Volume 95  ·  Issue 18  ·  2015

polycythemia vera (PV) is a clonal and chronic myeloproliferative tumor mainly caused by abnormal proliferation of red blood cells leading to increased red blood cell volume. Determining that JAK2 and MPL are the initiating mutant genes that cause PV will be negative throughout the Philadelphia chromosome (Ph^–) The study of myeloproliferative tumors has brought into the era of molecular targeting.

To explore the survival and the risk factors of poor prognosis in Chinese patients with polycythemia vera (PV).

A total of 816 patients with a definite diagnosis of PV were enrolled from August 1983 to June 2013 into this study. The standardized mortality ratio (SMR) was calculated by comparing the cumulative survival of 816 PV patients with age- and sex- and calendar year-matched healthy Chinese population from the national bureau of statistics of the People's Republic of China. The clinical features of diagnosis and prognosis of PV patients were analyzed by Cox regression to identify risk factors for the poor prognosis of PV and to develop a dynamic prognostic model in Chinese patients. The effects of different treatments on the development of acute myelocytic leukemia (AML) and post-PV myelofibrosis (post-PV MF) were determined by Kaplan-Meier analysis. JAK2 V617F allele burden (V617F%) was determined by quantitative real-time PCR in 104 patients.

The median follow-up time was 6(1-42) years. The 10-, 15- and 20-year overall survival (OS) was 89.50%, 76.70% and 64.70%, respectively. The SMR was 17.40(95% CI: 13.71-21.78). Cox regression analysis revealed that white blood cell(WBC)count >10×10 ⁹/L(HR=3.10, 95% CI: 1.47-6.53, P=0.003), age >60 years( HR=2.89, 95% CI: 1.84-4.53, P<0.001) and prior thrombosis (HR=2.66, 95% CI: 1.65-4.29, P<0.001)were significant predictors for the poor prognosis of PV. Based on the hazard radio, 816 patents were allocated into 4 categories with significantly different survival: low (sum of points=0; median survival no reached), intermediate 1 (sum of points=1; median survival 33.10(28.20-38.00) years), intermediate 2 (sum of points =2; median survival 23.00(16.08-29.92) years), high (sum of points =3; median survival 13.00(10.58-15.42) years). The mortality of high risk group was 5.37 fold higher than low risk patients. The 10- and 20-year survival of no post-PV MF were 89.50% and 79.60%, respectively, for interferon α (IFN-α); 73.80% and 43.50%, respectively, for hydroxyurea treatment; 82.20% and 71.40%, respectively, for alkylating agent treatment; and 80.00% and 38.20%, respectively, for no cytoreductive treatment. The treatment of exposure to IFN-α associated with a higher rate of no-post-PV MF survival(Log-rank=9.79,P=0.020). There were more post-PV MF patients with V617F% ≥50% compared with those V617F% <50%( P<0.001).

The mortality of PV patients is significantly higher than that of healthy Chinese population. The WBC count >10×10 ⁹/L, age>60 years, and prior thrombosis are identified as significant predictors for the prognosis of PV. The risk of post-PV MF transformation may be ameliorated by IFN-α via decreasing the burden of JAK2 V617F mutation.

To explore the mutational status of CALR, JAK2 and MPL genes in BCR-ABL negative myeloproliferative neoplasms(MPN)patients and the clinical features of MPN patients with these mutations.

A total of 246 patients with a definite diagnosis of BCR-ABL negative MPN were enrolled from January 2009 to January 2014 into this study. Among them, there were 48 cases of polycythemia vera (PV) patients, 171 cases of essential thrombocythemia (ET) patients and 27 cases of primary myelofibrosis (PMF) patients. And CALR, JAK2 V617F, 12 exons of JAK2 and MPL W515L/K genes were amplified by PCR and sequenced directly. Clinical features were also analyzed in patients.

