Wedelolactone Promotes the Chondrogenic Differentiation of Mesenchymal Stem Cells by Suppressing EZH2

Background and Objectives@#Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction ofarticular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation. @*Methods@#and Results: Real-time reverse transcription–polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of FOXO1 to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of FOXO1 that is dependent on the binding of miR-1271-5p to the FOXO1 3’-untranscribed region. @*Conclusions@#These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.

Effects of gene polymorphisms of β1 adrenergic receptor G1165C and A145G locus on myocardial hypertrophy and the efficacy in patients with hypertension / 中国医师进修杂志

Objective:To investigate the effect of gene polymorphism of β1 adrenergic receptor (β1-AR) G1165C and A145G locus on myocardial hypertrophy and the efficacy in patients with hypertension.Methods:Two hundred and twenty-seven cases of patients with hypertension admitted to Binhai County People′s Hospital from January to December 2019 were enrolled. Among them, there were 113 cases of hypertension with myocardial hypertrophy and 114 cases of hypertension without myocardial hypertrophy. In addition, 115 patients with normal physical examination during the same period were selected as the control group. DNA in the peripheral blood leukocytes was extracted, polymerase chain reaction-restriction fragment length polymorphism method was used to detect β1-AR G1165C and A145G locus gene polymorphism, and the differences in the efficacy of β blockers in hypertensive patients with different genotypes were compared.Results:There was no statistically significant differences in the distribution of β1-AR A145G genotypes among the three groups ( P>0.05). Compared with the healthy control group, the frequency of Gly/Gly genotype carrying β1-AR G1165C locus was higher in hypertension with myocardial hypertrophy group, and the frequency of Gly/Arg and Arg/Arg gene were lower; compared with hypertension without myocardial hypertrophy group, the frequency of Gly/Arg+Gly/Gly gene in hypertension with myocardial hypertrophy group was higher; taking Arg/Arg genotype as the control group, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive patients by 3.159 times ( OR = 3.159, 95% CI 1.240 - 7.412, P<0.05).The frequency of G1165C allele Arg in the hypertension with myocardial hypertrophy group was significantly lower than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); the frequency of G1165C allele Gly was significantly higher than that in the control group and the hypertension without myocardial hypertrophy group ( P<0.05); taking Arg/Arg genotype as the control, carrying Gly/Gly genotype could increase the risk of cardiac hypertrophy in hypertensive ( OR = 3.417, 95% CI 1.357 - 7.965, P<0.05). The left ventricular mass index of Gly/Gly genotype patients was (120.38 ± 28.41) g/m 2, which was significantly higher than (99.76 ± 25.16) g/m 2 and (90.30 ± 19.54) g/m 2 of Gly/Arg and Arg/Arg, with statistically significant differences ( F = 10.89, P<0.01). After the treatment, the resting heart rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure of patients with G1165C allele Arg hypertension with myocardial hypertrophy were lower than those with G1165C allele Gly, with statistically significant differences ( P<0.05). Conclusions:β1-AR G1165C gene polymorphism is related to the risk of myocardial hypertrophy in hypertensive patients. Carrying the G1165C allele Gly may increase the risk of susceptibility to cardiac hypertrophy, and β-blockers are more effective in hypertensive patients with myocardial hypertrophy who carry the G1165C allele Arg.

Prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients who achieved deep response / 中华内科杂志

Objective:To evaluate the effect of immune status on disease progression in patients with newly diagnosed multiple myeloma (NDMM) achieving deep response.Methods:Clinical data of 125 NDMM patients at Beijing Chaoyang Hospital from August 2015 to February 2020 were retrospectively analyzed who achieved very good partial response (VGPR) or better after front-line treatment. The immune status and its influence on progression-free survival (PFS) were analyzed.Results:(1) All patients received novel drug regimens, and 50.4% (63/125) patients followed by autologous stem cell transplantation (ASCT). The rate of complete response (CR) as best efficacy was 89.6%, in which 66.4% achieved CR and MRD negativity tested by second generation flow cytometry. (2) Cox multivariate analysis suggested that persistent severe immunoparesis 3 months and 6 months since the best response was an independent poor prognostic factor for PFS. (3) The 3-year PFS rate in the severe immunoparesis group was significantly lower than that in the control group (41.3% vs. 64.4%, P=0.021). (4) The 3-year PFS rates in patients with persistent severe immunoparesis at 3 months or 6 months were significantly lower (30.0% vs. 63.5%, P<0.001; 16.4% vs. 63.8%, P<0.001 respectively). (5) Even in those achieving CR and negative MRD, the 3-year PFS rate when severe immunoparesis lasted 6 months was significantly lower (22.2% vs. 83.2%, P=0.005). Conclusion:The immune status in NDMM patients achieving deep response is closely related to survival. Persistent severe immunoparesis indicates early progression of the disease.

