Mechanism of Chir99021 regulating Wnt / β⁃catenin signaling pathway inhibiting osteogenic differentiation of rat dental pulp stem cells / 解剖学报

Objective To explore the effect and mechanism of Chir99021 on osteogenic differentiation of rat dental pulp stem cells. Methods Primary rat dental pulp stem cells were isolated from rat dental pulp and verified by fluorescence immunoassay. Different concentrations of Chir99021 were set, and the cell proliferation was detected by CCK⁃8 to select the optimal concentration. Osteogenic differentiation was detected by alizarin red staining. The expression of osteogenic differentiation related genes and proteins recombinant wingless type MMTV integration site famity member 1 (Wnt1), Wnt3a and Wnt3a β⁃expression of catenin, axis inhibition protein 2(Axin 2), dentin sialophosphoprotein(OCN) and dentin matrix acidic phosphoprotein 1(DMP1) was detected by Real⁃time PCR and Western blotting. Results The positive expression of dentin sialophosphoprotein (DSPP) and vimentin indicated that rat dental pulp stem cells were successfully isolated. After osteogenic induction of rat dental pulp stem cells, calcium deposits significantly increased with the addition of glycogen synthase kinase⁃3β(GSK⁃3β) inhibitor Chir99021, calcium deposits were significanted reduced. After osteogenic differentiation of rat dental pulp stem cells, the expression of Wnt1, Wnt3a, β⁃catenin, Axin2, OCN and DMP1 increased, while the expression of Wnt1, Axin2, OCN and DMP1 decreased with the addition of Chir99021. Conclusion Chir99021 can inhibit the osteogenic differentiation of rat dental pulp stem cells after 7 days of induction.

Introduction on the update of the 5th edition WHO classifications of B-cell neoplasms / 中华病理学杂志

The 5th edition WHO classification of B-cell tumors is a systematic update to the fourth revised version of the classification. The changes include updated names of entities, sharpened diagnostic criteria, and upgrades from provisional to definite entities. This review focuses on the changes in the content of each chapter of B-cell tumors, facilitating domestic colleagues engaged in the diagnosis and treatment of lymphohematopoietic tumors to understand the latest progress and guide daily work.

Research progress of active probes targeting specific aminoacids / 药学学报

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Male Reproductive Injury is Blocked by Baicalin by Modulating Oxidative Stress and Apoptosis in Asthmatic Mice / 中国生物化学与分子生物学报

Reproductive health is an important issue in the field of population and health. As the most common respiratory disease in the world, asthma is linked with male reproductive dysfunction, but the related study is rarely reported. In this study, we analyzed the interventional effect of baicalin (BA) on male reproductive injury in asthmatic mice and its mechanism. Male BALB/c mice were randomly divided into three groups, namely as control group ( CK group), OVA-induced asthma model group ( OVA group) and baicalin intervention asthma group (OVA+BA group). The results showed that no significant difference was found in body weight among the three groups. In the OVA group, the testicular coefficient and sperm count decreased significantly, with sperm malformation rate increased significantly ( P < 0.05). In the baicalin intervention group, the testicular coefficient was increased significantly and sperm malformation rate decreased significantly ( P < 0. 05) ; Hematoxylin-eosin ( HE) staining showed that damaged basement membrane of seminiferous tubules, decreased the number of spermatogenic cells and reduced Johnson score were observed in OVA group. The seminiferous tubule diameter and seminiferous epithelium height were significantly increased (P < 0. 05), the basement membrane of seminiferous tubules was relatively complete and Johnson score gains in the OVA + BA group. Compared with control group, the contents of hydrogen peroxide ( H

Baicalin Promotes the Apoptosis of Respiratory Inflammatory Cells in Asthmatic Mice through Bitter Taste Receptors / 中国生物化学与分子生物学报

