Volume 99 ·  Issue 38 ·  2019

Colorectal cancer is one of the most common malignant tumors. Its incidence ranks third in the world, and its mortality ranks second in the world. It is the digestive system malignant tumor that accounts for the first morbidity and death in the world^[1]Seriously threatening the lives and health of the people. Recently, with the westernization of lifestyle and diet structure in China, the incidence of colorectal cancer is on the rise^[2,3,4]It has become the second-ranked malignant tumor in the digestive system and the first-ranked prevalence in China^[5,6]。 In 2018, it is estimated that there will be more than 521,000 new cases of colorectal cancer and about 248,000 deaths in my country. Both new and deaths are close to 30% of the world's colorectal cancer cases in the same period^[7]The burden of disease is heavy. Therefore, reducing the mortality and morbidity of colorectal cancer in China is not only an urgent and key clinical issue, but also a concrete measure to realize the grand strategy of "Healthy China" in the report of the 19th National Congress of the Communist Party of China.

antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (ANCA-associated vasculitis, AAV) is a group of systemic small vessel vasculitis characterized by the ability to detect ANCA in serum. 1982 Davies et al.^[1]This new IgG class antibody was unexpectedly discovered during the study of autoantibodies in the serum of patients with segmental necrotizing glomerulonephritis, which can react with normal human neutrophils. 1985 Van der Wonder et al.^[2]This similar autoantibody was found in the sera of patients with Wegener's granulomatosis (WG), and ANCA was gradually widely recognized. 1988 Falk et al.^[3]It is found that there are two types of ANCA positive fluorescence staining models, one is the perinuclear pattern (P-ANCA) that produces yellow-green fluorescence around the cell nucleus, and the other is the cytoplasmic pattern (C-ANCA) that produces scattered granular fluorescence in the cytoplasm. It is also found that myeloperoxidase (MPO) is the target antigen of P-ANCA. In 1990, proteinase 3 (PR3) was confirmed as a target antigen of C-ANCA^[4]。 Since then, more ANCA target antigens have been gradually discovered, and ANCA has also been found to be closely related to the pathogenesis, clinical manifestations and prognosis of some small vessel vasculitis. The 2012 Chapel Hill Consensus Conference (CHCC) proposed a new classification of vasculitis^[5]Encompasses granulomatosis with polyangiitis (GPA; formerly known as WG), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) and other small vessel vasculitis are classified as AAV, further proving the important role of ANCA in the pathogenesis and diagnosis and treatment of AAV. With the deepening of the research on AAV, the call for classifying AAV according to the different target antigens of ANCA is also increasing. Therefore, it is more important to detect ANCA in a timely and accurate manner.

To explore the expression and clinical significance of chemokine ligand 18 (CCL18) in Bronchoalveolar Lavage Fluid (BALF) of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).

From January 2016 to June 2017, BALF of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD group), patients with dermatomyositis-associated interstitial lung disease (DM-ILD group), and patients with primary Sjögren syndrome-associated interstitial lung disease (pSS-ILD group) of Peking University People′s Hospital were collected. According to the prognosis of each group of patients during hospitalization, they were divided into the discharged and the died. Besides, 30 patients without ILD served as a control group. Levels of CCL18 in BALF of all patients were tested by enzyme linked immunosorbent assay (ELISA). Cells in BALF of RA-ILD group, DM-ILD group and pSS-ILD group were collected and analyzed by absolute different cell counts. Results of high-resolution CT (HRCT) of these three groups were scored. In addition, the area under the curve (AUC) of CCL18 in predicting mortality during hospitalization was calculated.

A total of 38 patients with RA-ILD, 54 patients with DM-ILD, and 35 patients with pSS-ILD were enrolled. Levels of CCL18 of those discharged patients of RA-ILD, DM-ILD, and pSS-ILD groups were 8.27(3.62, 14.36), 11.04 (5.86, 17.38), 5.25(2.68, 8.21) μg/L, respectively, which were all significantly higher than that of the control group [2.54(1.26, 3.66) μg/L, all P<0.05]. Furthermore, levels of CCL18 of those deceased patients of RA-ILD and DM-ILD groups were 18.28 (13.82, 22.39), 18.81 (16.29, 22.90) μg/L, which were significantly higher than that of the discharged patients of same group (all P<0.05). Levels of CCL18 were positively correlated with lymphocyte percentage in BALF of RA-ILD, DM-ILD and pSS-ILD groups (r=0.4356, 0.4029, 0.3939, respectively, all P<0.05). Besides, levels of CCL18 were significantly correlated with HRCT scores of RA-ILD and DM-ILD groups (r=0.4242, 0.3319, respectively, both P<0.05). Areas under the curve (AUCs) of CCL18 to predict mortality during hospitalization of RA-ILD and DM-ILD groups were 0.860, 0.851, respectively.

