[Clinicopathological characteristics of gastric SMARCA4-deficient undifferentiated/rhabdoid carcinoma].

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.

[Expression level and prognostic value of PD-L1 in microsatellite instability-high gastric cancer].

Objective: To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer. Methods: The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers. Results: MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression (P<0.05, respectively). Combined positive score (CPS) was an independent risk factor (P=0.026, HR=8.385, 95%CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion (P=0.007) and infiltration depth (P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site (P=0.45). Conclusions: MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.

Cesarean scar pregnancy associated with uterine artery pseudoaneurysm: a case report.

Cesarean scar pregnancy (CSP) and uterine artery pseudoaneurysms (UAPs) are associated with massive uterine hemorrhage and mortality. As a result of their low prevalence, the occurrence of CSP and a UAP in the same patient is extremely rare. The authors describe a patient who was initially misdiagnosed with trophoblastic disease by ultrasonography. The lesion had a blood-rich area of 75 x 65 x 61 mm on ultrasonography. Pelvic angiography revealed a UAP in the right side of the uterus. The patient underwent uterine artery embolization (UAE) immediately after the correct diagnosis was confirmed. Curettage was undertaken under ultrasound guidance one week postoperatively. Histopathological examination of the resected tissue revealed degenerative chorionic villi and trophoblasts with blood clots. Serum levels of beta-human chorionic gonadotropin (ß-hCG) and uterine ultrasound recovered to normal levels two weeks and three months later, respectively.

Clinical analysis of diagnosis and treatment of 13 cases with cesarean scar pregnancy.

OBJECTIVE: To explore effective methods in diagnosing and treating cesarean scar pregnancy (CSP) after cesarean section. MATERIALS AND METHODS: The clinical data of 13 cases with CSP who were admitted to the present hospital from October 2009 to February 2012 were retrospectively analyzed. RESULTS: The agreement diagnostic rate was 92.3% (12/13). On the basis of transvaginal color Doppler ultrasonography 12 patients had medical therapy combined with uterine artery embolization (UAE) and curettage was successfully performed. One patient was diagnosed through an emergency setting due to symptomatology. CONCLUSION: Early accurate diagnosis of CSP is the key to perform proper and successful treatment.

Plasmonic Ag nanoparticles via environment-benign atmospheric microplasma electrochemistry.

Atmospheric-pressure microplasma-assisted electrochemistry was used to synthesize Ag nanoparticles (NPs) for plasmonic applications. It is shown that the size and dispersion of the nanoparticles can be controlled by variation of the microplasma-assisted electrochemical process parameters such as electrolyte concentration and temperature. Moreover, Ag NP synthesis is also achieved in the absence of a stabilizer, with additional control over the dispersion and NP formation possible. As the microplasma directly reduces Ag ions in solution, the incorporation of toxic reducing agents into the electrolytic solution is unnecessary, making this an environmentally friendly fabrication technique with strong potential for the design and growth of plasmonic nanostructures for a variety of applications. These experiments therefore link microplasma-assisted electrochemical synthesis parameters with plasmonic characteristics.

Molecular analysis of imipenem-resistant Acinetobacter baumannii isolated from US service members wounded in Iraq, 2003-2008.

Global dissemination of imipenem-resistant (IR) clones of Acinetobacter baumannii - A. calcoaceticus complex (ABC) have been frequently reported but the molecular epidemiological features of IR-ABC in military treatment facilities (MTFs) have not been described. We characterized 46 IR-ABC strains from a dataset of 298 ABC isolates collected from US service members hospitalized in different US MTFs domestically and overseas during 2003-2008. All IR strains carried the bla(OXA-51) gene and 40 also carried bla(OXA-23) on plasmids and/or chromosome; one carried bla(OXA-58) and four contained ISAbal located upstream of bla(OXA-51). Strains tended to cluster by pulsed-field gel electrophoresis profiles in time and location. Strains from two major clusters were identified as international clone I by multilocus sequence typing.

Methicillin-resistant Staphylococcus aureus infection in combat support hospitals in three regions of Iraq.

SUMMARYStaphylococcus aureus is a leading cause of infections in deployed service members. Based on a molecular epidemiological study of 182 MRSA isolates from patients in three U.S. Army combat support hospitals in separate regions in Iraq, USA300 clone was the most predominant (80%) pulsotype. This finding suggested that strain carriage from the home country by military personnel is epidemiologically more important than local acquisition.

[Ultrasonographic assessment and differentiation of spontaneous degenerating cystic thyroid nodules and papillary thyroid carcinomas].

