Volume 96  ·  Issue 02  ·  2016

Prostate cancer (Pca) is a common malignant tumor of the urinary system. In the world, its incidence and mortality rank second and seventh among male malignant tumors, respectively^[1]。 In China, the incidence of Pca has jumped to the first place in male urinary system malignant tumors, reaching 9.92/100,000, and showing an increasing trend year by year^[2]。 Therefore, more early screening, diagnosis and intervention for Pca patients are imminent. Circulating tumor cells (CTCs) were discovered by Ashworth in 1869^[3]In the peripheral blood of a patient who died of cancer, it was found that tumor cells that survived from the primary tumor or metastatic tumor by active or passive way and escaped immune killing. They had similar genetic characteristics and antigen expression to the primary tumor, and were closely related to the metastasis and recurrence of Pca and other cancers. The progress of the new detection methods of CTC and its application in Pca in recent years and related problems will be described as follows.

Influenza (referred to as influenza) virus belongs to Orthomyxoviridae (Orthomyxoviridae), mostly spherical granular, according to the virus nuclear protein and matrix protein antigen divided into three types A, B and C^[1]。 Influenza A virus is divided into several subtypes according to its surface hemagglutinin and neuraminidase. There are 16 subtypes of hemagglutinin (H1~ H16) and 9 subtypes of neuraminidase (N1~ N9)^[1], prevalent in humans are mainly the A H1N1 and A H3N2 subtypes^[2]； Both influenza B and C viruses have only one antigenic subtype, and the host species are limited, so influenza pandemics are less common^[3,4]。

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa).

A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed.

A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage.

The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

To investigate the relationship between interleukin-8 levels in expressed prostatic secretion and expressions of basic fibroblast growth factor (bFGF) and Bcl-2 in benign prostatic hyperplasia (BPH).

A series of 50 consecutive patients diagnosed with BPH and scheduled for transurethral resection of the prostate (TURP) were included. Patients were divided into two groups, simple BPH and BPH with chronic prostatitis (CP). The grade of inflammatory changes in the prostate was then determined blindly by two experienced pathologists, according to the classification system. Expressed prostatic secretion (EPS) was collected right before TURP for IL-8 detection using ELISA kits. The resected prostatic tissue was harvested for immunohistochemistry to measure the expression of Bcl-2 and bFGF.

A total of 30 (60%) patients were confirmed to have prostatic histologic inflammation. The volume of the prostate in BPH with CP was obviously larger than that in simple BPH (P=0.022). The NIH chronic prostatitis symptom index (NIH-CPSI) and international prostate symptom score (IPSS) of BPH with CP were both higher than those of simple BPH (P<0.05). Significantly increased levels of IL-8 were observed in EPS obtained from BPH patients with CP (mean level, 43.29 ng/L), compared with patients with simple BPH (mean level, 36.90 ng/L) (P=0.003). The expression of Bcl-2 in BPH with CP (mean level, 6.17) increased significantly, compared with those in simple BPH (mean level, 2.45) (P=0.013). The expression of bFGF in BPH with CP (mean level, 7.57) also obviously elevated, compared with those in simple BPH (mean level, 5.05) (P=0.008). Correlation coefficients of IL-8 levels in EPS and expression of Bcl-2 or bFGF indicated that IL-8 had strong correlation with Bcl-2 and bFGF respectively both in simple BPH and BPH with CP (0<R<1,P<0.05).

IL-8, Bcl-2 and bFGF are significantly up-regulated in BPH with CP patients, compared with simple BPH patients. Inflammation might play an important role in the outcome and development of benign prostatic hyperplasia and makes it more severe.

To explore the biological effect of prostate peripheral zones (PZs) stromal cells on the proliferation of prostate cells by overexpression of LMO2 gene.

Genes expressional distinction of different prostate stromal cells was screened by gene expression arrays. To validate the microarray data, real time-polymerase chain reaction (RT-PCR), Western blotting analysis were used to check the over expression of LMO2 in PZs cells.To compare the effect of stromal cells which overexpressed LMO2 gene on in vitro proliferation ability of BPH-1 and PC3 cell lines, cell proliferation was measured by CCK-8 and EdU assay. Cytokines chip was used to screen expression of cytokines in WPMY-1-LMO2 conditioned medium. The changes of BPH-1 and PC3 proliferation associated proteins were assessed by Western blotting.