Levels of CCL18 are elevated in BALF of CTD-ILD patients, and may be correlated with the severity and prognosis during hospitalization. CCL18 might be served as an indicator of the severity and prognosis of CTD-ILD.

To analyze the features of chest CT imaging in adult patients with bronchiectasis and explore its correlation with clinical characteristics.

From January 2010 to December 2017, patients with bronchiectasis diagnosed by chest high-resolution CT (HRCT) and aged at or above 18 years old in 5 general hospitals of Shandong province were included in the study. The correlations between the HRCT imaging features and etiology, clinical manifestations, lung function, sputum culture, prognosis and other characteristics were analyzed.

There were 410 bronchiectasis patients included in the study. The chest HRCT imaging of bronchiectasis were divided into three types, including columnar 46.8%, cystic 45.9% and varicose 7.3%, respectively. The HRCT imaging score was [6.0 (4.0, 7.0)]. In addition, the most common etiology of bronchiectasis was idiopathic (262, 69.3%). The proportion of idiopathic bronchiectasis in cystic bronchiectasis patients was significantly higher than that in columnar and varicose bronchiectasis (71.8% vs 58.3%, 50.0%; bothP<0.017). Compared with columnar bronchiectasis, patients with cystic bronchiectasis were more likely to suffer from clinical manifestations such as cough, dyspnea, fever and wet rales (P<0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 were more likely to suffer from cough, dyspnea, fever, wet rales and clubbing (P<0.017). The proportions of pulmonary ventilatory dysfunction were significantly greater in patients with cystic bronchiectasis and varicose bronchiectasis than columnar bronchiectasis (86.7%, 86.7% vs 51.0%; both P<0.017). The HRCT scores were significantly negatively correlated with pulmonary function (P<0.001). The number of acute exacerbations, hospitalizations, and bronchiectasis severe index scores in patients with cystic bronchiectasis were significantly higher than those with columnar bronchiectasis (P<0.017). There was a significantly positive correlation between HRCT scores and the number of acute exacerbations, hospitalizations and the bronchiectasis severity index scores (P<0.001). The mortality of patients with cystic and varicose bronchiectasis was significantly higher than that of patients with columnar bronchiectasis (9.0%, 10.0% vs 2.1%; both P<0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 had a higher mortality rate (15.9% vs 0.9%; P<0.017).

There is a correlation between HRCT findings and clinical manifestations in patients with bronchiectasis. The clinical manifestations, lung function and prognosis of patients with cystic bronchiectasis are worse than those of the columnar bronchiectasis; the higher the HRCT scores are, the worse the clinical manifestations, lung function and prognosis of the patients are.

To investigate the factors affecting the pathologic complete response (PCR) of the ipsilateral supraclavicular lymph node (ISLN) of breast cancer after neoadjuvant chemotherapy (NAC).

A total of 178 patients with breast cancer who had primary ipsilateral supraclavicular lymph node metastasis (ISLNM), receiving NAC and subsequent ISLN dissection, were retrospectively reviewed. The single factor and multi factor analysis were carried out by the chi square test and the Logistic regression model.

The enrolled patients were all female, 28 to 74 years old. The rate of PCR on the ISLN was 52.2%. Single factor analysis showed that KI67 expression level (χ²=7.717,P=0.005), breast PCR (bPCR) (χ²=33.564,P<0.001), and axillary PCR (aPCR) (χ²=31.750, P<0.001) were associated with the ISLN PCR. Multifactor analysis showed that KI67 expression level (OR=4.096, 95%CI: 1.176-14.263, P=0.027), bPCR (OR=4.452, 95%CI: 1.894-10.461, P<0.001) and aPCR (OR=5.183, 95%CI: 1.974-13.605, P<0.001) were independent predictors of ISLN PCR. The rate of PCR on the ISLN was 90.9% in the patients with KI67>30% and simultaneous breast and axilla PCR.

The PCR rate of the ISLN after neoadjuvant chemotherapy is higher than that of the breast and axillary PCR. The expression level of KI67, the bPCR and the aPCR are independent predictors of the PCR on the ISLN.

To evaluate the utility of a portable monitor at home for diagnosis of obstructive sleep apnea (OSA) in Chinese adults.

