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.

Advances in surgical treatment of hilar cholangiocarcinoma / 中华肝胆外科杂志

Hilar cholangiocarcinoma (HCCA) is the most common type of cholangiocarcinoma, with in sidious onset and a high degree of malignancy, and there are often lymph node metastasis and vascular invasion. R 0 resection by surgery is still the main treatment for cure. This article reviews the hot issues and their related advances in surgical treatment of hilar cholangiocarcinoma, including preoperative evaluation, surgical treatment and systematic treatment.

A new bibenzyl derivative from stems of Dendrobium officinale / 中国中药杂志

Eleven compounds were isolated from the 95% ethanol extract of the stems of Dendrobium officinale after water extraction by various modern chromatographic techniques, such as silica gel column chromatography(CC), octadecyl-silica(ODS) CC, Sephadex LH-20 CC, preparative thin layer chromatography(PTLC) and preparative high performance liquid chromatography(PHPLC). According to spectroscopic analyses(MS, 1D-NMR, 2D-NMR) combined with optical rotation data and calculated electronic circular dichroism(ECD), their structures were identified as dendrocandin Y(1), 4,4'-dihydroxybibenzyl(2), 3-hydroxy-4',5-dimethoxybibenzyl(3), 3,3'-dihydroxy-5-methoxybibenzyl(4), 3-hydroxy-3',4',5-trimethoxybibenzyl(5), crepidatin(6), alternariol(7), 4-hydroxy-3-methoxypropiophenone(8), 3-hydroxy-4,5-dimethoxypropiophenone(9), auriculatum A(10) and hyperalcohol(11). Among them, compound 1 was a new bibenzyl derivative; compounds 2 and 7-11 have not been previously reported from Dendrobium plants; compound 6 was reported from D.officinale for the first time. Compounds 3-6 exhibited potent antioxidant activity with IC_(50) values of 3.11-9.05 μmol·L~(-1) in ABTS radical scavenging assay. Compound 4 showed significant inhibitory effect on α-glucosidase, with IC_(50) value of 17.42 μmol·L~(-1), indicating that it boasted hypoglycemic activity.

Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma / 中国医学科学院学报

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Interference of CD38 monoclonal antibody in blood compatibility testing and its countermeasures: A general consensus among experts / 中国输血杂志

With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.

An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels / 中华血液学杂志

Objective@#To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison.@*Methods@#Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated.@*Results@#①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH.@*Conclusion@#The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Association of in-stent restenosis with serum Gal-3 and MMP-9 levels / 西安交通大学学报(医学版)

Objective To investigate the relationship of galectin-3 (Gal-3)and matrix metalloproteinase-9 (MMP-9)with in-stent restenosis (ISR).Methods We consecutively recruited 434 patients who had undergone successful drug eluting stent (DES)implantation.Then we divided them into ISR group (n=41)and NO-ISR group (n=393)according to the results of coronary angiography review.Independent risk factors for ISR were found out by multivariate analysis and the two groups were matched for these factors except for Gal-3 and MMP-9 .After elim-ination of the influence of confounders,serum Gal-3 and MMP-9 were compared between the groups and their rela-tions with the severity of ISR were analyzed.Patients were grouped based on Gal-3 and MMP-9 concentrations and major adverse cardiac events (MACEs)were compared between the two groups.Results After elimination of the influence of confounders,the results showed that serum levels of Gal-3 and MMP-9 were significantly higher in ISR group than in NO-ISR group (P＜0.001).Serum levels of Gal-3 and MMP-9 increased with the increased grade of classification.Serum levels of Gal-3 and MMP-9 were obviously higher in classes Ⅲ and Ⅳ ISR than in class Ⅰ (P＜0.05).Patients with higher levels of Gal-3 and MMP-9 had a higher incidence of MACEs (P＜0.01).ISR group had a higher incidence of MACEs than NO-ISR group (P＜0.05).Conclusion Serum levels of Gal-3 and MMP-9 are correlated with ISR and its severity,and they are independent risk factors for ISR.The rate of MACEs during follow-up period was increased with the increased levels of Gal-3 and MMP-9 .

