Volume 95  ·  Issue 16  ·  2015

After more than 30 years of development, noninvasive positive pressure ventilation (NPPV) has become one of the main methods for the treatment of sleep disorder of breathing (SDB) in the world. It is precisely because of the widespread application of this technology that the treatment of SDB has made breakthrough progress and spawned an emerging marginal interdisciplinary subject-sleep medicine. In China, sleep medicine started late, and the application of NPPV in SDB treatment was gradually popularized after the 21st century. In recent years, with the development of economy and the improvement of people's awareness, the growth rate of China's non-invasive ventilator market is in a leading position in the world; NPPV technology has been applied gradually to the treatment of respiratory failure in patients with severe acute respiratory syndrome (SARS) and chronic obstructive pulmonary disease, and has achieved good results^[1]。

obstructive sleep apnea (OSA) has been recognized as a serious health problem in modern society and can lead to multi-system impairment^[1]。 If the prevalence of OSA in adults is 2.1% to 4.1%, 28 to 55 million out of 1.34 billion Chinese suffer from OSA^[2,3]。 Estimated as 2 310 sleep monitoring needs per 100,000 people^[4]There are about 31 million people in China to be investigated. The difficulty of obtaining convenient sleep monitoring is one of the important reasons why most patients fail to diagnose and treat in time. Therefore, clinical, simplified and family-based diagnosis technology has received great attention and demand.

With the rapid development of plateau medicine and economic construction, advanced modern inspection instruments and equipment and highly educated talents are constantly introduced into medical laboratories, and more and more new technologies and methods are applied to clinical inspection work. Clinical inspection plays an increasingly important role in clinical diagnosis and treatment. In order to provide stable and reliable testing results for clinical diagnosis and treatment, medical laboratories must establish a comprehensive quality management system, which is the core of ensuring testing quality.

To explore the association between sleep disorders and dawn phenomenon in patients with type 2 diabetes mellitus (T2DM).

From July 2011 to July 2014 at Metabolic Disease Hospital, Tianjin Medical University, 316 T2DM patients on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index, i. e. those without sleep disorders (n=186) and those with sleep disorders (n=130). Biochemical parameters including hepatorenal functions, blood lipids, glycosylated hemoglobin (HbA1c) and fructosamine were detected. Oral glucose tolerance test, insulin releasing test and glucagon releasing test were performed to detect the inter-group differences of glucose concentration and α-cell and β-cell functions after fasting and glucose loading. And the correlation and regression analyses were performed between sleep disorders and other parameters.

The level of HbA1c, fructosamine, increment of fasting glucose and nocturnal nadir glucose, glucose increment before and after breakfast, 24 h mean glucose, fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and area under curve of insulin were significantly higher in patients with sleep disorders than those without sleep disorders (8.2%±2.0% vs 7.4%±1.7%, (0.33±0.10) vs (0.29±0.07) mmol/L, (1.511±0.294) vs (0.889±0.233) mmol/L, (2.144±0.400) vs (1.522±0.378) mmol/L, (9.917±1.800) vs (8.694±1.622) mmol/L, (13.49±4.68) vs (12.16±4.56) mU/L, 4.98±0.90 vs 3.82±0.82, (8.47±0.59) vs (8.25±0.54), all P<0.05). Insulin sensitivity index was lower in patients with sleep disorders than that in those without sleep disorders (-4.28±0.62 vs -4.03±0.52,P<0.05). The level of glucagon at each timepoint and area-under-curve of glucagon were significantly higher in patients with sleep disorders than those without sleep disorders. The levels of 0, 30, 180 min glucagon/insulin ratio and glucagon/glucose ratio were significantly higher in patients with sleep disorders (allP<0.05). Sleep disorder was positively correlated with HOMA-IR, glucagon/insulin ratio, increment of fasting glucose and nocturnal nadir glucose and dawn phenomenon (allP<0.05). Yet there was a negative correlation with insulin sensitivity index (P<0.05).

Sleep disorders are associated with dawn phenomenon. And improving sleep disorder helps to improve the dawn phenomenon and optimize overall glycemic control.

To observe the effects of chronic intermittent hypoxia (CIH) on myocardial cell apoptosis and explore the mechanism of microRNA-214 (miRNA-214) expression for myocardial cell apoptosis and cardiac dysfunction.

