Volume 96  ·  Issue 42  ·  2016

peripheral T-cell lymphoma (PTCL), also known as mature T-cell lymphoma, is a group of highly heterogeneous diseases derived from mature T cells or retrothymic T cells. PTCL accounts for 23% ~27% of non-Hodgkin's lymphoma in China, which is significantly higher than that in European and American countries. The overall prognosis of PTCL is poor, and the efficacy of traditional chemotherapy regimens for PTCL is not ideal. In recent years, with the in-depth understanding of PTCL molecular biology, some new therapeutic targets have been discovered, and many new drugs have continuously entered clinical research, bringing hope for achieving precise treatment of PTCL and improving efficacy.

Since the 4th edition of the World Health Organization (WHO) Classification of Hematopoietic and Lymphoid Tissue Tumors in 2008^[1]Since its release (hereinafter referred to as the 2008 edition), the clinical and basic research of lymphoid tissue tumors has made great progress. Some types of lymphomas need to be redefined, and some new subtypes have also been reported. May 15, 2016, 2008 editor-in-chief Swerdlow et al.^[2]InBloodThe journal published revised instructions for the new classification (hereinafter referred to as the 2016 edition). On this basis, we searched for relevant literatures, and by comparing the 2008 edition, the main updates in the above-mentioned 2016 edition classification revision instructions were interpreted as follows for the benefit of domestic readers.

To assess the association between daytime sleepiness and hypertension among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).

A total of 1 958 patients from Sleep Medicine Center of West China Hospital between January 2015 and January 2016 were included in the study. All subjects underwent one night polysomnography (PSG) and Epworth sleep scale (ESS) was estimated. The patients were divided into non-OSAHS group[apnea-hypopnea index (AHI)<5/h]and OSAHS group (AHI≥5/h) based on PSG, and then OSAHS group was further divided into those with and without daytime sleepiness groups according to ESS score (the cut point of ESS was 14). The association between blood pressure and risk of suffering from hypertension among patients with different degree of daytime sleepiness was explored by binary logistic regression.

There were 1 580 men and 378 women among the included patients, the mean age was (44.3±11.6) years old and the mean body mass index (BMI) was (26.4±3.8) kg/m². Among these patients, there were 267 non-OSAHS and 1 691 OSAHS patients (1 275 without daytime sleepiness and 416 with daytime sleepiness). The prevalence of hypertension was higher among OSAHS patients (53.9%vs 28.8%) than non-OSAHS group, and OSAHS patients had higher systolic blood pressure (SBP)[(126.3±0.4) vs (116.3±4.9) mmHg], diastolic blood pressure (DBP)[(82.4±0.3) vs (78.1±3.7) mmHg]and mean arterial pressure (MAP)[(97.0±0.3) vs (90.9±3.9) mmHg]than non-OSAHS group. And OSAHS with daytime sleepiness also had elevated DBP[(84.5±0.6) vs (81.7±0.3) mmHg]and MAP[(98.8±0.6) vs (96.5±0.3) mmHg]than those without sleepiness (allP<0.05). After controlling for age, sex, BMI, smoking, drinking, AHI and related sleep parameters, OSAHS combined with daytime sleepiness increased the odds of hypertension by 23% (OR=1.23, 95% CI: 1.01-1.65) compared to OSAHS without daytime sleepiness.

The daytime sleepiness is an independent risk factor of hypertension in OSAHS patients.

To observe the effect of non-invasive neurally adjusted ventilatory assist (NIV-NAVA) on patient-ventilator synchrony and effect of gas exchange in patients with acute exacerbation of chronic obstructive pulmonary disease compared with NIV-pressure support ventilation (PSV).

This was a prospective study of 40 patients with AECOPD given 30-min trials of NIV with NIV-PSV group (n=20) and NAVA group (n=20) in random order. Arterial blood gas analysis (ABGs), main asynchrony events and asynchrony index were quantified.

