoblasts from three groups - the control group, the HS group, and the HG+Pue (10-8-10-6 M) group - was cultivated for 72 h and evaluated using the methyl thiazolyltetrazolium (MTT) assay. RESULTS: The MTT values and the ALP activities in all experimental groups were significantly lower than those in the control group, and the MTT values and the ALP activities in the HG+Pue group were significantly higher than those in the HS group. Coll I mRNA expression in all experimental groups was significantly lower than that in the control group, while that in the HG+Pue group was significantly higher than that in the HG group. CONCLUSIONS: The proliferation and differentiation of osteoblasts and the expression of Coll I mRNA were inhibited by high glucose, but Pue can increase the proliferation and differentiation as well as the expression of Coll I mRNA in the osteoblasts, indicating that Pue could be therapeutically beneficial against DOP.

[Pigmented microcystic chromophobe renal cell carcinoma: a clinicopathologic analysis of five cases].

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People's Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions: Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.

[Clinicopathologic features of glomus tumor of the kidney].

Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and ß-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.

[Embryo implantation dysfunction via the decreased uterine dendritic cells's non-immune function after exposed to carbon disulfide].

Objective: To study the effect of CS2 on dendritic cells (DCs) in the uterus and the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor(fms-like tyrosine kinase-1, Flt-1), and to explore the toxic mechanism of CS2-induced embryo implantation dysfunction. Methods: The Kunming mice were randomly divided into control group,gestational day 4(GD4) exposure group and GD5 exposure group. The endpoints of each group(GD5, GD6, GD7) was set up according to their respective exposure time points. The mice in the exposure group were given intraperitoneal injection of CS2 at an injection dose of 631.4 mg/kg and the control group was given olive oil. The effect of CS2 on DCs in the uterus of pregnant mice was observed by flow cytometry. The levels of VEGF and Flt-1 were measured by Real-time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: In the GD4 and GD5 exposure groups, the number of DCs in the uterus of pregnant mice decreased at all endpoints and the GD5 endpoint in the GD4 exposure group decreased by 21%(P=0.039), when compared with the control group. In the GD4 exposure group, the levels of VEGF mRNA and protein in the uterus of the pregnant mice were 79% and 30% lower than those in the control group, respectively (P=0.03、P=0.017); the levels of Flt-1 mRNA and protein at the endpoints of GD6 and GD7 in the uterus decreased by 54%, 36%, 60% and 56%, respectively, when compared with the control group(P=0.017、P=0.012、P=0.004、P=0.007). In the GD5 exposure group, the levels of VEGF mRNA and protein in the uterus of pregnant mice at the endpoint of GD7 decreased by 62% and 36%, when compared with the control group (P=0.005、P=0.035); the levels of Flt-1 mRNA and protein in the uterus at the endpoint of GD7 decreased by 60% and 44%, respectively, when compared with the control group (P=0.004、P=0.009). Conclusion: CS2 reduced the number of DCs in the uterus of pregnant mice, and affected the non-immune function of DCs, which affected uterine angiogenesis, this may be one of the mechanisms of CS2-induced embryo implantation dysfunction.

Recognition of Core- and Polymerase-derived immunogenic peptides included in novel therapeutic vaccine by T cells from Chinese chronic hepatitis B patients.

Chronic hepatitis B (CHB) is one of the major public health challenges in the world. Due to a strong interplay between specific T-cell immunity and elimination of hepatitis B virus (HBV), efforts to develop novel immunotherapeutics are gaining attention. TG1050, a novel immunotherapy, has shown efficacy in an animal study. To support the clinical development of TG1050 in China, specific immunity to the fusion antigens of TG1050 was assessed in Chinese patients. One hundred and thirty subjects were divided into three groups as CHB patients, HBV spontaneous resolvers, and CHB patients with HBsAg loss after antiviral treatment. HBV-specific T-cell responses to pools of HBV Core or Polymerase genotype D peptides included in TG1050 were evaluated. HBV Core- or Polymerase-specific cells were detected in peripheral blood mononuclear cells (PBMCs) from the different cohorts. The frequencies and intensities of HBV Core-specific immune responses were significantly lower in CHB patients than in HBsAg loss subjects. In CHB patients, a dominant pool derived from Polymerase (Pol1) was the most immunogenic. CHB patients with low viral loads (<106 IU/mL) were more likely to have a positive response specific to the Core peptide pool. Overall, genotype D-derived peptides included in TG1050 could raise broad and functional T-cell responses in PBMCs from Chinese CHB patients infected with genotype B/C isolates. Core-specific immunogenic domains appeared as "hot spots" with the capacity to differentiate between CHB vs HBsAg loss subjects. These observations support the extended application and associated immune monitoring of TG1050 in China.