A total of 512 genes were identified as markedly differentially expressed in stromal cells originated from different zones. Among these genes, LMO2 gene was overexpression in peripheral zones stromal cells, and confirmed by RT-PCR and Western blotting. Expression level of LMO2 gene was significantly up-regulated in peripheral zones stromal cells compared with transitional zones stromal cells, increased by 3.36 folds on average (P<0.01). The proliferation of both PC3 and BPH-1 were found increased and STAT3 phosphorylation and CCND1 expression were increased after cultured in conditioned medium from stromal cells which stably expressed LMO2. Cytokines chip found increased FGF-9 and IL-11 expression in the medium supernatant reserved from LMO2-overexpressed stromal cell line.

Distinct gene expression exists among prostate stromal cells originated from different zones. LMO2 overexpressed stromal cells can induce prostate epithelial cell growth via paracrine of FGF-9, IL-11 or other cytokines.

To detect the effects of quercetin (Que) combined with 2-methoxyestradiol (2-ME) on the proliferation of androgen-dependent LNCaP human prostate cancer cells line and androgen-independent PC-3 human prostate cancer cells line, and to evaluate the antitumor effects of different combos of the two drugs.

After LNCaP and PC-3 cells were treated with different concentration of quercetin (0, 3.125, 6.25, 12.5, 25, 50, 100, 200 μmol/L) or 2-ME (0, 0.312 5, 0.625, 1.25, 2.5, 5, 10 μmol/L) for 48 h, the inhibitory rates of cell growth were tested using trypan blue staining method respectively. Then the concentration-effect curves were drawn and IC ₅₀ values were calculated. According to the fitted dose-effect curves and IC₅₀ values, appropriate concentrations of quercetin and 2-ME were selected to compose 16 different combos. Then cells were treated with different combos of Que and 2-ME for 48 h, and then the growth inhibitory rates of cell growth were detected. According to the equation and median-effect principle, the CI values of 16 different combos of Que and 2-ME were calculated to evaluate their antitumor effects.

The inhibition rate of LNCaP or PC-3 cell growth treated with varying doses of quercetin or 2-ME alone showed a dose-dependent increase respectively. The IC₅₀ values of quercetin and 2-ME were 23.29 μmol/L and 1.89 μmol/L for LNCaP cells; and 22.12 μmol/L and 1.74 μmol/L for PC-3 cells respectively. After treated with 16 combos of Que (5, 10, 20, 40 μmol/L) and 2-ME (0.5, 1, 3, 5 μmol/L) for 48 h, for LNCaP cells, lower dose of Que (5 and 10 μmol/L) with higher dose of 2-ME (3 and 5 μmol/L) showed synergistic activity, whereas for PC-3 cells, besides the above combination of Que 10 μmol/L and 2-ME 3 μmol/L, higher dose of quercetin (20 and 40 μmol/L) with higher dose of 2-ME (3 and 5 μmol/L) also showed synergistic activity.

Both quercetin and 2-methoxyestradiol could inhibit the growth of LNCaP and PC-3 human prostate cancer cells in a dose dependent manner. We confirmed that combinations of quercetin and 2-ME at appropriate concentrations have the potential for synergetic antiproliferative activity in vitro.

To improve knowledge about the clinical and pathological features of diffuse alveolar hemorrhage (DAH).

Six cases DAH with intact clinical and pathological data were retrospectively analyzed during the period from May 1999 to May 2015 in Beijing Hospital. There were altogether 2 males and 4 females, with age ranging from 32 to 68 years (mean 58.8 years). Specimens were obtained by autopsy (3 cases), open lung biopsy (2 cases) and renal biopsy (2 cases), including 1 case of open lung biopsy in 2003, renal biopsy in 2012.