There were no significant difference between the two groups on effect of gas exchange (P>0.05). Main asynchrony events during NIV-NAVA including autotriggering, ineffective efforts and double triggering were less frequent than NIV-PSV (P<0.05). The trigger delay in the NIV-NAVA group was markedly shorter than the NIV-PSV (62.20±8.91 vs 112.65±15.10)ms (P<0.001). The inspiratory/expiratory off-cycle delay was significantly shorter in the NIV-PSV group than that in the NIV-NAVA group (73.00±18.27 vs 187.95±39.24)ms (P<0.001). The occurrence of severe asynchrony (AI>10%) was also less under NAVA (P<0.05).

Both NIV-NAVA and NIV-PSV can improve gas exchange. As compared with NIV-PSV, NIV-NAVA can reduce main asynchrony events, improve patient-ventilator synchrony in patients with AECOPD.

To establish a Fisher discriminant model in order to predict the outcome of postoperative blood pressure for primary aldosteronism (PA).

A total of 83 cases from the First Affiliated Hospital of Chongqing Medical University were enrolled and divided into two groups: cure group and not cure group according to postoperative blood pressure. Fisher stepwise discriminant analysis was used to establish a discriminant model, and compared with aldosteronoma resolution score (ARS) and nomogram model by receiver operating characteristic curve.

Hypertension was cured in 52 cases, and 31 cases remained uncured. Patients in uncured group were older, and had bigger body mass index (BMI), longer duration of hypertension, higher serum triglyceride (TG), more types of antihypertensive drug, higher incidence of diabetes, smoking and alcohol intake, less typical nodules on computed tomography imaging, lower estimated glomerular filtration rate (eGFR) and high density lipoprotein cholesterol. The discriminant model based on BMI, types of antihypertensive drugs, typical nodules on CT, eGFR and TG was established and the cut-off value was 0.195 9, with a sensitivity of 86.5% and a specificity of 83.9%. The area under the curve was 0.857 (95% CI: 0.764-0.951), which was higher than that of ARS (0.733, 95% CI: 0.619-0.847) and the nomogram model (0.735, 95% CI: 0.619-0.851).

The Fisher discriminant model had a high value to predict the outcome of postoperative blood pressure in PA.

To compare the efficacy of hepatic resection (HR) in patients with Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and examine how that efficacy has changed over time in a large medical center.

A consecutive sample of 918 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ≥5 cm in diameter (n=582), 2-3 tumors with a maximum diameter>3 cm (n=223), or>3 tumors of any diameter (n=113). Hospital mortality and overall survival (OS) in each group were compared for the years 2001-2007 and 2008-2013.

Patients with >3 tumors showed the highest incidence of hospital mortality of all groups ( P<0.05). Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor>2-3 tumors >3+ tumors (allP<0.05). OS rate at 5 years ranged from 24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for the period 2008-2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (allP<0.05). However, in patients with 2-3 tumors, OS was only slightly higher during the more recent 6-year period (P=0.084).

Prognosis of three types of HCC was different. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all three types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

To study the effect of 10-Hydroxycamptothecine (10-HCPT) on the proliferation and apoptosis of human Fibroblast-like Synoviocyte (FLS) with Rheumatoid Arthritis (RA).

Different concentrations of 10-HCPT and Methotrexate (MTX) were used to treat FLS cells in RA and Osteoarthritis (OA) for different time (24, 48, and 72 hours), and FLS cells without 10-HCPT and MTX were served as the control group. CCK-8 assay were applied to determine the proliferation of FLS cells, Annexin-V APC/7-AAD staining were used to detect the apoptosis of FLS cells.

The survival rate of FLS cells were (66.68±0.48) %, 48 h; (60.09±0.95) %, 72 h and (44.05±1.29) %, 48 h; (30.63±1.79) %, 72 h, when the concentrations were 1.0 μg/ml and 10.0 μg/ml in 10-HCPT group. Compared with the control group, the survival rate of FLS cells in RA and OA both declined in treatment groups with different concentrations of 10-HCPT and MTX. With the extension of time, the survival rate of FLS cells declined significantly. Compared with the MTX group, there were no obvious differences in 10-HCPT group with 1.0 μg/ml. But the concentration of 10.0 μg/ml of 10-HCPT group showed obviously difference in the proliferation of FLS cells. The apoptosis rate of FLS cells were (66.68±0.48) %, 48 h; (60.09±0.95) %, 72 h and (44.05±1.29) %, 48 h; (30.63±1.79) %, 72 h, when the concentrations were 1.0 μg/ml and 10.0 μg/ml in 10-HCPT group. Compared with the control group, two concentrations of 10-HCPT and MTX induced higher apoptosis in FLS cells with RA and OA; with the extension of time (72 h), the rate of apoptosis was significantly enhanced ( P<0.05). When FLS cells with RA were treated for 48 h, apoptosis of 10-HCPT group was higher than that of MTX group. The 10.0 μg/ml of 10-HCPT had the highest effect.