A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection.

Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV-infected and treatment-naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty-nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma-glutamyltransferase-to-platelet ratio (GPR), red cell volume distribution width-to-platelet ratio (RPR), FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB-4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR-HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR-HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment-naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.

Highly sensitive and scalable AAO-based nano-fibre SERS substrate for sensing application.

Well-ordered periodic nanostructures are excellent substrates for many surface-enhanced Raman spectroscopy (SERS) applications. Conventional fabrication approaches such as high precision electron beam lithography or focused ion beam produce high resolution nano-features with great reproducibility at the expense of low throughput. In this work, a highly sensitive and scalable AAO-nano-fibre (ANF) SERS substrate is demonstrated by optimising the second anodisation time of the standard two-step anodisation of aluminium and performing an additional wet etching step on the resulting AAO substrate. The optimised ANF substrate exhibits SERS sensitivity that surpasses the AAO nanoholes and the metal-film-on-nanoparticles substrates. A detection limit of 0.1 nM is achieved with a signal-to-noise ratio of 2.6-3 using a low excitation power of 0.1 mW. The ANF substrate exhibits an enhancement factor of 9.28 × 106 and a standard deviation of no more than 8%. The results indicate that the highly sensitive and scalable ANF substrate is a promising substrate for commercial SERS application.

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis.

Ankylosing spondylitis (AS), a progressive disease of the spine, manifests as peripheral arthritis with tendon and ligament inflammation that restricts activity. AS is a rheumatoid autoimmune disease although the rheumatoid factor is absent in patients with AS. It is characterized by inflammatory changes such as elevated levels of serum inflammatory factors. The roles of Th1 and Th2 cytokines in autoimmune diseases are well known. However, the roles of these cytokines in the diagnosis and prognosis of AS is poorly understood. The aim of this study was to investigate the roles of Th1/Th2 cytokines in the diagnosis and prognosis of AS. The BASDAI activity, BASFI functional index, BASMI measurement score, and the levels of CRP and ESR were measured during the treatment of patients with active AS. The levels of IFN-γ and TNF-α (Th1 cytokines) and IL-4 and IL-10 (Th2 cytokines) were quantified. The levels of IL-4 and IL-10 were significantly low in the serum of patients with active AS, who also had high IFN-γ and TNF-α levels compared to those in the control individuals (P < 0.05). After treatment, the levels of IL-4 and IL-10 increased while those of IFN-γ and TNF-α decreased compared to those in individuals with active AS (P < 0.05). The disease activity index correlated positively with levels of IFN-γ and TNF-α and negatively with levels of IL-4 and IL-10, but not with that of CRP or ESR. Changes in the levels of Th1/2 cytokines in patients with AS may reflect disease activity and prognosis.

[Depletion of GP73 inhibits invasion and metastasis of hepatocellular carcinoma cells].

Objective: To explore the in vitro and in vivo effect of GP73 on the proliferation, invasion and metastasis in hepatocellular carcinoma. Methods: GP73 gene was knocked out using CRISPR/Cas9 gene editing system in H22 and HepG2 cells, and stable knock out strains were constructed. The knockout efficiency was measured by western blot. Colony formation assay was used to detect the effect of GP73 on long-term survival ability. Cells were then highly synchronized in G(1) phase upon treatment with cell synchronization reagents (mimosine), and the percentage of cells in G(2)/M phase at different time points was detected by flow cytometry. The invasive and metastasis abilities of hepatocellular carcinoma cells were detected by Transwell™ assay. Furthermore, the tumor formation abilities in vivo were examined using subcutaneous xenograft models. Results: The stable knock out strains of GP73 in H22 and HepG2 cells were successfully established via puromycin selection. The number of colonies of GP73 knock out groups in HepG2 and H22 cells 10 days after transfection were 400±70 and 248±60, respectively. They were significantly lower than those in the control groups (980±40 and 1 100±50, respectively; P<0.01). In addition, GP73 knockout slowed down the cell cycle progression. Moreover, the cell numbers that had migrated to the underside of the filters were 312±50 and 305±49 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 1 540±87 and 1 270±86 in the controls (P<0.01). For transwell invasion assay, the cell number that had invaded into the underside of the filters were 230±47 and 238±54 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 648±74 and 596±63 in the controls(P<0.01). Furthermore, the tumor volume of GP73 knockout group was (70±170) mm(3,) significantly smaller than (1 200±110)mm(3) of the control guoup (P<0.01). Conclusions: GP73 knockout decreases the proliferation, invasive and migratory abilities of HepG2 and H22 cells in vitro and in vivo. GP73 may contribute to tumorigenesis of hepatocellular carcinoma.