A total of 20 adult male Sprague-Dawley rats were randomized into two groups (n=10 each): for CIH group, the rats were raised in a CIH chamber 8 h daily for 6 weeks; for normal control (NC) group, the animal were exposed to normoxic air 7 h daily for 6 weeks. Hemodynamic values and myocardial function were measured via a cannula inserted into right common carotid artery. Myocardial cell apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. The expressions of miRNA-214 and hypoxia-inducible factor-1α (HIF-1α) mRNA were observed by real-time polymerase chain reaction (PCR). The expressions of such apoptosis-related proteins as fatty acid synthase (Fas), caspase 3, caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2-Associated X Protein (Bax) were detected by Western blot.

Compared with NC group, left ventricle end diastolic pressure (LVEDP) ((4.1±0.5) vs (2.7±0.4) mmHg, 1 mmHg=0.133 kPa) increased, maximal rate of pressure decline (-dp/dtmax) ((3 005±86) vs (5 918±112) mmHg/s), maximal rate of pressure development (+ dp/dtmax) ((4 118±76) vs (7 547±271) mmHg/s) and left ventricular systolic pressure (LVSP) ((90.7±2.5) vs (132.7±5.5) mmHg] decreased in CIH group (all P<0.001). There were significantly more TUNEL positive cells in CIH group versus NC group (P<0.001). The expression of miRNA-214 was significantly lower in CIH group than that in NC group (P<0.001). In addition, HIF-1α mRNA level was significantly higher in CIH group than that in NC group (P<0.001). The expressions of caspase 3, caspase 8, Fas and Bax increased significantly in CIH group versus NC group (allP<0.001), suggesting increased apoptosis of myocardial cells in CIH group. Compared with NC group, the expression of Bcl-2 decreased significantly in CIH group (P<0.001).

CIH may decrease the hemodynamic values and myocardial function in rats. The expression of miRNA-214 in CIH group is significantly depressed through accelerated apoptosis of myocardial cells.

To explore the effects of chronic intermittent hypoxia (CIH) on oxidative stress and inflammatory response and the interventional roles of adiponectin (Ad).

A total of 45 male Wistar rats were randomly divided into three groups of control group, CIH and CIH+ Ad (n=15 each). The control group breathed room air while the CIH and CIH+ Ad groups received CIH 8 h/d for 5 successive weeks. The CIH+ Ad group Ad had an injection of 10 μg once a week through tail vein. At the end of experiment (Day 35), comparison was performed among three groups about Ad, tumor necrosis factor α (TNF-α), C-reactive protein (CRP) and interleukin (IL) 6 from serum as well as malondialdehyde, superoxide dismutase (SOD), myeloperoxidase (MPO), reactive oxygen spieces (ROS) and nuclear factor (NF) κB from genioglossus.

Serum Ad level in CIH group was lower than those in control and CIH+ Ad groups ((4 208±2 239)vs(7 051±2 432)and (6 405±2 384) ng/ml, all P<0.05) with no statistic difference between control and CIH+ Ad groups. Both serum levels of TNF-α and CRP were higher in CIH group than those in control and CIH+ Ad groups ((70.87±35.16) vs (26.54±20.32) and (29.50±22.54) pg/ml, as well as(31.84±11.48)vs(22.68±9.63), (25.32±8.34)mg/L, allP<0.05)with no significant difference between control and CIH+ Ad groups. Serum IL-6 levels were all higher in CIH group and CIH+ Ad group than that in control group ((30.54±12.25) and (23.04±13.) vs (14.10±8.83) pg/ml, allP<0.05) with no significant difference between CIH and CIH+ Ad groups. Genioglossal malondialdehyde level was significantly elevated in CIH group than those in control and CIH+ Ad groups ((8.05±4.53) vs (5.18±3.03) and((5.74±3.06) nmol/mg, allP<0.01) with no significant difference between control and CIH+ Ad groups. Genioglossal SOD activity was lower in CIH+ Ad group than that in CIH group but higher than that in control group((42.42±23.17) vs (61.77±36.38) and (18.62±11.67) U/mg, allP<0.05). Genioglossal MPO levels were significantly higher in both CIH and CIH+ Ad groups than that in control group ((0.40±0.29) and (0.31±0.17) vs (0.17±0.08) μU/mg, allP<0.01), with no significance between CIH and CIH+ Ad groups. The relative level of total reactive oxygen species (ROS) in genioglossus of CIH+ Ad group was significantly lower than that in CIH group but higher than that in control group (1.94±1.01 vs 3.31±1.56 and 1.08±0.38 allP<0.05). The transcription of NF-κB was significantly higher in CIH group than that in control and CIH+ Ad groups (2.24±0.34 vs 0.78±0.21,P<0.05), but there was no statistical difference with CIH+ Ad group (1.04±0.27).