Compared with MTX, 10-HCPT had the higher efficacy of inhibiting proliferation and promoting apoptosis in FLS cells.

To investigate the risk factors associated with the disease free survival (DFS) for primary duodenal adenocarcinoma patients undergoing radical resection.

The clinicopathological data of 101 primary duodenal adenocarcinoma patients who underwent radical resection from January 2001 to October 2014 were retrospectively reviewed. Using SPSS 13.0 software, the survival curve was drawn by Kaplan-Meier method, and the survival rates were analyzed by Log-rank test.COX regression model was used to identify independent risk factors.

Among 101 patients, the main clinical manifestation were upper abdomen discomfort, abdominal pain, jaundice, gastrointestinal obstruction, hemorrhage, emaciation and so on. A total of 87 patients had the tumor located at the descending part of the duodenum. All the 101 patients underwent radical resection, and 85 patients received pancreatoduodenectomy while 16 patients underwent segmental resection. The median disease free survival time was 26 months and the postoperative 1, 3, 5 year DFS rate were 79.7%, 60.3% and 53.6%, respectively. The univariate analyses identified elevated preoperative CEA and CA19-9 level, T stage, lymph node state, vascular invasion and perineural invasion predicting a worse DFS(P<0.05). On multivariate analysis, positive lymph node state was an independent risk factor for DFS (RR=5.394, 95% CI: 1.624-17.913).

Radical resection is the best therapeutic method for primary duodenal adenocarcinoma; the positive lymph node state is the independent risk factor affecting the disease free survival of patients after radical resection.

To investigate the possibility of the Protein Phosphatase 2A (PP2A) inhibitor, LB100, in reversing acquired resistance to gefitinib in lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation.

Cell line NCI-H1975 and established primary culture cell line 44-1 with gefitinib resistance were sequenced to determine the mutation type of EGFR gene. Cells were treated with gefitinib alone or combined with LB100 to determine the half maximal inhibitory concentration (IC50), and sensitivity of 44-1 and NCI-1975 to gefitinib alone or combined with LB100 was compared. The volume of NCI-H1975 xenografts with different drug treatments was observed to determine the efficiency of gefitinib with or without LB100 in tumor growth inhibition.

Both 44-1 and NCI-1975 cells had double EGFR mutation (sensitive L858R mutation and resistant T790M mutation). Both cells showed significant gefitinib resistance (IC50: 23.0 μmol/L in 44-1, 16.7 μmol/L in NCI-1975). When combined with LB100, IC50 of gefitinib decreased to 6.9 μmol/L in 44-1 cell and decreased to 3.4 μmol/L in NCI-H1975 cells. In NCI-1975 xenografts experiments, LB100 enhanced the ability of gefitinib in tumor growth inhibition ( P<0.05).

LB100 reverses acquired resistance to gefitinib in lung adenocarcinoma cell lines.

To investigate the effect of dihydrotestosterone (DHT) on lectin-like ox- low-density lipoprotein (LDL) receptor(LOX-1)expression and foam cell formation in the female macrophage cell line J774.1.

In cultured J774.1 cells, after pretreated with DHT at concentrations of 1×10^-9 mol/L and 1×10^-8 mol/L, ox-LDL-induced LOX-1 expression and foam cell formation were investigated by quantitative real-time PCR, Western blotting, and oil-red O staining.