Clinically, the patients presented with cough, shortness of breath and dyspnea, including 5 cases of hemoptysis, 4 cases of fever, 3 cases of skin and mucosa bleeding, 2 cases of gross hematuria, 2 cases of microscopic hematuria, 3 cases of renal functional impairment. A total of 5 cases had different levels of elevated erythrocyte sedimentation rate and C-reactive protein, 6 cases had moderate anemia, hypoxemia, diffuse infiltrates with alveolar filling in chest CT. Serum antineutrophil cytoplasmic antibody was positive in 3 cases, anti-glomerular basement membrane antibody was present in 1 case. Pathological diagnosis: 2 cases of Granulomatosis with polyangiitis (GPA), 2 cases of Microscopic polyangiitis (MPA), 1 case of Goodpasture syndrome, 1 case of pulmonary veno-occlusive disease (PVOD). Prognosis: 3 cases died; 2 cases were discharged; 1 case received symptomatic treatment, follow-up after discharge.

The mainly clinical characteristics of DAH are varied degree of dyspnea, anemia, hypoxemia, and extensive ground-glass opacification or consolidation in image, with or without haemoptysis; diffuse acute or chronic pulmonary hemorrhage in lung tissue is the main pathological feature.

To evaluate the interference of hemoglobin variants J-Bangkok on glycated hemoglobin (HbA₁c) detected by five measurement systems.

Seventy cases of blood samples were collected at Zhongshan Hospital of Sun Yat-sen University from July 2012 to January 2014, the blood samples were divided into the normal control group (40 cases) and Hb J-Bangkok variant group (30 cases), and the normal control group was divided into healthy control group (20 cases) and diabetic group (20 cases). HbA₁c measurement systems were Primus Ultra2, Variant Ⅱ, Variant Ⅱ Turbo, Modular P and Leadman. Based on the standard of the American National Glycosylated Hemoglobin Standardization Program (NGSP), Primus Ultra2 was used as comparative system, and the other 4 systems were test systems. Comparative analysis and bias evaluation were conducted on the results from five detection systems in different groups, statistical analysis were used for evaluating the differences. The estimated average glucose (eAG) was calculated by HbA₁c values and fasting plasma glucose (FPG) of Hb J-Bangkok variant group with the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok produced significant clinical effect on HbA₁c results. HbA₁c ± 10% and relative bias at 6% and 9% HbA₁c were evaluation limits.

The differences of the 95% confidence interval (95%CI) between the test systems and the comparative system in control group were within ±0.7% HbA₁c, bias were less than 6%, there were no statistically significant difference (P>0.05). In Hb J-Bangkok group, the eAG calculated from HbA₁c measured by using Primus Ultra2, Modular P and Leadman were (8.14±2.99), (8.10±3.06) and (8.23±3.00)mmol/L, which had no statistically significant difference compared with FPG ((8.21±3.12)mmol/L, t=0.996, 1.091, 1.479, all P>0.05), and the differences of 95%CI between the results measured by Modular P and the comparative system were all within ±0.7% HbA₁c, bias were -4.3%-0.4% and -5.2%-4.9%, there were no statistically significant difference (P>0.05). At 6% and 9% HbA₁c concentrations, the mean differences of the results from the three detection systems were less than the clinically acceptable range. These results showed that the systems of Primus Ultra2, Modular P and Leadman were not affected by Hb J-Bangkok. However, the eAG values calculated from HbA₁c of Variant Ⅱ and Variant Ⅱ Turbo were (5.58±2.12) and(5.00±2.13)mmol/L, which showed statistically significant lower results compared with FPG level (t=12.29, 13.23 , all P<0.001). Compared with Primus Ultra2, the differences of 95%CI were outside of ± 0.7% HbA₁c, bias were -31.9%--12.0% and -42.0%- -17.6% , greater than 6%, showed a negative bias.At 6% and 9% HbA₁c concentrations, the mean differences of the results were all greater than the clinical acceptable range. These results indicated that Hb J-Bangkok had significantly clinical interference on Variant Ⅱ and Variant Ⅱ Turbo systems.

Hb J-Bangkok has different interference on different HbA₁c measurement systems, when performs the HbA₁c test, clinical laboratory should pay attention to identify Hb variants, and select the appropriate methods to measure the HbA₁c values in order to prevent the occurrence of interference by Hb variants.

To evaluate the safety and prognosis of allogenetic stem cells transplantation in younger patients with multiple myeloma.