CIH may induce oxidative stress and inflammation possibly through NF κB pathway while a supplement of Ad attenuates the above CIH-induced responses.

To identify the mutation of androgen receptor (AR) gene in a Uygur family with complete androgen insensitivity syndrome and elucidate its pathogenesis.

Two males with pseudohermaphroditism in this family were clinically diagnosed complete androgen insensitivity syndrome and by polymerase chain reaction (PCR) and DNA sequencing, we checked possible mutation of all exons and its splice site in AR gene. Two males with pseudohermaphroditism in this family were clinically diagnosed as complete androgen insensitivity syndrome and confirmed by PCR and DNA sequencing. And the possible mutations of all exons and splice sites in AR gene were examined.

A proband and another family member had c. 2157G>A, p.W719X nonsense mutation of AR gene and their mother was a mutation carrier of AR gene. Substitution (G->A) at position 2 157 of exon 4 of AR resulted in mutation (TGG->TGA) at codon 719 (termination codon). The nonsense mutation led to a truncation of 202 amino acids in AR protein. The mutations were absent in other family members.

The nonsense mutation at AR gene W719X, a confirmed cause of disease, is first-ever found in Chinese, especially Uygur population.

To analyze the phylogeny of the VP1 region of Coxsackie virus A4 (CVA4) from herpangina cases of Shenzhen in 2012 and 2014.

Real-time reverse transcription(RT)-PCR method was used to test virus such as human enterovirus71, coxsackievirus A16, coxsackievirus A4, coxsackievirus A6 and coxsackievirus A10. The VP1 gene of CVA4 positive samples were amplified by RT-PCR and sequenced.Then the homology and phylogeny analysis of the CVA4 VP1 region was performed.

The six CVA4 isolates identified in the herpangina cases during 2012 and 2014 were mostly closed with GIb genotypes. The nucleotide and amino acid homology between them were 94.1% (nucleotide mutation rate was 5.9%) and 98.3%, five amino acid mutation were found in CVA4 strain 2014 of Shenzhen: aa22N-S, aa34T-A, aa63N-S, aa165A-D, aa200T-A. The phylogenetic analysis based on VP1 region demonstrates that CVA4 strain of Shenzhen in 2012 had the nearest genetic relationship with CVA4 strain of Shandong isolated in 2010(KF150144). However, CVA4 strain of Shenzhen in 2014 had the nearest genetic relationship with CVA4 strain of Jilin (JQ715709)isolated in 2006.

It reveals that all CVA4 strains from the two outbreak of herpangina belong to genotype GIb, the degree of variation in VP1 region of CVA4 strain of Shenzhen in 2014 is obvious compared with that in 2012.There is an obvious difference on internal trend of evolution lineage between the CVA4 strains from 2012 and 2014.

To compare the outcomes of complicated and uncomplicated acute type B aortic dissection (C-ATBD, U-ATBD) after thoracic endovascular aortic repair (TEVAR) and to evaluate the safety and efficacy of TEVAR in patients with U-ATBD.

Between February 2011 and December 2013, sixty patients with type B aortic dissection were treated with TEVAR and were divided into C-ATBD group (n=42) and U-ATBD group (n=18). Postoperative complications and aortic remodeling were analyzed based on the clinical outcomes and computed tomography scans performed before and after operation.

The median follow up time was 21.7 (14.0-31.6) months. The 3 years cumulative all-cause survival rate was 85.4% in the C-ATBD group and 100% in the U-ATBD group without significant difference (χ²=2.52, P=0.11). The incidence of postoperative complications including type Ⅰa endoleak, stent graft-induced distal redissection and retrograde type A aortic dissection were equivalent in the two groups. The aortic enlargement rates at each level and false lumen regression rates on each aortic segment were similar between the two groups. At the level just distal to the celiac artery, there were significant interaction effects on the maximum total aortic diameter and false lumen diameter changes between time and group (P=0.01, P=0.02). C-ATBD group showed a tendency of expansion of maximum total aortic diameter and false lumen diameter compared to the U-ATBD group.

The acceptable early and midterm outcomes are similar between the two groups after TEVAR. U-ATBD group has a more favorable aortic remodeling than C-ATBD group. TEVAR is feasible and safe for the treatment of U-ATBD.