Chromosomal large fragment deletion induced by CRISPR/Cas9 gene editing system / 中华血液学杂志

Objective@#Using CRISPR-Cas9 gene editing technology to achieve a number of genes co-deletion on the same chromosome.@*Methods@#CRISPR-Cas9 lentiviral plasmid that could induce deletion of Aloxe3-Alox12b-Alox8 cluster genes located on mouse 11B3 chromosome was constructed via molecular clone. HEK293T cells were transfected to package lentivirus of CRISPR or Cas9 cDNA, then mouse NIH3T3 cells were infected by lentivirus and genomic DNA of these cells was extracted. The deleted fragment was amplified by PCR, TA clone, Sanger sequencing and other techniques were used to confirm the deletion of Aloxe3-Alox12b-Alox8 cluster genes.@*Results@#The CRISPR-Cas9 lentiviral plasmid, which could induce deletion of Aloxe3-Alox12b-Alox8 cluster genes, was successfully constructed. Deletion of target chromosome fragment (Aloxe3-Alox12b-Alox8 cluster genes) was verified by PCR. The deletion of Aloxe3-Alox12b-Alox8 cluster genes was affirmed by TA clone, Sanger sequencing, and the breakpoint junctions of the CRISPR-Cas9 system mediate cutting events were accurately recombined, insertion mutation did not occur between two cleavage sites at all.@*Conclusion@#Large fragment deletion of Aloxe3-Alox12b-Alox8 cluster genes located on mouse chromosome 11B3 was successfully induced by CRISPR-Cas9 gene editing system.

The use of placental mesenchymal stem cells to repair the damaged endometrium / 中国组织工程研究

BACKGROUND:Placental mesenchymal stem cells are rich in source and easily obtained, which can differentiate into osteoblasts, nerve cells and liver cells. Additionally, there is no immune rejection and ethical issues in the clinical application. Therefore, placental mesenchymal stem cells are considered to be a good source of adult stem cells.OBJECTIVE:To observe the effect of placental mesenchymal stem cell transplantation in the repair of endometrial lesions in rats.METHODS:Endometrial damage models were established in rats by means of thermal damage, and on the 15th day after modeling, these rat models were randomly divided into four groups (n=10 per group):intrauterine injection of 1 mL of allogeneic placenta mesenchymal stem cell suspension (intrauterine transplantation group), intrauterine injection of the same amount of PBS (intrauterine control group), tail vein injection of 1 mL of allogeneic placenta mesenchymal stem cell suspension (intravenous transplantation group), and tail vein injection of the same amount of PBS (intravenous control group). The female rats experiencing the third estrus after modeling were caged with male rats to observe whether the vaginal plug appeared. The female rats were killed the same day when the vaginal plug was observed, and uterus tissues were taken to detect the number of endometrial glands as well as perform immunohistochemistry and western blot detection.RESULTS AND CONCLUSION:The number of endometrial glands was highest in the intrauterine transplantation group followed by the intravenous transplantation group, and lowest in the two control groups (P < 0.05). The expression of integrin αvβ3 shown by immunohistochemistry and western blot was highest in the intrauterine transplantation group followed by the intravenous transplantation, and lowest in the two control groups (P < 0.05). These findings indicate that the placental mesenchymal stem cell transplantation can repair damaged endometrial tissues in rats to different degrees,by increasing endometrial glands count and improving the endometrial receptivity.

Application of placental mesenchymal stem cells / 中国组织工程研究

BACKGROUND:Placental mesenchymal stem cels are becoming a new source of seed cels because of wide range of sources, low immunogenicity and not involving ethical issues. OBJECTIVE:To elaborate the sources, biological characteristics and latest application of placental mesenchymal stem cels. METHODS:Literature search was performed in PubMed, ScienceDirect, OvidSP, CNKI databases for relevant literatures published from 2003 to 2015. The key words were “placenta, mesenchymal stem cels, placenta mesenchymal stem cels, cel transplantation, application mechanism” in Chinese and English, respectively. Then, 57 papers were further analyzed and reviewed in line with the theme. RESULTS AND CONCLUSION:Placental mesenchymal stem cels have been isolated and cultured successfuly, and confirmed to have multi-differentiation potential. A large number of placental mesenchymal stem cels have been used in the experimental animal and clinical researches, and they have a great potential in bone tissue engineering, revascularizaion and nerve repair. However, the specific mechanism underlying the application of placental mesenchymal stem cels is not clear. In order to ensure the safety and effectiveness, there are stil many problems to be further studied before placental mesenchymal stem cels are widely used in clinic.

