Volume 97  ·  Issue 28  ·  2017

Fulminant type 1 diabetes (FT1DM) is a new subtype of type 1 diabetes, which mostly occurs in Asian countries, with the highest incidence in Japan, followed by Korea and China, and rarely reported in European and American populations. This disease mostly starts with ketosis or ketoacidosis, which is manifested as sudden onset, severe metabolic disorder, significant increase in blood sugar and normal or mild increase in glycosylated hemoglobin (HbA1c), and can be combined with serious complications such as rhabdomyolysis, acute renal failure, cardiac arrest, cerebral edema, and multiple organ failure^[1,2]If not diagnosed and rescued in time, it often leads to the death of the patient in a short time. In addition, due to the almost complete and irreversible damage to islet function, patients require long-term insulin replacement therapy, with large blood sugar fluctuations and a significantly increased risk of hypoglycemia. Therefore, as an acute and critical disease among endocrine and metabolic diseases, FT1DM should be highly valued.

Cardiovascular disease (CVD) is the most common cause of disability and death in patients with type 2 diabetes mellitus (T2DM), and its risk of occurrence is 2-4 times higher than that of non-diabetic patients^[1]。 Glucagon-like peptide 1 (GLP-1) is an incretin whose main biological role is to participate in the regulation of blood glucose homeostasis. Natural GLP-1 is easily inactivated by dipeptidyl peptidase 4 (DPP-4) rapidly, and its half-life is only 1~2 min, so its clinical application value is limited. GLP-1 receptor agonist (GLP-1RA) is protected from rapid degradation of DPP-4 due to altered amino acid sequence. At present, there are many kinds of GLP-1RA listed abroad. Short-acting preparations include exenatide and lixisenatide, and long-acting preparations include liraglutide, exenatide weekly preparations, abiglutide, dulaglutide, etc. Among them, exenatide and liraglutide are two kinds of GLP-1RA currently on the market in China. Exenatide is the first GLP-1RA approved for marketing, with only 53% homology to the amino acid sequence of human GLP-1. Liraglutide is the second marketed GLP-1RA and has 97% homology to human GLP-1. Recent studies have shown that GLP-1RA has a protective effect on the cardiovascular system^[2]。 In this paper, the cardiovascular protective effect of GLP-1RA and its potential mechanism are described.

Intra-aortic balloon counterpulsation (IABP) is the most widely used mechanical circulation assistance device at present. It is a catheter with balloon inserted into the descending aorta distal to the left subclavian and above the renal artery through the arterial system. The balloon is inflated in the diastolic phase of the heart and deflated in the systolic phase of the heart, which plays a role in assisting the heart. In 1952, Kantrowitz's experiment provided a theoretical basis for counterpulsation technology. In 1958, Harken first proposed the concept of intra-aortic balloon counterpulsation. In the early 1960s, Class et al. began to explore the method of intra-aortic balloon counterpulsation. In 1968, Kantrowitz was first used in the treatment of cardiogenic shock and was successful^[1]。 In 1973, IABP was first used to assist cardiopulmonary bypass shutdown during cardiac surgery. With the progress of technology, the continuous improvement of counterpulsation device and balloon catheter, IABP has become more and more widely used in clinical practice, and has become an indispensable means for the treatment of severe cardiac patients. IABP has been clinically used for half a century. About 1 million patients worldwide have received adjuvant IABP therapy, and about 70,000 patients in the United States are implanted with IABP every year. There is no relevant statistical data in China.

To evaluate glycated hemoglobing A1c (HbA1c) in diagnosing metabolic syndrome (MS) in Chinese subjects aged over 50 years.

A community-based cross-sectional survey was conducted between October 2010 and January 2011 in Shipai community, Guangzhou. A total of 1 494 subjects aged over 50 years were investigated. Questionnaire survey and physical examination were performed among all participants. Fasting blood samples were obtained to measure plasma glucose (FPG), blood lipids and HbA1c. MS was defined by the criteria of International Diabetes Federation (IDF), National Cholesterol Education Program-Adult Treatment Panel Ⅲ (ATP Ⅲ)(2005) and Chinese Diabetes Society (CDS), respectively. Receiver operating characteristic (ROC) curves were plotted to explore the accuracy of HbA1c for diagnosing MS.