To explore the effects of increased body mass index (BMI) on immediate clinical efficacy of radical gastrectomy in patients with gastric cancer.

The data of 258 patients undergoing radical gastrectomy were collected retrospectively from January 2009 to January 2013. They were grouped by BMI into obese (BMI≥25 kg/m^2,n=118) and non-obese (BMI<25 kg/m^2,n=140) groups. And their intra and post-operative findings and survivals were compared between two groups. Follow-ups until January 2014 were conducted by outpatient visits, mail and telephone. SPSS 17.0 software was used for statistical analysis.

For obese and non-obese groups, operative durations were (208.6±60.9), (178.1±62.5) min and number of lymph node dissection (23.4±8.3), (29.8±12.2) pieces respectively. And the difference was statistically significant (P<0.05). And blood loss, overall incidence of postoperative complications, the number of metastatic lymph node dissection were (272.4±128.8) ml, 30.5% (36/118), (7.9±8.8) pieces and (260.8±160.4) ml, 24.3%(34/140), (8.6±10.2) pieces respectively. And the differences were not statistically significant (P>0.05). The median follow-up period was 23 months. And the difference of cumulative survival was not statistically significant (χ²=1.199, P=0.274).

Obesity is not an independent prognostic foactor for gastric cancer. But its related complications should be actively handled preoperatively. Intraoperative procedures are strictly performed. And postoperative nutritional supports are needed to lower the incidence of complications and imporve the prognosis.

To summarize the echocardiograhic features of atrial appendage aneurysm (AAA) in fetuses, children and adults and evaluate the value of echocardiography in the diagnosis of AAA.

The AAA echocardiographic features of 6 fetuses, 1 child and 4 adults were retrospectively analyzed. And the diagnoses were confirmed by autopsy, postnatal follow-ups, computed tomography (CT) and surgery.

Left atrial appendage aneurysm was more common than right atrial appendage aneurysm. AAA had the same echocardiographic characteristics in fetuses, children and adults. And it was usually combined with other complex cardiac malformations in fetuses while single cardiac abnormality was predominant in children and adults.

Fetuses, children and adults with AAA may be found by echocardiography in time so that echocardigraphy has an important role in diagnosing AAA.

To explore the expressions of TUBB3 (β-tubulin Ⅲ) and γ-synuclein (SNCG) in colorectal adenocarcinoma and their clinical significance.

The expressions of TUBB3 and γ-synuclein were detected by SP immunohistochemistry in 180 cases of colorectal adenocarcinoma.

TUBB3 protein positive rate was 82.2% and γ-synuclein protein positive rate 73.9% in colorectal adenocarcinoma. And there were insignificant differences of positive expression between TUBB3 and γ-synuclein ( P>0.05). The positive expression of TUBB3 was not correlated with gender, age, histological differentiation, depth of tumor invasion or clinical stage (P>0.05). The positive expression of γ-synuclein was closely correlated with depth of tumor invasion and clinical stage (P<0.05), but with gender, age or histological differentiation (P>0.05). The positive expressions of TUBB3 and γ-synuclein were correlated in colorectal adenocarcinoma (r=0.154, P<0.05).

γ-synuclein, detected by immunohistochemistry is better than TUBB3 in colorectal adenocarcinoma. And γ-synuclein may be used as a new prognostic biomarker and therapeutic target.

To evaluate the performance of trainees after finishing hands-on training of endoscopic retrograde cholangiopancreatography (ERCP) at our hospital.

Questionnaire was distributed to 46 trainees of ERCP training over the past 5 years. And the effects of training duration, case volume and hospital facilities on ERCP performance were examined.

A total of 41 valid questionnaires (89.1%) were retrieved. And 34 trainees (82.9%) worked at tertiary medical centers. The mean training duration was 8.9 months. Compared with trainees with less annual ERCP volume (TL) (<4 cases per month,n=23), trainees with more volume (TM) (≥4 cases per month, n=18) had a higher rate of successful cannulation and precut by a needle knife (both P<0.05). More endoscopists could perform ERCP and more duodenoscopes were stocked at hospitals of TM compared with TL (bothP<0.05). The results of trainee self-evaluation showed that the major influencing factors of post-training ERCP performance were hospital supports, handling capacity and case volume.

After hands-on training, the trainee performance of ERCP is influenced by such multiple factors as handling capacity and hospital supports, etc.

