Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma / 中华病理学杂志

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

Clinical research progress on the antidepressant effects of ketamine / 四川精神卫生

Ketamine has gained increasing attention as a novel antidepressant. This article reviews the clinical studies on the antidepressant and anti-suicidal properties of ketamine and its enantiomers （R-ketamine， S-ketamine）.

Social function in long-term hospitalized patients with stable schizophrenia and its influential factors / 中国神经精神疾病杂志

Objective To explore social function of long-term hospitalized patients with stable schizophrenia and its influential factors to provide scientific evidence for improving social function in long-term hospitalized patients with schizophrenia. Methods A total of 75 long-term hospitalized patients with stable schizophrenia were enrolled. The Social Functional Rating Scale (SFRS), Positive and Negative Syndrome Scale (PANSS), Insight and Treatment Attitude Questionnaire (ITAQ), Rating Scale for Extrapyramdal Side Effects (RSESE) and MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) were used to assess social function, clinical symptoms and cognitive function of patients. Bivariate correlation analysis and linear regression were used to examine the correlations between social function and clinical symptoms as well as cognitive function. Results The average score of SFRS was (53.6 ±9.3). Linear regression analysis showed that negative symptom of PANSS (B= 0.322, P=0.009), speed of processing (B=-0.428, P<0.001), working memory (B=-0.191, P=0.020)and RESES (B=0.918, P=0.002) were significantly associated with social function. The Sobel test showed significant indirect effects between negative symptom and social function, which were significantly mediated by working memory (Z=3.367, P<0.001) and speed of processing (Z=1.995, P=0.046). Conclusion Social function of long-term hospitalized patients with stable schizophrenia is influenced by negative symptom, speed of processing, working memory and extrapyramdal side effects. There is a mediating effect between PANSS negative symptoms and SFRS in working memory and processing speed.

Influence of reducing antipsychotic drug dose on psychotic symptoms in schizophrenia stabilization period / 中国神经精神疾病杂志

Objective To investigate the effect of reducing antipsychotic dose on clinical symptoms in patients with stable schizophrenia. Methods Seventy-five patients with stable schizophrenia taking olanzapine or risperidone were enrolled. Patients were randomly divided into dose reduction group (37 cases) and maintenance group (38 cases). The dose of the risperidone or olanzapine was gradually reduced by 50％ in the dose reduction group within six months whereas remained unchanged in the maintenance group. The Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale (CDRS), Personal and Social Performance Scale (PSP), Insight and Treatment Attitude Questionnaire (ITAQ) and Extrapyramidal Side Effects Scale (RSESE) were assessed at baseline, 3 months, 6 months and 12 months. Results There were one and two cases dropped out due to the relapse in dose reduction group and in maintenance group, respectively. The recurrence rates were 2.7％ in dose reduction group and 5.3％ in maintenance group (P<0.05). The interaction effects of PANSS positive symptoms, negative symptoms and general pathological symptoms, ITAQ,RSESE, PSP were significant (P<0.05). The main effect of PANSS negative symptoms and PSP group was significant (P<0.05). Compared with the maintenance group, PANSS negative symptoms of the dose reduction group were significantly lower at 6 and 12 months (P<0.05). PSP scores were significantly higher in the dose reduction group than in maintenance group (P<0.05) at 3, 6 and 12 months. Conclusion Reducing the dose of risperidone or olanzapine slowly in patients with stable schizophrenia within six months reduces negative symptoms and adverse reaction, improves social function without increasing positive symptoms.

Progress of CALR gene mutation in myeloproliferative neoplasm / 白血病·淋巴瘤

Myeloproliferative neoplasm (MPN) is a kind of clone hematopoietic stem cell disease characterized by one or more myeloid cell lines hyperproliferation, including bcr-abl gene positive chronic myeloid leukemia (CML) and bcr-abl negative MPN, the later representing polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A big stride has been made since the discovery of JAK2 and MPL gene mutations. However, the exact genetic basis of JAK2/MPL mutation double negative in MPN patients is still unclear. It has been reported recently that a new CALR mutation is discovered in the JAK2/MPL unmutated MPN patients who show unique clinical presentations, which provides a new diagnostic and prognosis-accessing criteria. The paper reviews CALR mutation and genetic mechanism mediating MPN.