After excluding subjects with missing data, the remaining 1 473 subjects had a median age of 61 years (55-68 years). An HbA1c threshold of 6.1% yielded the highest combination of sensitivity (52.1%) and specificity (84.3%) for diagnosing MS. Using HbA1c≥5.7% as definition of dysglycemia, the prevalence of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 48.7%, 57.1% and 50.8%, respectively. The κ coefficients were 0.853, 0.768 and 0.730, respectively. Using HbA1c≥6.1% as definition of dysglycemia, the prevalences of MS (IDF), MS (ATP Ⅲ) and MS (CDS) were 41.2%, 45.8% and 39.1%, respectively. The κ coefficients were 0.923, 0.880 and 0.881, respectively. The optimal HbA1c threshold with the highest level of agreement according to IDF, ATP Ⅲ and CDS criteria were 6.1%, 6.3% and 6.3%, respectively.

An HbA1c threshold of 6.1% showed a high specificity for diagnosing MS in Chinese subjects aged over 50 years in community-based setting. The optimal HbA1c threshold may vary according to different criteria and populations.

To investigate the relationship between serum uric acid (SUA) levels and high sensitive C-reactive protein (hs-CRP) in patients with type 2 diabetes mellitus (T2DM).

A total of 400 patients who were hospitalized in the Department of Endocrinology and Metabolism of Jinshan Branch, Shanghai Sixth People′s Hospital between April 2014 and December 2015 were divided into normouricemia (NUA, n=319) group and hyperuricemia (HUA, n=81) group according to the presence of HUA. Clinical features of the two groups were compared. Patients were further stratified into quartiles based on SUA levels, and then association between hs-CRP and SUA was analyzed.

Compared to the NUA group, the patients with HUA had higher hs-CRP concentration [2.12 (1.15, 6.73) mg/L vs 1.14 (0.52, 3.44) mg/L, P<0.001], erythrocyte sedimentation rate (ESR) [19.0 (10.5, 29.5) mm/h vs 12.0 (8.0, 17.0) mm/h,P<0.001], body mass index (BMI) [(25.2±3.6) kg/m² vs (23.6±3.6) kg/m^2,P<0.001], and homeostasis model assessment-2 of insulin resistance (HOMA2-IR) index [1.88 (1.11, 2.94) vs 1.27 (0.77, 2.00),P<0.001]. After adjusting for age, the median level of hs-CRP of female with HUA was higher than that of male, female with NUA, and male with NUA (2.59, 1.94, 1.25 and 1.09 mg/L, respectively,P<0.001). There was significant difference in the prevalence of HUA among the patients with underweight, normal weight, overweight, and obesity (0, 12.3%, 21.6% and 25.8%, respectively,P=0.002). After adjusting for age and gender, duration of diabetes, BMI, serum lipids, level of SUA was still correlated with hs-CRP, HOMA2-IR, fasting C-peptide, blood urea nitrogen, serum creatinine, Cystatin C, microalbuminuria, respectively(all P<0.05). The level of SUA was positively associated with the increase of hs-CRP level (P=0.001). Multiple linear regression analysis showed that there was an independent and positive association between SUA and hs-CRP levels.

SUA was independently associated with hs-CRP in T2DM patients, which suggested that chronic inflammation exists in HUA patients.

To explore whether diabetes mellitus (DM) impairs functions of bone marrow-derived endothelial progenitor cells (BM-EPC) and circulating EPC.

Diabetic model of rabbit was induced by Alloxan injection and the rabbits were then randomly divided into three groups: BM-EPC group, circulating EPC group, and DM group, with six rabbits in each group. Another 6 normal rabbits were enrolled as normal control group as well. 8 weeks later, BM-EPC and circulating EPC from diabetic and healthy rabbits were isolated and cultured. Colony number, proliferation, adhesion and tube formation function were detected. Exogenous diabetic BM-EPC and circulating EPC were analyzed for therapeutic efficacy in acute ischemia model of diabetic rabbits. Left ventricular (LV) function was assessed using Echocardiography. Capillary density and fibrosis area were evaluated by confocal laser scanning microscope (CLSM) and Masson-trichrome staining. The mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was analyzed using real-time quantitive PCR.