Asthma is a heterogeneous disease that affects three hundred million people worldwide. About half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (Tas2rs) are expressed in respiratory system, and Tas2rs might be used as new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. Based on this situation, we studied the effect of bitter compound baicalin (BA) on the apoptosis of inflammatory cells in the respiratory tract of asthmatic mice and its relationship with bitter signal transduction. Male BALB/c mice were selected as the tested animals randomly divided into control group (CK), asthma mouse model group stimulated by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA) and intragastric administration of BA intervention OVA-induced asthma group (OVA + BA). The results showed that inflammatory cells infiltration, alveolar septum thickening and diminished alveolarspaces were observed in the OVA group after HE staining. The above symptoms were significantly alleviated in OVA+BA group. The total number of inflammatory cells and classified cell count in the bronchoalveolar lavage fluid of mice in OVA group were increased, and the number of inflammatory cells in BA intervention group were decreased significantly (P < 0. 05). Analysis of real-time quantitative PCR showed that the expression levels of mucin Muc5ac were significantly increased in the lung in OVA group (P <0. 05), while the expression levels of Muc5ac in OVA+BA group were significantly lower than that in OVA group (P <0. 05). The expression of Tas2r108, Tas2r126, Tas2r135, Tas2r143 and their downstream signal transduction molecules α-gust and Trpm5 were down-regulated in OVA group (P < 0. 05). In OVA group, the transcription of pro-apoptotic factors P53, Bax and Casp3 was inhibited, and decreased activity of caspase3 was detected, whereas the transcription of anti-apoptotic factor Bcl2 was up-regulated (P < 0. 05). In OVA+BA group, the transcription of tested Tas2rs genes and downstream signal transduction molecules (P < 0. 05), as well as pro-apoptotic genes P53, Bax and Casp3 were all up-regulated associated with the decreased Bcl2 expression and increased caspase3 activity (P < 0. 05). Our results suggest that BA might function as a bitter taste receptor agonist to mediate the regulation of respiratory tract inflammatory cells apoptosis by activating the bitter signal transduction system, and thus to reduce the lung inflammation and injury in asthmatic mice.

Distribution Characteristics of Traditional Chinese Medicine Syndromes for Abnormal Uterine Bleeding Associated with Ovulatory Dysfunction: A Clinical and Epidemiological Investigation / 中国实验方剂学杂志

Objective:To explore the distribution characteristics of traditional Chinese medicine （TCM） syndromes of abnormal uterine bleeding associated with ovulatory dysfunction （AUB-O）. Method:A clinical and epidemiological investigation was conducted in 6 688 patients with AUB-O from the provincial， municipal， and county/district hospitals in 29 provinces， autonomous regions， and municipalities across China to identify the distribution characteristics of their TCM syndromes. Result:The AUB-O patients nationwide were mainly differentiated into the kidney Qi deficiency syndrome （17.34%）， the spleen Qi deficiency syndrome （13.25%）， the Qi and blood deficiency syndrome （12.62%）， the Qi deficiency and blood stasis syndrome （8.45%）， and the kidney Yin deficiency syndrome （6.88%）. AUB-O resulted from Qi deficiency， Yin deficiency， and blood deficiency， often involving the kidney， spleen and liver. The analysis of the regional distribution of TCM syndromes in AUB-O patients revealed that kidney Qi deficiency， spleen Qi deficiency， and Qi and blood deficiency were the shared syndromes. However， due to regional discrepancy， the TCM syndrome varied widely from one geographic region to another. The kidney Qi deficiency syndrome was more frequently seen in North China， Northwest China， Southwest China， and East China， but less frequently in central China， Northeast China， and South China. The spleen Qi deficiency syndrome occurred most frequently in central China， while the East China had the highest frequency of Qi and blood deficiency syndrome. The spleen and kidney deficiency syndrome was mostly present in central China， North China， and Southwest China， the Qi deficiency （kidney deficiency） and blood stasis syndrome in Northwest China， South China， and North China， the kidney Yin deficiency syndrome in East China， Northwest China， and Northeast China， the deficiency-heat syndrome in Southwest China and East China， the kidney Yang deficiency syndrome in South China， the liver depression and blood heat syndrome in Northeast China， and the liver depression and spleen deficiency syndrome in central China. The diagnostic criteria for the kidney Qi deficiency， spleen Qi deficiency， Qi and blood deficiency， Qi deficiency and blood stasis， and kidney Yin deficiency syndromes were not significantly different from the previous ones. The distinctive symptoms for the kidney Qi deficiency syndrome were irregular vaginal bleeding， heavy menstrual flow， or shortened menstrual cycle， back soreness and pain， and forgetfulness， while those for the spleen Qi deficiency syndrome mainly included the shortened menstrual cycle， mental fatigue， lack of strength， poor appetite， loose stool， and white tongue coating. The Qi and blood deficiency syndrome were mainly manifested as the shortness of breath， laziness to speak， pale complexion， dizziness， and palpitation. The Qi deficiency and blood stasis syndrome were mainly judged by the scanty menstrual flow frequently or occasionally accompanied by blood clots， mental fatigue， lack of strength， and dark purple tongue. The ovulatory bleeding， dizziness， tinnitus， vexing heat in chest， palms and soles， and night sweat were the characteristic signs for the kidney Yin deficiency syndrome. Conclusion:There exist certain rules in the geographical distribution of TCM syndromes of AUB-O patients， which has provided a reference for the clinical treatment of AUB-O in accordance with the local conditions.

