Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

Effect of Scutellaria baicalensis Georgi on metabolism in RSV infection mice based on metabolomics / 药学学报

This study, aiming at finding biomarkers which can assist in the diagnosis of respiratory syncytial virus (RSV) pneumonia and analyzing the metabolic pathways of anti-RSV activity of Scutellaria baicalensis Georgi (SG)., explores the improvement effect of SG on mice models infected by RSV with the metabolomics technology based on UPLC-Q-Exactive HF X-MS. Mice models affected by RSV are established by nasal drip method and the changes of body weight, rectal temperature and pathological damage of lung tissue are evaluated. The lung tissue samples of mice in each group are collected and analyzed by UPLC-Q-Exactive HF X-MS. The differential metabolites of SG drug intervention are explored by metabolomics technology, and the metabolic pathways regulated by SG are analyzed. The results show that SG can significantly improve the pathological state of the lung tissue of the mice and make its body weight and rectal temperature tend to be normal. In the lung tissue samples, 46 biomarkers, such as guanine, L-asparagine, and arachidonic acid, are screened for disease development in RSV model mice. SG improved RSV infection by recalling 22 potential biomarkers, such as uric acid, arachidonic acid, and alanine. The 22 potential markers mainly involved 11 abnormal metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, and arachidonic acid metabolism, alanine, aspartic acid and glutamate metabolism are closely related to the five metabolic pathways. SG improves RSV-infected mice mainly by regulating amino acids, lipids, cofactors and vitamins and nucleotide metabolites. All animal experiments were conducted under the guidance and approval of the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine. (approval number: SDUTCM20210311001).

Cardiac shock wave therapy for coronary heart disease: an updated meta-analysis

Abstract Introduction: The aim of this article is to study the efficacy and safety of cardiac shock wave therapy (CSWT) in the treatment of coronary heart disease (CAD). Methods: A comprehensive search of electronic databases and a manual search of conference papers and abstracts were performed until September 30, 2018. The studies using RevMan 5.3 and STATA 14.0 softwares were reviewed, and meta-analyses were performed on 13 indicators, such as a six-min walking distance test (6MWT), New York Heart Association (NYHA) functional class, Seattle Angina Questionnaire (SAQ) score, angina class (Canadian Cardiology Society [CCS]), etc. Results: A total of 26 articles were included. The total patient population was 855, of which 781 patients were treated with CSWT. Meta-analyses indicated that 6MWT (mean difference [MD] 75.64, 95% confidence interval [CI] 49.03, 102.25, P<0.00001) and NYHA (MD -0.70, 95% CI -0.92) in the CSWT group were comparable to those in the conventional revascularization group (MD -0.70, 95% CI -0.92, -0.49, P<0.00001). SAQ (MD 10.75, 95% CI 6.66, 14.83, P<0.00001), CCS (MD -0.99, 95% CI -1.13, -0.84, P<0.00001), nitrate dosage (MD -1.84, 95% CI -2.77, -1.12, P<0.00001), LVEF (MD 3.77, 95% CI 2.17, 5.37, P<0.00001), and SSS (MD -4.29, 95% CI -5.61, -2.96, P<0.00001), SRS (MD -2.90, 95% CI -4.85, -0.95, P=0.004), and the exercise test (standard mean difference 0.57, 95% CI 0.12, 1.02, P=0.01) all showed significant differences. Conclusion: CSWT may offer beneficial effects to patients with CAD, but more large-scale clinical studies are needed to further verify its therapeutic effect.

Detection of Amino Acids and Polypeptides by Electrospray Ionization-Ion Mobility Spectrometry / 分析化学

The electrospray ionization-ion mobility spectrometric (ESI-IMS) technique has the potential as an analytical separation tool in analyzing polypeptides and amino acids for fast screening unknown samples in anti-chemical and biological terror attacks. A method for detecting several polypeptides and amino acids was developed based on ESI-IMS using air as drift gas at room temperature. The ion mobility of four amino acids and two polypeptides dissolved in methanol was determined on the system at elution rate of 2 mL/ min. The spectra of these compounds had characteristics of finger-printing maps. The limit of detection of this instrument for Substance P could reach 855 ng / mL in 1 min. The results showed that a small, self-contained ESI-IMS instrument with reservoirs of air could be used to quickly detect and accurately identify polypeptides and amino acids.