Colony number, proliferation, adhesion and tube formation function of diabetic circulating EPC were significantly reduced compared with healthy rabbits. DM impaired tube-forming ability of BM-EPC, but did not influence colony number, proliferation and adhesion function. Compared with circulating EPC and control group, BM-EPC group had fewer fibrosis area (6.98%±0.94% vs 13.03%±2.97% and 15.84%±4.74%, both P=0.001), higher capillary density [(792±87) vs (528±71) and (372±77) vessels/mm^2, both P<0.001], higher mRNA expression of VEGF (6.25±2.33 vs 2.19±1.01 and 1.55±0.52, bothP<0.001) and bFGF (6.38±2.65 vs 1.24±0.76 and 1.18±0.82, bothP<0.001), higher left ventricular ejection fraction (LVEF) (61%±4% vs 47%±5% and 50%±10%, bothP<0.05).

DM not only impaired functions of circulating EPC, but also influenced tube formation function of BM-EPC. Auto transplantation of BM-EPC may rescue the ischemic myocardium by neovascularization and paracrine effect in diabetic rabbits.

To investigate the effect of the single lumen endobronchial tube and the double lumen endobronchial tube on ventilation and lung injury in patients with esophageal cancer undergoing combined thoracoscopic and laparoscopic esophagectomy.

Sixty patients with esophageal cancer undergoing combined thoracoscopic and laparoscopic esophagectomy were divided into single lumen endobronchial tube group (D group, n=30) and double lumen endobronchial tube group (S, n=30) according to the random number table. Blood samples were harvested at the moment of tracheal intubation (T₀), after artificial pneumothorax (one lung ventilation) 30 min (T₁), after artificial pneumothorax (one lung ventilation) 90 min (T₂), artificial pneumothorax over (double lung ventilation) 30 min (T₃) and after extubation 30 min (T₄) for arterial blood gas analysis. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SpO₂), oxygen tension (PaO₂), carbon dioxide partial pressure (PaCO₂) and airway pressure (PAW) were recorded at T₀-T₄. The incidences of pneumonia of two groups were record at 3 days after operation.

There were no obvious differences in HR, MAP, SpO₂, PaO₂, PaCO₂ between two groups at T₀-T₄ (P>0.05). Compared with T₀, the levels of HR and PaO₂ were increased remarkably at T₁-T₃ (P<0.05), the levels of PaCO₂ were increased remarkably at T₁-T₄ (P<0.01), and the levels of Paw were increased remarkably at T₁-T₃ (P<0.01). Compared with S group, the levels of Paw were decreased remarkably at T₁-T₂ (29.5±3.7 vs 21.3±2.1, P=0.001; 30.7±4.8 vs 20.3±2.3, P=0.001). There were no obvious differences in the levels of TNF-α, IL-6, IL-8 in Bronchoalveolar Lavage Fluid (BALF) between two groups at T₀ (P>0.05). Compared with T₀, the levels of TNF-α, IL-6, IL-8 in BALF were increased remarkably at T₃, T₅ (P<0.05). Compared with S group, the levels of TNF-α, IL-6, IL-8 in D group in BALF were decreased remarkably at T₃, T₅ (P<0.05). Compared with S group, the incidence of pneumonia in D group were decreased remarkably at 3 days after operation (4(13.3%) vs 11(36.7%),P=0.017).

The ventilation effect of the single lumen endobronchial tube on lung injury for patients with esophageal cancer undergoing combined thoracoscopic and laparoscopic esophagectomy is the same as that of the double lumen endobronchial tube, however the single lumen endobronchial tube has less injury on the lung.

To explore the impact of antifungal therapy in mechanically ventilated patients with Candida spp. colonization in lower respiratory tract.

In this retrospective study, patients required mechanical ventilation with pulmonary Candida spp. colonization admitted into the intensive care unit (ICU) between July 2012 and June 2016 were included. The patients were divided into the treatment group and control group according to whether or not they received antifungal therapy. The isolation rate of multidrug-resistant (MDR) bacteria, the incidence of ventilator-associated pneumonia (VAP), duration of mechanical ventilation, length of ICU stay, total length of hospital stay, the 28-day mortality and the overall mortality were compared between the two groups.

Totally, 101 patients were studied. The number of cases in treatment group was 56 and the control group was 45. The treatment group had a lower incidence of MDR bacteria isolation rate and VAP compared with the control group (16.1% vs 33.3%, 5.4% vs 17.8% respectively, both P<0.05). There were significant differences in the duration of mechanical ventilation [(17.3±5.7) days vs (22.5±7.2) days,P<0.05], length of ICU stay [(23.3±5.6) days vs (28.7 ±4.8) days,P<0.05] and the average length of hospital stay [(36.2±8.7) days vs (43.6±9.0) days,P<0.05)] in the treatment group compared with the control group. There were no statistical difference between the two groups in the 28-day mortality and the overall mortality.