Therapeutic Effect of Convalescent Plasma Transfusion on Fulminant Viral Infectious Diseases--Review / 中国实验血液学杂志

Novel coronavirus disease 2019 (COVID-19) has started to erupt in Wuhan since December 2019, and then the cases of COVID-19 increased rapidly, the epidemic situation spreaded to most area of China. Owing to the lack of specific drugs at present, convalescent plasma therapy becomes an alternative treatment. However, the choice of the donor, suitable patients, timing of treatment, administrate dose, the advantages and disadvantages of the treatment are not clear. This article reviews the clinical studies and case reports of convalescent plasma therapy in several previous viral infectious diseases in order to provide clues for the treatment of COVID-19.

Plasma MiR-181b and MiR-194 As Biomarkers for Acute Graft- Versus-Host Disease and Significance of Their Changes / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical correlation of expression level changes of miR-181b and miR-194 to the pathogenesis of acute graft-versus-host disease (aGVHD), and determine plasma miR-181b and miR-194 as the potential biomarkers for aGVHD.@*METHODS@#The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at before HSCT, 15 days after HSCT and onset of aGVHD. The expression levels of miR-181b and miR-194 were detected by quantitative real-time PCR. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD.@*RESULTS@#MiR-181b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD (P0.05). The expressions of plasma miR-181b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with non-GVHD patients (P<0.05). Moreover, these elevated miRNAs were detected before aGVHD. The AUC of miR-181b predicting aGVHD was 0.91±0.05 (specificity was 0.94, sensitivity was 0.69). The AUC of miR-194 predicting aGVHD was 0.91±0.06 (specificity was 0.94, sensitivity was 0.77).@*CONCLUSION@#MiR-181b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.

Inhibition of Respiratory Bitter Taste Signal Transduction is Related to Asthma in Mice / 中国生物化学与分子生物学报

Because the large number of people is suffering from asthma, and about half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (T2Rs) are expressed in various tissues, and T2Rs might be used as the new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. In this study, the relationship between the development and exacerbation of asthma and bitter signal transduction was analyzed by establishing the asthma model in the C57BL/6 mice. The present results showed that the total number of white blood cells and the number of eosinophil, neutrophil, lymphocyte and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly increased (P < 0. 05), accompanied with the up-regulation of Muc5ac gene expression (P< 0. 01) and asthma-like pathologically changes in mice lungs in OVA or OVA+SO

Concentration-dependent effects of nitric oxide on tumors and chemosensitivity / 药学学报

The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.