Eighty nine patients suspected of OSA underwent overnight, unattended home sleep apnea testing (HSAT) with a portable monitor (Nox-T3, Nox Medical Inc. Iceland)followed by an in-laboratory polysomnogram (PSG) with simultaneous portable monitor (PM) recording within one week. PSG and PM recorder were scored according to recommended guidelines by independent technicians. The correlation between PSG apnea hypopnea index (AHI) and PM respiratory disturbance index (RDI) were evaluated.

Sleep testing showed RDI was (30.0±20.9) events/h on HSAT, and (33.4±22.4) events/h on in-laboratory PM recording. Apnea-hypopnea index (AHI) on PSG was (35.1±23.7) events/h. There was significantly statistical difference among the three group (P<0.001). Both RDI on HSAT and RDI on in-laboratory PM correlated significantly with AHI on PSG (r=0.877, P<0.001 and r=0.962, P<0.001, respectively). Bland-Altman analysis of AHI on PSG versus RDI on HSAT showed a mean difference of 4.4 events/h; limits of agreement was -17.6 to 26.5 events/h. Closer agreements were present when comparing the simultaneous recordings, with AHI on PSG versus RDI on in-laboratory PM showing a mean difference of 1.4 events/h, and limits of agreement was -11.3 to 14.2 events/h. Based on a threshold of AHI≥5 events/h, RDI on HSAT had 98.8% sensitivity, 40.0% specificity. Using an AHI ≥ 15 events/h, RDI on HSAT had 91.5% sensitivity, 76.5% specificity.

Type 3 PM has a good diagnostic value for adult OSA patients and there is close agreement between the Type 3 portable monitor and PSG.

To evaluate the efficacy and safety of resection of lumbar nerve sheath tumors via muscle-pedicle open-door laminoplasty approach.

From March 2016 to June 2018, 6 patients (4 males and 2 females, average age (45±14) years) with lumbar spinal nerve sheath tumors received surgical treatment via muscle-pedicleopen-door laminoplasty approach in the Department of Spinal Surgery, the Affiliated Hospital of Qingdao University. The operation time, blood loss, cerebral spinal fluid (CSF) leakage, and pre- and post-operative Oswestry Disability Index (ODI) and low back and leg pain visual analogue scale (VAS) were recorded for all patients. Cobb angle of lumbar lordosis was measured on the standing lateral X-ray before and 6 months after surgery. Bone fusion was observed in computed tomography at six months after surgery.

Total tumor resection was achieved in all the 6 patients. The operation time was from 76 to 117 minutes (average, (102±15) minutes). The blood loss was from 160 to 280 ml (average, (256±24) ml). No CSF leakage was observed in this cohort.All patients were followed up for more than 6 months. ODI and VAS for low back and leg pain were much better at one month after operation than those before the operation(t=7.70, 8.63,11.31, all P<0.05). The Cobb angle of lumbar lordosis before operation and at six months after the operation were comparable in all six patients(t=0.70, P>0.05). Bone fusion was observed in computed tomography at six months after surgery. No bone necrosis or absorption, no lamina dislodgement or spinal stenosis was occurred.

The muscle-pedicle open-door laminoplasty approach is proved effective and safe to incise nerve sheath tumors in the lumbar spine. Some blood supply of lamina can be kept intact to accelerate bone fusion.

To investigate the therapeutic effects of first phase renal puncture and drainage guided by B ultrasound and second phase percutaneous nephrolithotomy(PCNL) in the treatment of urinary calculi complicated with pyonephrosis.

From January 2014 to April 2018, 28 patients with upper ureteral segment and kidney calculi complicated with pyonephrosis were collected. All patients received the pyonephrosis puncture under B ultrasound. After the inflammation was controlled and the clinical situation improved, the second phase was treated by PCNL. During the operation, routine in dwelling ureteral stent drainage and renal fistula wereperformed. The outcomes of the operation were observed.

A total of 28 cases were successfully punctured, the obstruction was relieved and the inflammation was controlled. Additionally, the second phase of PCNL surgery was successful, and there were no significant stone residues after PCNL. There were no complications such as severe systemic inflammatory response syndrome and severe hemorrhage. After 3 to 12 months of follow-up, renal function was restored to varying degrees, and there were no renal failure patients who needednephrectomy.

Early diagnosis of urinary calculi complicated with pyonephrosis is the key to successful treatment. Active and effective B ultrasound-guided renal puncture and drainage, drainage of pus, and removal of urinary obstruction can improve the safety of the second phase of PCNL, and thus it attaches great importance to the treatment of pyonephrosis.