Human beings often have a strong fear and helplessness after encountering major catastrophic events (such as losing a loved one, earthquakes, car accidents, etc.), which can cause anxiety, depression, self-injury or suicidal behavior, and lead to psychological problems such as post-traumatic stress disorder or mental illness; Such diseases are often recurrent, difficult to eradicate, and extremely harmful. At present, the clinical treatment for post-traumatic stress disorder and other related psychological problems and mental illnesses is to constantly expose patients to painful memories, so that they slowly adapt to desensitization. However, this process may aggravate the psychological trauma of patients, which may lead to recurrence or even aggravation of the disease.

To explore the pneumoperitoneum-mediated renoprotective effects of preconditioning, mobilizing and homing of endothelial progenitor cells (EPCs) in rats.

A total of 40 rats were randomized by a numerical table into 5 groups of gasless (C), pneumoperitoneum injury (Pp), long-term pneumoperitoneum preconditioning (P-L), mid-term pneumoperitoneum preconditioning (P-M) and short-term pneumoperitoneum preconditioning (P-S). C group had a pneumoperitoneum pressure of 0 mmHg; Pp group 15 mmHg, time 60 min; P-L, P-M, P-S groups were deflated and deflated preconditioning before pneumoperitoneum, then the same as Pp group, P-L group: inflation time was 25 min, gas discharge time 10 min; P-M group: 15 min, 10 min; P-S group: 5 min, 10 min. At 24 h post-operation, the animals were sacrificed by destroying cervical spine. And the specimens of venous blood and kidneys were harvested. Also the extent of renal injury, the homing of EPCs, the proliferation and angiogenesis of renal endothelial cell and the expression of angiogenic growth factor were analyzed.

Compared with Pp group, P-L, P-M and P-S groups exhibited significant improvements in renal function, morphology and histological score(1.88±0.35, 1.63±0.52, 1.75±0.46 vs 2.38±0.52, all P<0.05). The histological scores of P-M and P-S groups improved significantly versus P-L group (bothP<0.05). P-M and P-S groups showed no significant difference in histological score (P>0.05). The number of EPCs in kidneys increased in P-L, P-M and P-S groups versus Pp group (2.18%±0.14%, 2.87%±0.29%, 2.90%± 0.24% vs 1.73%± 0.19%, allP<0.05). The EPCs numbers of P-M and P-S groups were more than that of P-L group (bothP<0.05). And no significant difference existed between P-M and P-S groups (P>0.05). Compared with Pp group, EPCs of P-L, P-M and P-S groups markedly increased in kidneys. No significant difference existed between P-M and P-S groups, but P-L group was the lowest. Also there was an up-regulated expression of stromal cell derived factor 1-α in pretreated kidneys versus Pp group (allP<0.05). And P-M and P-S groups increased markedly.

Pneumoperitoneum-mediated preconditioning protects against kidney injury by promoting EPC homing and enhancing endothelial cell and vascular proliferations. And short and medium-term preconditioning protocols are more effective for protecting kidneys.

To explore the mechanisms of endothelial progenitor cells (EPCs)on promoting osteogenic differentiation of marrow stromal cells (MSCs).

EPCs and MSCs were isolated and cultured successfully from C57BL/7 murine bone marrow by in vitro amplification. EPC-conditioned medium (CM) was extracted to detect the concentrations of vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGFβ1), platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), stromal cell-derived factor 1 (SDF-1) and basic fibroblast growth factor (bFGF) by enzyme-linked immunosorbent assay (ELISA). After 14 days of induction, alizarin red staining was used to detect every group's calcium salt deposition. And analyses were conducted for the effects of above mentioned antibodies of cytokines on osteogenic differentiation of MSCs.

Positive rates of EPCs were 79.3%, 79.5%, 76.4% for VEGFR2, CD34 and CD133 respectively, and EPCs could form tube-like structure on matrigel. EPCs secreted VEGF, TGFβ1, PDGF, IGF-1, SDF-1 and bFGF. MSC/EPC group formed more mineralized nodules than MSC group, and semi-quantitative results showed the optical density of MSC/EPC group was higher than that of MSC group(0.733±0.032 vs 0.236±0.020,P<0.001). The number of formed mineralized nodules of 50% EPC-CM group were more than those of 25% EPC-CM group, and semi-quantitative results showed that the optical density of 50% EPC-CM group was higher than that of 25% EPC-CM group(0.637±0.028 vs 0.336±0.024,P<0.001), the number of formed mineralized nodules of 25% EPC-CM group were more than those of 0 EPC-CM group, and semi-quantitative results showed that the optical density of 25%EPC-CM group was higher than that of 0 EPC-CM group(0.336±0.024 vs 0.239±0.013,P=0.004). On the basis of 50% of EPC-CM, the number of formed mineralized nodules significantly declined in the presence of anti-VEGF antibody, anti-TGFβ1 antibody, anti-IGF-1 antibody(P<0.01).