Expression of DNA binding / differentiation inhibitory protein 2 in colon adenocarcinoma and its relationship with cell proliferation / 中国综合临床

Objective:To detect the expression of inhibitor of DNA binding-2(ID-2) in colorectal adenocarcinoma and analyze its relationship with proliferation.Methods:A total of 67 patients with colorectal adenocarcinoma diagnosed in North China University of Science and Technology Affiliated Hospital were selected from November 2014 to September 2015, tumor tissue as the research objects.All patients underwent radical operation.The tumor tissue was taken as the observation group, and the normal colonic mucosa tissue>3 cm from the edge of the tumor was taken as the control group.Immunohistochemistry was used to detect the expression of ID-2 of the two groups and the Ki67 of cancer tissue.SW480 cell line of ID-2 overexpression was constructed.The expression of proliferating cell nuclear antigen(PCNA)was detected by Western Blot.Cell activity was detected by CCK-8 test.Correlation was analyzed between ID-2 and Ki67 by pearman correlation analysis.Prognostic value of ID-2 was analyzed by Kaplan-Meier survival analysis and Log-rank test in colorectal adenocarcinoma.Results:The positive rate of ID-2 was 49.3%(33/67) in the observation group, which was higher than 9.0%(6/67) in the control group, and the difference between the two groups was was statistically significant(χ 2=23.927, P<0.05). In the observation group, the expression of ID-2 was statistically significant in different invasion depth(serosa and extraserosa was 68.7%(22/32), serosa and extraserosa was 31.4%(11/35)), degree of differentiation(low differentiation was 80.0%(8/10), medium differentiation was 57.9%(11/19), high differentiation was 36.8%(14/38)), clinical stage(Ⅲ and Ⅳ stage were 64.3%(18/28), Ⅰ and Ⅱ stage were 38.5%(15/39)), lymph node metastasis(metastasis was 70.8%(17/24), no metastasis was 37.2%(16/43)) and tumor thrombus(yes was 75.0%(12/16), no was 41.2%(21/51)). The difference was statistically significant (χ 2 value were 6.311, 4.023, 4.349, 6.967 and 5.575, respectively, all P<0.05). Positive correlation was found between ID-2 and Ki67( r=0.65, P<0.05). Survival analysis showed that the expression of ID-2 was related to the prognosis of patients (X2=5.29, P=0.013). Compared with empty vector transfection group and blank control group, the expressions of PCNA and the activity ID-2 overexpression colon cancer cells increased( P<0.05). Conclusion:The higher expression of ID-2 is related to clinicopathological features and prognosis in colorectal adenocarcinoma.The abnormal expression of ID-2 may play a role in regulating the proliferation of colon adenocarcinoma.

Risk factors for postoperative pulmonary venous obstruction after correction of total anomalous pulmonary venous connection / 中华胸心血管外科杂志

Objective:To analyze the risk factors for postoperative pulmonary venous obstruction after correction of total anomalous pulmonary venous connection(TAPVC).Methods:We retrospectively reviewed all patients undergoing operative repair of TAPVC in our institution from December 2013 to January 2018. Patients with functionally univentricular circulations or atrial isomerism were excluded. Patients were divided into two groups according to whether there was pulmonary vein obstruction. The clinical variables of the two groups were compared. Variables for the multivariable analysis were chosen if there was statistical significance on univariable analysis.Results:145 patients were included, 91(63%) males, aged 4(2, 8)months and weight 5.5(4.5, 7.5)kg. Mean follow-up interval was(51±23) months. Postoperative obstruction developed in 27 patients(18.6%). The differences of anatomic type[supracardiac 18(67%) vs.59(50%), cardiac 4(15%) vs. 50(42%), infracardiac 3(11%) vs. 1(1%), mixed 2(7%) vs. 8(7%), P=0.003], preoperative obstruction[yes 19(70%) vs. 37(31%), no 8(30%) vs. 81(69%), P<0.001], associated cardiac lesions[yes 13(48%) vs. 27(23%), no 14(52%) vs. 91(77%), P=0.008] and bypass time[109(89, 129)min vs. 88(70, 110)min, P=0.002] between two groups were statistical significant. A multivariable model showed preoperative obstruction( P<0.001) and bypass time( P=0.009) were associated with postoperative obstruction. Conclusion:The incidence of pulmonary vein obstruction after correction of TAPVC was still high. If there was preoperative obstruction, or the bypass time was too long during operation, the surveillance of pulmonary vein obstruction should be strengthened after operation.

