Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Protective Effect of Flos Puerariae，Hoveniae Semen， and Their Compatibility on Acute Alcoholic Gastric Mucosal Injury in Mice and Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the improvement effect of Flos Puerariae， Hoveniae Semen， and their compatibility on acute alcoholic gastric mucosal injury， and lay a foundation for further development of Flos Puerariae， Hoveniae Semen， and their compatibility in the prevention and treatment of alcohol-induced multiple organ injury. MethodThe acute alcohol-induced gastric mucosal injury model of mice was established by multiple intragastric administration of 56% Hongxing Erguotou liquor （15 mL·kg-1）. A total of 120 male ICR mice were randomly divided into 8 groups， namely， the blank group， model group， omeprazole group （0.026 g·kg-1）， Flos Puerariae-Hoveniae Semen （compatibility） high， medium， and low-dose groups （29.2，14.6， 7.3 g·kg-1）， Flos Puerariae group （19.5 g·kg-1）， and Hoveniae Semen group （19.5 g·kg-1）， with 15 mice in each group. After one week of adaptive feeding， the animals were pre-administrated with the corresponding drug at the rate of 10 mL·kg-1 for 3 d. From the 4th day， after 1 h of administration， Erguotou liquid was administrated at the rate of 15 mL·kg-1 and the blank group was administrated with the same volume of deionized water to record the drunkenness and sober up time. The administration was lasted for 3 d. One hour after the last administration， the eyeballs were removed and the mice were sacrificed. The concentration of ethanol in serum was determined by gas chromatograph， and the activity of ethanol dehydrogenase （ADH） in gastric mucosa was determined by ultraviolet-vis spectrophotometer. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric mucosa. Serum inflammatory factors were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of nuclear transcription factor-κB （NF-κB） p65 and NF-κB inhibitory protein α （IκBα） were detected by real-time polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in serum of mice in the model group was increased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues was increased （P<0.01）， and the mRNA expression of IκBα was decreased （P<0.01）. As compared with the model group， the drunkenness time of the omeprazole group， high and medium-dose compatibility groups， and Flos Puerariae group was prolonged （P<0.05）， the sober up time of the high and medium-dose compatibility groups was shortened （P<0.05）， the ethanol concentration in the serum of the high-dose compatibility group was decreased （P<0.05）， the ADH activity in the gastric mucosa of the omeprazole group and high and medium-dose compatibility groups was increased （P<0.05）， the macroscopic injury score of the high， medium， and low-dose compatibility groups and Flos Puerariae group was decreased （P<0.05）， the score of pathological injury in the omeprazole group， high， medium， and low-dose compatibility groups， and Flos Puerariae group was decreased （P<0.01）， the expression of IL-6 in serum of all drug groups was decreased （P<0.05）， the expression of IL-1β in serum of the omeprazole group， high， medium， and low-dose Flos Puerariae groups， and Hoveniae Semen group was decreased （P<0.05）， the expression of TNF-α in serum of high and medium-dose groups was decreased （P<0.05）， the mRNA expression of NF-κB p65 in gastric mucosa tissues of all drug groups was decreased （P<0.05）， and the mRNA expression of IκBα in gastric mucosa tissues of the omeprazole group and high， medium， and low-dose compatibility groups was increased （P<0.05）. As compared with the high-dose compatibility group， the drunkenness time in the low-dose compatibility group and Hoveniae Semen group was shortened （P<0.01）， the sober up time in the Flos Puerariae and Hoveniae Semen groups was prolonged （P<0.01）， the concentration of ethanol in the serum of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group increased （P<0.05）， the macroscopic injury score of the medium and low-dose compatibility groups and Hoveniae Semen group was increased （P<0.05）， the pathological injury score of the medium and low-dose compatibility groups， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， the content of IL-1β in serum of low-dose compatibility group， Flos Puerariae group， and Hoveniae Semen group was increased （P<0.01）， and the mRNA expression of IκBα in gastric mucosa of the Flos Puerariae group and Hoveniae Semen group was decreased （P<0.05）. As compared with the medium-dose compatibility group， the drunkenness time in the Hoveniae Semen group was shortened （P<0.05）， the sober up time in the Flos Puerariae group was prolonged （P<0.05）， the pathological injury score in the Flos Puerariae group and Hoveniae Semen group was increased （P<0.01）， and the content of IL-1β in serum of the low-dose compatibility group， the Flos Puerariae group， and Hoveniae Semen group was increased （P<0.05）. As compared with the low-dose compatibility group， the pathological injury score of the Hoveniae Semen group was increased （P<0.05）. ConclusionFlos Puerariae， Hoveniae Semen， and their compatibility play a role in preventing and treating acute alcoholic gastric mucosal injury in mice， which may be related to the inhibition of the expression of NF-κB signal pathway in gastric mucosa， and the high-dose compatibility group has the optimal effect.

Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

BACKGROUND@#All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. @*METHODS@#ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. @*RESULTS@#We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. @*CONCLUSIONS@#Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

A retrospective cohort study of tracheal intubation for meconium suction in nonvigorous neonates / 中国当代儿科杂志

OBJECTIVES@#To study the feasibility of tracheal intubation for meconium suction immediately after birth of nonvigorous neonates born through meconium-stained amniotic fluid (MSAF).@*METHODS@#A retrospective cohort study was performed on nonvigorous neonates born through MSAF who were admitted to the Department of Neonatology, Zhecheng People's Hospital. The neonates without meconium suction who were admitted from July 1, 2017 to June 30, 2018 were enrolled as the control group. The neonates who underwent meconium suction from July 1, 2018 to June 30, 2019 were enrolled as the suction group. The two groups were compared in terms of the mortality rate and the incidence rates of neonatal meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn, pneumothorax, and pulmonary hemorrhage.@*RESULTS@#There were 80 neonates in the control group and 71 in the suction group. There were no significant differences between the two groups in the incidence rates of MAS (11% vs 7%), persistent pulmonary hypertension of the newborn (5% vs 4%), pneumothorax (3% vs 1%), and death (0% vs 1%). Compared with the control group, the suction group had a significantly lower proportion of neonates requiring oxygen inhalation (16% vs 33%, P<0.05), noninvasive respiratory support (25% vs 41%, P<0.05) or mechanical ventilation (10% vs 23%, P<0.05) and significantly shorter duration of noninvasive ventilation [(58±24) hours vs (83±41) hours, P<0.05] and length of hospital stay [6(4, 8) days vs 7(5, 10) days, P<0.05].@*CONCLUSIONS@#Although tracheal intubation for meconium suction immediately after birth may shorten the duration of respiratory support for mild respiratory problems, it cannot reduce the incidence rate of MAS, mortality rate, or the incidence rate of serious complications in nonvigorous infants born through MSAF.

The level of regulatory T lymphocyte detected by flow cytometry in chimeric antigen receptor T cell immunotherapy and its clinical significance / 中华检验医学杂志