Biotransformation of quercetin by Gliocladium deliquescens NRRL 1086 / 中国天然药物

With an attempt to synthesize high-value isoquercitrin (quercetin-3-O-β-D-glucopyranoside), we carried out the biotransformation of quercetin (1) by Gliocladium deliquescens NRRL 1086. Along with the aimed product quercetin 3-O-β-D-glycoside (2), three additional metabolites, 2-protocatechuoyl-phlorogucinol carboxylic acid (3), 2,4,6-trihydroxybenzoic acid (4), and protocatechuic acid (5), were also isolated. The time-course experiments revealed that there were two metabolic routes, regio-selectivity glycosylation and quercetin 2,3-dioxygenation, co-existing in the culture. Both glycosylation and oxidative cleavage rapidly took place after quercetin feeding; about 98% quercetin were consumed within the initial 8 h and the oxdized product (2-protocatechuoyl-phlorogucinol carboxylic acid) was hydrolyzed into two phenolic compounds (2,4,6-trihydroxybenzoic acid and protocatechuic acid). We also investigated the impact of glucose content and metal ions on the two reactions and found that high concentrations of glucose significantly inhibited the oxidative cleavage and improved the yield of isoquercitrin and that Ca, Fe, Mn, Mg, and Zn inhibited glycosylation. To test the promiscuity of this culture, we selected other four flavonols as substrates; the results demonstrated its high regio-selectivity glycosylation ability towards flavonols at C-3 hydroxyl. In conclusion, our findings indicated that the versatile microbe of G. deliquescens NRRL 1086 maitained abundant enzymes, deserving further research.

The diagnostic value of IL-10 and IL-6 level in cerebrospinal fluid for primary central nervous system lymphoma / 中华检验医学杂志

Objective To investigate the expression of Interleukin 6 ( IL-6 ) and interleukin 10 (IL-10) in cerebrospinal fluid(CSF) in patients with primary central nervous system lymphoma.Methods Forty cases of primary central nervous system lymphoma ( PCNSL) , 11 cases of secondary central nervous system lymphomas( SCNS) , 20 cases of brain metastase, 20 cases of central nervous system infection and 16 cases of other nervous system disease( ONSD) were collected during the period from July 2013 to December 2015 in Fudan University Hua Shan Hospital North.Enzyme linked immunosorbent assay was used to detect the levels of IL-6 and IL-10 in serum and cerebrospinal fluid.The overall level of each group was compared using Kruskal-Wallis test.Two independent samples were compared by U Mann-Whitney test.The diagnostic value of IL-6 and IL-10 levels for PCNSL was evaluated by ROC curve.Results In PCNSL group, BM group, SCNSL group, CNSI group and ONSD group, the serum levels of IL-6 and IL-10 were not statistically significant ( H values were 4.165 and 5.368, respectively, P>0.05).IL-6 levels in CSF were significantly higher in CNSI[623.73 (1018.77-184.37) pg/ml] than those in other groups ( ZPCNSL =51.36, ZSCNSL =28.18, ZBM =51.50, ZCNSI =85.45, ZONSD =42.16, P<0.05 ) .The levels of IL-10 in CSF were significantly higher in CNSI and PCNSL than those in other groups ( ZPCNSL =74.50, ZSCNSL =34.68, ZBM =35.35, ZCNSI =72.95, ZONSD =15.66, P<0.05).The levels of IL-10 in CSF in PCNSL group[64.88(20.03-206.14)pg/ml]was significantly higher than in SCNSL group[6.28(2.78-18.87)pg/ml, Z=-3.753,P<0.05], BM group[7.30(3.72 -14.49) pg/ml, Z=-5.034,P<0.05] and ONSD group [3.14(2.931-4.20)pg/ml, Z=-5.786,P<0.05].The area under the ROC curve of IL-6 and IL-10 levels in CSF was 0.461 and 0.806 respectively for the diagnosis of PCNSL.When IL-10 was 19.62 pg/ml, the sensitivity was 77.5% ( 31/40 ) and the specificity was 70.1% ( 47/67 ) .The area under the ROC curve of CSF IL-6 and IL-10 levels was 0.861 and 0.718 respectively for the diagnosis of CNSI.When IL-6 was 155.12 pg/ml, the sensitivity was 80.0% (16/20) and the specificity was 90.8% (79/87).When IL-10 was 26.76 pg/ml, the sensitivity was 80.0% ( 16/20 ) and the specificity was 66.7% ( 58/87 ) . Conclusion The expression levels of IL-6 and IL-10 in CSF can be used as an indicator for the differential diagnosis of primary central nervous system lymphoma.