The application of stemic-pulmonary shunt in staged operation for tetralogy of Fallot with hypoplasia pulmonary arteries / 中华胸心血管外科杂志

Objective:The study aimed to evaluate the effect of systemic-pulmonary shunt(SPS) on the infants with tetralogy of Fallot(TOF) with hypoplasia pulmonary arteries.Methods:Among 949 infants less than three-year-old who underwent surgical intervention between January 2010 and December 2015, 853 infants underwent one-stage primary repair(group Ⅰ), whereas 96 infants underwent SPS(group Ⅱ). Among them, 546 were males and 403 were females. The average age and average weight at operation were 13 months and 9.4 kg, respectively. 20.8% infants had clinical symptoms before operation. Perioperative and follow-up parameters were assessed including age, weight, sex, transcutaneous oxygen saturation(SPO 2), preoperative clinic symptom, ratio of McGoon, NAKATA index, Z score of pulmonary annulus, left ventricular end diastolic diameter(LVEDD). Results:There were 28(3.0%) early postoperative deaths in the whole group. And no significant difference in mortality was found between group Ⅰ(2.9%) and group Ⅱ(3.1%). Compared with group Ⅰ, age and weight were significantly lower in patients in group Ⅱ[(0.95±0.56)years old vs.(1.09±0.59)years old] and[(8.6±1.8)kg vs.(9.5±2.1)kg], respectively. Patients in group Ⅱ had a lower SPO 2(0.75±0.09 vs. 0.85±0.09) and was more prone to appear hypoxic spell(30.2% vs. 19.7%) than patients in group Ⅰ. Patients in group Ⅱ had a more poor development in pulmonary artery. The ratio of McGoon, NAKATA index and Z score of pulmonary annulus in group Ⅱ were significantly less than that in group Ⅰ[1.4±0.3 vs. 1.9±0.5, (124±43)mm 2/m 2 vs.(222±88)mm 2/m 2 and-4.3±2.6 vs.-2.3±2.1], respectively. There was no difference of extubation time bewteen two groups. SPO 2 rose significantly from 0.75 to 0.83 after SPS. And after SPS, the diameter of main pulmonary artery, the ratio of McGoon, NAKATA index and Z score of pulmonary annulus increased significantly from 6.4 mm, 1.42, 126.4 mm 2/m 2 and -4.3 to 9.2 mm, 1.83, 212.6 mm 2/m 2 and -2.4, respectively. Moreover, LVEDD also increased significantly from 21.2 mm to 24.5 mm after SPS. Conclusion:SPS is safe and effective for little infants with anoxic spell and hypoplasia pulmonary arteries. SPS can improve oxygenation significantly and delay the age for radical surgery. SPS also promote the growth of the pulmonary arteries, pulmonary valve annulus and left ventricular, and it facilitates the preservation of pulmonary valve annulus and reduce the rate of transannular patching in a portion of infants.