Clinical analysis of 44 cases of leukemia complicated with active tuberculosis-a single-center report / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prevalence, clinical features, diagnosis, potential risk factors, anti-tuberculosis treatment efficacy and prognosis of the patients with leukemia complicated with active tuberculosis (TB).</p><p><b>METHODS</b>A retrospective study was performed to analyze the clinical characteristics, relevant examination data, diagnosis methods and follow-up data about 44 leukemia cases complicated with active TB from January 2006 to December 2011 in our single center.</p><p><b>RESULTS</b>The prevalence of leukemia complicated with active TB was 1.70% (pulmonary TB 1.35%, extra-pulmonary TB 0.35%) and no statistically significant difference was found between each subgroup of acute and chronic leukemia groups (P>0.05). Most of the patients were men, with a male to female ratio of 2.14:1, the median age of 40 years old (range 16 to 78), presenting as atypical clinical manifestations, such as high fever, cough, and so on. Eighteen patients (40.9%) were diagnosed with definitely etiological evidence while the other 26 patients (59.1%) were diagnosed clinically. The extra-pulmonary TB group had a higher purified protein derivative (PPD) test positive rate than that of the pulmonary TB group (88.9% vs 42.9%, P=0.020). The chest CT and T-cell spot of tuberculosis test (T-SPOT.TB) were helpful tools for diagnosis. The potential risk factors included age, sex, nutritional status, neutropenia, decreased cellular immunity, type and course of leukemia, etc. The significant differences in age, gender, administration route of immunosuppressive drugs were found between neutropenic and non-neutropenic groups (P<0.05). The efficacy of first-line anti-tuberculosis therapy was 83.7% and the total course to cure TB was around 12 months. Four patients were dead due to pulmonary TB with a 9.1% attributable mortality.</p><p><b>CONCLUSION</b>The prevalence of leukemia complicated with active TB is higher than the general population in our single center. The main characteristics including various potential risk factors, atypical clinical features, diagnoses mainly made by clinical features were found in our patients with leukemia complicated with active TB. However, it showed that these patients demonstrated good responses to the first-line anti-tuberculosis therapy and relative lower attributable mortality.</p>

Inhibition of tumor growth and metastasis via local administration of recombinant human endostatin adenovirus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The growth and metastasis of solid tumors are dependent on angiogenesis. Endostatin, the C-terminal proteolytic fragment of collagen XVIII, is a potent endogenous angiogenesis inhibitor. The authors designed a topical antiangiogenic gene therapy with recombinant human endostatin adenovirus (Ad-hEndo) and assessed its effects on the inhibition of angiogenesis in vitro, and tumor growth and metastasis in vivo.</p><p><b>METHODS</b>Malignant cells (A549) were infected with Ad-hEndo. The expression of recombinant protein and the inhibition of cultured human umbilical vein endothelial were investigated. Immunodeficient A549 nude mice were treated with intratumoral injection of Ad-hEndo, the empty vector Ad-control or saline (NS). The dose-response, side effects, and serum concentration of endostatin were observed.</p><p><b>RESULTS</b>Recombinant endostatin protein was detected in the infected tumor cells with different MOI Ad-hEndo and its inhibitory effect on endothelial cells growth was shown. In animal study, the volume of tumor and the number of pulmonary metastatic lesions in the Ad-hEndo treatment group were significantly smaller than those in the control groups (P<0.05).</p><p><b>CONCLUSION</b>The present findings provide evidence of the anti-tumor effects of the endostatin and may be important for the further use of it in topical antiangiogenic gene therapy of cancer.</p>