To observe the effect of parathyroid hormone-related protein (PTHrp) receptor on the proliferation of tibial growth plate chondrocytes in chronic renal insufficiency (CRI) young rats.

Two-week-old male SD rats were randomly divided into two groups: (1) Sham group (n=6), only left ureter was exposed; (2) CRI group(n=6), left ureter was ligated to induce chronic renal insufficiency. Rats were sacrificed 2 weeks after operation and the blood concentration of PTHrp was detected by intracardiac blood sampling. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. The level of PTHrp receptor in chondrocytes was observed by immunohistochemistry and quantitative analysis was completed by Western blot. The proliferation rate of chondrocytes from two groups at 24 h was detected by using 5-ethynyl-2′-deoxyuridine (EDU) technique. Three types of PTHrp receptor mRNA plasmids (overexpressed, empty vector and knockdown) were used to treat the chondrocytes from CRI group. The mRNA and protein levels of PTHrp receptor were detected after 24 h and 48 h intervention, respectively. The chondrocyte proliferation rate at 24 h was detected by EDU.

Blood concentration of PTHrp in CRI group was higher than that in Sham group [(1.36±0.42) ng/L vs (0.77±0.21) ng/L, t=3.913, P=0.001]. The results of Western blot showed that the level of PTHrp receptor in growth plate chondrocytes from CRI group decreased (0.15±0.07 vs 0.41±0.13, t=5.569, P<0.001). Chondrocyte proliferation rate of CRI group was lower than that in Sham group at 24 h [(11.3±3.1)% vs (24.6±5.7)%, t=6.482, P<0.001]. The mRNA and protein levels of PTHrp receptor increased in chondrocytes of CRI group after intervention with overexpressed plasmid. The chondrocyte proliferation rate increased at 24 h. On the contrary, the mRNA and protein levels of PTHrp receptor decreased afer intervention with knockdown plasmid, and the chondrocyte proliferation rate also decreased [overexpression: (22.8±6.5)%, empty carrier: (10.2±4.3)%, knockdown: (5.6±2.1)%, F=29.840, P<0.001].

Increased PTHrp concentration in the blood of CRI young rats leads to decreased PTHrp receptors in growth plate chondrocytes, which results in decreasing PTHrp activity and proliferation rate of chondrocyte.

To observe the effect of KLF3 on the expression of STAT3 in breast cancer cells, and to explore the potential mechanism of KLF3 affecting the movement, migration and invasion of breast cancer cells.

Firstly, the expression of STAT3 was detected by Western blot, real-time fluorescent quantitative PCR, luciferase reporter system and chromatin immunoprecipitation in breast cancer cells. Secondly, the STAT3 promoter mutant was constructed. The plasmid further confirmed the effect of KLF3 on the activity of STAT3 promoter; the cell scratching test and Transwell method were used to detect the ability of cell movement, migration and invasion. Finally, animal experiments were conducted to verify the effect of knockdown of KLF3 on tumor metastasis in animals.

In breast cancer cells, knockdown of KLF3 promoted STAT3 protein expression. The mRNA level of STAT3 was increased by (3.58±0.65) fold after knockdown of KLF3 in MDA-MB-231 cells, while the mRNA level of STAT3 was increased by (2.28±0.19) fold after KLF3 knockdown in MCF-7 cells (P<0.001). KLF3 boundto the promoter region of STAT3. The transcriptional activity of STAT3 increased by (2.47±0.87) fold after knockdown of KLF3 in MDA-MB-231 cells, while the transcriptional activity of STAT3 increased by (2.63±0.65) fold after KLF3 knockdown in MCF-7 cells, P<0.01. KLF3 knockdown inhibitedthe movement,migrate and invade of breast cancer cells. Based on this, silence STAT3 partially reversed the function of KLF3. Knockdown of KLF3 promotedtumor metastasis in mice.

KLF3 knockdown can promote the transcriptional activity of STAT3, which promotes the protein expression of the latter. KLF3 can affect the movement, migration and invasion of breast cancer cells through STAT3. KLF3 may be a potential target for the treatment of metastatic breast cancer.

To detect the expression of micro RNA(miRNA, miR)-30bin pancreatic cancer stem cells (PCSCs) and to observe the regulatory effect of miR-30b on epithelial-mesenchymal transformation (EMT) process, migration and invasion of PCSCs.