Surgical treatment and mid-term results of functional single ventricle associated with total anomalous pulmonary venous connection / 中国胸心血管外科临床杂志

@#Objective    To evaluate the mid-term results of surgical treatment for functional single ventricle associated with total anomalous pulmonary venous connection. Methods    We reviewed the clinical data and follow-up results of 12 patients in our hospital who underwent both single ventricle series palliation and total anomalous pulmonary venous connection correction from 2008 to 2018. There were 6 males and 6 females at age of 2.3 (1-21) years. Univariable and multivariable Cox proportional hazard regression methods were performed. The Kaplan-Meier method was used to estimate the survival rate. Results    All patients were successfully removed from extracorporeal circulation. The cardiopulmonary bypass time was 113.8±42.5 min. The myocardial block time was 57.7±31.7 min. There were 3 in-hospital deaths and 4 late deaths. The causes of death in hospital were pulmonary hypertension, pulmonary hemorrhage, and hypoxemia. During follow-up, the cause of death was heart failure. The survival rate at 1 year and 3 years was 58.3%(95%CI 27% to 80%) and 40% (95%CI 13% to 65%), respectively. Median follow-up was 48.3 months (range: 1 to 118 months). Conclusion    Functional single ventricle combined with complete pulmonary venous drainage is a serious clinical disease, with poor therapeutic effect and high overall mortality.

The effect of four compounds of astragalus isoflavones on the differentiation of PC 12 cells / 药学实践杂志

Objective To investigate the effects of calycosin, formononetin, calycosin-7-glucoside and ononin on PC 12 cells differentiation. Methods PC 12 cells were cultured and treated with different concentrations of nerve growth factor (NGF), calycosin, formononetin, calycosin-7-glucoside and ononin for 5 days, once a day, 3 times in a row. The neurite outgrowth of PC 12 cells was observed and the expression of β III-tubulin were measured by immunofluorescence. Results Compared with the vehicle group, neurite outgrowth and the expression of β III tubulin in PC 12 cells had not promoted by calycosin, formononetin, calycosin-7-glucoside and ononin (0.01-10.00 μmol/L). Conclusion PC 12 cells differentiation could not be induced by calycosin, formononetin, calycosin-7-glucoside and ononin.

Application of smart hospital related technology in hospital construction / 中华医院管理杂志

The authors discussed the meaning of smart hospital and the importance of Internet, cloud computing, supercomputer and other related technologies on the construction of smart hospital, summarized the construction status of smart hospital in China, and pointed out the problems such as lack of long-term planning for information construction, obvious island effect of information system, insufficient data processing capacity, and slow development of intelligent medical care. Based on the construction practice of smart hospital in Beijing Tiantan Hospital, the authors believe that the innovation and application of artificial intelligence technology will support intelligent medical treatment, supercomputer will become the standard configuration of high-level smart hospitals, and hospital infrastructure will affect the level of smart hospitals.

Causes and management of reoperation for mitral regurgitation in children with congenital heart disease / 中华胸心血管外科杂志

Objective:To explore the causes and management of reoperation for mitral regurgitation in children with congenital heart disease.Methods:Twenty-four patients required reoperation for moderate to severe mitral regurgitation after mitral valve repair. The median age was 6.7 years, ranging 7 months to 14 years; and their median weight was 18.5 kg, ranging 9.2 to 47.0 kg. Among the patients who underwent reoperation for mitral insufficiency, mitral valvuloplasty was performed in 23 cases and mitral valve replacement was performed in 1 case. Reoperation for mitral valvuloplasty was performed in 7 cases after repair for partial endocardial cushion defect, 3 cases after repair for complete endocardial cushion defect, 11 cases after mitral valvuloplasty combined with other intracardiac malformations, 3 cases after mitral valvuloplasty. Reoperation for mitral replacement was performed in 1 case after mitral valvuloplasty. Reasons for reoperation included enlargement of annulus, prolapse of valves, cleft of valves, perforation of valves, avulsion of original suture and hemolysis.Results:There was no early and later death during the follow-up. Enlarged mitral annulus in 21 cases, cleft valve in 14 cases, valve prolapse in 9 cases, valve perforation in 3 cases, relaxation of tendon chord in 1 case, shortening of tendon chord in 1 case, loss of tendon chord in 2 cases and avulsion of original suture in 3 cases were confirmed. Mitral annuloplasty, annular junction contraction, cleft closure, aberrant orifice closure, Chordae shortening or neo-chordae implantation, prosthetic ring and mitral valve replacement were performed in these cases. The mean cardiopulmonary bypass time and aorta clamp time were(129.8±69.9)min and(69.1±41.1)min. Echocardiograghy revealed slight and mild mitral regurgitation in 21 cases, moderate mitral regurgitation in 2 cases and severe mitral regurgitation in 1 case. During the follow-up for 7 to 84 months. Six months after discharge, 21 cases showed slight and mild mitral regurgitation and 3 cases had moderate mitral regurgitation.Conclusion:The main reasons for reoperation of mitral insufficiency in children are mainly due to the progress of valvular disease or inappropriate suture in the first operation. The clinical results were excellent after reoperation for mitral valve insufficiency.