Objective:To investigate the characteristics of changes in peripheral blood regulatory T lymphocyte (Treg) levels in patients with B-cell lymphoma who received chimeric antigen receptor (CAR)-T cell immunotherapy, and the relationship between Treg levels and optimal efficacy and treatment response.Methods:The data of 23 patients with relapsed/refractory B-cell malignancies who received CD19/CD22 CAR-T cell immunotherapy in Wuhan Tongji Hospital from 2019 to 2021 were retrospectively studied. The enrolled patients were divided into complete remission (CR) group (8 cases), partial remission (PR) group (7 cases) and no response(NR) group (8 cases) according to Lugano′s revised lymphoma efficacy evaluation criteria. A total of 16 patients with B-cell lymphoma who did not receive CAR-T cell immunotherapy during the same period in Wuhan Tongji Hospital were collected as the control group.In different periods during CAR-T cell immunotherapy, multicolor flow cytometry(MFC) was used to dynamically detect peripheral blood the proportion of Treg in CD4 +T cells (Treg/CD4 +T), the proportion of lymphocytes (Treg/Lym), the proportion of Treg in white blood cells (Treg/WBC), and the absolute number of Treg (Treg#). The trend of Treg levels over time, as well as the differences in Treg levels in patients with different prognosis groups in different periods were analyzed.According to the proportion of Treg and the median level of absolute number within 1 to 15 days after CAR-T cell infusion, the patients were divided into a low-level group with 11 cases and a high-level group with 12 cases. The statistical differences in the peak value of CAR-T copy, iron protein, and IL-6 were compared between various groups. Independent samples t test, Mann-Whitney U test, Cox-Stuart trend existence test and one-way analysis of variance was used in statistical analysis. Results:In the 23 patients who received CAR-T cell immunotherapy, the mean values of Treg/CD4 +T and Treg/Lym before CAR-T cell infusion were (20.42±7.96)% and (13.61±7.13)%, respectively, which were significantly higher than that of the control group [(7.33±3.61)%, t=5.893, P<0.001; (1.91±0.90)%, t=6.53, P<0.001]. The number of Treg in the meantime was significantly lower [(1.81±1.52)/μl<(13.66±9.89)/μl, t=4.261, P<0.001]. After infusion, Treg/CD4 +T and Treg/Lym all remarkably decreased ( P<0.001),Treg/WBC increased significantly( P=0.01). The mean values of Treg/CD4 +T (12.87±1.93)%, Treg/Lym (6.35±2.84)%, and Treg/WBC (0.05±0.05)% in the patients with CR as the best response group were lower than those in the PR group [(29.68±5.49)%( P<0.01), (21.85±2.1)%( P<0.01), 0.50±0.69( P<0.05)] before CAR-T cell immunotherapy. Patients with lower mean Treg/CD4 +T within 1 to 15 days after reinfusion of CAR-T cells had higher peak CAR-T copy number ( P<0.05). Conclusion:Treg/CD4 +T and Treg/Lym were increased and then decreased during CAR-T treatment in B cell malignancies. The patients with lower proportions of Treg before infusion have favorable treatment efficacy. Besides, patients with lower Treg/CD4 +T after infusion have better CAR-T cell expansion. In the process of CAR-T cell immunotherapy, the use of MFC to dynamically monitor the proportion of Treg has certain clinical significance for the prediction of the optimal efficacy of immunotherapy and the prediction of treatment response.

Effect of Fangji Huangqitang on Function of Human Umbilical Vein Endothelial Cells / 中国实验方剂学杂志

Objective:To study the effects of Fangji Huangqitang（FJHQT） on migration， adhesion，invasion and tube formation of human umbilical vein endothelial cells （HUVECs） induced by vascular endothelial growth factor （VEGF）. Method:HUVECs were induced by VEGF （20 μg·L^-1） <italic>in vitro</italic>. The effects of FJHQT （0.25，0.5，1 g·L^-1） on HUVECs were detected by methyl thiazolyl tetrazolium（MTT）， scratch repair， transwell migration， adhesion， invasion and tube formation. Protein in HUVECs was extracted and protein expression levels of phosphorylated Janus kinase 1 （p-JAK1） were detected by Western blot. Result:Compared with control group， VEGF （20 μg·L^-1） can increase the proliferation， scratch repair， transwell migration， adhesion， invasion and tube formation of HUVECs cells （<italic>P</italic><0.01）， compared with VEGF group， FJHQT （0.25，0.5，1 g·L^-1） ，there is no significant effect on the proliferation of HUVECs induced by VEGF for 24 hours， but it can significantly reduce the scratch repair， migration， adhesion， invasion and tube formation of HUVECs induced by VEGF within 24 hours （<italic>P</italic><0.05）. Compared with blank group， VEGF could induce abnormal elevation of p-JAK1 in HUVECs （<italic>P</italic><0.01）， while FJHQT （0.25，0.5，1 g·L^-1） could significantly reduce the expression levels of p-JAK1 （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:FJHQT can inhibit the migration， adhesion and invasion of HUVECs， the mechanism may be related to JAK1.