Treatment of respiratory Candida spp. colonization in mechanically ventilated patients may reduce isolation rate of MDR bacteria, the incidence of VAP, duration of mechanical ventilation, length of ICU stay and total length of hospital stay.

To investigate the safety and feasibility of mini-flank open nephron sparing surgery (MI-OPN) via retroperitoneal route for the treatment of centrally located renal tumor.

From May 2013 to April 2015, twenty-four cases of centrally located renal tumor were treated with MI-OPN via retroperitoneal route in Zhongshan Hospital. All cases were included in this study with whose clinical data and long term follow-up information retrospectively analyzed.

With the assistance of intraoperative ultrasonography to confirm tumor location and boundary, MI-OPN was successfully performed in all cases. Mean tumor maximum diameter was 3.3±0.6 cm, mean operation time was 113±16 minutes, mean ischemia time was 31±6 min, and mean estimated blood loss was 102±46 ml. Mean postoperative hospital stay was 5.0±0.8 days, postoperative complication was found in one patient (4%). The mean pre- and postoperative serum creatinine were 77.1±20.1 μmol/L and 90.3±20.0 μmol/L. Pathological examination confirmed negative surgical margin in all cases, with 18 cases of clear cell renal cell carcinoma, 2 cases of papillary renal cell carcinoma, 2 cases of chromophobe renal carcinoma, 1 case of renal oncocytoma and 1 case of renal angiomyolipoma. In up to 12-36 months postoperative follow-up, no local recurrence or systemic progression was witnessed.

For the treatment of centrally localized renal tumor, MI-OPN via retroperitoneal route is a safe and feasible operation method. Importantly, rupture of the tumor capsule was effectively avoided during tumor resection with the assistance of ultrasonic position-setting. Furthermore, incidence of severe postoperative complications such as bleeding and damage of collection system were not found since surgical wound of kidney sewn tightly and finely. The last but not the least, by placing ice slush in retroperitoneal cavity, impairment of renal function caused by renal artery clamping can be alleviated due to decreased metabolism.

To discuss the experience of diagnosis and treatment of transurethral resection of paraganglioma in urinary bladder.

This retrospective study included 8 patients who underwent transurethral resection of paraganglioma in bladder from October 2009 to April 2015. Four males and 4 females were enrolled. The age ranged from 33 to 77 years (mean: 50.4 years), with a clinical course from 1 month to 8 years. Five cases presented with hypertension and 4 had high level of noradrenaline in blood. Preoperative ultrasound, CT and MRI were performed on every patient and the results showed all tumors were solitary and limited in bladder wall. Six patients received conventional transurethral electroresection and the other 2 patients received transurethral resection with thulium laser.Postoperative follow-up of each case was recorded.

All tumors were excised successfully without converting to open surgery. The maximum diameter of tumors ranged from 1.0 to 4.5 cm (mean: 2.3 cm), operative time varied from 15 to 35 min (mean: 28.1 min) and intraoperative blood loss ranged from 20 to 50 ml (mean: 31.9 ml). The variation of blood pressure during operation was 10 to 160 mmHg (mean: 66.3 mmHg). The loss of follow-up occurred in 1 case, tumor recurrence occurred in 1 case at 3 months after surgery and the follow-up data of other patients was normal.

The diagnosis of paraganglioma in bladder should be combined with clinical symptoms, biochemical and imaging examination for some cases. Transurethral resection of tumors is a safe and reliable surgical manner.

To explore the mechanism of Yes-associated protein 1 (Yap1) in angiotensinⅡ(AngⅡ)-induced pulmonary fibrosis.

In vivo, 18 male Wistar rats were randomly divided into three equal groups with 6 rats in each group, including control group, bleomycin-treated group (BLM), and BLM+ AngⅡ group. 28 days later, the lung tissues in all groups were harvested for the HE and Masson staining as well as the immunohistochemical (IHC) staining for Yap1. In vitro, the isolated fibroblasts were treated with 10^-7 mmol/L AngⅡor the AngⅡ-targeted inhibitor irbesartan for the scheduled time for mRNA and protein expressions of Yap1, PDZ-binding motif (TAZ), and collagen Ⅰusing PCR and Western blot, as well as the translocation test from the nucleus to the cytoplasm of Yap1 and TAZ. Subsequently, the fibroblasts were assigned into 4 groups: the empty plasmid (vector) group, the vector+ AngⅡ group, the Yap1 shRNA group, and the Yap1 shRNA+ AngⅡ group. Western blot was used to detect the relative expressions of Yap1, TAZ, Smad3 and collagen Ⅰ. The CCK-8 and EdU assays were performed to determine the proliferative capacity.