EPCs promote osteogenic differentiation of MSCs probably through the paracrine effects of VEGF, TGFβ1 and IGF-1.

To explore the possible effects of metformin on regulating the Notch1 expression and the polarization of RAW264.7 macrophages.

RAW264.7 macrophages were divided into two groups according to different metformin concentrations (0, 1, 5, 10 mmol/L) and treatment length (0, 12, 24, 48 h). The expressions of interleukin-1β (IL-1β) and interleukin-10 (IL-10) mRNA were detected by real time quantity-polymerase chain reaction (RTQ-PCR). RAW264.7 macrophages were divided into control, metformin-treated, lipopolysaccharide (LPS)-treated and LPS-metformin-treated groups. Then the expressions of IL-1β, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), arginase 1 (Arg1), IL-10, interleukin-4 (IL-4), macrophage galactose-type lectin-1 (Mgl1) and Notch1 mRNA were detected with RTQ-PCR. The expression of Notch1 protein was examined by Western blot.

At the concentrations of 0-10 mmol/L for 0-48 h, metformin in concentration and time-dependent ways promoted the expression of IL-10 mRNA and inhibited the mRNA expression of IL-1β in RAW264.7 macrophages (bothP<0.05). In metformin-treated cells, the expressions of Arg1 (P=0.009), IL-10 (P=0.015) and IL-4 (P=0.001) mRNA increased while the expressions of IL-1β (P=0.001) and IL-6 (P=0.032) mRNA decreased. And it was the same as the levels of Notch1 mRNA (P=0.004) and protein. The LPS-treated group could up-regulate the expressions of IL-1β (P<0.001), IL-6 (P=0.002), TNF-α (P=0.005) mRNA and Notch1 (P=0.002) mRNA (protein). And there was a declining trend for the expressions of Arg1, IL-10, IL-4 and Mgl1 mRNA in macrophages (both P>0.05). On the contrary, in LPS-metformin-treated cells, the gene expressions of IL-1β (P<0.001), IL-6 (P=0.005), TNF-α (P=0.029) and Notch1 (P=0.006) mRNA (along with protein) were down-regulated while Arg1 (P=0.005), IL-10 (P<0.001), IL-4 (P<0.001) and Mgl1 (P=0.001) mRNA expressions up-regulated.

Metformin regulates RAW264.7 macrophages with/without LPS toward a M2 phenotype. And Notch1 signaling may play a critical role.

To explore the effects of calcipotriol on the expression of S100A8 in human keratinocytes.

Cultured HaCaT cells were divided into 4 groups of blank without interventions, tumor necrosis factor-alpha (TNF-α) 24 h stimulation with 100 ng/ml TNF-α, calcipotriol 24 h stimulation with 10^-5-10^-9 mol/L calcipotriol and calcipotriol+ TNF-α 24 h stimulation. The relative expression of S100A8 mRNA was detected and calculated by real-time quantitative polymerase chain reaction (PCR).

The relative expression of S100A8 mRNA was up-regulated to (19.623±3.486) folds (P<0.01) under a 24 h stimulation of 100 ng/ml TNF-α versus blank. The expression of S100A8 was up-regulated to (5.029±1.056) and (2.848±0.612) folds (bothP<0.01) when cultured for 24 h with 10^-7, 10^-8 mol/L calcipotriol versus blank respectively. And the expression of S100A8 was down-regulated to (59.51±3.31)% (P<0.05) when cultured with 10^-5 mol/L calcipotriol+ TNF-α versus TNF-α-stimulated cells. The expression of S100A8 was up-regulated to (1.873±0.153) folds (P<0.01) when cultured with 10^-7 mol/L calcipotriol+ TNF-α versus TNF-α-stimulated cells.

TNF-α induces a high expression of S100A8 in cultured human keratinocytesin vitro. Calcipotriol bi-directionally affects the expression of S100A8: A high concentration (10^-5 mol/L) calcipotriol down-regulates while a low concentration (10^-7-10^-8 mol/L) calcipotriol up-regulates the expression of S100A8.