Specific cytotoxicity of natural killer cells against hepatocellular carcinoma and potential mechanism / 军事医学

Objective To evaluate the cytotoxicity of natural killer(NK)-92 cell lines against various human hepatocellular carcinoma cells(HCCs)and to explore the potential mechanism.Methods We established a culture method of NK-92 cell lines in vitro.Lactate debydrogenase(LDH)cytotoxicity assays and cytokine release assays were performed to determine whether NK-92 cell lines could recognize and kill HCCs in vitro.At the same time,Nu/Nu mices were housed. Subcutaneous(sc)xenografts HepG2 models of human hepatocellular carcinoma were established.1×107NK-92 cells were intravenously(iv)injected through the tail vein on days 2,9,16,23 while the control group was injected with PBS in the same way.Tumor size, tumor volume, tumor mass and mouse survival status were closely observed in experimental and control groups.Mice were euthanized when tumor-bearing time reached 28 days.Xenograft tissues were taken for general observation.Sections were cut and processed for HE staining and immunofluorescence staining.The expression of glypican-3(GPC3)protein in xenografts tissue was clearly defined.Results NK-92 cell lines that were chronically cultured in vitro and maintained typical phenotypic characteristics of NK cells with good cellular activity.Enhanced cytotoxicity and IFN-γ production of NK-92 cell lines were identified by LDH and ELISA,indicating that NK-92 cell lines could recognize and kill different kinds of HCCs.In addition,NK-92 cell lines efficiently suppressed the growth of HCC xenografts in vivo.Tumor volume in experimental group was significantly reduced compared with control group and there was low a GPC 3 expression in experimental group through immunofluorescence and immunohistochemistry results, pointing to the possibility that the cytotoxicity of NK cells was correlated with GPC3 +HCCs.Conclusion NK cells provide a promising means of therapeutic intervention for HCCs.NK-92 cell lines could eliminate HCC cells in vitro and in vivo.The cytotoxicity of NK-92 cell lines may work by killing the GPC3-positive cells in the liver cancer tissue.In addition to the anti-tumor effect, NK cells also have cytotoxicity on pathogens such as bacteria and viruses.

Establishment and practice of post management system for nursing staff in operating room / 中华护理杂志

According to the professional characteristics of the operating room,on the basis of basic principles of hierarchical management and post management of nursing department,taking clinical needs as guiding ideology,combined with the development needs of surgical departments,we developed the operating room nursing staff management model,and set up 23 jobs.We adjusted it accordingly in practice,and constantly optimized nurses' career plan by providing clinical,teaching,research,management and other multi-channel development direction,meanwhile provided better quality care for patients.

Establishment and practice of post management system for nursing staff in operating room / 中华护理杂志

According to the professional characteristics of the operating room,on the basis of basic principles of hierarchical management and post management of nursing department,taking clinical needs as guiding ideology,combined with the development needs of surgical departments,we developed the operating room nursing staff management model,and set up 23 jobs.We adjusted it accordingly in practice,and constantly optimized nurses' career plan by providing clinical,teaching,research,management and other multi-channel development direction,meanwhile provided better quality care for patients.

Study on in vitro Antimicrobial Activity of Traditional Chinese Medicine Herbal Pair of Euphorbia humifusa Willd. and Portulaca oleracea L / 中国药师

Objective:To study the in vitro antimicrobial activity of traditional Chinese medicine herbal pair of euphorbia humifusa Willd. and portulaca oleracea L. . Methods: The antibacterial effect in vitro of the traditional Chinese medicine herbal pair and the single herb of euphorbia humifusa Willd. and portulaca oleracea L. was studied on staphylococcus aureus, escherichia coli and pseudo-monas aeruginosa by the 2-fold dilution method and the broth micro-dilution method in a 96-well plate. The minimum inhibitory con-centration ( MIC) , minimum bactericidal concentration ( MBC) and the diameter of inhibition zone were determined. Results:The ex-perimental strains showed the different sensitivity among the traditional Chinese medicine herbal pair and the single herb. The antibac-terial and bactericidal activity of the traditional Chinese medicine herbal pair was the most obvious(P<0. 05). As the temperature in-creasing, the antibacterial activity of all water extract on different experimental strains changed. The results of MIC and MBC showed that the effects of water extract on escherichia coli were strongest, that of stapphylococcus aureus were secong, ant that of pseudomonas aeruginosa were relatively weak. Conclusion:The traditional Chinese medicine herbal pair of euphorbia humifusa Willd. and portulaca oleracea L. has antibacterial and bactericidal activity in varying degrees on the experimental strains with some differences, and the changes in the application forms of traditional Chinese medicines has great influence on the antibacterial and bactericidal ability.