Among 246 cases of BCR-ABL-negative MPN patients, 52 cases (21.1%) had CALR mutation, 121 cases (49.2%) JAK2 V617F mutation, 0 case (0) 12 exons of JAK2 mutation, and 2 cases (0.8%) MPL W515L/K mutation, respectively. These mutations were found existing exclusively. In PV patients, the white blood cell and platelet counts in JAK2 V617F mutated group were higher than those in wild-type JAK2 V617F group, while the level of hemoglobin was higher in wild-type JAK2 V617F group(all P<0.05). In ET patients, the white blood cell count, the level of hemoglobin, the frequency of thromboembolic events and risk stratification in JAK2 V617F mutated group were higher than those in CALR mutated group(allP<0.05). In PMF patients, the level of hemoglobin in JAK2 V617F mutated group were significantly higher than those in CALR mutated group(P<0.05).

The proliferative level of bone marrow, risk of thromboembolic events and stratification are lower in CALR mutated patients than those in JAK2 V617F mutated patients. The pathogenic mechanism of mutated gene should be further investigated in future.

To analyze the clinical features of elderly patients with polythemia vera (PV)

Statistical analyses were performed for the clinical features of 68 PV patients of age ≥60 years and 72 PV patients of age <60 years from January 2009 to December 2013 in our hospital.

Compared with younger patients, elderly patients with PV had higher incidences of thrombosis(54.4%(37/68) vs 30.6%(22/72), P=0.004), more risk factors of cardio-cerebrovascular(63.2%(43/68)vs 36.1%(26/72), P=0.001), higher white blood cell counts((13.9±3.8)×10⁹/L vs (7.8±2.2)×10⁹/L, P=0.000) and higher JAK2 V617F allele burden(62%(30%-81%) vs 41%(26%-63%), P=0.035). There was higher incidences of vascular complications in elderly patients with PV (54.4%(37/68)vs 30.6%(22/72), P=0.004). Myelofibrosis transformation occurred with higher frequency in elderly patients with PV (11.8%(8/68)vs 2.8%(2/72), P=0.039). And there was no significant difference in the frequency of leukemia transformation between elderly patients and younger patients(4.4%(3/68)vs 0(0/72), P=0.112). There was higher mortality rate in elderly patients with PV(14.7%(10/86)vs 4.2%(3/72), P=0.032).

There are more risk factors in elderly patients with PV. The elderly patients with PV has high risk to complicat with thrombosis and transformated to myelofibrosis and leukemia. Prevention or delay of these complications is currently the goal of treatment, so that it could reduce the mortality rate and disease progression.

To analyze the clinical characteristics and laboratory data, treatment and prognosis of polycythemia vera (PV) and provide evidence for screening of high-risk population and looking for measures to reduce complecations.

A retrospective study was performed among 70 patients with PV from May 2005 to May 2014, 43 males and 27 females, aged (56.6±13.1) to collect the data about characteristics, laboratory data, myelogram chromosome, karyotypes, BCR/ABL and JAK2 V617F genes, as well as lactate dehydrogenase(LDH) and so on.

At diagnosis, there were 42 cases (60.00%) had symptoms, 25 cases(35.71%)had thrombosis and embolism. Hemorrhage occurred in 3 cases (4.29%), splenomegaly in 48 cases(68.57%), hepatomegaly in 7 cases(10.00%). The average hemoglobin at diagnosis was 195.17 g/L, the white blood cells count was 10.12×10⁹/L, the platelet count was 295×10⁹/L. The chromosome karyotypes were all normal. The positive percentage of JAK2 V617F mutation was 87.69%(57/65). The disease outcomes were myelofibrosis for 3 paitents, death from ineffective treatment after transforming to myelofibrosis and then biphenotype acute leukemia for 1 patient, and death from cardiorespiratory failure for 2 patients. The level of erythropoietin in JAK2 V617F mutated group were significantly lower than those in wild-type JAK2 V617F group(P<0.05). The level of hemoglobin and platelet counts in JAK2 V617F mutated group were significantly higher than those in wild-type JAK2 V617F group(bothP<0.05)

PV is one of meyloproliferation neoplasm, characterized by abnormally increasing blood cells, thrombosis and transforming to other myeloproliferative neoplasms.

To test the hypothesis that the polymorphisms in EDNRA gene are associated with the susceptibility to high-altitude polycythemia (HAPC) in Tibetans at the Qinghai-Tibetan Plateau in China.