A combination of lenalidomide, bortezomib, and dexamethasone (RVD) provides deep-er responses in patients with newly diagnosed multiple myeloma / 中国肿瘤临床

Objective: This study investigated the efficacy and safety of a combination of lenalidomide, bortezomib, and dexametha-sone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical features and responses of 48 patients with NDMM who were treated with RVD from January 2015 to May 2019 in Beijing Chaoyang Hospital were retrospectively analyzed. Results: The median age of the 48 patients was 59 years (range: 34-79). Among these, 44 patients were Durie-Salmon stageⅢ, 15 were ISS stageⅡ, 19 were ISS stageⅢ, and 12 had plasmacytoma; 32.5% of all patients were cytogenetic high-risk. All patients re-ceived a median of four cycles (range: 1-9) of the RVD regimen as induction treatment. The overall response rate was 97.9%, with 35.4% of patients achieving complete response (CR) or better. The rate of very good partial remission (VGPR) or better was increased from 64.1% (after two cycles) to 84.6% (after four cycles). The mean collection of CD34+cells was 4.2 (± 2.6)×106/kg. Negative minimal residual disease (MRD), as indicated by next-generation flow (NGF), was achieved in 20.6% of patients after induction. Two patients with positive MRD after induction became MRD negative after transplantation. Two patients developed grade 3 or 4 hematologic toxic-ity. No nonhematologic toxicity of grade 3 or 4 was observed. Conclusions: In patients with NDMM, RVD treatment resulted in signifi-cantly improved response rates and exhibited an acceptable risk-benefit profile, with no adverse impact on stem cell collection. RVD combined with transplantation significantly improved the negative rate of MRD, as indicated by NGF.

The effects of two perfusion methods in the treatment of left coronary artery abnormality originated from pulmonary artery / 中华胸心血管外科杂志

Objective To investigate the applicate effects in the treatment of left coronary artery abnormality originated from pulmonary artery(ALCAPA) with two perfusion methods of Medium-low temperature-full flow and Low-temperature-low flow.Methods From April 2010 to August 2018, 51 children with ALCAPA were treated with direct coronary artery trans-plantation in Beijing Anzhen Hospital.According to the circulated perfusion method, All of cases were divided into two groups:the Medium-low temperature full flow(group A) and Low-temperature low flow(group B); All patients underwent ALCAPA correct operation under general anesthesia by intravenous inhalation and extracorporeal circulation , and the combined cardiac malformations at the same period.Results The whole of 51 children, including 27 males and 24 females, the aweraged age was(29.19 ±19.43)months(8-36 months), the aweraged weight was(11.73 ±9.99)kg(7.4 -35.0 kg).The cardiotho-racic ratio(C/T) was 0.70 ±0.09.In group A, 24 patients, including 13 males and 11 females, the aweraged age 3 -36 (28.64 ±16.30) months, the aweraged weight 7.4-31.0(12.25 ±10.33) kg, and the cardiothoracic ratio(C/T) 0.71 ± 0.07.Group B included 27 patients, including 15 males and 12 females, the aweraged age 5-31(25.85 ±16.60) months, the aweraged weight 6.7-35.0(10.38 ±3.67)kg, and the cardiothoracic ratio(C/T) of 0.69 ±0.06.The postoperative ear-ly death were 5 cases in the whole group, there were 3 cases in group A and 2 cases in group B, all of them were died of low cardiac output syndrome.Extracorporeal membrane oxygenation(ECMO) support for 7 cases of 5 in group A and 2 in group B. There was no statistically significant difference in in-hospital mortality between the two groups(P >0.05).The Intraoperative extracorporeal circulation time, ascending aorta occlusion time, the number and amount of myocardial cold arrest fluid perfu-sion, postoperative extracorporeal circulation assistance time, the incidence of ventricular fibrillation, ICU residence time, and ventilator assistance time were significantly lower in group B than group A, all with statistically significant differences(P<0. 05).A total of 42 cases were followed up after the operation, the follow-up time 17(3-29) months and the left ventricular e-jection fraction increased from 0.53 ±0.15 to 0.66 ±0.14(P<0.05), there was no statistically significant difference between two groups.Conclusion The perfusion modes of Low-temperature-low flow in the correct operation of ALCAPA can effectively shorten the time of aortic occlusion , improve the effect of intraoperative myocardial protection , reduce intraoperative visual field return blood volume, and reduce postoperative low cardiac output.To improve the curative effect of operation.