Diagnostic Cut-Off Value of RDW for Screening Thalassemia and the Combined Determination of MCV, MCH, HBA / 中国实验血液学杂志

OBJECTIVE@#To explore the value of red cell distribution width (RDW), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin (Hb) A2 combined determination scheme for screening thalassemia.@*METHODS@#The RDW levels of thalassemia group and healthy control group were detected and compared. The efficiency of RDW for screening thalassemia was evaluated by receiver operating characteristic (ROC) curve. The diagnostic cut-off value of RDW was also acquired by Youden index. Then, 3 groups for thalassemia screening scheme were set, including MCV+MCH+HBA @*RESULTS@#The RDW level in thalassemia group was significantly higher than that in healthy control group (P15.15, when the Youden index was the biggest among all data. The sensitivity, specificity, positive predictive value, negative predictive value, false negative rate and consistency rate of MCV+MCH+RDW(>15.15)+HBA @*CONCLUSION@#The diagnostic cut-off value of RDW for thalassemia screening has been established. The group of MCV(<82.0 fl)+MCH(<27.0 pg)+HBA

Efficacy and Relapse Prediction Model of Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation（allo-HSCT） on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.@*METHODS@#The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.@*RESULTS@#Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival （OS） rates in one and three years were 86.4% and 61.8%, and the progress-free survival （PFS） rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.@*CONCLUSION@#The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.

Analysis of the Risk Factors for Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the risk factors affecting hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).@*METHODS@#The clinical data of 153 patients underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were selected and retrospectively analyzed. The incidence, median time and treatment outcome of HC should be observed. Multivariate analysis was used to observe the risk factors of HC in patients, including sex, age, diagnosis, disease status before transplantation, transplantation type, ATG and CTX in the pretreatment scheme, stem cell source, neutrophil and platelet implantation time; CMV, EBV and BKV infection, and acute graft-versus-host disease(aGVHD).@*RESULTS@#Among 153 patients underwent allogeneic hematopoietic stem cell transplantation, 25 (16.34%) patients had HC, the median occurance time was 31 days, all patients achieved complete remission after treatment, no bladder irritation and bladder contracture were left. The results of univariate and multivariate Logistic regression analysis showed that the type of transplantation, ATG, CMV viremia before treatment, aGVHD (r=1.036, 3.234, 3.298 and 2.817, respectively) were the independent risk factors of HC.@*CONCLUSION@#The urinary BKV detections in the patients with HC are positive, mainly occured during the period from day +13 to days +56. HLA haplotype, pretreatment including ATG, and CMV viremia, and aGVHD are the independent risk factors for HC after allo-HSCT.

Heterologous expression of a novel β-glucosidase BglD2 and its application in polydatin-hydrolyzing / 生物工程学报

A novel β-glucosidase BglD2 with glucose and ethanol tolerant properties was screened and cloned from the deep-sea bacterium Bacillus sp. D1. The application potential of BglD2 toward polydatin-hydrolyzing was also evaluated. BglD2 exhibited the maximal β-glucosidase activity at 45 °C and pH 6.5. BglD2 maintained approximately 50% of its origin activity after incubation at 30 °C and pH 6.5 for 20 h. BglD2 could hydrolyze a variety of substrates containing β (1→3), β (1→4), and β (1→6) bonds. The activity of β-glucosidase was enhanced to 2.0 fold and 2.3 fold by 100 mmol/L glucose and 150 mmol/L xylose, respectively. BglD2 possessed ethanol-stimulated and -tolerant properties. At 30 °C, the activity of BglD2 enhanced to 1.2 fold in the presence of 10% ethanol and even remained 60% in 25% ethanol. BglD2 could hydrolyze polydatin to produce resveratrol. At 35 °C, BglD2 hydrolyzed 86% polydatin after incubation for 2 h. Thus, BglD2 possessed glucose and ethanol tolerant properties and can be used as the potential candidate of catalyst for the production of resveratrol from polydatin.

