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Dislocation or subluxation of mandible could occur suddenly without Patient's awareness of its forthcoming. Patient may discover suddenly during yawning, laughing, or when the mouth is wide open that he or she could not close the jaw. It may cause serve anxiety and apprehension, that may put the patient in such a nervous state that may worsen the condition, and also may spastically tense the muscles associated with dislocation. We treated 37 patients in the past and found that, although five patients could be manipulated to have their dislocated jaw reduced to the normal state, we found that a majority of the cases could not be manipulated without supplementing with other adjunctive methods such as acupuncture at the pertinent acupoints, or injections of local anesthetic around the temporomandibular joint area. Twenty-seven patients were successful to have the dislocation or subluxation reduced, five patients required local anesthetic for reduction and 1 patient had to have the reduction done in the operating room under deep sedation. We found acupuncture is valuable in reducing the mandibular subluxation and dislocation. Three acupoints in calming down the patients were a valuable aid during treatment. LI 4 which is known to reduce pain in head and neck region could increase pain threshold and decrease anxiety associated with discomfort encountered during reduction treatment Additional acupoints such as P 6 (Neikuan), Ext l(Yintang), and H 7 (Shenmen) are valuable for the patients who are tense and nervous. Those acupoints are also could be utilizied as additional aid to ease the spasm of the muscles associated with subluxation and dislocation. Post-operative care includes stabilization at the head and neck region. [ABSTRACT FROM AUTHOR]

We examined patients wearing a metal ring on the left 4th finger with abnormally increased Cardiac Troponin I (which is known to increase in the presence of myocardial injury or left ventricular hypertrophy) of 5-14ng BDORT units (depending on the ring and individual) at left ventricle compared with normal value of Ing BDORT units or less. Although shape of the ECG does not change significantly regardless of whether metal rings are on or not, when rings are on, the Bi-Digital O-Ring Test evaluation of trace of ECG revealed 'Vulnerable Period of Rising Part of T-wave' of ECG waves (which correspond to the left ventricle and AV node) become abnormal with increased Cardiac Troponin 1. DHEA in various parts of the body reduced significantly and maximum decrease in DHEA was found when metal ring was on the left 4th and 5th fingers. Telomere reduced with each of the 5 fingers, but the 2nd , 4th , and 5th fingers produced the maximum reduction of telomere. When metal ring was inserted onto the left Ist finger and left 2nd finger. Cardiac Troponin I did not change significantly. Additional abnormality was found when patients with cancer wore metal ring(s); namely both Cardiac Troponin I and cancer parameters, such as Integrin 5 1 and Oncogen C-fos Ab2, increase anywhere between 4-12 times. However, when the ring was cut. creating a 1mm or longer empty space, no increase in cancer markers and Cardiac Troponin I were observed. Similar findings were found with metal bracelets. [ABSTRACT FROM AUTHOR]

One minute downward pressure on the tip of any one of the front 3 teeth (1st incisor, 2nd incisor, and canine) at the right and left sides of the upper and lower jaw by a wooden toothpick induced temporary disappearance (20 min~4 hours) of abnormally increased pain parameters (pain grading, Substance P, & TXB2), and cancer parameters (Telomere, Integrin [alpha]5ß1, Oncogene C-fos Ab2, etc. of Astrocytoma, Glioblastoma, squamous cell carcinoma of esophagus, adenocarcinoma of lung, breast cancer, adenocarcinoma of colon, prostate cancer). The effect included temporary disappearance of headache, toothache, chest and abdominal pain, and backache, often with improved memory & concentration. Since these beneficial changes resembled the effects of giving one optimal dose of DHEA, increase of DHEA was measured. Above mechanical stimulation of one of these front teeth increased abnormally reduced DHEA levels of less than 10 ng to norml 100~130 ng BDORT units and normal cell (NC) telomeres from markedly reduced values to near normal values, and improved acetylcholine in the Hippocampus. Large organ representation areas for the Adrenal gland & Hippocampus may exist at these front teeth. This method can be used for emergency pain control and can explain the beneficial effect of bruxism and tooth brushing, through the increase of DHEA levels and activities of the Hippocampus by increasing Acetylcholine. Increasing NC telomere to optimally high level resulted in disappearance of pain and improvement or significant reduction of malignant tumor. Repeated daily press needle stimulation of True ST. 36 increased NC telomere 450-700 ng BDORT units. One optimal dose of DHEA increased NC telomere 525 ng DBORT units and eliminated the pain and abnormally increased cancer parameters; effect of one optimal dose lasted 0.5-11 months. One optimal dose of Boswellia Serrata or Astragalus not only increased NC telomere 650 ng BDORT units, eliminating pain and cancer parameters, but also reduced the size of the Astrocytoma grade I by 10-20% and the Glioblastoma by 15-90% in less than 2-6 months in some patients, as long as high NC telomere is maintained. [ABSTRACT FROM AUTHOR]