Clinicopathological analysis of cervical basaloid squamous cell carcinoma / 中华妇产科杂志

Objective To investigate the clinical and histopathological features of cervical basal squamous cell carcinoma (BSCC). Methods A retrospective analysis of 10 cases of cervical BSCC was carried out. The clinical data and all the pathological sections were reviewed, the related immunohistochemical results were statistically analyzed, the clinicopathological features were analyzed, and then followed the prognosis. Results (1) Clinical features:the median onset age of BSCC in cervix was 51 years old (ranged 35-69 years old), 5 of them were postmenopausal women. Vaginal bleeding was often seen in clinic (7 cases). Of the 10 cervical BSCC patients, 5 tested HPV types. All of them were HPV positive, including 2 cases of HPV 16 positive and 1 case of high-risk HPV positive. At the time of colposcopy, 3 cases showed exogenous nodular mass, 3 cases showed endogenous infiltrating mass, and 4 cases had unclear type of mass.(2)Treatment:of the 10 patients, 8 underwent hysterectomy+bilateral adnexal excision+pelvic lymphadenectomy, of which 6 underwent radiotherapy or chemotherapy after operation. Radiotherapy and chemotherapy were performed only in 2 cases. (3) Pathological features: histologically, the tumor cells were nests and stripe like growth, which were composed of basal like tumor cells. The cells had obvious heteromorphosis, less cytoplasm, deep dyed nuclei and common nuclear mitosis, and there were often palisade like structures around the cell nests, and some cells in the center of the cell nests were found to have acne like necrosis. It could be mixed with normal squamous cell carcinoma and squamous epithelial lesion. Among the 10 patients, 6 had immunohistochemical results. BSCC mainly expressed p16 and squamous cell markers such as p63, cytokeratin (CK) 5/6 and p40 protein, the positive expression rates were 3/3, 3/3, 2/2 and 3/3, respectively.A few expressed CK7 protein, and the positive expression rate was 1/3. (4) Prognosis:follow-up time ranged from 1 week to 64 months, and 2 cases were lost to follow-up. Among the 8 follow-up patients, 3 had iliac bone, lung or skin metastasis, and 5 had no recurrence or metastasis during the follow-up period. Conclusions BSCC of cervix is a rare malignant tumor of cervix associated with high-risk HPV infection, p16 is more positive. The treatment is similar to that of normal cervical squamous cell carcinoma. Surgical resection and radiotherapy and chemotherapy are the most effective methods according to the clinical stage . At present, the disease is considered to be highly aggressive and the poor prognosis.

Prognosis-related clinicopathologic characteristics of FIGO stage Ⅰ Müllerian adenosarcoma of uterus / 中华病理学杂志

Objective@#To investigate the clinicopathological features of FIGO stage Ⅰ uterine Müllerian adenosarcoma and clinical prognosis.@*Methods@#Fifteen cases of uterine Müllerian adenosarcoma at FIGO stage Ⅰ were collected at PLA General Hospital from 2005 to 2017. Twelve cases with complete follow-up data were divided into 2 groups: group A (7 patients with survival) and group B(5 patients of death or tumor progression). Clinicopathologic features were compared between the two groups.@*Results@#The median age of the patients was 43 years and 56 years, and the tumor size was 4.3 cm and 7.3 cm for group A and B, respectively. Cases in group A were FIGO ⅠA and ⅠB stage tumors and were mainly low grade in histology (5/7) with rare tumor hemorrhagec, necrosis (1/7) and sarcomatous overgrowth. In contrast, most cases in group B were high grade sarcomas(3/5) with frequent hemorrhage, necrosis(3/5) and sarcomatous overgrowth(4/5). Most cases of group A expressed ER, PR and CD10 (6/7) and low Ki-67 index of ≤20%(5/7). While most group B cases lost expression of ER and PR (3/5), significantly reduced expression of CD10 and higher Ki-67 index of ≥30%(4/5).@*Conclusions@#Most of uterine adenosarcomas are of low malignant potential. The main prognostic indicator is advanced tumor stage. For patients at stage Ⅰ, sarcomatous overgrowth, high-grade histology, deep myometrial invasion, decreased or absent expression of CD10, ER and PR, increased Ki-67 index(≥30%) and hemorrhagic necrosis may indicate poor prognosis. Müllerian adenosarcomas arising from endomeriosis may present unusual growth patterns.