We enrolled 63 Tibetan HAPC patients and 131 healthy, age-and gender-matched control Tibetans. All subjects came from Yushu area of Qinghai where the altitude was over 3 500 meters. Five SNPs of EDNRA gene (rs10003447, rs1801708, rs2048894, rs5335 and rs6841581) were genotyped by the Sequenom MassARRAY SNP assays.

None of five SNPs in EDNRA gene were associated with HAPC risk (P=0.742; P=0.733; P=0.828; P=0.417; P=0.096).

EDNRA gene is likely to have adaptive benefits for high altitude environment. However, it is not protective against HAPC in Tibetans.

To retrospectively explore the clinical features and risk factors of nosocomially acquired candidemia.

Retrospective analyses were conducted for general information, underlying diseases, risk factors, clinical features and laboratory tests of blood culture Candida-positive cases at Beijing Hospital from January 1, 2006 to December 31, 2011. Comparisons were made with regards to the clinical features, prognostic factors, risk factors of candidemia pathogen distribution between dead and survival groups and Candida albicans vs non-Candida albicans groups. Statistical analysis was performed with SPSS 19.0.

A total of 30 Candida albicans and 35 non-candida albicans cases were recruited. Their mean age was (76±14) years and total in-hospital fatality rate 58.5% (38/65). The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, ratio of APACHEⅡ score >24 points, ratio of shock, primary diagnosis time (from onset to reporting time of positive outcome of blood culture) and ratio of serum albumin ≤30 g/L of death group were (28.7±8.6) score, 55.3% (21/38), 71.1% (27/38), (138.7±50.4) h, 47.4% (18/38) respectively. And the values were significantly higher than those of survival group, i. e. (20.1±8.0) score, 29.6% (8/27), 44.4% (12/27), (127.2±50.2) h and 22.2% (6/27) respectively. Multivariate Logistic regression analysis showed that shock ( OR=4.821, P=0.030), primary diagnosis time (OR=1.594, P=0.027) and APACHEⅡ score (OR=1.096, P=0.032) were independent risk factors for death. However continuous blood purification therapy was an independent protective factor (OR=0.014, P=0.004). And diabetes was an independent risk factors for non-Candida albicans infection (OR=4.426, P=0.016).

Advanced age, more underlying diseases, severe clinical conditions and high fatality rate are the major clinical characteristics of candidemia. Shock, APACHEⅡ score and primary diagnosis time are independent risk factors for death. Continuous blood purification therapy is a protective factor. And diabetes is an independent risk factor for non-Candida albicans candidemia.

To explore the clinical characteristics and prognosis of patients with chronic kidney disease with unprotected left main (ULM) coronary artery disease undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).

A total of 601 unprotected left main coronary artery disease patients were recruited. According to the values of endogenous creatinine clearance rate (Ccr), they were divided into three groups of <45 ml/min ( n=40), 45-59 ml/min (n=96) and ≥60 ml/min (n=465). Retrospective comparisons were made for the clinical parameters and prognosis of ULM patients in different Ccr groups with different therapies.

In Ccr ≥60 ml/min group, the valves of left ventricular ejection fraction (LVEF) were lower in patients undergoing CABG. Patients with complete total occlusion (CTO) and complete revascularizations were much more than those undergoing PCI. In Ccr ≥60 ml/min and Ccr 45-59 ml/min groups, multivessel disease was frequent in CABG-treated patients. No significant difference existed among three groups in major adverse cardiac and cerebrovascular event (MACCE), overall mortality or cardiac mortality.

PCI is both safe and efficacious for chronic renal insufficiency patients with ULM.

To compare the efficacies of tricuspid valve replacement versus plasty for moderate-to-severe tricuspid regurgitation with right heart failure.

From January 2003 to June 2008, a total of 228 patients with right heart failure undergoing tricuspid valve operations were selected. And the procedures included tricuspid valve plasty (n=127) and tricuspid valve replacement (n=101). During a follow-up period of 65 months, their perioperative data were collected to evaluate the surgical outcomes.