The data presented in this article was collected after reviewing clinical findings gathered from using various anxiety control methods on apprehensive patients. We examined clinical applications of the eye movement (EM) component of Eye Movement Desensitization (EMD) on fearful dental patients who have histories of traumatic dental experiences. We also used Bi-Digital O-Ring Test (BDORT) to select the proper dosage of sedative to minimize the adverse side effects. For patients who did not respond well to EM, we used BDORT to select the proper sedative medication and its dosage. In certain difficult cases, we supplemented these techniques with acupuncture to augment the sedative effects. Findings were based on the clinical impressions and assessments of both the patients and the operating team. Results showed that EM, although effective in enabling patients to undergo non-invasive dental procedures such as clinical examination and simple prophylaxis, had only limited beneficial effect with invasive procedures such as extraction, drilling, and injections, etc. We also found that BDORT greatly reduced adverse side effects of sedatives such as hypertension, hypotension, hypoxia, tachycardia, bradycardia, nausea, and vomiting. For most apprehensive patients, we found that EMD and acupuncture combined with BDORT predetermined dosage for the submucosal sedation enabled these patients to undergo the complete dental treatment. The authors try to explain the mechanism of BDORT and EM in terms of visual awareness (or consciousness) and preferred patterns, where neurons in the brain respond to the actions and/or direction of movement. The authors believe that BDORT and EM could have better results if the persons performing BDORT have visual awareness and are focused on the task; whereas in EM, the patient's eye on the therapist's hand movements. A more focused approach via visual pathway will result in more favorable results in EM. Likewise, performing BDORT absentmindedly could lead to false results if visual awareness (or consciousness) is absent. 'Preferred pattern' will arouse neurons in the brain to cause conscientiousness, and performing BDORT with 'open eyes' arouse the necessary visual awareness that is necessary for the successful performance of BDORT tasks. [ABSTRACT FROM AUTHOR]

Though there are articles and case reports about using acupuncture to detoxify and to break the narcotic addiction, few articles describe in the West about using acupuncture therapy to treat the emergence of acute withdrawal symptom due to heroin, opium, or morphine. Most often the method of treatment are using the methadone or benzodiazepine and phenoziazine drugs this article describes many years of clinical experience with non-drug approach to treat the acute withdrawal symptoms with acupuncture therapy. Unlike the drug approach, which usually has side effects, there is no adverse effect with acupuncture therapy. [ABSTRACT FROM AUTHOR]

Many of the acupuncture points on the face, according to classic acupuncture textbooks, could be used to treat facial pain, paralysis, and toothache. But it is not specified which acupuncture point would be effective for which tooth. Many of these points, when used for the treatment of dental pain, often fail. From an anatomical point of view, we describe which acupuncture point to use for each specific area for effective treatment of dental pain. Also, we emphasize the importance of the depth of needle insertion, especially the necessity to touch the facial bone, for effective pain treatment. When performed properly, acupuncture can be very effective for relief of dental pain. [ABSTRACT FROM AUTHOR]