Detecting JAK2 V617F mutation in myeloproliferative neoplasms by microarray based digital PCR / 中华检验医学杂志

Objective To evaluate the sensitivity, repeatability and accuracy of microarray digital PCR system in detecting JAK2 V617F mutation, which was closely related to myeloproliferative neoplasms (MPN).Methods All of the 31 MPN patients with JAK2 V617F mutation, including 18 cases of polycythemia vera(PVs),11 primary thrombocythemias (ETs) and 2 primary myelofibrosis (PMFs), were collected from Huashan Hospital, Fudan University during 2014 -2015, while 10 normal controls and 6 cases with abnormal increased hemoglobin were involved.Human erythroleukemia cell line ( HEL ) and colorectal cancer cell SW480 were used as the mutant and the wild type control, respectively.The sensitivity of microarray digital PCR were verified by detecting the gradient diluted mutation standard harboring 30%, 10%, 1%, 0.1%and 0.01%mutant allele burden, respectively .Repeatability was evaluated by detecting 1%and 10% mutated samples for 5 times, respectively.MGB probe real time PCR was selected as the reference method to verify the accuracy of the digital PCR.Results With digital PCR, the accurate quantitation of JAK2 V617F mutation was achieved down to 0.1%, which is approximate to 0.16 copies per microliter.The results obtained from the two kinds of technique showed a high correlation by linear regression analysis (R2 =0.998 3).The results of repeated samples showed CVs as 17.18% for 1%mutant allele burden and 7.50%for 10%.Among all cases, the 31 patients known mutated were detected as positive and 10 controls as negative by both digital PCR and Real time PCR.In another 6 cases, 2 were found JAK2 V617F mutation of low allele burdens of 0.37% and 0.18% by digital PCR but detected as negative by real time PCR.Conclusions Microarray digital PCR offers a higher sensitivity and better repeatability than real time PCR which could help detect rare JAK2 V617F mutations in MPNs accurately.

Effects of rosiglitazone on the proliferation of and expressions of β-catenin and cyclin D1 in HaCaT cells / 中华皮肤科杂志

Objective To estimate the effects ot rosiglitazone on cultured HaCaT human keratinocytes and their possible mechanism.Methods HaCaT cells were cultured and treated with different concentrations ( 10,20,40,80 μ mol/L) of rosiglitazone or solvent for 24,48,72 and 96 hours,respectively.Cell proliferation was detected with methyl thiazolyl tetrazolium (MTT) assay.Western blot was performed to measure the protein expression of β-catenin and cyclin D1.Results Compared with the solvent-treated cells,the proliferation of HaCaT cells was significantly inhibited by 18.9％,23.7％,35.1％ and 44.6％ (all P＜ 0.05) after treatment with rosiglitazone of 10,20,40 and 80 μmol/L,respectively,for 48 hours.The expressions of β-catenin and cyclin D 1 were significantly lower in rosiglitazone-treated HaCaT cells than in solvent-treated cells (all P ＜ 0.05).Conclusion Rosiglitazone could inhibit the proliferation of HaCaT cells,likely by downregulating the expressions of β-catenin and cyclin D 1.

Advance on mediastinal gray zone lymphoma / 白血病·淋巴瘤

As a distinct clinicopathological entity, mediastinal gray zone lymphoma cannot be classified by using differential diagnostic criteria. The cases represent a spectrum of tumors having characteristics of both primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma (cHL). In the 2008 WHO Classification, a novel category designated B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu) has been created to include these neoplasms. The main features of BCLu are clearly different from those of conventional mediastinal large B-cell lymphomas. Diagnosis of BCLu requires a multiparameter approach incorporating morphological, immunophenotypic, immunohistochemical and other features. These lymphomas generally have a more aggressive clinical course and poorer outcome. There is no consensus on the optimum treatment, while the recommended therapies for aggressive B-cell lymphomas might be effective options.