Objective: To analyze the features of degenerating cystic thyroid nodules (DCTN) on conventional ultrasound and contrast-enhanced ultrasound (CEUS), and to explore the differentiation between DCTN and papillary thyroid carcinomas (PTC). Methods: A total of 46 DCTN (39 cases, including 12 males and 27 females, with an age range of 25 to 76 years) and 36 PTC (32 cases, including 8 males and 24 females, with an age range of 23 to 68 years) diagnosed via fine- needle aspiration (FNA) or surgery from February 2019 to January 2020 in the First Affiliated Hospital of Nanchang University were enrolled. The size, shape, margin, echogenicity, presence of shadowing, calcification and vascularity of DCTN and PTC were retrospectively evaluated, and 28 DCTN and 30 PTC underwent CEUS were separately analyzed and compared.The t test, χ² test or Fisher's exact test were implemented to compare the features of ultrasound among the two groups. The binary Logistic regression test was performed to determine whether the feature whose difference was statistically significant was an independent predictive risk factor. Results: A univariate analysis indicated that DCTN more frequently showed wider-than-tall shapes, marked hypoechogenicity, well-defined margin and no or dot-lined enhancement (wider-than-tall shapes: 36 vs. 17, χ2=8.511; well-defined margin: 30 vs. 15, χ2=4.523; marked hypoechogenicity: 27 vs. 9, χ2=9.310; no or dot-lined enhancement: 24 vs. 3, χ2=33.369; all P＜0.05). A multivariate analysis demonstrated that wider-than-tall shapes, well-defined margin and marked hypoechogenicity were independent predictors for DCTN (OR values were 5.204, 3.134 and 5.042, P values were 0.003, 0.031, and 0.003, respectively). Among 28 DCTN, 15 showed a decrease in mean maximum diameter (24.3±11.4 mm) with a mean time span of (18.6±10.5) months between the presence and absence of suspicious ultrasound features. Conclusions: Compared with PTC, DCTN shows the ultrasound characteristics of wider-than-tall shapes, well-defined margin, marked hypoechogenicity and no or dot-lined enhancement pattern. Ultrasound follow-up can help to identify spontaneous DCTN.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin.

The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.

A novel rat model of chronic heart failure following myocardial infarction.

In this report, we describe an improved method for the establishment of reproducible congestive heart failure (CHF) in a rat model. The area of myocardial infarction (MI) after ligation of the left anterior descending (LAD) coronary artery was quantified. Histological changes, heart function detected by echocardiography and isolated Langendorff perfusion, and selected biochemical factors were monitored after ligation of the LAD. Contrary to previous beliefs, thoracotomy in the second intercostal space provided a much better visualization of and easier access to the LAD and significantly reduced the mortality rate. Surface electrocardiogram (ECG) showed that the S-T interval was arched raised upward immediately after ligation. Typical morphological and functional changes of CHF were observed after LAD ligation. Cardiomyocytes in the infarcted zone were depleted and deranged. Biochemical analysis and enzyme-linked immunosorbent assay (ELISA) showed that superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and nitric oxide (NO) levels were significantly lowered in rats with MI than in the normal and sham groups, whereas serum malondialdehyde (MDA), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin (cTnT) and C-reactive protein (CRP) levels were elevated. After MI, N-terminal pro-brain natriuretic peptide (NT-proBNP) was increased but insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) in culture supernatant were lower than in the normal and sham groups. We present an improved model for maximal reproducibility of experimental CHF in rats which allows the study of molecular and physiological variables in relation to CHF.

Enhanced angiotensin converting enzyme 2 regulates the insulin/Akt signalling pathway by blockade of macrophage migration inhibitory factor expression.

BACKGROUND AND PURPOSE: Macrophage migration inhibitory factor (MIF) is now known to be a pro-inflammatory cytokine associated with insulin resistance. Our aim was to investigate whether angiotensin converting enzyme 2 (ACE2) could modulate the expression of MIF and the insulin/Akt-endothelial nitric oxide (NO) synthase (eNOS) signalling in a human endothelial cell line (EAhy926). EXPERIMENTAL APPROACH: A recombinant plasmid encompassing human ACE2 gene was constructed and transfected into the EAhy926 cells. The mRNA, phosphorylation and protein levels of p22phox, MIF, Akt and eNOS in endothelial cells were determined by real-time PCR and Western blot analysis, respectively. KEY RESULTS: Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells. In addition, Ang II diminished insulin-stimulated phosphorylation of Akt (at Ser(473)) and eNOS (at Ser(1177)) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells. CONCLUSIONS AND IMPLICATIONS: The results reveal that gene transfer of ACE2 regulated Ang II-mediated impairment of insulin signalling and involved the Akt-eNOS phosphorylation pathway. These beneficial effects of ACE2 overexpression appear to result mainly from blocking MIF expression in endothelial cells, suggesting that the ACE2 gene may be a novel therapeutic target for diseases related to inflammation and insulin resistance.

Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1.

Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha9beta1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha9beta1, we have generated mice lacking expression of the alpha9 subunit. Mice homozygous for a null mutation in the alpha9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha9(-/-) mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha9 deficiency could be one cause of congenital chylothorax.

Reduced occurrence of ventilator-associated pneumonia after cardiac surgery using preoperative 0.2% chlorhexidine oral rinse: results from a single-centre single-blinded randomized trial.