The abnormal liver function rate and average pulmonary artery systolic pressure in tricuspid valve plasty group were lower than those in tricuspid valve replacement group (P=0.023, 0.033). In replacement group, average aortic cross-clamping time, cardiopulmonary bypass time, ventilation time and stay length of intensive care unit (ICU), the usage of inotropic drug was significantly higher than repair group (P<0.01). The early complication rate (15.8%) and case fatality rate (6.3%) of repair group were much lower than those of replacement group (27.3%, 16.8%)(P=0.042, 0.011). Long-term follow-ups revealed that the tricuspid valve thrombosis rate in replacement group was higher than that in repair group (P=0.036). And the recurrence rate of moderate-to-severe tricuspid regurgitation in repair group was higher than that in replacement group (28.7% vs 8.8%)(P=0.011). The survival rate of patients in repair group was much higher than that of replacement group at 3 months, 1, 3, 5 years post-operation. However, the differences were not statistically significant (P=0.231, 0.089, 0.133, 0.078).

For moderate-to-severe tricuspid regurgitation leading to right heart failure, the early efficacy of tricuspid valve plasty is much better than that of tricuspid valve replacement. The mid-term recurrence rate after tricuspid valve repair is higher than that of replacement.

The identify the gene defect of an inherited FⅦ deficiency patient.

The promoter, all the exons and exon-intron boundaries and 3' UTR ofF7 gene of the proband were analyzed by direct sequencing. The defected mutations were confirmed by sequencing the complementary strand. The mutations would be screened in the related database and 150 healthy donors to identify the SNP. By splice site prediction, we analyzed the pathogenesis of defected mutations.

Genetic analysis revealed G to A transition at 15975 in the intron 6 of F7 gene (IVS6-1G>A)and A to G transition at 16813 in the intron 7 ofF7 gene (IVS7+ 7 A>G). According to the fruitfly, the acceptor site could not be recognized when a G to A substitution took place. The closest candidate splice site was located 132 bp downstream. The distance was probably too far to allow the use of the cryptic splice site and resulted in the skipping of exon6. A to G transition at 16813 in the intron 7 ofF7 gene could not change the splice site, but modify a different molecular interaction that is important for the splice process.

The heterozygous mutation of IVS6-1G>A combined with polymorphism of IVS7+ 7 A>G inF7 gene relates to the FⅦ deficiency.

To investigate the clinical application of neutrophil/lymphocyte count ratio in the diagnosis of lung bacterial infections in the elderly.

Complete blood count(CBC), white blood cell volume- conductivity-scatter(VCS) parameters, C-reactive protein(CRP) and neutrophil CD64 index (CD64 index) of patients older than or equal to 60 years with pulmonary bacterial infections(n=140), tuberculosis(n=35), non-lung bacterial infections (n=86), no infections or controls(n=100) and healthy people (n=278) were detected. Neutrophil/lymphocyte count ratio (NLCR)is calculated through the percentage of neutrophils (NE) divided by the percentage of lymphocytes (LY).

Youden Index of NLCR(46.1%) was greater than that of WBC, NE and CD64, and second only to CRP(53.5%) by means of comparison of multiple parameters for diagnosis of bacterial infections in part of cases. After the increase in the number of cases and types of the disease, the CRP levels of pulmonary bacterial infections, tuberculosis, non-lung bacterial infections, no infections or controls were 31.5(11.3-104.8), 3.7(1.5-12.7), 41.7(10.5-82.4), 2.4(1.2-4.0)mg/L, respectively. NLCR levels of them were 6.9(3.2-13.8), 2.7(1.8-3.6), 4.5(3.0-9.0), 2.2(1.7-2.9), 1.7(1.4-2.0); WBC levels of those groups were 7.4(5.7-11.1)×10⁹/L, 6.2(5.3-7.1)×10⁹/L, 6.5(5.2-8.5)×10⁹/L, 5.7(4.7-6.9)×10⁹/L, 6.0(5.3-6.8)×10⁹/L; NE levels of those groups were 79.2(65.7-85.0)%, 63.3(55.9-69.1)%, 74.0(65.3-82.6)%, 62.1(55.3-66.7)%, 56.4(51.8-60.6)%, respectively. The differences were statistically significant(Chi-square value=162.628, 277.763, 49.653, 218.758, P<0.001); CRP, NLCR, WBC, NE of patients with pulmonary bacterial infections were significantly higher than non-lung bacterial infections and the controls (P<0.001). There was no difference in CRP, WBC, NE and NLCR levels between lung bacterial infections and tuberculosis(P>0.05). The sensitivity of NLCR for diagnosis of pulmonary bacterial infections was 77.0%, which is equal to CRP, and higher than that of WBC, NE.There was a high sensitivity (87.1%) for diagnosing pulmonary bacterial infections in the elderly by combination of NLCR and CRP. The sensitivity of NLCR for diagnosis of pulmonary bacterial infections was 67.7%, which was higher than that of NE(43.4%) in patients with lung bacterial infections had a normal WBC. Although the correlation between NLCR and types of bacterial infections had not been found, the positive rate of bacterial culture of patients with increased NLCR(40.2%) was much higher than that with normal ones(9.1%). NLCR levels of patients with poor prognosis was 11.2(7.4-26.1), which is significantly higher than that of patients with good prognosis in cases with pulmonary bacterial infections (Z=-3.460, P=0.001).