[Clinical analysis of 36 cases of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4].

Objective: To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients. Methods: A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD). Results: All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO(2) improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months. Conclusion: Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.

Hormonal and reproductive factors and risk of esophageal cancer in women: a meta-analysis.

Currently published studies on the relationship between hormonal and reproductive factors and esophageal cancer (EC) risk in women have yielded contradictory findings. For a better understanding of this relationship, we first performed this meta-analysis by pooling all available publications. Sixteen independent studies were retrieved after a comprehensive search in PubMed and Embase databases. The pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were calculated. The pooled RRs implicated that hormone replacement therapy was negatively associated with the risk of EC (RR = 0.72, 95% CI 0.60-0.86, P < 0.001) and esophageal squamous cell carcinoma (RR = 0.68, 95% CI 0.48-0.97, P = 0.031). Menopausal women were at an increased risk of EC (RR = 1.47, 95% CI 1.07-2.03, P = 0.018), particularly esophageal squamous cell carcinoma (RR = 1.66, 95% CI 1.12-2.48, P = 0.012). Additionally, decreased risk of EC (RR = 0.79, 95% CI 0.68-0.92, P = 0.003) and esophageal adenocarcinoma (RR = 0.66, 95% CI 0.53-0.82, P < 0.001) was demonstrated among women with breast-feeding history. Moreover, such associations were more significant among Caucasians, but not Asians. Our study suggests that menopause is an independent risk factor for EC, while hormone replacement therapy and breast-feeding history play a protective role against EC, particularly among Caucasians. All results are consistent with the hypothesis that effects of estrogen may lower the risk of EC in women.

[Comparative proteomics study on lung tissue in early stage of burn-blast combined injury in rats].

OBJECTIVE: To explore changes in the proteomics of lung tissue in early stage of burn-blast combined injury in rats. METHODS: According to a random digital table, a total number of 18 Sprague Dawley (SD) rats were divided into burn-blast combined injury group (n=9) and blast injury group (n=9). Lung protein samples were collected at 6 h post injury. 2-DE was performed to separate proteins. After silver staining, the protein of differential expression were analyzed by PQ Quest and then identified by matrix-assisted laser desorption/ionization time of fight mass spectrometry (MALDI-TOF-MS). The features of the changes of proteomics of rat lung after burn-blast combined injury were studied by biological spectrometry, protein bank and reference article analysis technique. At same time, pathologic changes of the lung were monitored after injury. RESULTS: After removing death drain during the experiment, each group contained 8 rats and the results were analyzed statistically. Well focused and distinct 2-DE maps with good reproducibility were obtained, means of 736±47 and 782±30 protein spots were detected from the blast injury group and burn-blast combined injury group and the matching rates were 91%. From the two groups, 14 differential protein spots expressions were analyzed by MALDI-TOF-MS, of which 10 proteins were up-regulated and 4 proteins were down-regulated in burn-blast combined injury group. 12 different expression proteins were identified in the lung through 2-DE, mass spectrometry and protein date base, including heat shock 27 protein 1, heat shock 70 protein 1, carbonic anhydrase 2, cytochrome c oxidase, ATP synthase subunit alpha, Ca(2+) -transporting ATPase et al, which took part in stress reaction, metabolism, immune response and cytoskeleton. CONCLUSIONS: Burn-blast combined injury could induce dramatically changes of proteomics in lung tissue at early stage. The mechanism probably involves several proteins associated with oxidative stress, energy metabolism, immune response and cytoskeleton.