We retrospectively investigated 32 young patients (median age: 45 years) diagnosed with multiple myeloma and received allogenetic stem cells transplantation in Changzheng Hospital. The non-relapse mortality, disease-related mortality, incidences of acute and chronic graft-versus-host disease (GVHD), and survivals of the patients were analyzed.

Transplantation was successful in 31 of all the patients. Response could be evaluated in 28 patients. The complete response (CR)rate before transplantation was 25.0% (8/32), which rose to 82.1% (23/28) after transplantation.And 53.1% (17/32) of the patients developed acute GVHD, with 43.8% (14/32) developing grade Ⅰ-Ⅱ; 40.6% (13/32) of the patients developed chronic GVHD, with no extensive one. The median follow-up time was 18.1 (0.4-145.8) months.Sixteen patients died, including 10 cases of non-relapse deaths and 6 cases of disease-related deaths. The non-relapse mortality within 100 days was 9.4% (3/32). The 1-, 2-and 3-year non-relapse mortality rates were 21.9% (7/32), 28.1% (9/32) and 31.3% (10/32), respectively. The common causes of non-relapse mortality were pulmonary infection (7/10), acute GVHD (1/10), acute renal failure (1/10), and acute myocardial infarction (1/10). The disease-related mortality was 18.8% (6/32). The 1-, 2-and 3-year progression-free survival rates were 61.6%, 42.2%, and 37.5%, respectively. The median duration of progression-free survival was 20.3 months. The 1-, 2-and 3-years overall survival were 68.4%, 52.4% and 42.8%, respectively. The median duration of overall survival was 28.3 months. Patients that survived for over 2 years were all alive at the end of the follow-up.

Allogenetic stem cell transplantation may be a promising curative therapeutic choice for young multiple myeloma patients. Transplantation-related death is the primary factor of prognosis. Pulmonary infection with infectious shock is the most common cause of non-relapse mortality. Prevention of infection after transplantation is the key to improve survivals.

To study the epidemiologic characteristics of pediatric spinal cord injury without radiologic abnormality.

A retrospective analysis was performed and 120 cases of children with spinal cord injury without radiologic abnormality were admitted in China Rehabilitation Research Center from January 2005 to December 2014.The gender, age, causes of injury, injury condition and complication were analyzed. All cases were divided into two groups (0-7 years old and 8-13 years old) according to age.

One hundred and twenty cases included 31 boys (25.8%) and 89 girls (74.2%). Most of the children were 0-7 years old (96 cases, 80.0%). The top 3 causes of spinal cord injury were sports activities (60 cases, 50.0%), traffic accident (25 cases, 29.2%) and other trauma (11 cases, 12.5%). Seventy-one cases were low-energy injury (59.2%) and 49 cases were high-energy trauma (40.8%), most of low-energy injury were completely injured (56 cases, 78.9%). The complication rate was 59.2% and the top 3 complications were urinary infection (35 cases, 29.2%), hydronephrosis (12 cases, 10.0%) and pressure ulcers (10 cases, 8.3%).

It is needed to pay more attention to pediatric spinal cord injury without radiologic abnormality caused by low-energy injury, especially children aged 0-7 years old with history of slight injury, and be careful about spinal cord injury without radiologic abnormality result from high-energy damage.

To evaluate the prevalence of asymptomatic carotid artery stenosis in patients with arteriosclerosis obliterans of lower extremities, and evaluate its effect on the treatment strategies for lower extremity artery lesions.

Totally 348 patients with arteriosclerosis obliterans of lower extremities who had no cerebrovascular symptoms or events in the past were enrolled from September 2012 to September 2014 in the Department of Vascular Surgery, Peking Union Medical College Hospital. Preoperative color doppler ultrasonography results of carotid arteries and demographic characteristics were retrospectively collected. The peak systolic velocity and the presence of plaque on gray-scale in the internal carotid arteries were used for diagnosing and grading internal carotid artery stenosis. A stenosis ≥50% was diagnosed as carotid artery stenosis. Binary logistic regression analysis was used to evaluate related risk factors. Treatment strategies for the artery lesions of lower extremities were compared between those with and without asymptomatic carotid artery stenosis.