Since the mid-1990s, eye movement desensitization (EMD) has been used in the realm of clinical psychology and psychiatry as a nonpharmacotherapeutic modality for the treatment of phobias, post-traumatic symptoms, and various psychotrauma cases. EMD can also be incorporated into the use of hypnosis, although the two are not the same thing. This study examined various clinical applications of the eye movement component of EMD (known as alternating bilateral stimulation (ABS)) on fearful dental patients who had a history of traumatic dental experiences. Findings were based on the clinical impressions and assessments of both the patients and the operating team. Results show that ABS, while effective for enabling patients to undergo non-invasive dental procedures such as clinical examinations and simple prophylaxis, has only limited beneficial effect for extremely fearful patients who must undergo invasive procedures such as extraction, drilling, and injections. Nevertheless, ABS is effective for mild to moderate patient phobia and anxiety. Although EMD is more effective than ABS, ABS is simple and easy for patients and clinicians to perform during treatment and can be performed readily in the dental office. [ABSTRACT FROM AUTHOR]

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1)., Methods: We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021., Results: The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT., Conclusions: Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lu, Zhang, Zhao, Xiong, Sun, Cao, Wei, Zhou, Liu, Yang, Zhang, Lu and Lu.)

We retrospectively analyzed the outcomes of 240 pediatric SAA patients who underwent unmanipulated alternative HSCT between September 2012 and November 2020 at our center. The incidence of GF (PGF + SGF) was higher in the UCBD cohort compared to the MUD and HID cohorts [(13.5% ± 6.5%) vs (0%), and (1.6% ± 5.3%), respectively, p  = .0001]. The incidence of platelet engraftment within 180 days post-HSCT was lower in the UCBD cohort (82.4% ± 2.3%) compared to the HID group (96.2% ± 1.3%) and the MUD group (97.4% ± 0.5%) ( p  = .020). the median duration time for platelet engraftment in the UCBD cohort was 29 days, longer than in HID cohort 14 days and the MUD cohort 13 days ( p  = .005). UCBD cohort had a lower 3-year failure-free survival (FFS) (70.5% ± 8.4%) compared to the HID cohort (81.1% ± 4.3%) and the MUD cohort (92.5% ± 3.1%) ( p  = .030) and lower 3-year GVHD/relapse free survival (GRFS) (63.3% ± 9.5.4%) compared to the HID cohort (75.5% ± 6.8%) and MUD cohort (87.9% ± 4.5%) ( p  = .002). UCBD-HSCT had inferior FFS and GRFS compared to an HSCT with an HID or MUD in pediatric patients with acquired SAA. A UCBD-HSCT had a higher GF and lower incidence of platelet engraftment and longer platelet engraftment time.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy characterized by poor prognosis even following an allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 15 patients diagnosed with BPDCN who underwent an allo-HSCT with myeloablative conditioning (MAC) at our center. The male to female ratio was 11:4. The median age of 36 (range: 6-70) years, all patients initially presented with extramedullary lesions (13 with cutaneous lesions, 1 in the breast and 1 in the lymph nodes) and involved the bone marrow, two cases were diagnosed as central nervous system leukemia (CNSL). Nine patients were in CR1 and six patients were in CR2 status prior to HSCT. All patients received the MAC regimen and an unmanipulated graft. All patients successfully engraftment and achieved full donor chimerism. One patient developed poor graft function, three patients developed aGVHD (Grade I, II, and IV), and seven patients developed cGVHD (mild in 6; moderate in 1). The median follow-up time for survival was 34 (range: 6-64) months. The primary endpoint, overall leukemia-free survival (LFS) rate and overall survival rate was 73.3 ± 10.5%. Allo-HSCT with MAC is a valid option for BPDCN patients in complete remission.

We analyzed the outcomes of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH) who underwent either a haploidentical donor (HID) or a matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). Seventeen patients received an HSCT from an HID and 15 patients received an HSCT from an MUD. The median follow-up time of the surviving patients was 36 months (range: 12-96 months). No significant differences were observed in the 3-year overall survival (OS) between the HID and MUD cohorts (74.1%±11.4% vs. 93.3%±6.4%, respectively, p =.222) or in the 3-year failure-free survival (68.8%±11.8% vs. 86.7%±8.8%, respectively, p =.307). Treatment-related mortality occurred in five patients. A univariate analysis of risk factors revealed platelet engraftment failure negatively impacted OS and FFS. We conclude that HID and MUD-HSCT are feasible and can be effective options for those PNH patients with concomitant bone marrow failure, recurrent life-threatening thrombosis, and uncontrollable hemolysis.