In vivo, severe lung fibrosis and increased Yap1 expression of IHC staining were found in BLM group. Additionally, more severe lung fibrosis and higher Yap1 expression were detected in the BLM+ AngⅡ group than the BLM group (both P<0.05).In vitro, both the mRNA and protein relative expressions of Yap1, TAZ and collagenⅠ were markedly higher in AngⅡ-treated groups than the control group (all P<0.05). Meanwhile, the relative expression of phosphorylated Yap1 reached its peak at 2 h after AngⅡ stimulation. In the protein translocation tests, after treated with AngⅡ for 24 h, the relative protein levels of Yap1 and TAZ in the nucleus of the AngⅡ group were significantly higher than those in the control group (0.382±0.007 vs 0.031±0.001, 1.097±0.030 vs 0.357±0.015). However, the relative protein expressions in the cytoplasm of the AngⅡ group were obviously less than that in the control group (0.323±0.058 vs 0.418±0.044, 0.858±0.059 vs 1.201±0.015). Compared with the AngⅡ group, the expressions of Yap1 and TAZ in the AngⅡ+ irbesartan group were higher in cytoplasm (0.598±0.060 vs 0.323±0.058, 1.495±0.052 vs 0.858±0.059), while lower in the nucleus (0.323±0.058 vs 0.418±0.044, 0.858±0.059 vs 1.201±0.015) (allP<0.05). Furthermore, the relative protein expressions of Yap1, TAZ, Smad3 and collagenⅠin Yap1 shRNA+ AngⅡ group were distinctly lower than the vector+ AngⅡ group (allP<0.05). In the cell proliferation tests, the absorbance and the percentage of EdU positive cells of vector+ AngⅡ group exceeded that of vector group (bothP<0.05). However, the absorbance and the percentage of EdU positive cells in the Yap1 shRNA+ AngⅡgroup were less than the vector+ AngⅡ group (bothP<0.05).

AngiotensinⅡ promoted the collagen synthesis and cell proliferation in primary lung fibroblasts by increasing the Yap1 activity, leading to the progress of fibrosis.

To explore the effects of roxithromycin (RXM) on glucocorticoid resistance of human bronchial epithelial cells exposed to smoke and its mechanism.

Beas-2B cells as the research object were grouped into: control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+ 10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM intervention in the RXM+ 10%CSE group, complete culture solution intervention in the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half inhibitory concentration (IC50-Dex) were calculated; the expression of histone deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western blotting (WB).

In response to dexamethasone at the concentration of 10^-9, 10^-8, 10^-7 and 10^-6 mol/L successively, the IL-8 inhibition rates of RXM+ 10%CSE group [(27.55±3.81)%, (49.60±1.45)%, (55.36±3.36)%, (60.32±3.13)%, respectively] were lower than those of control group [(32.85±2.56)%, (57.12±2.81)%, (60.81±2.08)%, (67.24±3.50)%, respectively], but higher than those of 10%CSE group [(19.15±1.69)%, (37.02±2.30)%, (47.15±2.01)%, (52.09±1.57)%, respectively] (allP<0.05). In contrast, the IC50-Dex of RXM+ 10%CSE group [(4.94±1.62)×10^-8] was significantly higher than that of control group [(1.75±0.77)×10^-8], but lower than that of 10%CSE group [(2.92±0.78)×10^-7] (both P<0.01). The expression of HDAC2 protein of 10%CSE group (0.011±0.004 from IF and 0.46±0.10 from WB) was lower than that of control group (0.037±0.005 and 0.91±0.06, correspondingly), while RXM+ 10%CSE group (0.025±0.005 and 0.77±0.09, correspondingly) was lower than that of control group but higher than that of 10%CSE group (allP<0.05).

Roxithromycin may restrain tobacco smoke exposure-induced glucocorticoid resistance in human bronchial epithelial cells through upregulating HDAC2 expression.