Seventy-seven (22.1%) patients were found to have carotid artery stenosis. Forty-four (12.6%) patients were found to have a stenosis ≥70% or occlusion. Smoking (OR=2.122, 95% CI: 1.143-3.940), coronary artery disease (OR=1.939, 95% CI: 1.058-3.552) and hypertension (OR=1.882, 95% CI: 1.025-3.457) were found to be related risk factors. In patients combined with asymptomatic carotid stenosis, open surgery with general anesthesia was less frequently used than those without asymptomatic carotid stenosis (6.5% vs 18.1%, χ ²=6.142, P=0.013).

Prevalence of asymptomatic carotid artery stenosis is high in patients with arteriosclerosis obliterans of lower extremities. Smoking, coronary artery disease and hypertension are related risk factors.

To establish macrophage iron overload model in vitro by co-culture macrophages with iron, and to explore the effect of iron overload on cell reactive oxygen species (ROS) and the impact of ROS on macrophages.

Iron overload group were treated with different concentrations (0, 5, 10, 20, 40, 80 μmol/L respectively) of ferric ammonium citrate (FAC). The control group was the group of macrophages without FAC treatment. We detected the number and state of cells, metabolic activity, the change of phagocytosis, the levels of ROS and reactive nitrogen, and changes of related oxidative stress signaling pathways in different groups. Changes in the above indexes were detected after application of deferasirox (DFX) to remove iron and the antioxidant N -acetylcysteine (NAC) to clear excess oxidative stress.

(1)The levels of labile iron pool (LIP) in macrophages co-cultivated with iron was increased with the increase of iron concentration in a dose-dependent manner. The LIP levels was the highest in the macrophages treated with 80 μmol/L. (2)The increase of FAC concentration, the metabolic activity of macrophages in the 5 FAC-treated groups decreased to 51.58%, 40.98%, 16.23%, 3.46%, and 0.05% of the activity level of the control group (all P< 0.05). The group with the metabolic activity decreased to 16.23% (20 μmol/L) was selected as the iron overload group for the following experiments. (3)Compared with the control group, the number of macrophages in the iron overload group reduced to 32.80% (P<0.05), and the state of cells changed from adherence to partial suspension. The phagocytosis of macrophages in the iron overload group reduced to 20.40% of the control group (P<0.05). (4)Our further experiment showed that the levels of ROS and the activity nitrogen in the iron overload group increased by 7.71-and 1.45-fold compared with the control group (bothP<0.05). The RT-PCR showed up-regulated mRNA expression of genes related with ROS production, i. e. nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX 4) gene related with ROS production and inducible nitric oxide synthase (iNOS) gene related with reactive nitrogen production, down-regulated mRNA expression of glutathione peroxidase 1 (GPX1) gene which participated in ROS clearance. Moreover, mRNA expression of phosphatidylinositol-3-kinase (PI3K) gene involved in oxidative stress signaling pathway in the iron overload group was up-regulated, while fork head protein O3 (FOXO3) which regulated oxidative stress through negative feedback showed a down-regulation level of mRNA expression compared with the control group. (5)After iron chelation and antioxidant treatment, the above-mentioned damage in the iron overload group were partially reversed.

The damages of iron overload on macrophages may be mediated by inducing oxidative stress and activating oxidative stress signaling pathways. Our established model provides a method to explore the mechanism of iron overload on macrophage, and may shed some new light on possible therapeutic target in treating iron overload patients.

To study the effect of autologous adipose stromal vascular fraction (SVF) injection into corpora cavernosa on the hypertension-associated erectile dysfunction (ED) in rats and its possible mechanism.

Healthy male spontaneously hypertensive rats (SHR) at 30-week (n=40) and homologous rats with normal blood pressure (WKY) (n=20) were selected. Noninvasive blood pressure meter was used to measure the systolic blood pressure (SBP) at the tail. Cervical subcutaneous injection of apomorphine was applied to test penile erectile function. The rats with ED were divided into hypertension-associated ED rats treated with autologous SVF injection into corpora cavernosa (ED-SHR-SVF group) (n=8) and hypertension-associated ED rats treated with phosphate buffered saline (PBS) injection into corpora cavernosa (ED-SHR-PBS group) (n=8). The intracavernosal pressure (ICP) was measured in each group. Western blot and RT-PCR were conducted to test protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) in corpora cavernosa.