Aim: To construct an edaravone-encapsulated liposomes (EDV-LIPs) formulation against acute ischemic stroke. Methods: EDV-LIPs were prepared by the film dispersion method. The biosafety was evaluated both in vitro and in vivo by flow cytometry and the histological staining method. Biodistribution and therapeutic effect of EDV-LIPs against acute ischemic stroke was investigated by fluorescent imaging, the behavior test, laser speckle imaging and triphenyltetrazolium chloride staining. Results: The nanoliposomes had a long circulation time and could accumulate in the brain lesion region in ischemic stroke rats. EDV-LIPs show good biosafety. EDV-LIPs could restore more cerebral blood flow, reduce infarct volume and decrease neuronal apoptosis. Conclusion: EDV-LIPs provide an effective alternative for drug-targeted delivery against acute ischemic stroke.

Background: Syphilis is a chronic infectious disease caused by Treponema pallidum (Tp) infection, which causes local inflammation in the host. TpF1 is an oligomeric protein expressed by the Tp-infected host that can induce the host immune response. There are few studies regarding the role of TpF1 in macrophage activation and the subsequent release of cytokines., Objective: The objective of this study is to elucidate the effects of TpF1 on the pathological process of Syphilis. In addition, we explored how purinergic 2X7 (P2X7R) induced NOD-like receptor family protein 3 (NLRP3) -dependent release of interleukin-1β (IL-1β) and the underlying mechanisms., Methods: We explored the influence of TpF1 on cytokine release by macrophages using qRT-PCR and ELISA. The specific phenotype of activated macrophages was determined by flow cytometry., Results: TpF1 was able to activate macrophages and induce the M1 macrophage phenotype. Moreover, TpF1 activated the NLRP3 inflammasome in macrophages, which was mediated by P2X7R., Conclusion: The Tp-induced protein TpF1 is able to induce macrophage activation and P2X7R-induced NLRP3-dependent release of IL-1β. Our findings provide a theoretical basis for clarifying the clinical symptoms and pathogenesis of syphilis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective : The outcomes of alternative donor hematopoietic stem cell transplantation (HSCT) with unmanipulated grafts for Inherited bone marrow failure syndromes (IBMFS) are discouraging. Our study is to demonstrate that IBMFS with disease-specific characteristics requires a tailored conditioning regimens to enhance engraftment and reduce regimen related toxicities. Methods : We retrospectively analyzed 42 patients diagnosed with IBMFS and transplanted with an alternative donor graft at our center from November 2012 to August 2018. Twenty-seven patients had Fanconi anemia (FA), 7 had dyskeratosis congenita (DC), and 8 had severe congenital neutropenia (SCN). Patients received ex-vivo unmanipulated alternative donor grafts from a matched unrelated donor (MUD) ( n  = 22), haploidentical donor (HID) ( n  = 17) and unrelated cord blood donor (UCBD) ( n  = 3). FA and DC patient subgroups received reduce intensified conditioning (RIC), while SCN patients received a myeloablative conditioning (MAC) regimen. Results : The median follow-up time for the surviving patients was 38 months (range: 9-63 months). The failure-free survival (FFS) for entire cohort was 76.1%, and was 72.4%, 100% and 56.2% for patients with FA, DC and SCN, respectively. There were no primary graft failures. The cumulative incidence of aGVHD at day 100 was 48.1%. The cumulative incidence of cGVHD at 1 and 3 years was 35.0% and 69.3%, respectively. Conclusion : HSCT using alternative donors with unmanipulated grafts and disease-specific conditioning regimens for IBMFS patients shows promising survival.