[Effect of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury].

OBJECTIVE: To explore the role of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury. METHODS: According to the random digital table, a total number of 32 Wistar rats were divided into 4 groups: sham burn (group A), burn group (group B), 12-week post burn recovery group (group C), and 12-week post burn recovery plus a second burn injury group (group D). In group A and group B, lung tissues were harvested on post burn day 4. After received first burn injury 12 weeks, the group C and group D received separately a second sham burn injury and burn injury. Lung tissues were harvested on post burn day 4 after the second burn injury. All tissues were examined for cells apoptosis by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). Pulmonary fibrosis was assessed by Masson trichrome staining and Sirius red staining. The protein expression levels of cleaved Caspase-3, Bax and Bcl-2 were assessed by Western blot. RESULTS: Both Masson trichrome staining and Sirius red staining showed obvious pulmonary fibrosis in group C and group D. The apoptosis rates of group B, C and D were significantly higher than that in group A ((15.50±3.30)%, (7.88±3.10)%, (15.88±3.23)% vs (2.10±1.07)%, all P<0.05). Compared to group A, cleaved Caspase-3 levels were significantly higher in group B, C and D ((0.59±0.11), (0.33±0.08), (0.73±0.13) vs (0.16±0.05), all P<0.05). The ratio of Bax/Bcl-2 in group B, C and D also increased significantly ((2.08±0.30), (0.83±0.09), (1.54±0.12) vs (0.64±0.05), all P<0.05). CONCLUSION: Severe burn injury can induce pulmonary fibrosis and mitochondrial apoptosis may play an important role in the development of pulmonary fibrosis.

[Clinicopathologic analysis of anastomosing hemangioma of the kidney and adrenal gland].

Objective: To investigate the clinical and histopathologic characteristics, diagnosis, differential diagnosis and prognostic features of anastomosing hemangioma. Methods: Five cases of anastomosing hemangioma of the kidney and adrenal gland were collected, the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed with review of literature. Results: Three patients were male and two were female with ages ranging from 47 to 77 years; three were located in adrenal gland and 2 originated from the kidney. Clinically, 4 tumors were incidentally identified, 1 presented as edema of lower extremity. By radiography, all presented as a well-demarcated, oval, solid and low-density mass. Grossly, the tumors ranged in maximum diameter from 1.6 to 2.5 cm (mean 2.1 cm). Microscopically, the tumors consisted of anastomosing sinusoidal capillary-sized vessels lined by a single layer of flattened, cubical to hobnail endothelial cells, setting in an pauci-cellular stroma of edematous and hyaline changes. Other commonly seen features included vaguely lobular growth pattern (3/5), hemorrhage and thrombosis (5/5), intravascular growth pattern (5/5), eosinophilic intracytoplasmic hyaline globules (1/5) and extramedullary hematopoiesis (3/5). The tumor cells were typically bland-appearing and mitoses were scarce, with 1 case demonstrating cellular foci of tumor with slight pleomorphism and increased mitoses (2/50 HPF). Immunohistochemical studies showed the tumor cells expressed endothelial cells markers. Follow-up information was available for all 5 patients and showed no evidence of tumor recurrence or metastasis within 6 to 52 months (mean 30 months). Conclusions: Anastomosing hemangioma is a rare, benign subtype of capillary hemangioma that predominantly affects the urologic organs and adrenal glands; it is needed to distinguish it histologically from a series of benign or malignant tumors that feature a richly vascular stroma. Careful attentions to its characteristic morphology with the judicious use of immunohistochemistry can help distinguish this tumor from its many mimickers.

Monolithic high-index contrast grating: a material independent high-reflectance VCSEL mirror.

In this paper we present an extensive theoretical and numerical analysis of monolithic high-index contrast grating, facilitating simple manufacture of compact mirrors for very broad spectrum of vertical-cavity surface-emitting lasers (VCSELs) emitting from ultraviolet to mid-infrared. We provide the theoretical background explaining the phenomenon of high reflectance in monolithic subwavelength gratings. In addition, by using a three-dimensional, fully vectorial optical model, verified by comparison with the experiment, we investigate the optimal parameters of high-index contrast grating enabling more than 99.99% reflectance in the diversity of photonic materials and in the broad range of wavelengths.