The tail SBP in SHR rats was significantly higher than that in WKY rats ((197.47±6.82) mmHg vs (125.23±4.65) mmHg, P<0.05). The erectile rate in SHR rats was 60% (24/40), and that in WKY rats was 100% (20/20). After 5 V electrical stimulation, the ICP in the ED-SHR-SVF group was significantly higher than in the ED-SHR-PBS group ((83.42±3.21) mmHg vs (52.37±3.11) mmHg,P<0.05). The protein and mRNA expressions of eNOS in the ED-SHR-SVF group were significantly higher than in the ED-SHR-PBS group (0.43±0.03 vs 0.18±0.05, 0.92±0.05 vs 0.41±0.06, bothP<0.05).

High blood pressure can cause ED in rats, which could be mitigated by autologous SVF injection. The mechanism may be related to up-regulation of eNOS expression in corpus cavernosa.

To investigate the effect of Toll-like receptor 2 (TLR2) on the inhibition role of sevoflurane on airway inflammation in asthmatic mice.

The lung tissue samples of C₅₇ BL/6 mice used in this study were from previous research, including control group, asthma group and sevoflurane group, 8 samples in each group. Twenty-four specific pathogen free female TLR2 gene deletion (TLR2^-/-) mice were randomly assigned to control group, asthma group and sevoflurane group, with 8 mice in each group. Asthma group and sevoflurane group were then sensitized and challenged with ovalbumin (OVA) to establish asthma model, combined with repeated inhalation of 3% sevoflurane in sevoflurane group. In C₅₇ mice, expression levels of TLR2 were detected using Western blotting analyses. In TLR2^-/- mice, numbers of differential inflammatory cells were investigated; levels of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA); lung tissue inflammation was detected with HE staining.

In lung tissues from C₅₇ mice, levels of protein expression of TLR2 in asthma group (0.547±0.042) were higher than those in control group (0.312±0.023) (P=0.023) and sevoflurane group (0.287±0.033) (P=0.020). In TLR2^-/- mice, the number of total cells ((83.13±19.43)×10³/ml), numbers of differential inflammatory cells and TNF-α level ((546±16) pg/ml) in BALF in sevoflurane group were lower than those in asthma group ((206.43±41.82)×10³/ml, (732±41) pg/ml), but still higher than those in control group ((44.64±7.17)×10³/ml, (380±24) pg/ml) (all P<0.05); lung tissue inflammation was inhibited in sevoflurane group than in asthma group, but still more obvious than that in control group.

Toll like receptor 2 involved in the anti-inflammatory effect of sevoflurane on asthmatic airway inflammation in mice.

To study the effect of sub-anesthetic doses of isoflurane and propofol on the postoperative cognitive function of rats with mild cognitive impairment (MCI) following orthopedic operation.

Male sprague-dawley rats (n=100) were randomly divided into sham group and model group.Bilateral carotid artery was separated with no bilateral narrowing in the sham operation group while bilateral carotid artery was occluded in model group.After 30 days, Morris Water Maze test were used to select MCI rats. The proportion of the value that average escape latency in model group minused average escape latency in sham group less than 20% was marked as MCI rats. After 36 days, the rats with mild cognitive impairment were randomly divided into 4 groups (n=18). Iso group: Isoflurane (1.9%) 3 h, combination group: propofol (20 mg·kg^-1·h^-1)+ isoflurane (1%) 3 h. Inhibitor with these two groups were respectively used the selective KCC2 inhibitor-DIOA 30 μg 15 min before anesthesia. Then rats received an open tibial fracture on the hind paw with an intramedullary fixation. The rats in sham group were only sutured skin incision. At the day 7 postoperatively, the Y maze test were used to test the change of cognition, nissl staining was used to observe the neurons apoptosis. Immunofluorescence was adopted to observe the neurons expressing GAD67/KCC2 and Western blot were applied to observe the protein level of KCC2 in hippocampus.