DHT at concentrations of 1×10^-9 mol/L and 1×10^-8 mol/L inhibited ox-LDL-induced LOX-1 mRNA (2.81±0.46 and 2.29±0.21 vs 4.71±0.31, both P<0.01) and protein expression (1.35±0.06 and 1.09±0.04 vs 1.75±0.11, bothP<0.05). The effect was partly reversed by the androgen receptor (AR) blocker flutamide (87.6%,P=0.004). Oil-red O staining also revealed that DHT at concentrations of 1×10^-9 mol/L and 1×10^-8 mol/L suppressed ox-LDL-induced foam cell formation as quantified by the number of foam cells per high-power field (HPF) (36.0±3.0 and 29.1±1.3 vs 45.9±3.7, both P<0.05) and by the area of oil-red O stained particles per HPF (7 983±1 035 and 4 060±390 vs 14 750±2 489, bothP<0.05).

DHT at concentrations of 1×10^-9 mol/L and 1×10^-8 mol/L decreases LOX-1 expression and foam cell formation via AR.

To investigate the role of hypoxia on the regulation of innate immunity of human corneal epithelium.

Telomerase-immortalized human epithelial cells (THCEs) were incubated under normoxia (21% O₂) or hypoxic (1% O₂) conditions respectively. After 6, 12, 24, 48 h culture, the mRNA and protein levels of toll like receptor 4 (TLR4) were measured by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. After 24 h culture, THCEs of each group were challenged respectively with TLR4 ligand lipopolysaccharide (LPS) (1 μg/ml) for 6 h. RT-PCR was used to assess the mRNA level of myeloid differentiation factor 88 (MyD88), interleukin(IL)6, IL-8 and tumor necrosis factor α (TNF-α). Western blot was used to examine the protein level of inhibitor of nuclear factor kappa-B α (IκBα) and phosphorylated IκBα (p-IκBα). Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of the inflammatory cytokines IL-6, IL-8 and TNF-α.

The results of RT-PCR and Western blot analysis showed that the expression of TLR4 downregulated 90% and 55% respectively after hypoxic exposure for 48 h. Hypoxia also inhibited LPS-induced secretion of IL-6, IL-8, TNF-α, expression of MyD88 and activation of NF-κB. The mRNA level of MyD88 was diminished 63%, and the protein expression of p-IκBα was also lowered. Meanwhile, the secretions of IL-6, IL-8 and TNF-α under hypoxia were reduced (31%, 55% and 50% respectively).

Hypoxia attenuated immune and inflammatory response of the cornea epithelium by suppressing TLR4 signaling, and could enhance cell susceptibility to microorganism infection.

To investigate the feasibility of the remote control endovascular robotic system in interventional angiography.

The endovascular robotic system Heifetz™ and the matched steerable catheter Mirage™ were used to cannulate all the target vessels in the vascular model and cerebral arteries originated from the aorta of Bama mini-pigs under fluoroscopic guidance. The technical success rate, cannulation time and exposure dose were all collected and compared with the result of using conventional techniques.

All the target vessels were successfully cannulated.The average cannulation time for the steerable catheter into left subclavian artery, left common carotid artery, brachiocephalic artery, right common carotid artery and right subclavian artery in the vascular model was (21.3±2.8)s, (28.8±5.2)s, (17.7±2.6)s, (31.5±5.1)s and (24.2±3.7) s, respectively, while the average exposure dose was (9.3±1.2)mGy, (12.4±2.2)mGy, (7.4±1.2)mGy, (14.2±2.5)mGy and( 10.4±1.9)mGy, respectively. The endovascular robotic system completed the cerebral angiography in Bama mini-pigs successfully. The average cannulation time for left innominate artery, right innominate artery, right subclavian artery, common internal carotid trunk, left internal carotid artery and right internal carotid artery was (41.5±6.8)s, (29.1±3.7)s, (40.7±5.5)s, (40.1±5.8)s, (59.6±9.0)s and( 60.3±10.1)s, respectively, while the average exposure dose was (40.6±6.5)mGy, (36.0±5.2)mGy, (39.8±6.1)mGy, (43.9±6.7)mGy, (51.0±7.4)mGy and( 50.1±7.8)mGy, respectively. There was no significant difference between robotic and conventional group in success rate, cannulation time and exposure dose.

The remote digital control endovascular robotic system could cannulate the target vessel in both vascular model and complete the cerebral angiography in Bama mini-pigs, which shows the feasibility of using this robotic system in endovascular intervention procedures under remote control.