NLCR is a simple, rapid and economic parameter of blood leukocyte, which is helpful in diagnosis and differentiation of elderly patients with lung bacterial infections, especially the cases without increasing WBC. NLCR, combined CRP can improve the diagnostic sensitivity for lung bacterial infections, and that be used for the prognostic evaluation of patients with pulmonary bacterial infections in the elderly.

To explore the risk factors of portal hypertensive gastropathy (PHG) in patients with hepatitis B associated cirrhosis and establish a Logistic regression model of noninvasive prediction.

The clinical data of 234 hospitalized patients with hepatitis B associated cirrhosis from March 2012 to March 2014 were analyzed retrospectively. The dependent variable was the occurrence of PHG while the independent variables were screened by binary Logistic analysis. Multivariate Logistic regression was used for further analysis of significant noninvasive independent variables. Logistic regression model was established and odds ratio was calculated for each factor. The accuracy, sensitivity and specificity of model were evaluated by the curve of receiver operating characteristic (ROC).

According to univariate Logistic regression, the risk factors included hepatic dysfunction, albumin (ALB), bilirubin (TB), prothrombin time (PT), platelet (PLT), white blood cell (WBC), portal vein diameter, spleen index, splenic vein diameter, diameter ratio, PLT to spleen volume ratio, esophageal varices (EV) and gastric varices (GV). Multivariate analysis showed that hepatic dysfunction (X1), TB (X2), PLT (X3) and splenic vein diameter (X4) were the major occurring factors for PHG. The established regression model was Logit P=-2.667+ 2.186X1-2.167X2+ 0.725X3+ 0.976X4. The accuracy of model for PHG was 79.1% with a sensitivity of 77.2% and a specificity of 80.8%.

Hepatic dysfunction, TB, PLT and splenic vein diameter are risk factors for PHG and the noninvasive predicted Logistic regression model was Logit P=-2.667+ 2.186X1-2.167X2+ 0.725X3+ 0.976X4.

To compare the expression of matrix metalloproteinase-9 (MMP9) and observe the change of cigarette smoke-induced pulmonary injury in Wistar and spontaneously hypertensive (SH) rats.

A total of 10 male Wistar rats and 10 male SH rats were randomly divided into four groups of Wistar control, Wistar cigarette smoking, SH control and SH cigarette smoking (n=5 each). The control groups were fed routinely while the cigarette smoking groups were placed into a homemade organic glass box and exposed to cigarette smoking for twice daily 6 days a week. After 8-week treatment, general condition, lung function and pathological changes of lung tissues were detected. The expressions of nuclear factor (NF)-κB, IκB-α and MMP9 were determined by Western blot. And real-time polymerase chain reaction (RT-PCR) was employed to detect the mRNA levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Immunohistochemistry was used to detect the expression of MMP9 in lung tissue.