The rate of time spent in novel arm, the number of surviving neurons, the number of neurons expressing GAD67/KCC2 and protein expression levels of KCC2 in hippocampus in combination group were (52.94±2.04)%, (176.81±13.07), (196.72±8.02), (80.67±3.46)% respectively. The indexes in sham group were (53.44±2.45)%, (183.79±10.88), (207.45±13.17), (81.42±3.59)%, respectively. There was no significant difference compared with the sham group (all P>0.05). However these indexes in above two groups were higher than that in Iso group( (36.10±1.57)%, (97.21±8.23), (158.94±13.47), (43.22±4.91)%, allP<0.05). The indexes in inhibitor with Iso groups, combination group was lower compared with groups without inhibitor respectively (allP<0.05).

Compared with isoflurane, sub-anesthetic doses of isoflurane and propofol has no significant effect on postoperative cognition in rats with MCI, and its mechanism is to maintain KCC2 expression in hippocampus.

A 60-year-old male was admitted to the hospital on January 22, 2014 due to "dry mouth, polydipsia, polyuria for more than 3 years and bone pain for 3 months". The patient developed dry mouth, polydipsia, and polyuria without obvious trigger since July 2010. He needed to drink water once every 20 minutes, about 200 ml each time. He liked cold drinks, accompanied by increased urine output (>6 L per day), and nocturia 5~6 times/d. In the local hospital, the urine specific gravity was 1.005~1.008, and the serum sodium (Na) was 149.5 mmol/L, and the rest was roughly normal. After the water-free-pressure test, he was diagnosed as "central diabetes insipidus". Desmopressin acetate 1 mg was administered orally every 8 hours, and the symptoms of dry mouth were alleviated, and the urine output was reduced compared with before. In October 2010, I went to our hospital to check the MRI of the saddle area: the short T1 signal in the posterior pituitary lobe was unclear; The pituitary stem was slightly thicker (3.5 mm), consistent with the central diabetes insipidus presentation. In November 2013, the patient developed bone pain, which was obvious in both lower limbs, without redness and swelling, increased skin temperature, accompanied by protuberance of the middle tibia, tenderness, aggravated after activity, and intermittent fever, with a maximum body temperature of about 38 ℃, accompanied by loss of appetite, fatigue, and weight loss (weight loss of about 10 kg in the past year). Blood test routine in local hospital: white blood cell count (WBC) 10.9×10⁹/L, neutrophil percentage (Neut%) 0.702, hemoglobin (HGB) 124.6 g/L, platelets 443×10⁹/L; Blood biochemistry was roughly normal; Urinary routine: specific gravity 1.010, urine protein, urine occult blood, urine white blood cells and urine glucose were all normal; Fecal occult blood negative (-); Erythrocyte sedimentation rate (ESR) 74 mm/1 h, ferritin 409.8 μ g/L (normal value 30.0~400.0 μ g/L), tumor indexes: glycoprotein antigen 724: 12 800 U/L (normal value 0~8 200 U/L), alpha-fetoprotein, glycoprotein antigen 199, carcinoembryonic antigen and prostate specific antigen were not abnormal; Immunoglobulin, complement and thyroid function were normal; Testosterone 1.7 nmol/L (5.6-30.5 nmol/L), prolactin 493.0 mU/L (55.1-383.7 mU/L); Serum cortisol was 206.1 nmol/L (171.0-536.0 nmol/L), adrenocorticotropic hormone (ACTH) was 9.28 ng/L; Right tibia X-ray: low density area of middle right tibia; Bilateral tibial CT: bilateral tibial medullary cavity density uneven, multiple subcortical cystic degeneration, local bone destruction; MRI of sellar region: the posterior pituitary gland is unclear, the pituitary stem is thickened, and the enhancement is uneven in the enhancement scan; Compared with the old film in 2010, the pituitary stem was significantly thicker (6.4 mm) than before. PET-CT: multiple bone density abnormalities and damaged areas within the scan range, increased fluodeoxyglucose uptake, myeloma? Metastasis? Biopsy of the right tibial lesion was performed. Pathology: (right tibial puncture) A large number of lipid-containing histiocytes and scattered lymphoid and plasma cell infiltration were seen in the fibrous tissue of small stripes of hyperplasia, and a few degenerative necrotic tissues and suspected epithelial tissues were seen locally. On January 22, 2014, he was admitted to the hospital with "the causes of polydipsia, polyuria, bone pain and fever to be investigated". Since the onset of the disease, the spirit, appetite and sleep are poor, defecation is normal, nocturia is 3 to 4 times, and the weight has lost about 10 kg in the past year. Previous: Increased blood pressure has occurred in the last 3 months. Personal history: smoked 1 pack/d × more than 20 years, and quit smoking for more than 10 years. Occasionally drinking. The history of marriage and childbirth and family history are not special.