Application of diffusion tensor imaging in prognosis evaluation in patients with moderate and severe diffuse axonal injury / 中华创伤杂志

Objective To investigate the application of diffusion tensor imaging (DTI) in evaluating prognosis of patients with moderate and severe diffuse axonal injury (DAI).Methods A prospective cohort study was made on 35 patients with moderate and severe DAI,who were enrolled from June 2013 to December 2015 as study group.There were 21 males and 14 females,with age of (55.1 ± 11.6) years.The Glasgow coma scale (GCS) was (8.2 ± 2.9)points on admission.Moderate DAI was seen in 20 patients and severe DAI in 15 patients.Other 15 healthy volunteers were selected as control group.Fractional anisotropy (FA) was measured by DTI in three areas of interests as follows:the corpus callosum,thalamus,and brainstem areas.Glasgow outcome scale (GOS) was adopted to assess the prognosis of DAI patients at 6 months after the injury.The FA values of the three areas between study group and control group as well as FA values of patients when they were admitted to hospital and 6 months after injury were measured.In this way,the relationship between the FA values of different areas of interests in DAI patients on admission and the prognosis 6 months after injury was analyzed.Results The FA values of the corpus callosum,thalamus and brainstem area in study group were all lower than those in control group (P ＜ 0.05).Further,FA values of the corpus callosum,thalamus,brainstem area in severe DAI patients were lower than those of moderate DAI patients (P ＜ 0.05).FA values of the corpus callosum,thalamus,brain stem areas in DAI patients at 6 months after injury were lower than those of corresponding areas when DAI patients were admitted to hospital (P ＜ 0.05).FA values of the corpus callosum,thalamus and brain stem on admission were significantly positively correlated with GOS at 6 months after injury (P ＜ O.05).Conclusions Lower FA values of the corpus callosum,thalamus and brainstem area in patients with moderate and severe DAI are associated with more severe injury and worse prognosis.DTI scans can be used as a valuable tool to evaluate the prognosis of DAI patients.

Expression and clinical significance of MMR protein and MLH1 promoter methylation testing in endometrial cancer / 中华妇产科杂志

Objective To explore the expression and clinical significance of mismatch repair (MMR)protein and MLH1 promoter methylation testing in endometrial cancer(EC). Methods A total of 420 cases with EC diagnosed by the surgical pathology examination from the Department of Pathology of PLA General Hospital, MLH1,MSH2,MSH6 and PMS2 protein in EC were detected by immunohistochemistry and methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA) testing. Results (1)Of the 420 tumor cases, the total expression loss rate of MMR protein was 34.5%(145/420), the expression loss rates of MLH1,MSH2,MSH6 and PMS2 protein were respectively 17.1%(72/420), 8.1% (34/420), 7.4%(31/420), 26.2%(110/420)and loss rates of MLH1 and PMS2,MSH2 and MSH6 were 16.7%(70/420), 6.2%(26/420). When there was a loss of MMR protein expression, any one or more protein expression deletions in MLH1, PMS2, MSH2 and MSH6, it could be Lynch syndrome related endometrial carcinoma(LS-EC). The expression loss rate of MMR protein in the poorly differentiated endometrioid adenocarcinoma was higher than that in the well differentiated endometrioid adenocarcinoma(P<0.05).(2) The expression loss rate of MMR and PMS2 protein had statistically significant between the endometrioid adenocarcinoma and non-endometrioid adenocarcinoma(P<0.01). The expression loss rate of MSH2 protein had statistically significant in the stage Ⅲ(P<0.01). Moreover, there were also significant differences in depth of myometrial invasion and lymph node metastasis between the expression loss rate of MMR protein (P<0.05).(3)The expression loss rate of MLH1 protein was 72 cases and 57 cases had MLH1 promoter methylation testing(excluding those who were not qualified for DNA testing). The positive rate was 47.4% (27/57). Therefore, these patients were sporadic endometrial cancer, not non-LS-EC. Conclusions MMR protein may be play an important role in the development of endometrial cancer and be indicated poor prognosis. Immunohistochemical staining and MLH1 promoter methylation detection may be play an important role in the screening of the LS-EC.