Effects of Electroacupuncture at Zhongji and Guanyuan on Urge Urinary Incontinence after Stroke / 中国康复理论与实践

Objective:To observe the effects of electroacupuncture on urge urinary incontinence after stroke. Methods:From May, 2015 to May, 2018, 40 patients with urge urinary incontinence after stroke were randomly divided into control group (n = 20) and electroacupuncture group (n = 20). Both groups accepted routine rehabilitation, while the electroacupuncture group accepted electroacupuncture at Zhongji (CV3) and Guanyuan (CV4) in addition, for four weeks. They recorded the urination log (72 hours), and were assessed with Incontinence Scale, and tested with urodynamics before and after treatment. Results:There were 17 cases in the control group and 18 in the electroacupuncture group finishing the trial. The total number of urination, the number of urge incontinence and the number of calls for urination carer at night decreased, the average volume of urine increased, and the score of Incontinence Scale decreased (|t| > 4.770, P < 0.001) in both groups, which were better in the electroacupuncture group than in the control group (|t| > 2.962, P < 0.01). The maximum cystometric bladder capacity and bladder compliance increased in both groups, while the maximum bladder pressure and maximum detrusor pressure decreased after treatment (|t| > 4.052, P < 0.001), which were better in the electroacupuncture group than in the control group (|t| > 2.716, P < 0.05). Conclusion:Electroacupuncture at Zhongji and Guanyuan is effective on urge urinary incontinence, which relates with reducing detrusor and bladder pressure, increasing bladder volume, and improving bladder compliance.

Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies / 中华血液学杂志

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.

Clinicopathological features of T-lymphoblastic lymphoma with Langerhans cell histiocytosis in the same lymph node / 中华病理学杂志

To investigate the clinicopathological features, immunophenotypes, genetics and prognosis of T-lymphocyte lymphoma/myeloid sarcoma combined with Langerhans cell histiocytyosis (coexistence of T-LBL/MS and LCH). Clinical and pathological data of the 6 patients with coexistence of T-LBL/MS and LCH were analyzed, who were diagnosed at the Foshan Hospital of Sun Yat-sen University and the Friendship Hospital of Capital Medical University, from December 2013 to April 2019. The hematoxylin and eosin stain, immunohitochemistry (EnVision) and in situ hybridization were used. Related literatures were reviewed. Four patients were T-LBL combined with LCH, 1 was T-LBL/MS combined with LCH, and 1 was MS combined with LCH. There were 2 male and 4 female patients, with age ranged from 5 to 77 years old (median, 59 years old). Three patients represented with only multiple lymph node swelling. The other 3 displayed both multiple lymph node swelling, and skin/liver or spleen lesions. Lymph node structure was destroyed in 5 cases, while 3 cases had several residual atrophic follicles. Histologically, there were two types of tumor cells: one type of the abnormal lymphoid-cells exhibited small to medium-sized blast cells, typically showing a nested distribution, and these cells were mainly identified in residual follicles and paracortical areas; the other type of histiocytoid cells had a large cell size and abundant pale or dichromatic cytoplasm. Their nuclei were irregularly shaped, showing folded appearance and nuclear grooves. These cells were mainly present in marginal sinus, medullary sinus and interstitial area between follicles. Eosinophil infiltration in the background was not evident in any of the cases. The lymphoid-cells of medium size showed TdT+/CD99+/CD7+, with variable expression of CD34/MPO/CD2/CD3. Ki-67 index was mostly 30%-50%. However, the histiocytoid cells showed phenotype of CD1a+/S-100+/Langerin+/-, while CD163/CD68 were positive in some degree. These cells did not express any T or B cell markers. The Ki-67 index mostly ranged between 10%-20%. None of the cases had Epstin-Barr viral infection. Among the 6 patients, 4 patients were followed up (6-63 months, median time, 18.5 months), of whom 1 patient died of the disease and 3 patients were alive at the end of follow-up. T-LBL/MS combined with LCH is a rare mixed type of immature hematopoietic disease, and mainly occurs in lymph node and skin. The clinical course is overall aggressive. Therefore, it is helpful to recognize and identify the two pathologic components in the same tissue for accurate diagnosis and proper treatment.