Analysis of economic benefits of Chinese medicine eco-agriculture based on multiple stakeholders / 中国中药杂志

As the most advanced environment-friendly production model in the international society, ecological agriculture of Chinese materia medica(CMM) is the only way for the development of modern agriculture. With the proposal of the declaration on ecolo-gical agriculture of CMM, "Don't grab land from farmland, don't be enemies of grass and insects, don't be afraid of barren slopes and forests, and live up to the green and green mountains", the ecological planting of CMM has blossomed all over the country, and formed a scientific theory, technology and model. Based on the theory and method of economics, this paper expounds the comprehensive benefits and development advantages of ecological agriculture of CMM from the perspectives of farmers(producers), patients(consumers) and the country. From the perspective of medicinal farmers, the input and output income of conventional agriculture and ecological agriculture of CMM such as Panax ginseng, Astragalus propinquus, Atractylodes lancea, and Bupleurum chinense were compared, and it was found that ecological agriculture of CMM had obvious advantages in net income, average annual income and input-output ratio, which could better promote farmers' income. From the perspective of patients, according to the same dose, the content of active ingredients in ecologically planted CMMs is significantly higher than that in conventionally-planted herbs, and the amount of effective substances taken by patients is also higher, so as to achieve better therapeutic effect. At the national level, ecological planting of CMM is the key to ensuring the high-quality development of CMM industry, increasing farmers' income, ensuring the safety of people's drug use and promoting the sustainable development of agriculture. It is also an important part of realizing the harmonious development of economy, society and environment and promoting ecological civilization. In general, the declaration on ecological agriculture of CMM embo-dies the core characteristics and goals of ecological agriculture, and also points of the path and vision of ecological agriculture of CMM in the future. The declaration will guide production practice, promote the benefit of farmers, and lay the foundation for the sustainable development of CMM industry.

Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

Renal Pathology and Cytogenetic Examination in Multiple Myeloma Patients with Renal Impairment--Retrospective Analysis / 中国实验血液学杂志

OBJECTIVE@#To explore the renal pathology and cytogenetic features in the multiple myeloma (MM) patients with renal impairment.@*METHODS@#The clinical data of newly diagnosed MM patients with renal impairment in our hospital from January 2009 to January 2019 were analyzed retrospectively, and the relationship between FISH results and results of renal pathological exanimation was analyzed statistically by using SPSS 20.0.@*RESULTS@#A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that out of 20 patients, 7 cases presented interstitial nephritis, among which 3 cases were negative for FISH, and in the remaining cases the rate of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 42.86%, 28.57%, 28.57%, 28.57% and 14.29% respectively, the detection positive rate was statistically significantly lower as compared with total probe positive rate (P＜0.01). There were 6 cases of cast nephropathy, among which IgH rearrangement, the rate of 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 66.67%, 50%, 66.67%, 50% and 0% respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were 4 cases of acute tubular necrosis, among which the detection rates of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion was 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were one case of amyloidosis, and one case of tubular nephropathy with amyloidosis, the detection with 5 probes were all positive. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion.@*CONCLUSION@#FISH in the MM patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate possible renal pathological types to guide prognosis.

Safety and Effectiveness Analysis of Percutaneous Microwave Thermal Ablation Therapy Combined Brachytherapy for Lung Malignant Lesion / 中国肺癌杂志

BACKGROUND@#Microwave ablation and radioactive seed implantation are therapeutic options for patients with advanced lung cancer and lung metastases lesion who are not surgical candidates. However, reports on therapeutic effectiveness and safety of the two combination treatments methods have been limited to small case series. This research was to assess the clinical outcome and safety of radioactive seed implantation combined with computed tomography (CT)-guided microwave ablation for the treatment of advanced lung cancer and lung metastases lesion.@*METHODS@#The clinical data of 21 advanced lung cancer and lung metastases patients who received treatment at author hospital during the period from May 2018 to December 2018 were retrospectively analyzed. The patients were divided into two groups by whether received extra percutaneous microwave thermal ablation therapy. The short-term effectiveness and safety were analyzed.@*RESULTS@#The efficacy of control group was 28.75%, and the efficacy of experiment group was 14.28%. The rate of adverse reaction between two groups has no significantly difference (P>0.05).@*CONCLUSIONS@#Seed implantation combined with CT-guided microwave ablation for advanced lung cancer and lung metastases is safety and effective.