Both cigarette smoking groups were marantic along with intermittent cough and polypnea. Resistance index (RI) in Wistar control, Wistar cigarette smoking, SH control and SH cigarette smoking groups was (0.23±0.04), (0.33±0.05), (0.33±0.02) and (0.46±0.08) cmH₂O·s·ml^-1 respectively. RI increased in Wistar cigarette smoking group versus Wistar control group. And SH cigarette smoking group was significantly higher than SH control and Wistar cigarette smoking groups (P<0.05). Hematoxylin & eosin staining demonstrated that the lesion of chronic bronchitic inflammation and emphysema existed in two cigarette smoking groups while it was more severe in SH rats than Wistar rats. The mean alveolar number (MAN) was significantly reduced in two cigarette smoking groups compared with that in control groups (P<0.05, respectively). And mean lining interval (MLI), damage index (DI), bronchial smooth muscle index and collagen index significantly increased in Wistar cigarette smoking group compared with Wistar control group, SH cigarette smoking group significantly increased than that in SH control and Wistar cigarette smoking groups (P<0.05, respectively). On Western blot, the protein level of NF-κB in Wistar control, Wistar cigarette smoking, SH control and SH cigarette smoking groups was (0.322±0.014), (0.558±0.044), (0.373±0.029) and (1.156±0.197) respectively. The protein level of MMP9 in these groups was (0.255±0.070), (0.456±0.089), (0.594±0.184) and (0.847±0.138) respectively. The protein levels of NF-κB and MMP9 increased obviously in Wistar cigarette smoking group versus Wistar control group and those in SH cigarette smoking group were significantly higher than SH control and Wistar cigarette smoking groups (P<0.05). Additionally, IκB-α expression in SH cigarette smoking group was markedly decreased in comparison to that in SH control group and Wistar cigarette smoking group (P<0.05). The mRNA level of TNF-α increased obviously in two cigarette smoking groups in comparison to those in controls (P<0.05) and the mRNA level of IL-6 significantly increased in the SH cigarette smoking group compared with SH control group and Wistar cigarette smoking group (P<0.05). As for immunohistochemistry, the MMP9 positive cells were prominently distributed in the lungs of cigarette smoking groups versus the stained cells in the control group. And SH cigarette smoking group was significantly higher than Wistar cigarette smoking group (P<0.05).

Both Wistar and SH rats induced by cigarette smoking may have an onset of lung injury symptom analogous to chronic obstructive pulmonary disease and SH rat are more severe.

To explore the role of stromal cell derived factor-1(SDF-1)/CXCR4 axis in acute infarct myocardium after an implantation of bone marrow mesenchymal stem cells(MSCs) in rats.

The animals were anesthetized by an intraperitoneal injection of pentobarbital sodium. Left anterior thoracotomy through 3/4 intercostals region was performed and then left anterior descending coronary arteries were ligated for modeling acute myocardial infarction. The MSCs were injected into the area of acute infarct myocardium after a 10-minute ligation of left anterior descending coronary artery.The different concentration and expression of SDF-1/CXCR4 in the area of acute myocardial infarction and left ventricular function were analyzed.

At day 28 post-transplantation, the vascular density in MSCs implant group were significantly higher than that in control group(P<0.05). And left ventricular function in MSCs implant group improved significantly than that in control group too(P<0.05). At the same time, the expressions of SDF-1 and CXCR4 in topical injection sites of infarct myocardium were significantly higher than those in control group(P<0.05). In MSCs implant group, the level of SDF-1/CXCR4 peaked at Day 1 post-transplantation and then it declined.

After the implantation of MSCs into acute infarct myocardium, there is vascular regeneration and the level of SDF-1/CXCR4 increases so that left ventricular function improves. And the mechanism may be due to an up-regulation of SDF-1/CXCR4 axis.

To compare the safety and efficiency of preoperative endoscopic sphincterotomy (POES) versus intraoperative endoscopic sphincterotomy (IOES) in patients with gallbladder and common bile duct stones.

Multiple electronic databases were searched for prospective, randomized, controlled trials on the safety and effectiveness of POES versus IOES. And the outcome parameters of clearance rate, post-procedural complications and hospital stay were analyzed.