Efficacy Analysis of Unrelated Cord Blood Transplantation in the Treatment of Juvenile Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Juvenile myelomonocytic leukemia (JMML).@*METHODS@#The clinical data of 5 children with JMML who were treated with unrelated UCBT from October 2011 to July 2019 were retrospectively analyzed. The age of onset for the five children (male) ranged from 0.4 to 5.0 years old, with a median age of 1.5 years old. All the patients received myeloablative conditioning regimen without ATG to whom cyclosporine A (CsA) with short-term mycophenolate mofetil (MMF) was given for GVHD prophylaxis.@*RESULTS@#Four children acquired engraftment. One patient received secondary haploidentical hematopoietic stem cell transplantation because of the failure in the first unrelated UCBT. Grade Ⅲ to Ⅳ aGVHD occurred in 2 cases and was controlled, and none of the patients developed cGVHD. Three cases achieved long-time disease free survival，and no patient relapsed.@*CONCLUSION@#UCBT is an effective treatment for children with JMML.

Detection and application value of varicella-zoster virus in saliva of patients with herpes zoster / 医学研究生学报

ObjectiveTo assess the clinical application value of saliva samples from patients with herpes zosterzoster.MethodsSaliva and serum samples of 55 patients with herpes zoster were collected. Patients were split into mild and moderate group and serious group based on the clinical score table. Paid a follow-up visit for the occurrence of PHN three months after the lesion healed. Real-time fluorescence quantitative PCR was used to detect varicella-zoster virus load in saliva and serum, and then observed and verified by transmission electron microscope.ResultsThe positive rates of VZV DNA in saliva and blood samples were 87% and 85% respectively. Transmission electron microscopy showed virus pellets in saliva of patients. The VZV DNA load in saliva in serious group (5.79±2.94) copies/mLwas overtopped than that in mild to moderate group (3.06±2.59) copies/mL (t=3.58, P=0.00). Compared the viral loads in saliva of PHN group(5.82±3.12) copies/mL and non-PHN group (3.84±2.96) copies/mL, t=1.54, P=0.13.ConclusionThe positive rate of VZV DNA in saliva of herpes zoster patients is high, the load is related to clinical symptoms. So saliva can be used for the diagnosis of HZ and assessing the patients′ condition.

Endemic situation of schistosomiasis in Hunan Province in 2019 / 中国血吸虫病防治杂志

Objective To analyze the endemic situation of schistosomiasis in Hunan Province in 2019, so as to provide insights into the achievement of transmission interruption of schistosomiasis in the province in 2020. Methods The data pertaining to Schistosoma japonicum infections in humans and livestock and snail status were captured from Hunan Province in 2019 and analyzed. Results Schistosomiasis was endemic in 281 townships (towns) from 41 counties (districts) of 6 cities in Hunan Province by the end of 2019. A total of 991 900 persons received blood testing in Hunan Province in 2019, and 22 773 were positive for the blood testing, with sero-prevalence of 2.30%. All stool examinations were negative in 22 933 individuals detected. The high sero-prevalence was seen in Nanxian County, Anxiang County and Ziyang District. Currently, there were 5 034 cases with advanced schistosomiasis detected in Hunan Province, and they were predominantly identified in Yuanjiang City, Heshan District and Yueyang County. There were 44 963 bovines fenced in schistosomiasis-endemic villages in Hunan Province in 2019, which were predominantly distributed in Yuanjiang City, Hanshou County and Ziyang District, and no positives were detected in 1 996 bovines receiving blood testing or 20 684 bovines receiving stool examinations. In 2019, there were snail habitats of 1.73 billion m2 found in Hunan Province, which were mainly found in Yuanjiang City, Hanshou County and Yueyang County. Conclusion The endemic situation of schistosomiasis further decreases in Hunan Province in 2019; however, there is still a risk of schistosomiasis transmission in local areas of the province.