A 66-year-old female was admitted to our hospital on November 24, 2015 due to "fever, abdominal pain, turbidity of peritoneal dialysis fluid for 15 days, aggravation with diarrhea for 5 days". The patient was diagnosed with chronic glomerulonephritis 20 years ago, and then developed an increase in serum creatinine, which reached 736 μ mol/L 7 years ago. That is, regular peritoneal dialysis treatment was started, and the regimen was gradually increased to 5 times/d, with 2 L of peritoneal dialysis fluid exchanged each time. When the patient developed the first peritonitis 5 years ago, there was no bacterial growth in peritoneal dialysis fluid culture, and the anti-infection efficacy of intraperitoneal administration of "vancomycin + ceftazidime" was not good. After that, "Candida quizemon" appeared by culture, the peritoneal dialysis tube was removed and changed to hemodialysis, and the tube was replaced to start peritoneal dialysis after 30 days of treatment with fluconazole. When the second peritonitis occurred 2 years ago, no pathogenic bacteria were cultured, and it improved after 2 weeks of treatment with "vancomycin + ceftazidime" again. A decrease in ultrafiltration volume on peritoneal dialysis to an average of 250-350 ml per day began to occur 10 months ago. Fifteen days ago, the patient had turbidity of peritoneal dialysis fluid with abdominal pain without inducement, and the body temperature fluctuated between 37.0 and 38.7 ℃. The peripheral blood white blood cells were 11.0×10⁹/L, neutrophils 87%, hemoglobin 91 g/L, platelets 274×10⁹/L. C-reactive protein (CRP) 170 mg/L. Peritoneal dialysis fluid routine: number of nucleated cells 124/mm³, multinucleated cells accounted for 64% and were cultured as Staphylococcus epidermidis. The patients were treated with "vancomycin 1.0 g/time, once every 5 days; ceftazidime 1.0 g/time, once/d" in the peritoneal dialysis fluid, and the abdominal pain symptoms were alleviated. After 3 days, the number of routine nucleated cells in the peritoneal dialysis fluid was reduced to 2~3/mm³。 Five days ago, the patient developed diarrhea after eating unclean diet, recurrent abdominal pain, peritoneal dialysis fluid became turbid again, no fever, and the number of nucleated cells in peritoneal dialysis fluid increased to 9 250/mm³Multinucleated cells accounted for 94%; Peripheral blood leukocytes 40.1×10⁹/L, neutrophils 96.5%, CRP 180 mg/L. Four days ago, ceftazidime was adjusted to cefoperazone and sulbactam sodium 1.5 g/time, once/d, added to peritoneal dialysis solution, and oral fluconazole 150 mg/time, once/d, but the above symptoms still did not improve, so he was admitted to the hospital.