Progress of circulating cell-free DNA in B-cell neoplasms / 白血病·淋巴瘤

Circulating cell-free DNA (cfDNA) is a kind of free DNA in circulating blood, including circulating tumor DNA (ctDNA) deriving from tumor cells and DNA deriving from normal tissue cells. CtDNA is a specific tumor DNA in cfDNA. CfDNA could reflect the status of tumor to a certain extent, which plays an important role in tumor diagnosis, disease monitoring, treatment evaluation, prognosis and recurrence judgement, and has a potential clinical value as a simple, effective and noninvasive "liquid biopsy"technology. As a new concept, the number of cfDNA analysis in B-cell tumors is increasing, such as the relationship between tumor-specific gene mutations, methylation changes, minimal residual disease (MRD) and prognosis, recurrence, monitoring of treatment effects, targeted therapy by using cfDNA sequencing technology.

A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO.@*Methods@#Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×109/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×109/L.@*Results@#A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×109/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×109/L) at 4th week, 8th week and 12th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×109/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild.@*Conclusion@#Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

New strategy for cardio-cerebrovascular diseases: baroreflex activation therapy / 药学实践杂志

The incident number and death toll of cardio-cerebrovascular diseases increase continuously in China.The impairment of arterial baroreflex (ABR) is closely related to the genesis and development of cardio-cerebrovascular diseases (such as hypertension and chronic heart failure).Barostim neoTM (by American CRVx.Inc) can reduce blood pressure and heart rate by electrically stimulating carotid sinus baroreceptors and activating baroreflex.Therefore, it can be used to treat resistant hypertension, heart failure and end-stage renal disease, etc.The mechanism of baroreflex activation therapy (BAT) includes inhibiting sympathetic nervous system and rennin-angiotensin system, and increasing the activity of vagus nerve.Thus it improves baroreflex sensitivity and heart rate variability, and restores the structure and function of key organs.

Diagnostic value of SUVmax/ADCmin obtained by 11 C-choline PET/MR in patients with prostate cancer / 中华核医学与分子影像杂志

Objective To evaluate the value of SUVmax/ADCmin obtained by 11 C?choline PET/MR imaging in the differential diagnosis of benign and malignant prostate disease. Methods Suspicious prostate cancer patients who underwent PET/MR before transperineal prostate biopsy in People′s Liberation Army General Hospital from April 2014 to January 2015 were observed. Prostate gland was divided into five dis?tricts. A ROI with the diameter of 1 cm was drawn at the highest radioactivity concentration and/or lowest ADC signal area in each district, and SUVmax , ADCmin and SUVmax/ADCmin were then calculated. Taking the pathological results as the gold standard, malignant and benign prostate disease districts were separated. Pearson correlation analysis and two?sample t test were used for statistical analysis. Results Biopsy pathol?ogy showed 9 cases were malignant ( 25 prostate cancer districts, and 20 benign prostate disease districts) , and 6 cases were benign (30 benign prostate disease districts). The SUVmax had a negative correlation with ADCmin( r=-0.521, P<0?05) . The SUVmax/ADCmin of benign and malignant districts was significantly dif?ferent(5.67±3.03 and 13?76±7.13; t=6.9, P<0.01). The ROC AUC for ADCmin, SUVmax and SUVmax/ADCmin were 0?880, 0?809 and 0.898. Using SUVmax/ADCmin of 7.78 as a cutoff, the sensitivity, specificity and accuracy of 11 C?choline PET/MR imaging for differentiating the benign and malignant prostate lesions were 84.0%(21/25), 86.0%(43/50) and 85.3%(64/75), respectively. Conclusions Simultaneous 11C?choline PET/MR could be used for detecting prostate cancer. SUVmax/ADCmin may serve as an effective diag?nostic indicator for differentiating benign and malignant prostate lesions.