Effect of integrated schistosomiasis control measures in Hunan Province from 2004 to 2019 / 中国血吸虫病防治杂志

Objective To examine the effect of the integrated schistosomiasis control measures in Hunan Province from 2004 to 2019, so as to provide insights into the development of the schistosomiasis elimination strategy. Methods The integrated schistosomiasis control measures implemented by the health, agriculture, water resources, forestry, land and resources sectors were retrospectively collected in Hunan Province from 2004 to 2019, and the completion of each measure, cost of control measures, Schistosoma japonicum infections in humans and bovines, and snail status were analyzed each year. An index system for assessing the integrated schistosomiasis control effect was constructed using the Delphi method to calculate the integrated schistosomiasis control effect index. In addition, a cost-effect analysis was performed in terms of the decline in the prevalence of S. japonicum infections in humans and bovines, areas with snails in inner embankments, and areas with infected snails. Results A total of 7 110 926 500 Yuan were invested into the integrated schistosomiasis control program of Hunan Province from 2004 to 2019. During the 16-year period, a total of 277 437.12 hm2 snail habitats received molluscicidal treatments, 6 927 230 person-times given expanded chemotherapy, 2 116 247 bovine-times given expanded chemotherapy, 954 850 harmless toilets built, 290 359 bovines fenced, 136 666 bovines eliminated, 141 905 machines used to replace bovines, 39 048.63 hm2 water lands improved as dry lands, 724.12 km irrigation regions improved, 3 994 300 populations covered with safe water, 191 102.89 hm2 forests planted and 38 535.27 hm2 lands leveled. The prevalence of S. japonicum infections was 4.29% in humans and 4.48% in bovines in Hunan Province in 2004, with 2 449.37 hm2 snail habitats in inner embankments and 3 423.74 hm2 infected snail areas. In 2019, the prevalence of S. japonicum infections reduced to 0 in both humans and bovines, and areas of snail habitats reduced to 540.92 hm2 (77.92% reductions), while the areas with infected snails reduced to 0. The overall integrated schistosomiasis control effect index appeared a tendency towards a rise over years since 2004, and the integrated schistosomiasis control effect index was 97.35 in 2019; the annual mean costs for a 1% reduction in the prevalence of S. japonicum infections in 100 populations and 100 bovines were 70.11 Yuan and 4 204.78 Yuan, and the annual mean costs for a 1% reduction in the snail areas in inner embankments and infected snail areas were 2 010.20 Yuan and 1 298.09 Yuan, respectively. Conclusions The integrated control measures achieve remarkable effectiveness for schistosomiasis control in Hunan Province, with a remarkable decline in the prevalence of S. japonicum infections in humans and bovines and great shrinking of snail areas in inner embankments and infected snail areas. Adequate fund investment is required to improve the integrated schistosomiasis control measures and consolidate the control achievements.

Efficacy Analysis of Unrelated Cord Blood Transplantation for High-Risk Refractory AML1-ETO Positive Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT).@*METHODS@#Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen，and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD.@*RESULTS@#The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×10/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×10/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)＞0.5×10/L and platelet 20×10/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival.@*CONCLUSION@#UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.

Effects of High Cytomegalovirus DNA Load on Immune Reconstitution and Clinical Outcomes after Single Unrelated Cord Blood Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT).@*METHODS@#Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation.@*RESULTS@#The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×10 /L vs 0.25×10 /L, P=0.015 and 2.53×10 /L vs 1.36×10 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8 T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×10 /L vs 0.10×10 /L, P=0.038 and 1.62×10 /L vs 0.68×10 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively.@*CONCLUSION@#The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8 T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.