Subtype classification of Garden III femoral neck fractures in the elderly based on frontal Garden index and its clinical significance / 中国骨伤

<p><b>OBJECTIVE</b>To retrospectively study postoperative Garden III femoral neck fractures in the elderly so as to explore the different degree of displacement of Garden III femoral neck fracture, and discuss the basis and clinical significance of the subtype classification.</p><p><b>METHODS</b>A total of 492 patients with complete clinical data out of the 1397 patients with femoral neck fractures treated by closed reduction and internal fixation with cannulated compression screws from September 2005 to September 2010 were included in the study. Each patient's frontal Garden Index was measured. On the basis of the frontal Garden Index, these cases were divided into three types:type A, which frontal Garden Index was more than or equal to 140°, included 53 males and 84 females with an average age of(65.3±7.2) years old ranging from 60 to 75 years old; type B, more than 120°and less than 140°, included 79 males and 172 females with an average age of (67.5±3.6) years old;and type C, less than or equal to 120°, included 38 males and 66 with an average age of(68.6±5.7) years old. Aspects were followed up including complications, consequences and hip joint function. The fracture healing and femoral head necrosis were compared among three types.</p><p><b>RESULTS</b>Operative incision of 492 cases was primary healing, and no infection and other complications occurred. All patients were followed up from 2 to 10 years with an average of 6.3 years, the healing of femoral neck fracture occurred in 432 cases, and the total union rate was 87.8%. Femoral head necrosis occurred in 83 cases, and the total necrosis rate of femoral head was 16.9%. The nonunion rate of type A was 6.6%, type B was 13.5%, and type C was 16.3%, there were significant differences among three types(²2AB=4.377,=0.036;²2AC=5.872,=0.015;²2BC=0.469, PBC=0.494). The necrosis rate of femoral head of group A was 8.8%, group B was 16.7%, and group C was 27.9%, there were significant differences among three groups(²2AB=4.704,=0.030;²2AC=15.317,=0.000;²2BC=5.715,=0.017).</p><p><b>CONCLUSIONS</b>It is different for the degree of displacement of Garden III femoral neck fracture in the elderly. Based on frontal Garden Index to differentiate degree of fracture displacement, Garden III femoral neck fracture would be divided into A, B and C subtypes. The prognosis of Garden III femoral neck fracture in the elderly is negatively related to its degree of displacement, which has clinical significance to make treatment plan for Garden III femoral neck fracture in the elderly.</p>

Molecular Mechanism of Parthenolide Improving Insulin Resistance Induced by Insulin / 医药导报

Objective To investigate the reversal effect and molecular mechanisms of NF-κB inhibitor parthenolide (PTL) on insulin resistance ( IR). Methods HepG2 cells were treated with insulin at different concentrations and time points, the glucose consumption of HepG2 cells was measured via glucose oxidase method to determine the best concentrations and time for establishing insulin-induced insulin resistance on HepG2 cells. After modeling, different concentrations of PTL were added in cells for 24 h for determining cell activity and glucose-consumption. Q-PCR was used to detect the expression of NF-κB and IκBα mRNA in cells, and western blot was used to detect the expression of protein IκBα. Results The best reaction time and concentration for insulin inducing resistance of HepG2 cells were 24 h and at 10 μg·mL-1 . The optimum acting dose of PTL was 20 μmol·L-1 . NF-κB activity was significantly reduced (P<0. 05), IκBα degradation was significantly inhibited (P<0. 05) compared to HepG2 cells with insulin resistance upon intervention on insulin resistance HepG2 cells by PTL. Conclusion PTL can inhibit IκBα degradation and disassociation of it from NF-κB, which in turn improves insulin resistance, providing theo-retical basis for preventing and treating diabetes with PTL.

Deguelin down-regulates the expression of cyclin D1 gene in zebrafish embroys through the whole mount in situ hybridization / 中国组织工程研究

BACKGROUND:In the early development of zebrafish embryos, cels divide and proliferate rapidly, but low concentration of deguelin can delay the development of zebrafish embryos. OBJECTIVE:To observe the effect of different concentrations of deguelin on cyclin D1 gene expression in zebrafish embryos. METHODS:Though normal fertilization, zebrafish embryos that incubated to the 2-cel stage (about 0.75 hour after fertilization) and shield stage (6 hours after fertilization) were colected and put into 12-wel plates treated with 100, 200, 400 nmol/L deguelin at 28.5℃in an incubator til the shield period and 24 hours after fertilization, respectively. Simultaneously embroys treated with 1% dimethyl sulfoxide solution were as a control group, cultured in the same conditions. Cyclin D1 RNA probes were prepared for the whole mountin situhybridization, observing staining by an upright fluorescent microscope camera to detect the effect of deguelin on cyclin D1 expression in zebrafish embryos. RESULTS AND CONCLUSION:Deguelin showed significant negative regulation on the expression of cyclin D1 gene in zebrafish embryos. Cyclin D1 expressed in outsourcing cels in embryos of shield stage, and a significant reduction in the expression of cyclin D1 came up with the increasing concentrations of deguelin. In the 400 nmol/L deguelin treatment group, there was nearly no expression of cyclin D1. Cyclin D1 expressed in the brain, central nervous system, immature eye, somites, trunk, and tail of embryos at 24 hours after fertilization, and reduced significantly in the 100 nmol/L deguelin treatment group, especialy in the proliferative area. In the 200 and 400 nmol/L treatment groups, the embryonic development slowed down signficantly, and cyclin D1 gene mainly expressed in the dorsal ectoderm cels.