Gaucher's disease, also known as glucoencephalosidosis, is an autosomal recessive disease of glucose and lipid metabolism. Because of the defect of β-glucocerebrosidase, the substrate glucocerebroside cannot be degraded normally, and it is stored in large quantities in monocyte-macrophage lysosomes, resulting in cell swelling. The affected tissues and organs appear pathological and progressive aggravation, mainly manifested as splenomegaly, hepatomegaly, anemia, thrombocytopenia, skeletal system injury or neurological lesions^[1,2]。 Patients are divided into three types according to whether the nervous system is involved or not and the acute or slow onset: type I (non-neurological, chronic, adult), type II (neurological-acute) and type III (neurological-subacute), among which type I is the most common type, accounting for 95%^[1]。 There are significant differences in the incidence of Gaucher's disease among different ethnic groups, and there are no accurate epidemiological survey data in China at present. In this study, the clinical data and gene mutation analysis of three families with type II Gaucher disease were carried out. After the genetic etiology was defined, the prenatal genetic diagnosis of amniotic fluid or villi provided guidance for the fertility of three families when the mother of the child was repregnant.

A 56-year-old male was admitted to the First Affiliated Hospital of Zhejiang University on September 16, 2016 due to "diarrhea for nearly 1 year, aggravated with abdominal distension and fever for 1 month". One year ago, the patient had more stool frequency and no pus and blood. He took "berberine and probiotics" by himself, and the effect was good. Six months ago, I had a thin mucous stool, and the color of the stool was dark. One month ago, the diarrhea was aggravated, accompanied by low fever, mucous defecation 10-20 times/d, blood in the stool, abdominal distension and tenesmus. More than 20 days ago, he was hospitalized in Jinhua Hospital of Zhejiang University. Blood test routine: white blood cells 14.5×10⁹/L, C-reactive protein 66.3 mg/L; Fecal cultures: Clumomonas testosteronis. Colonoscopy: extensive lesion of left colon, ulcerative colitis (Figure 1)？ Pathology: Chronic inflammation of mucosa and inflammatory exudation necrosis; Abdominal CT: Thickening and exudation of left colon wall, inflammatory bowel disease considered (Figure 2，Figure 3)； Digital subtraction angiography (DSA): inferior mesenteric artery arteriovenous malformation (AVM), inferior mesenteric vein occlusion (Figure 4)。 After treatment with mesalazine, cefoperazone and low molecular weight heparin, the diarrhea was slightly relieved, but abdominal distension and left lower abdominal mass were gradually obvious, and the maximum daily body temperature was 37.8~38.6 ℃. The body weight has lost 6 kg in the past 1 month. A 20-year history of hypertension, blood pressure remains stable. The history of tuberculosis and surgery were denied, and the family history was not special. Physical examination: body temperature 37.9 ℃, pulse 107 beats/min, breathing 22 beats/min, blood pressure 113/83 mmHg (1 mmHg =0.133 kPa), clear mind, soft spirit, no special heart and lung, slightly swollen abdomen, intestinal mass accessible to the left lower abdomen, tenderness, no rebound pain, attenuated intestinal sound, and edema of both lower limbs.

Child, female, 8 years old. The main reason is "paroxysmal skin bleeding on the face, back, limbs and palms for half a year", and I went to the Department of Endocrinology of our hospital on August 16, 2016. Six months ago, the patient developed local diffuse bleeding on the skin of the face, back, arms, palms, fingertips and calves, which was pale red or colorless foamy liquid, and the bleeding location was uncertain, with more frequency on the face and palms (Figure 1), the amount is about a few milliliters, the bleeding stops spontaneously in an instant, and no skin damage can be seen to the naked eye after wiping. Bleeding intervals vary; Bleeding was not related to mood, activity, eating, temperature, and was not accompanied by fever, joint and muscle pain, or other discomfort symptoms. He went to many hospitals successively, and the blood, urine, fecal routine, liver and kidney function, coagulation time, autoantibodies, immunoglobulins, complement, coagulation factors, abdominal B-ultrasound and other examinations were all "normal". The diagnosis is unknown, and he has taken vitamin C, rutin and "Chinese medicine decoction", but the curative effect is not good. The patient was in good health, delivered naturally at full term, and had no history of infectious diseases such as hepatitis and tuberculosis. No intellectual disability, good academic performance, no menarche. There is no history of similar disease or hematological disorders in the family.