CD24, CD44 and EpCAM triple-positive PCSCs in pancreatic ductal adenocarcinoma(PDAC) cell line PANC-1 were sorted out by flow cytometry and the expression of Nanog and Oct4 were evaluated. The expression profile of miR-30 family in PCSCs and common cancer cells was analyzed, and the memberwith the most obvious differential expression was selected.miR-30b mimic was transfected into PCSCs and then RT-qPCR or Western Blot were performed to investigate the expression of EMT markers. The effect of miR-30b on the migration and invasion ability of PCSCs was detected by Transwell assay. Then, miR-30b agomir was transfected into PCSCs and inoculated in nude mice to study the effect of mir-30b on the tumorigenic ability.

PCSCs accounted for 4.52-8.09% of the total. The mRNA and protein levels of Oct4 and Nanog of PCSCswere significantly higher than those of PANC-1(P<0.001). The expression levels of miR-30b, c and d were significantly down-regulated, among which miR-30b was the most significant. After miR-30b overexpression in PCSCs, E-cadherin was significantly up-regulated (P<0.001), N-cadherin (P<0.001) and transcription factor Snail (P<0.001) were significantly down-regulated, while vimentin expression was not significantly changed. Transwell assay showed that both migration and invasiveness of PCSCs were significantly decreased after transfection (P<0.001). In vivo experiments, the tumor volume and weight of the nude mice injected with PCSCs overexpressing miR-30b were also significantly lower than those of the control group (P<0.01).

CD24, CD44 and EpCAMtriple positive PCSCs in pancreatic cancer cells showed obvious stemness characteristics. miR-30b can reverse the EMT process of PCSCs, reduce their migration and invasion, and inhibit the tumorigenicity of PCSCs.

Non-traumatic anterior interosseous nerve injury syndrome is a relatively rare peripheral neuropathy in clinic, which is manifested by limited active flexion of the thumb and the distal segment of the index finger, accompanied by varying degrees of pain in the forearm and cubital fossa, and no numbness of the fingers. Neuroelectrophysiology showed abnormal innervation muscles of anterior interosseous nerves. Neuro-ultrasound found that the disease can be presented as a simple anterior interosseous neuritis or as a subtype of idiopathic brachial plexus neuritis.

This article reports the long diagnosis and treatment of a patient with juvenile onset pancytopenia. The initial manifestation of the patient was skin and mucous membrane hemorrhage, and the examination showed thrombocytopenia. It has since progressed to pancytopenia with the discovery of light chain kappa M protein. The patient has a long course of disease, complete medical history and examination data are lacking, and the diagnosis is extremely difficult. First of all, starting from the hematological diseases that lead to pancytopenia, attempts to explain the whole picture of the disease by monism failed. After that, try pluralism and break it one by one. The patient had complete M protein assessment, bone marrow smear and PET-CT, and the diagnosis of active multiple myeloma was clear. Iron tetrathesis and bone marrow iron staining support iron deficiency anemia. The genes of congenital thrombocytopenia, systemic autoimmune diseases and infection screening were all negative, and the cause of thrombocytopenia was considered as primary immune thrombocytopenia. The patient was finally diagnosed with multiple myeloma, combined with iron deficiency anemia and primary immune thrombocytopenia.

A patient with MELAS syndrome was examined by laboratory and neuroimaging, and genetic testing was performed to analyze the characteristics of MELAS syndrome, so as to improve the early clinical diagnosis rate. In patients whose clinical characteristics are highly suspected of MELAS syndrome, if the hotspot mutation test is negative, further detection sites need to be added, among which the m.10158T>T/C mutation site should be focused on to improve the disease diagnosis rate.

Long-term peritoneal dialysis will affect the physiological structure and function of peritoneum to varying degrees, and eventually lead to ultrafiltration failure. Angiogenesis is an important pathological change, and also plays an important role in peritoneal inflammation and peritoneal fibrosis. This paper reviews the mechanism of peritoneal angiogenesis in recent years, focusing on the important signaling pathways, cytokines and intervention pathways, so as to provide reference for the prevention and treatment of peritoneal angiogenesis in the future.

Bronchial asthma (asthma for short) is a common chronic inflammatory disease of the airways characterized by reversible airflow restriction. At present, it is believed that air pollution is one of the factors that cause the onset and acute exacerbation of asthma. In this paper, the research progress on the effects of air pollution on asthma in recent years is reviewed from several aspects, such as the influence of air pollution on the epidemiological characteristics of asthma, the influence on acute exacerbation, the mechanism of air pollution inducing asthma, the control means and the prospect.