There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy  versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78%  vs.  37%; p<0.01) and more with complex cytogenetics (44%  vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft- versus -host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1%  vs. 11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs. 11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Liu, Sun, Zhang, Zhou, Wei, Xiong, Cao, Lu, Yang, Zhang, Lu and Lu.)

Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.

The occurrence of antibiotic resistance genes (ARGs) and their associated environmental factors in estuaries are poorly understood. In this study, we comprehensively analyzed ARGs in both water and sediments from inlet to outlet of the Yangtze Estuary, China. The relative abundances of ARGs were higher in the turbidity maximum zone (TMZ) than other sites, implying that suspended particulate matter (SPM) was the major reservoir for ARGs in water. ARGs showed an increasing trend from inlet to outlet in sediments. Positively correlation between intI1 and sul1 in both water and sediments indicated that sul1 may be regulated by intI1. Correlation analysis and redundancy analysis showed that the spatial variations of estuarine ARGs were positively correlated with sample properties (e.g., temperature, SPM, pH) and chemical pollutants (e.g., heavy metals and antibiotic residues), among which chemical pollutants were the major drivers for the ARG distribution in both water and sediments., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Two anti-thymocyte globulin (ATG) forms are used in graft-versus-host disease (GVHD) prophylaxis during haploidentical hematopoietic stem cell transplantations (haplo-HSCTs): ATG-thymoglobulin (ATG-T) and ATG-fresenious (ATG-F). However, comparable dosages for haplo-HSCT remain unclear. We compared and evaluated the effects of ATG-T (7.5 mg/kg) or ATG-F (20 mg/kg) dosages in a relatively homogenous population in haplotype HSCT settings. Patients administered ATG-T 7.5 mg/kg (n = 81) or ATG-F 20 mg/kg (n = 35) as part of GVHD prophylaxis during haplo-HSCT were enrolled. Incidence and severity of GVHD, Epstein-Barr virus (EBV) infection, and immune cell recovery were compared using the Mann-Whitney U rank test and chi-square test. Cumulative incidences of GVHD, EBV infection and its subgroups, and relapse mortality were computed; overall survival (OS) was analyzed using the Kaplan-Meier method, with the log-rank test used for univariate comparison. Risk factors for OS were analyzed by the Cox proportional hazards model. Incidence and cumulative incidence of all grades of acute GVHD and subgroups were comparable in both groups (all p > 0.05); however, cumulative incidence of any grade and limited chronic GVHD was significantly higher in the ATG-T group (p = 0.002, p = 0.007, respectively). Cumulative incidences of EBV infections, EBV-DNAemia, and EBV-related diseases were similar; relapse mortality and OS rates were comparable between both groups (all p > 0.05). ATG-T dosage (7.5 mg/kg) appeared comparable to ATG-F dosage (20 mg/kg) for haplo-HSCT. Currently approved ATG-T and ATG-F doses appear efficient to balance the risk-benefit ratio of GVHD, OS, relapse mortality, and EBV infection in haplo-HSCT.

Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective alternative to HLA-matched transplantation. However, Epstein-Barr virus (EBV) infection causes morbidity and mortality in patients undergoing haplo-HSCT. Here, we retrospectively evaluated the incidence and risk factors of EBV-DNAemia and EBV-associated diseases in 131 patients who underwent haplo-HSCT. Patients were classified into the no EBV infection groups, EBV-DNAemia group and EBV-associated disease group. Cumulative incidences of acute graft-vs-host disease, EBV infections, overall survival (OS), and relapse were analyzed. The cumulative incidences of EBV-DNAemia and EBV-associated disease were 26.9% and 33.3%, respectively. In multivariate analysis, cytomegalovirus (CMV)-DNAemia was confirmed as an independent risk factor associated with EBV-DNAemia and EBV-associated disease. Patients with EBV-associated disease had higher transplant-related mortality (TRM) rates and lower OS rates, but similar relapse rates. Overall, these findings demonstrated the cumulative incidences of EBV-DNAemia and EBV-associated disease and identified correlations of EBV infection with TRM, relapse, and OS. Additionally, CMV-DNAemia was a risk factor for EBV-DNAemia and EBV-associated disease., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multifunctional nanoclusters based on Fe 3 O 4 nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated Fe 3 O 4 nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic Fe 3 O 4 @F127 nanoclusters via facile ultrasonic treatment. During this process, drug molecules can also be introduced into the nanoclusters and therefore the targeted drug delivery system was formed. Next, we verified the feasibility of the nanoclusters as drug delivery vehicles and magnetic contrast agents. The nanoclusters have an average size of 200 nm and remained stable in water for long periods. Folic acid-modified nanoclusters showed an enhanced intracellular uptake into HepG2 cells by using both cellular iron amount analysis and flow cytometry analysis. Besides, Fe 3 O 4 @F127@FA nanoclusters showed good compatibility in the tested concentration range and good sensitivity in T 2 -weighted MRI. The magnetic nanoclusters combined with drug delivery properties have greatly increased the significance in the diagnosis and therapy of diseases, which are suitable for systematical administration of hydrophobic drugs and simultaneously MRI diagnosis., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Many studies have examined the acute toxicity of nanoparticles (NPs) towards model bacteria. In this study, we report the time-dependent effects of ZnO NPs on native, selected Zn-resistant and dominant bacteria in estuarine waters. An initial inhibition of bacterial growth followed by a recovery at 24 h was observed, and this rebound phenomenon was particularly notable when the raw water samples were treated with relatively high ZnO NP concentrations (1 and 10 mg/L).By comparing the groups treated with Zn 2+ , Zn 2+ was shown to largely explain the acute cytotoxic effect of ZnO NPs on bacteria in raw waters. Furthermore, similar to the native bacteria, especially the dominant bacteria, the viability of Escherichia coli (E. coli) decreased with the increasing treatments time and the concentrations of ZnO NPs in water with different salinities. Moreover, the expression of Zn-resistance genes including zntA and zntR in E. coli suggested that the Zn-resistance system in E. coli can be activated to defend against the stress of Zn 2+ released from ZnO NPs, and salinity may promote this process in estuarine aquatic systems. Thus, the effect of ZnO NPs on bacteria in estuarine water bodies is likely determined by the synergistic effect of environmental salinity and dissolved Zn ions. As such, our findings are of high relevance and importance for understanding the ecological disturbances caused by anthropogenic NPs in estuarine environments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Haploidentical hematopoietic stem cell transplant (haplo-HSCT) recipients are at high risk for Epstein Barr virus (EBV)-related diseases. EBV-specific CD8 + cytotoxic T cells can control EBV-infected B cell expansion; however, no studies have investigated EBV-specific immune reconstitution after HSCT, particularly haplo-HSCT. Therefore, in this study, we aimed to characterize EBV-specific immune cell reconstitution after haplo-HSCT., Methods: HLA-A*1101 and HLA-A*0201 pentamers folded with immunodominant EBV peptides were used to detect EBV-specific CD8 + T cells by flow cytometry in peripheral blood mononuclear cells from 19 haplo-HSCT recipients and the results were compared with those in controls. We also compared the EBV-specific pentamer-binding cell frequencies in patients with or without EBV-related diseases by flow cytometry., Results: Pentamer-binding EBV-specific CD8 + T cells were detected at + 30, + 60 and + 90 days after haplo-HSCT in EBV-seropositive patients subjected to haplo-HSCT from an EBV-seropositive donor. The frequencies of the HLA-A*0201/BMLF1-GLC pentamer in haplo-HSCT patients at + 30 days were significantly lower than those in HLA-A*0201-positive healthy controls (p = 0.019) and patients at + 60 days (p = 0.003). The frequencies of the HLA-A*1101/LMP2-SSC pentamer at + 30, + 60, and + 90 days were significantly decreased compared with those in healthy controls (p = 0.009, 0.019, and 0.039, respectively); however, the frequencies of the HLA-A*1101/LMP2-SSC pentamer did not differ significantly among patients at + 30, + 60, and + 90 days (p = 0.886). There was a significant difference in the frequency of the HLA-A*0201/BMLF1-GLC pentamer at + 60 days between patients with and without EBV-related diseases (p = 0.024). Patients with EBV-related diseases showed lower percentages of HLA-A*0201/BMLF1-GLC specific CD8 + T cells., Conclusions: Haplo-HSCT recipients could generate EBV-specific CD8 + T cells within + 30 days after transplantation. The HLA-A*0201/BMLF1-GLC pentamer cell frequency at + 60 days may be a useful indicator for monitoring EBV-related diseases in patients after haplo-HSCT. Transfusion with EBV-CTLs within 60 days after haplo-HSCT may have prophylactic effects against EBV-related diseases.