Clinically, the main therapeutic effect of glucocorticoid (GC) is its anti-inflammatory effect. Therefore, the anti-inflammatory mechanism of GC is most valued. The main mechanism of anti-inflammatory effect of GC is gene effect (also called genomic effect). In recent years, it has been recognized that the rapid effect (non-gene effect) is another important mechanism of GS, which is characterized by its rapid onset of action^[1]。 Some scholars have used this mechanism of action of GC for inhalation administration, and believe that high-dose budesonide suspension for inhalation (BIS) can also effectively activate the non-genetic pathway of action of hormones to produce rapid effects. Let's talk about our views here and discuss them with experts and colleagues.

According to the latest Global Asthma Initiative (GINA), bronchial asthma (asthma) is a heterogeneous disease, usually characterized by chronic airway inflammation, including respiratory symptoms such as wheezing, shortness of breath, chest tightness, cough that change over time, and with variable expiratory airflow restriction. Viral infection can both trigger and aggravate asthma^[1]。 It must be mentioned that Mycoplasma pneumoniae (MP), as an atypical pathogen, not only can cause lower respiratory infection, but also is closely related to the occurrence, development and acute exacerbation of asthma. In recent years, more studies have found that the incidence and degree of acute MP infection are higher in patients with asthma or allergic airway inflammation. Therefore, many researchers have devoted themselves to the study of the increased susceptibility of asthma to MP and its mechanism, trying to solve this clinical problem. This article mainly summarizes the relevant new molecular mechanisms at present as follows.

Bronchial asthma (abbreviated as asthma) is a chronic inflammatory disease of the airway involving a variety of cells and cellular components. As the course of the disease prolongs and progresses, the airway can produce irreversible narrowing and remodeling. Compared with adults, children's respiratory tract and lung development are not fully mature, and their sensitivity to air pollutants is higher, so they are the high risk population of asthma. A large sample survey in Europe showed that^[1]Of all asthma cases, 14% can be attributed to exposure to high traffic traffic roads; Assuming a causal relationship between traffic-related air pollution exposure and asthma, 15% of asthma symptom attacks are caused by air pollution exposure. Surveys in our country show^[2]Compared with 2000, the cumulative prevalence of childhood asthma in China has increased by 52.8% and the current prevalence has increased by 50.6% in the past 10 years. Accelerated urbanization, rapid industrial development, and lifestyle changes have aggravated air pollution, which is related to the increase of asthma in children^[3]。 In recent years, air pollution in China is serious, and its adverse health effects have attracted attention all over the world. The adverse effects of air pollution on childhood asthma must be paid attention to.

When a person is in a plateau environment for a long time, due to hypoxia, red blood cell excessive proliferation, blood viscosity increases, and a series of clinical symptoms such as dizziness, headache, shortness of breath, etc., which is called high-altitude polycythemia (HAPC)^[1]。 According to the standard of the 6th International Conference on Altitude Medicine in 2004, for people living at an altitude>2 500 m for a long time, the hemoglobin (Hb)>210 g/L in men and>190 g/L in women should be considered as HAPC, which has great influence on bone marrow hematopoietic system, coagulation function, lung function, immune function, renal function, cardiovascular system, central nervous system, liver, digestive tract and other organs^[2,3]。 The pathogenesis of HAPC is complex and has not been fully understood at present. It is generally believed that the balance of erythropoiesis is the characteristic of physiological hematopoiesis. Any cause of imbalance between mature red blood cells and immature red blood cells, and between erythropoiesis and erythropoiesis death may lead to hematopoietic pathology. HAPC is the result of these balance imbalances. Any link and any factor affecting these balance in the hypoxic environment of plateau may lead to the occurrence of HAPC.