Therapeutic Effect of CT-guided ¹²⁵I Seed Implantation on Advanced Lung Cancer and Pulmonary Metastatic Carcinoma / 中国肺癌杂志

BACKGROUND@#Primary lung cancer and metastatic lung cancer are common malignant tumors of the lung and are the main cause of cancer-related death. Advanced lung cancer and lung metastatic cancer are mainly treated by systemic therapy, and local treatment is also an effective treatment for the refractory or recurrent lesions in the lungs after systemic treatment. ¹²⁵I radioactive particle implantation, as an efficient conformal radiotherapy, has a certain control effect on localized lung cancer. The purpose of this study was to investigate the clinical efficacy and safety of computed tomography (CT) guided percutaneous puncture of lung tissue with ¹²⁵I radioactive particle implantation in the treatment of advanced lung cancer and lung metastatic cancer.@*METHODS@#Continuouslycollectedthe clinical and pathological data of 105 patients with advanced lung cancer and metastatic lung cancer treated by ¹²⁵I radioactive seed implantation in the Department of Thoracic Surgery, First Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2014 to November 30, 2018. The patients were followed until March, 2019. The clinical efficacy and complications of seedimplantation were analyzed.@*RESULTS@#A total of 105 patients were included in the study, 78 patients with advanced lung cancer and 27 patients with lung metastases. The median survival time after seed therapy was 395 days. The 1-year survival rate was about 78.1%, and the 2-year survival rate was about 56.1%. Seed implantation for advanced lung cancer is equivalent to lung metastasis. Seed combined with radiofrequency ablation, microwave ablation, and chemotherapy did not improve seed treatment. However, particle combined with external radiation therapy has a significant survival disadvantage compared with simple seed therapy.@*CONCLUSIONS@#The CT-guided ¹²⁵I radioactive seed implantation has controllable complications and can be used as a safe and effective treatment for advanced lung cancer and lung metastases.

Effect of Ermiaosan on M1/M2 Polarization of Bone Marrow Derived-macrophages / 中国实验方剂学杂志

Objective:To explore the effect of Ermiaosan（EMS） on the polarization of M1 by lipopolysaccharide（LPS）+interferon(IFN)-γ and M2 induced by interleukin(IL)-4+IL-13 in rat bone marrow-derived macrophages. Method:Macrophages from rat bone marrow were extracted in vitro, stimulated by macrophage colony stimulating factor(M-CSF), induced to macrophages (marked by F4/80), stimulated by LPS+IFN-γ and induced to polarize to M1，while stimulated by IL-4+IL-13 and induced to polarize to M2. After adding different concentrations of EMS (0.2，0.4，0.8 g·L-1), the phenotypes of M1 and M2 were detected by immunofluorescence, and the effect of EMS on M1(marked by CD68 and iNOS)/M2(marked by CD206 and Arginase) polarization of macrophages from rat bone marrow was detected. Result:Compared with control group, LPS + IFN-γ could increase the polarization of M1 (P<0.01)，while IL-4+IL-13 could increase the polarization of M2 (P<0.01); compared with LPS+IFN-γ/IL-4+IL-13 group, EMS (0.2，0.4，0.8 g·L-1) could inhibit the polarization of M1 induced by LPS+IFN -γ for 24 hours (P<0.05), but had no significant effect on polarization of M2 induced by IL-4+IL-13. Conclusion:EMS can inhibit M1 polarization induced by LPS+IFN - γ, but has no effect on M2 polarization induced by IL-4+IL-13.