The patient, a 72-year-old male, was admitted to the hospital on 22 February 2016 due to "4 months of post-traumatic pain in the right upper arm". The patient accidentally injured his right upper arm when lifting heavy objects 4 months before admission. The pain was immediately not severe, untreated, the pain did not improve, there was nocturnal pain, and sometimes he felt numbness in his forearm and arm. X-ray film 6 days before admission showed osteolytic destruction of the right humerus. He complained of frequent coughing and expectoration since childhood, without hemoptysis. He has 2 sons and 1 daughter, both of whom are healthy, and his spouse has had 2 spontaneous abortions. Parents are not intimate married, denying family genetic history. Physical examination at admission: temperature 36.7 ℃, pulse 70 beats/min, breathing 16 beats/min, blood pressure 135/80 mmHg (1 mmHg =0.133 kPa). Anemic appearance, no skin bleeding, unpalpable superficial lymph nodes, no sinus tenderness, sternal tenderness, wet rales can be heard in both lower lungs, apical beat located 1 cm within the midline of the right clavicle of the 5th intercostal, rhythm is uniform, and no murmur is heard. The liver and spleen were not palpated under the costs, and there was no percussion pain in the kidney area. The right upper arm is swollen and tender, and the skin temperature is not high. Due to pain, the movement of the right shoulder joint is limited, and the movement of the right elbow joint and wrist joint is normal. Laboratory test: blood routine: white blood cells 4.35×10⁹/L, hemoglobin 72 g/L, platelets 267×10⁹/L, erythrocyte sedimentation rate 145 mm/1 h, C-reactive protein 2.6 mg/L, blood biochemistry showed albumin 32 g/L, globulin 57 g/L, creatinine 221.8 μ mol/L, urea nitrogen 10.6 mmol/L, uric acid 528 μ mol/L, β 2 microglobulin 8.21 mg/L, calcium 2.17 mmol/L. MRI showed bone destruction and soft tissue mass formation in the middle of right humerus, and ultrasound-guided tumor puncture pathology showed small round cell tumor, tending to plasmacytoma. Immunohistochemical LCA, EMA, CK broad spectrum, CD20, CD38, P53, Ki-67 positive rate 20%, supporting plasmacytoma. PET/CT examination showed bone destruction of right middle humerus and sternum body, soft tissue occupation and increased metabolism, slight increase in soft tissue shadows and metabolism in medullary cavity of left middle humerus and right upper femur, multiple patch shadows and abnormal metabolism in both lungs, increased metabolism of both hilar lymph nodes, inversion of thoracic and abdominal viscera, and normal soft tissue shadows and metabolism of both maxillary sinuses. CT of the thorax and abdomen showed bilateral symmetry of the thorax, acceptable transparency of both lungs, patchy high-density shadows beside the spine of the lower lobes of both lungs, blurred boundaries, increased and disordered lung texture, visible columnar thickening of the bronchus, mediastinum centering, and total visceral inversion. Pulmonary function test Pulmonary ventilation function was roughly normal. Cardiogram and echocardiogram showed mirror dextrocardia. Bone marrow smear cytology showed multiple myeloma (10.5% naive plasma cells, 15.5% naive plasma cells, 9.5% mature plasma cells). The protein electrophoresis showed an abnormal dense band in the γ region, accounting for about 21.45%, and the monoclonal immunoglobulin was IgG-lambda type. Acinetobacter ruxeri and Acinetobacter baumannii were detected by sputum culture twice. Diagnosis: Kartagener's syndrome with multiple myeloma.

Renal transplant recipient, female, 32 years old. The patient was diagnosed with chronic renal insufficiency stage 5 due to increased serum creatinine for more than 1 year, regular hemodialysis for half a year, oliguria after dialysis, and urine volume of about 300 ml/d. He was diagnosed with chronic renal insufficiency stage 5. On January 18, 2014, he underwent allogeneic kidney transplantation in the renal transplantation department of the Third Affiliated Hospital of Sun Yat-sen University. The donor kidney was from a cardiac death donor (DCD) 6-year-old girl, right kidney. During kidney retrieval, the proximal ureter of the donor kidney was sharply injured by scissors at 2 cm proximal to the renal hilum, and the transverse diameter of the ureter was transected by 2/3. The lateral ureter accompanying blood vessels were transected, and the medial accompanying blood vessels were intact (Figure 1)。 During the repair of donor kidney, continuous end-to-end ureteral anastomosis was performed with 4-0 absorbable slightly warped suture to repair the transverse injury, and 6F pig tail was left in the ureteral lumen. During the transplantation, the donor renal artery and vein were anastomosed end-to-side with the external iliac artery and vein of the recipient, and the ureter was trimmed to the appropriate length, and then the tunnel anti-reflux anastomosis under the vesicoplasma muscular layer of ureterovesical mucosa was performed. The patient recovered smoothly in the early postoperative period, and the serum creatinine was 75 μ mol/L at the time of discharge 11 d postoperatively. The ureteral stent was removed in the outpatient clinic 1 month after the operation, and the patient developed fever 1 day after the stent was removed. Color ultrasound and CT examination were performed in the hospital, which showed that there was a huge fluid cyst between the lower pole of the transplanted kidney and the bladder (Figure 2), the cystic fluid creatinine test suggested that the property was urine. Diagnosis: Transplanted kidney ureteral urine leakage, the leakage location is the proximal ureteral injury site (Figure 3)。 The patient underwent urinary cyst puncture and catheter drainage, transplanted nephrostomy and catheter drainage, retrograde ureteral catheterization, retention of urinary catheter and anti-infection treatment (Table 1), and finally completely recovered. Serum creatinine was 80 μ mol/L at 18 months after operation, and no complications such as ureteral dilatation and transplanted hydronephrosis were found in color ultrasound.