The child was a 2-year-old male. He was admitted to hospital with the main complaint of "finding a mass in the left scrotum for 1 d". Physical examination: body temperature 36.6 ℃, blood pressure 81/55 mmHg (1 mmHg =0.133 kPa), penis and scrotum are well developed, the mass in the left scrotum is about 1.0 cm ×1.0 cm ×1.0 cm, tough in texture, clear in boundary, no tenderness, light transmission test (-), no redness and swelling of the scrotum, bilateral testicles are located in the scrotum and accessible, the size and texture are acceptable, and the movement is good. There is no obvious mass in the bilateral groin. Laboratory tests: serum alpha-fetoprotein 2.05 μ g/L (normal 0-9 μ g/L), β human chorionic gonadotropin 0.18 U/L. Color ultrasound of the scrotum: solid mass below the left testis, hypoechoic in the middle and hyperechoic in the periphery. No obvious abnormalities were observed in the double testis, double epididymis and inguinal areas (Figure 1)； Enhanced CT: A round-like abnormal low-density shadow was seen below the testis in the left scrotum. No obvious enhancement was seen after enhancement, with clear edges and a size of about 0.86 cm ×0.86 cm ×0.68 cm. It was considered as a space-occupying lesion in the left scrotum, benign tumor, and epidermoid cyst may be (Figure 2)。

Colorectal cancer is one of the most common malignancies of the digestive tract. The worldwide incidence of colorectal cancer is the third highest among malignancies in men and the second highest among women. Changes in eating habits and lifestyle make the incidence of colorectal cancer in Asia gradually close to that in Europe and America^[1]。 Since 1991, the incidence and mortality of colorectal cancer in China have been increasing steadily. In the scope of cancer, the incidence and mortality of colorectal cancer rank fourth and fifth^[2,3]。 Colorectal cancer is essentially a genetic disease involving progressive molecular genetic changes and related histomorphological changes. The accumulation of oncogene mutations leads to spontaneous colonic epithelial cell proliferation, which usually progresses slowly over 10 to 40 years, first leading to colonic adenomas and then canceration in a few individuals^[4]Intestinal microorganisms are considered to be the etiology that may trigger the development of this series of events.

The traditional concept believes that neutrophils act as the first line of defense of the body's innate immunity by phagocytosis of exogenous pathogenic microorganisms. In 2004, Brinkmann et al.^[1]It was found that activated neutrophils can release deaggregated chromatin and intracellular proteins to the extracellular, forming a silk-like structure-neutrophil extracellular traps (NETs). Intranuclear histones and highly expressed antimicrobial peptides and granzymes in cytoplasm attach to extracellular chromatin, and cooperatively play the role of trapping and killing pathogens. Subsequently, a large number of studies have found that NETs are not only involved in the clearance of exogenous pathogens, but also involved in aseptic inflammatory processes in the body, including chronic diseases, autoimmune diseases, thrombosis, and cancer occurrence and metastasis^[1,2,3,4]。 In order to further reveal how NETs play a role in the development of these diseases, it is first necessary to confirm the massive activation of neutrophils and the release of NETs under pathological conditions. At present, the quantitative and qualitative analysis of NETs has been achieved by the detection technology, but there are some differences in sensitivity, timeliness and specificity of various methods.

Tsutsugamushi disease is a natural epidemic disease caused by infection with Rickettsia tsutsugamushi, which hosts chigger larvae and rats, and also infects humans, spreading through chiggers in long grass or dirty dirt on the floor. The infection was characterized by flu-like symptoms presenting as fever, headache, and myalgia that lasted about 1 week. In some cases, the disease can progress to severe or even multiple organ dysfunction, and even if correctly treated with doxycycline, its mortality rate should not be underestimated. Its multiple organ dysfunction can involve all major systems, the most common one is respiratory failure. If the disease progresses to this severe stage, supportive treatment such as ventilator and strengthened monitoring are urgently needed to reduce the mortality rate. At present, there have been a lot of studies on non-severe scrub typhus disease, but the diagnosis and treatment of severe scrub typhus disease is still a major clinical problem. There are reports on the diagnosis and treatment of severe cases in Southeast Asia and India, and their prognosis is not ideal. Early detection of disease progression and correct treatment is an effective means to improve prognosis. The progress of diagnosis and treatment of this disease is summarized as follows.