Clinical Efficacy of Tongqiao Huoxuetang Plus Acupuncture on Post-stroke Cognitive Impairment and Its Effect on Neurotransmitters and Neurological Function of Patients / 中国实验方剂学杂志

Objective::To explore the clinical efficacy of Tongqiao Huoxuetang plus acupuncture on post-stroke cognitive impairment (PSCI) and its effect on neurotransmitters and neurological function of patients. Method::Totally 122 PSCI patients admitted in our hospital from January 2017 to March 2019 were randomly divided into observation group and control group by simple random number table method, with 61 patients in each group. Both groups were given oral donepezil hydrochloride tablets. The control group was given acupuncture treatment, while the observation group was given Tongqiao Huoxuetang plus acupuncture in addition to therapy of control group. All patients were treated continuously for 4 weeks. The clinical efficacy was compared between two groups. Before and after treatment, the general cognitive function of two groups was tested by mini-mental state examination (MMSE), changes of their neurologic impairment and daily living ability were evaluated by National institutes of health stroke scale (NIHSS) and Barthel index (BI) respectively, and euzymelinked immunosorbent assay was adopted to test the levels of neurotransmitters [acetyl choline (ACh), dopamine (DA), noradrenaline (NE), 5-hydroxytryptamine (5-HT)] and neurologic impairment markers [neuronspecific enolase (NSE), visinin-like protein-1 (VILIP-1), myelin basic protein (MBP)]. And the occurrence of adverse reactions was recorded. Result::The overall effective rate of the observation group was 91.8% (56/61), which was much higher than 78.7% (48/61) of control group (P<0.05). After treatment, both groups saw much higher MMSE and BI scores but lower NIHHS scores than before treatment (P<0.05), and above indicators in observation group were improved more significantly than those in control group over the same period after treatment (P<0.05). The levels of serum ACh, DA, NE and 5-HT after treatment were obviously higher than those before treatment (P<0.05), and observation group had significantly higher ACh, DA, NE and 5-HT levels than control group over the same period (P<0.05). After treatment, both groups witnessed a great decrease in NSE, VILIP-1, MBP (P<0.05), while the observation group saw dramatically lower NSE, VILIP-1, MBP levels than control group over the same period after treatment (P<0.05). Neither of two groups saw serious adverse reactions. Conclusion::In treating PSCI, Tongqiao Huoxuetang plus acupuncture can significantly improve neurological function of the patients, which may be due to increase of neurotransmitters. Besides, Tongqiao Huoxuetang plus acupuncture is proved to be generally effective in promoting the recovery of patients' neurological function and enhancing their abilities in daily life, with a good tolerance among patients.

Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway / 神经科学通报·英文版

The correct differentiation of oligodendrocyte precursor cells (OPCs) is essential for the myelination and remyelination processes in the central nervous system. Determining the regulatory mechanism is fundamental to the treatment of demyelinating diseases. By analyzing the RNA sequencing data of different neural cells, we found that cyclin-dependent kinase 18 (CDK18) is exclusively expressed in oligodendrocytes. In vivo studies showed that the expression level of CDK18 gradually increased along with myelin formation during development and in the remyelination phase in a lysophosphatidylcholine-induced demyelination model, and was distinctively highly expressed in oligodendrocytes. In vitro overexpression and interference experiments revealed that CDK18 directly promotes the differentiation of OPCs, without affecting their proliferation or apoptosis. Mechanistically, CDK18 activated the RAS/mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinase pathway, thus promoting OPC differentiation. The results of the present study suggest that CDK18 is a promising cell-type specific target to treat demyelinating disease.

Molecular genetic diagnosis of a carrier with rare α-thalassemia mutations / 中华医学遗传学杂志

OBJECTIVE@#To explore the cause of inconsistent genotypes for an α-thalassemia carrier by using two commercial genotyping kits.@*METHODS@#GAP-PCR and PCR-reverse dot blotting (PCR-RDB) were employed to determine the genotype of the carrier, while Sanger sequencing was used to verify the results.@*RESULTS@#Sequencing analysis demonstrated that the subject has carried a α1 globin gene with a 3.7 kb heterozygous deletion. In addition, two novel mutations, IVS-II-55(T>G) and IVS-II-119(G>TCGGCCC), were found in intron 2 of α2 globin gene.@*CONCLUSION@#The two mutations located in the binding regions of PCR primers have caused failure of PCR amplification and misreading of the genotype. Combination of clinical and hematological phenotypes is indispensible to infer the genotype of carriers for accurate diagnosis.

Shikimic Acid Promotes Oligodendrocyte Precursor Cell Differentiation and Accelerates Remyelination in Mice / 神经科学通报·英文版

The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.