Bone morphogenetic protein (BMP) is one of the members of the transforming growth factor beta (TGF-β) family, which includes TGF-β, growth differentiation factor, anti-Muschi tube hormone and activin^[1]。 BMP is the first protein found to be effective in inducing ectopic bone formation implanted subcutaneously in rats^[2]。 Subsequent studies have shown that BMP has different roles in different tissues, and can regulate the proliferation, differentiation and apoptosis of many kinds of cells. BMP is primarily signaled through type I and type II transmembrane serine/threonine kinase receptors. Intracellularly, the Smad protein is responsible for transmitting signals from the activated BMP receptor complex into the nucleus. Many studies have found that the disturbance of BMP signaling pathway is related to the occurrence and development of many diseases, such as bone diseases, cardiovascular diseases and tumors. Genetic analysis proved that gene mutations in BMP signaling pathway or related gene mutations affecting this signaling pathway can lead to atherosclerosis, vascular calcification, pulmonary hypertension, hereditary hemorrhagic telangiectasia (HHT) and tumor angiogenesis.

Clinical research is a simple scientific research carried out in a complex clinical environment. The contradiction between scientificity and feasibility is prominent, and it is restricted by ethics. It is necessary to ensure medical quality and medical safety. It is particularly important to obtain theory, method and technical support from the perspective of research methods. The above-mentioned problems and contradictions are more concentrated in the research and design stage and the implementation stage. The existing technical means can solve many problems, but there are still limitations. At present, the problems that are not solved well by technical means need to be introduced new research methods. Therefore, this paper expounds the history and current situation of qualitative research in clinical research design and implementation, and discusses its value and application prospect in improving the design and organization of clinical research protocol.

Lung cancer is a malignant tumor that seriously threatens human health and has a high mortality rate^[1]。 At present, the samples used to study and analyze tumor genes are mostly from lung tissue biopsy or surgery. However, these methods are all invasive, and it is not possible to obtain specimens multiple times to track the disease and changes in tumor genetic status. In recent years, a new detection technology-liquid biopsy has come out, which has brought new hope for accurate diagnosis and individualized treatment of lung cancer. Liquid biopsy can dynamically feedback the progress of lung cancer by detecting circulating tumor cells (CTC), circulating tumor nucleic acids [including circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA)], exosomes and other tumor-derived biomarkers in body fluids (mainly peripheral blood, followed by saliva, urine, pleural and peritoneal effusion, etc.), which is a relatively non-invasive way, and provides a simple and quick means for early diagnosis, disease assessment, efficacy tracking and prognosis prediction of lung cancer. It is briefly introduced as follows.

Esophageal fibrovascular polyps are rare clinical lesions, accounting for about 1% of all esophageal tumor lesions. Hundreds of cases of this lesion have been reported so far. With the continuous development of endoscopic technology, the detection and diagnosis rate of esophageal fibrovascular polyps is also increasing. Although fibrovascular polyps are benign lesions, their volume can increase continuously. When polyps increase to a considerable volume, they can seriously affect the quality of life of patients and even cause fatal complications^[1]。 Therefore, the diagnosis and treatment of esophageal fibrovascular polyps deserve long-term attention. This article discusses the pathogenesis characteristics, diagnosis and treatment progress of esophageal fibrovascular polyps, so as to provide useful clues for future clinical work.

Prostate cancer is one of the common malignant tumors in elderly men. It is estimated that the incidence of prostate cancer in men in the United States will exceed that of lung cancer in 2016, ranking first among male cancers, and the mortality rate is second only to lung cancer^[1]。 Although the incidence of prostate cancer in China is obviously lower than that in the United States, the incidence of prostate cancer in China has been increasing year by year in recent years, and it has increasingly become a disease that threatens the health of elderly men in China. At present, endocrine therapy is the main treatment for advanced prostate cancer, but the disease will almost always progress to metastatic castration-resistant prostate cancer (mCRPC). The following focuses on the current status of therapeutic drugs and some existing problems of mCRPC.