A 59-year-old male was admitted to the hospital after physical examination and B-ultrasound showed that the spleen occupied space for 2 weeks. No abdominal pain, no fear of cold, fever, no gingival bleeding. There was no abnormal weight loss. Physical examination: No yellow staining and bleeding spots on the skin, flat abdomen, no varicose veins on the abdominal wall, no intestinal pattern and peristaltic waves. Soft abdomen, no tenderness and rebound pain in the whole abdomen, no muscle guard, no abnormal mass palpable, and no subcostal palpable liver and spleen. Laboratory tests: Hepatitis B surface antibody (HBSAB) positive. Liver and kidney function, complement and immunoglobulin (IgA, IgG, IgM) were normal, tumor indexes were normal, and erythrocyte sedimentation rate and C-reactive protein were normal. Nuclear magnetic resonance (MRI): A round mass with a size of about 3.3 cm ×3.5 cm was seen at the edge of the spleen. T1WI and T2WI showed low signal, and the lesions were unevenly enhanced on enhanced scan. The volume of the liver is not large, and the proportion of each lobe is coordinated; Small round long T1 and long T2 signal foci were found in the parenchyma of liver and kidney, but no enhancement was found in the enhancement scan. The hilar region is well structured. The outer edge of the liver is smooth and neat. The gallbladder is not large, the cyst wall is not thickened, and there is no abnormal signal shadow in the cavity. There were no obvious abnormalities in the shape, size and signal intensity of the pancreas. No enlarged lymph nodes were seen retroperitoneally. Clinical diagnosis: space-occupying mass of the spleen. Multiple small cysts in the liver and kidneys. Laparoscopic splenectomy was performed under general anesthesia. During the operation, the spleen was about 8.0 cm ×6.0 cm in size, soft in texture, and had no obvious adhesion to the surrounding tissues. The completely removed spleen was broken in a bag in the abdominal cavity and isolated from the abdominal cavity. A small incision was made in the posterior lower abdomen and the bag was taken out of the abdominal cavity. Gross pathology: a pile of broken spleen tissue, 12.5 cm ×10.0 cm ×3.8 cm in size, part of the spleen has envelope, and in the gray-red substance, there is a free mass, 4.0 cm ×3.5 cm ×3.0 cm in size, without envelope, the cut surface is tough, and there are multiple dark red circular areas scattered around the gray-white center, with a diameter of 0.4~0.6 cm. Microscopically, hemangiomatous nodular structures were seen in the mass, which resembled granulomatous nodules at low magnification. Hemangioma-like nodules vary in size. The center of the nodule is a rich fissure-like or sinus-like vascular lumen, and the vascular endothelial cells are swollen. Red blood cells can be seen between some vascular lumens, and a naive vascular lumen formed by single cells can be seen. There were proliferative spindle-shaped cells between the vascular lacunae, with unclear cell boundaries and no obvious abnormalities. There were hyaline collagen fibers between nodules, and many lymphocytes and plasma cells infiltrated in the interstitial collagen fibers between nodules, old hemorrhage and hemosiderin deposition. Immunohistochemistry showed that CD34 (+), CD31 (+) and CD8 partial sinus lacunar endothelium (+) in nodular capillaries; Scattered venule-like vessels CD31 (+) between nodules. Intranodular and internodular spindle cells SMA (+), Actin (+). Pathological diagnosis: sclerosing hemangiomatous nodular transformation of the (spleen).

Helicobacter pylori (Helicobacter pylori, HP) a gram-negative microaerobic pathogen. Studies have shown that HP infection is associated with peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma (MALT), gastric malignant tumors and other gastrointestinal diseases. It has been reported that the infection rate of HP in adults in China reaches 40% ~60%^[1]。 Although the classic triple therapy composed of two antibiotics plus one proton pump inhibitor (PPI) to eradicate HP has achieved remarkable efficacy in the past long-term clinical application, due to the increasing antibiotic resistance rate year by year and the influence of antibiotic-related side effects, the patient compliance is poor, which affects the anti-HP therapeutic effect to a certain extent. The eradication rate of triple therapy is gradually declining, and most reports have been far lower by 80%^[2]。 Therefore, it is particularly important to explore new adjuvant treatment options. In recent years, with the increasing research on microecological preparations, the combined application of probiotic preparations on the basis of triple drugs aims to reduce the side effects of triple therapy and improve the eradication rate of HP, and the adjuvant therapy combined with probiotics has aroused greater interest and attention.