Five trials with 631 patients (POES, n=318; IOES, n=313) were analyzed. Although the overall rates of common bile duct stone clearance were similar between POES and IOES (RR 0.96, 95% CI: 0.91-1.01; P=0.13), the failure rate of CBD cannulation was significantly higher for IOES (RR 2.54, 95% CI: 1.23-5.26; P=0.01) during endoscopic retrograde cholangiopancreatography (ERCP). The pooled RR after POES for overall complication rates was similar to that for IOES (RR 1.56, 95% CI: 0.94-2.59; P=0.09). However, as compared with IOES, the RR risk of ERCP-related complications was significantly higher for POES (RR 2.27, 95% CI: 1.18-4.40, P=0.01). No significant inter-group differences existed in morbidity after laparoscopic cholecystectomy or subsequent conversion into open surgery. In subgroup analyses, the rates of hemorrhage, perforation, cholangitis, cholecystitis, and gastric ulceration showed no significant inter-group differences.

With regards to stone clearance and overall complication rate, POES is comparable to IOES in patients with gallbladder and common bile duct stones. However, IOES has a lowered incidence of ERCP-related pancreatitis and a shorter hospital stay.

As a new type of vascular diseases in the world, venous vascular malformations have become the most frequent and common lesions in congenital vascular malformations. In the past, it was often called cavernous hemangioma. Its pathological characteristics and clinical manifestations are essentially different from hemangioma. Its lifelong progressive development is the main source of health hazard of this disease. Severe venous vascular malformation syndrome is a large area severe venous vascular malformation combined with multiple organ involvement and accompanied by significant coagulation dysfunction syndrome, which is relatively rare in the world. At present, in view of the lack of understanding of severe venous vascular malformation syndrome in the world and the lack of uniform name, the author temporarily uses this name to explain and discuss the rare cases of systemic multiple severe venous malformation syndrome in clinic.

BCR/ABL fusion gene-negative myeloproliferative neoplasm (MPN) is a group of malignant myeloproliferative diseases originating from pluripotent hematopoietic stem cells, including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). 90% of PV, half of ET and PMF patients have mutations in JAK2 V617F gene^[1]In 2008, the WHO regarded JAK2 V617F mutation as one of the main diagnostic criteria for PV, ET and PMF. 3% ~5% of patients had MPL gene mutations. Recently, it was found that 30% ~50% of ET and PMF without JAK2 and MPL gene mutations had CALR gene mutations^[2,3,4]The diagnostic criteria have not been included at present. The clinical manifestation of MPN is a chronic process, and the main risks are thrombosis and hemorrhage, and the potential for transformation into acute leukemia. Recent studies have shown that bone marrow angiogenesis plays an important role in MPN including ET, PV, and PMF^[5,6]Bone marrow microvessel density (MVD) is associated with vascular embolism, an important clinical manifestation of PV and ET^[7], associated with poor prognosis of MPN^[8]。

Sepsis refers to a systemic inflammatory response syndrome caused by infection, with clinically confirmed presence of bacteria or highly suspected foci of infection; Severe sepsis refers to sepsis accompanied by organ dysfunction and/or signs of hypoperfusion and hypotension; Septic shock refers to severe sepsis that is still accompanied by uncorrectable persistent hypotension after sufficient fluid resuscitation, and even may be accompanied by multiple organ (more than one) dysfunction. The incidence and mortality of severe sepsis and septic shock remain high. About 1.5 million patients in North America and Europe each year, with mortality rates ranging from 35% to 50%^[1]。 The pathophysiological changes of these patients are large, which causes the pharmacokinetics (PK) of antimicrobial drugs to change accordingly. In addition, the infected pathogenic bacteria are often multi-drug resistant bacteria, so conventional antimicrobial treatment is easy to lead to treatment failure.

Allergic asthma is an allergic disease with abnormal immune function, and the incidence rate is 5% ~16%^[1]。 The number of patients with allergic asthma in China is also increasing year by year, especially the incidence of childhood asthma is on the rise. From 1994 to 2009, the incidence of childhood asthma doubled. Allergy to house dust mite allergens is a major risk factor for rising asthma incidence^[2]Therefore, allergic asthma treatment for house dust mites is one of the main research directions.