Since mechanical ventilation after cardiac surgery increases the risk of ventilator-associated pneumonia (VAP), we conducted a prospective randomized controlled trial to investigate the effect of preoperative 0.2% chlorhexidine on postoperative VAP. Ninety-four patients scheduled for heart surgery were randomized to a chlorhexidine group (N = 47) or control (saline) group (N = 47). On the day before surgery, patients gargled three times with 0.2% chlorhexidine or saline 30 min after each meal and 5 min after teeth brushing at bedtime. VAP occurred in 8.5% of the chlorhexidine group and in 23.4% of the controls. Preoperative chlorhexidine mouthwash reduced the incidence of postoperative VAP significantly.

The effects of media properties on the horseradish peroxidase-catalyzed fluorogenic reaction.

The effects of media properties including buffers, acidity, solvents and surfactant on horseradish peroxidase-catalyzed fluorogenic reaction were investigated. The results showed that the so-called non-fluorescent hydrogen donors were in fact fluorescent. There existed an acid-base equilibrium in the fluorescent dimer product. For p -hydroxyphenylpropionic acid, a pK(a) value of 8.0 for the product was obtained from its titration curve. The product fluorescence increased with higher pH, however, a longer time was needed to reach the reaction equilibrium due to the pH mismatch problem. Cationic micelles cetyltrimethylammonium bromide and cetyltrimethylammonium chloride could reduce the pH mismatch and offered a way to further increase the determination sensitivity. Finally, a micelle-enhanced flow-injection analysis of horseradish peroxidase is suggested.

Pathogenesis of extrinsic allergic alveolitis and pulmonary fibrosis induced by streptomyces thermohygroscopicus.

There were 48 strains of thermophilic actinomyces isolated from the specimens of mouldy hay and sputum of the patients suffering from farmer's lung (FL). Streptomyces thermohygroscopicus (STHs), one strain of them, was used for this investigation. The microorganisms were injected into the lungs of rabbits and rats by thyrocrico- or tracheocentesis. The results showed that the pathological changes in the lungs including macrophage alveolitis, granuloma formation and diffuse interstitial were similar to that induced by other thermophilic actinomyces. IgG and C3 deposition in the lesions were also observed by immunofluorescence examination. Specific immunocomplexes in the sera of some animals were detected by ELISA with the STH-antisera. The results suggested that STHs was possibly one of the pathogens responsible for FL in China's countryside.

The prevalence of NIDDM and IGT and related factors among residents in some areas of Hubei Province, China.

The epidemiological survey of prevalence of NIDDM (non-insulin dependent diabetes mellitus) and IGT(impaired glucose tolerance) was conducted among 9450 residents aged 25-70 in some areas of Hubei Province, China. The results show that NIDDM and IGT prevalences are 2.62% and 4.48%, respectively. There is no significant difference between male and female (P > 0.05). The NIDDM prevalence in cities is slightly higher than that in countryside, but the difference is not significant (P > 0.05). However, the IGT prevalence in city is significantly higher than that in countryside (P < 0.01). The prevalence of both NIDDM and IGT is increasing along with the age of the population. It is also significantly related to the family history of NIDDM, hypertension, and high body mass index (BMI). By using stepwise logistic regression to analyse the risk factors of NIDDM, age (OR = 1.86), BMI(OR = 2.69), family history (OR = 2.84) and hypertension (OR = 2.23) entered the model (significance level is alpha = 0.05).

[Clinical use of polysomnography (PSG)].

The clinical diagnoses in 695 cases using PSG were analysed. The results are as follows: Obstructive sleep apnea syndrome (OSAS) in 482 cases (69.4%), chronic obstructive pulmonary diseases with nocturnal hypoxemia in 25 cases (3.6%), epilepsy in 31 cases (4.5%), other sleep disorders in 5 cases (0.7%), and essentially normal in 152 cases (21.9%). Some parameters of PSG in 65 cases with OSAS and those in 2 cases before and after treatment were analysed. It is emphasized that PSG is using for diagnosis of different types of OSAS with appraisable seriousness and of other related sleep disorders. The method and indications of PSG were discussed.

[Synchronous spectrofluorimetry for simultaneous determination of riboflavin and pyridoxine and its application in multivitamin preparations].

A new method for the simultaneous determination of riboflavin and pyridoxine by synchronous spectrofluorimetry is described. The measurement was carried out in a buffer solution of pH 7 with delta lambda = 58 nm for synchronous scanning. Under the experimental conditions two peaks appeared at 526 nm and 389 nm in the obtained synchronous fluorescence spectrum, corresponding to riboflavin and pyridoxine, respectively. This method was proved to be simple and specific. The fluorescence relative intensity is linearly related with concentration over the range of 0-1 microgram/ml and 0-1.5 micrograms/ml for riboflavin and pyridoxine, respectively. The detection limit was 0.5 ng/ml for riboflavin and 1 ng/ml for pyridoxine. The relative errors of the measurements were less than 5% for artificial samples. The proposed method has been applied to the analyses of riboflavin and pyridoxine in three kinds of commercial multivitamin preparations. The obtained synchronous spectra of multivitamin preparations coincided with those of the mixed standard solution of riboflavin and pyridoxine. Recoveries of 93.5-105.7% were obtained.