The article "Incidence and Risk Factors of Pulmonary Hypertension in Patients with Congenital Heart Disease" was published in Chinese Medical Journal, Issue 32, 2014^[1]。 Right cardiac catheterization was used as a means to investigate the incidence of pulmonary hypertension in patients with congenital heart disease, and the risk factors of pulmonary hypertension were analyzed. After reading it, I benefited a lot, but I also felt that the English translation of the medical term "pulmonary arterial hypertension" as "pulmonary arterial hypertension" in this article was inappropriate, so I put forward a discussion here.

Thank you very much for your interest in this article. I agree with your letter that "Pulmonary arterial hypertension (PAH)" should be translated as "Pulmonary arterial hypertension" and "Pulmonary hypertension (PH)" should be translated as "Pulmonary arterial hypertension". In this article, the clinical classification of Pulmonary arterial hypertension in patients with congenital heart disease, according to the guidelines of the Nice Conference of the 2013 World Congress on Pulmonary hypertension, belongs to PAH, and its clear English expression is "Pulmonary arterial hypertension associated with congenital heart diseases", which most domestic scholars are used to translating as "congenital heart disease Pulmonary hypertension".

Thrombopoietin (TPO) is produced in the liver and regulates hematopoietic stem cell and megakaryocyte proliferation and differentiation, known as pan-hematopoietic factor. TPO activates downstream signaling pathways through its receptor c – MPL (also known as MPL) and promotes cell survival and proliferation. Because TPO plays an important role in hematopoiesis, alterations in its receptors and hormones lead to the development of diseases: e.g. congenital and acquired thrombocytemia, penia. Dysregulation of TPO expression or functional alteration of c-MPL can lead to aplastic anemia (AA).

Abdominal aortic aneurysm (AAA) is dangerous and is the 10th leading cause of death in men over the age of 60. The number of deaths caused by AAA rupture in the United States is 15,000 per year^[1]。 Known risk factors are male sex, smoking, advanced age, genetic predisposition, abnormal lipid metabolism, and hypertension. The histological manifestations of AAA were massive infiltration of inflammatory cells in the media and adventitia, rupture of elastic fibers and degradation of the media, but the etiology was unknown. Selecting safe, reliable and reproducible animal models plays an important role in understanding the mechanism of AAA occurrence, and also provides reference value for new drugs and surgical methods.

The 2014 World Health Organization (WHO) Global Tuberculosis Report shows that there were more than 480,000 new cases of multidrug-resistant tuberculosis (MDR – TB) worldwide in 2013^[1]。 The chemotherapy regimen of MDR-TB still cannot achieve satisfactory efficacy, and the adverse reactions are large, the treatment cost is high, and the treatment success rate is only 48%. The development and development of new anti-tuberculosis drugs is imminent. Bedaquilin (trade name Snarui, formerly known as TMC-207, also known as R207910) is the first new anti-tuberculosis drug on the market in the past 50 years, and belongs to the diarylquinoline class. In December 2012, the U.S. Food and Drug Administration (FDA) accelerated the approval of bedaquiline for the treatment of MDR-TB. In June 2013, the WHO issued the Interim Strategic Guidance for Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis.^[2]。 A series of studies have shown that the drug has high anti-tuberculosis activity and good clinical therapeutic effect^[3,4,5,6]。 Its anti-tuberculosis effect and its research progress are summarized as follows.

At present, breast cancer is one of the malignant tumors with the highest incidence rate in women, and its mortality rate is increasing year by year in China, which seriously threatens the life and health of women. Adjuvant treatment of breast cancer can significantly improve the prognosis of patients, but some patients still have primary or secondary drug resistance. It is an urgent problem to clarify the mechanism of drug resistance in adjuvant therapy of breast cancer and find the effective target to reverse drug resistance. Most previous studies have focused on tumor cells themselves, and the role of tumor microenvironment in the development of breast cancer is attracting more and more researchers' attention. Among them, cancer-associated fibroblasts (CAF) are one of the important components in the tumor microenvironment. By secreting higher levels of growth factors, chemokines, matrix metalloproteinases, etc., they can not only promote the occurrence and development of breast cancer, but also induce drug resistance to breast cancer treatment^[1,2]。 Therefore, the new treatment model targeting it will provide new ideas for the comprehensive treatment of breast cancer. At the same time, CAF also plays an important role in the prognosis of breast cancer. This article reviews the effect of CAF on therapeutic resistance in breast cancer and its prognostic value.