Bortezomib depresses osteoblast apoptosis induced by mouse myeloma cells / 中国实验血液学杂志

The purpose of this study was to explore the effect of proteasome inhibitor, bortezomib (Bzb), on osteoblast in pathologic status of myeloma bone disease. The myeloma bone disease was modeled by co-culture of mouse myeloma cell RPMI8226 with osteoblast line MC-3T3E1 from mouse calvaria, and intervenient culture of supernatant. The inhibitory effect of Bzb on proliferation of MC-3T3E1 assayed by modified MTT method, the apoptosis of MC-3T3E1 cells was determined by flow cytometry with Annexin V/PI staining, the expressions of osteoblast markers, Runx2/cbfa1, osteocalcin (OCN) and osterix (OSX) in MC-3T3E1 treated with Bzb were detected by RT-PCR and Western blot respectively. Experiments were divided into 3 group: single cultured, co-cultured and supernatant-interveniently cultured groups. The results showed the Bzb in higher concentration inhibited proliferation of MC-3T3E1 cells in a dose-dependent manner, with the IC(50) of 38.1 nmol/L for 48 hours, the Bzb in low concentration (5 nmol/L) did not show the inhibitory effect on proliferation of MC-3T3E1 in single cultured group (p>0.10), but could decrease apoptotic rate of MC-3T3E1 by 32.5% and 24.6% respectively in cocultured and supernatant-interveniently cultured groups, moreover increased the expression of osteoblast-related gene OSX, OCN mRNA and protein (p<0.05), while no obvious change of Runx2/cbfa1 expression was observed (p>0.05). It is concluded that the proteasome inhibitor, Bzb, in low concentration promotes the activity of osteoblast internal mechanisms, and prevents the apoptosis of osteoblasts induced by myeloma cells. In addition, it can up-regulate transcription and expression of osteoblast markers related to Runx2/cbfa1 path way, thus may protect osteoblasts in myeloma bone disease.

A retrospective study on the long-term clinical outcomes of 310 porcelain laminate veneers / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the long-term clinical outcomes of porcelain laminate veneers 1-8 years following delivery.</p><p><b>METHODS</b>A total of 310 feldspathic porcelain laminate veneers on anterior teeth or premolars in 49 patients were included in the present study 1-8 years following delivery. All the subjects underwent a detailed clinical examination utilizing modified United States Public Health Service (USPHS) criteria. Restoration integrity, abrasion, color satisfaction, marginal discoloration, marginal adaptation, secondary caries, postoperative sensitivity, and gingival index (GI) of the prostheses were evaluated according to modified USPHS criteria. The 1-8 year survival rates of the veneers were statistically analyzed using the life table method.</p><p><b>RESULTS</b>The survival rates of porcelain laminate veneers were 98.7%, 98.0%, 93.8%, 93.2%, 89.7%, 81.8%, 76.3%, and 76.3% in 1 to 8 years, respectively.</p><p><b>CONCLUSIONS</b>The long-term clinical outcomes of porcelain laminate veneers are satisfying.</p>

The pathway of absorption and conveying of puerarin microemulsion-in-oil / 药学学报

The best absorption location of puerarin microemulsion-in-oil in intestine parva of rat and pharmacokinetic characteristics, and the pathway of absorption and conveying of puerarin microemulsion were studied. In situ rat perfusion method was used to investigate the intestinal absorption of puerarin. Through the changes of drug concentration in blocked and unblocked lymphs, to determine the pathway of absorption and conveying. Puerarin microemulsion-in-oil can be absorbed in any part of intestine, and the K(a), P(app) of every part is ileum > duodenum > jejunum > colon, and the K(a), P(app) of ileum is significantly larger than that of others. The absorption rate of different concentrations is not significantly different (P > 0.05). The puerarin transited by gastrointestinal tract, about 36.8% is absorbed by the lymphatic channels to enter the systemic circulation and 63.2% is absorbed by the non-lymphatic channels. The best part of intestine to absorb puerarin microemulsion is ileum, and it is passive transport. The pathway of conveying is lymphoid and non-lymphoid transit.

Cognitive Impairment in Alzheimer Disease / 中国心理卫生杂志

Objective:to study cognitive impairment of patients with Alzheimer disease (AD). Method:62 patients with AD and 159 normal elderly were tested with MMSE. Result:The patients group had lower scores in all subtests except that of naming. Level of education had positive correlation with the total score, subscores of attention and calculation, understanding, and describe graph. Conclusion:MMSE can be used in clinical assessment of cognitive function of patients with AD.