In the contaminated coastal sediments, variations of microbial community can reflect the impact of anthropogenic activities. The identification, evaluation and monitoring of the potential bio-indicator species and biomarker communities are vital for the ecological studies in sedimentary environments. Based on the high-throughput sequencing, the microbial communities were characterized in the sediments along the Yangtze Estuary and its coastal area. The results showed that the structure and composition of microbial communities varied greatly among different sampling sites at the phyla level, especially for Euryarchaeota. Metabolic pathway and quantitative PCR analyses suggested that the methane metabolism-related microbes were mainly included in the phylum of Euryarchaeota. Elevated abundances of methane metabolism-related microbes were found at Shidongkou (SDK) and Wusongkou (WSK), where microbes were seriously impacted by the wastewater treatment plant (WWTP) effluent and urban runoff. By comparing with the Euryarchaeota in WWTP sludge, the relatively high abundance of Euryarchaeota in sediment at SDK may be mainly related to the massive growth of indigenous species, promoted by anthropogenic nutrients. Moreover, redundancy discriminant analysis and correlation analysis revealed that methanogens and methanotrophs mainly respond to the nutrients and metals, such as total organic carbon, total phosphorus, total nitrogen, SO 4 2- , NO 2 - , NH 4 + , Cr, and Zn, which were often related to human activities. Network analyses showed that the species related to the metabolism of methane may play a vital role in the interassociation among different microbial communities. Therefore, methanogens, methanotrophs and their community compositions could be considered as potential bio-indicator species and biomarker communities, indicating anthropogenic activities in the sediments along the Yangtze Estuary and its coastal area., (Copyright © 2018 Elsevier B.V. All rights reserved.)

An alternating magnetic field (AMF)/Ag multi-alloying combined process was applied to the solidification of Cu⁻14Fe alloy to study its effects on the microstructure and properties of the resulting samples. The applied AMF and Ag multi-alloying had positive effects on the refinement of the primary Fe phase and precipitation of Fe solute atoms, respectively. These results indicated that the combined AMF/Ag multi-alloying process was effective to improve the distribution of the primary Fe phase and reduce the Fe content of the Cu matrix, which increased the conductivity of the alloy. The application of the combined AMF/Ag multi-alloying process to the solidification of Cu⁻Fe alloy provided samples with improved comprehensive properties compared with those of samples solidified using a single process (AMF or Ag multi-alloying).

The facile fabrication of multifunctional nanocomposites (Fe 3 O 4 /HBC@F127) consisting of superparamagnetic Fe 3 O 4 nanoparticles and fluorescent organic hexa- peri -hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid-polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a T 2 relaxivity ( r 2 ) of 214.61 mM -1 s -1 , which may be used as T 2 -weighted MR imaging agents. In vitro imaging studies indicated that the nanocomposites had good MR and fluorescence imaging effects with low cytotoxicity. Besides, the developed nanocomposites could also be applied as drug delivery vehicles. Doxorubicin (DOX) loaded Fe 3 O 4 /HBC@F127 nanocomposites significantly inhibited the growth of human hepatoma cells (HepG2). These findings suggested that the facile synthesized multifunctional nanocomposites may be used as a platform for dual mode imaging (both MR and fluorescence) and drug delivery., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Antibiotics resistance genes (ARGs) are considered as an emerging pollutant among various environments. As a sink of ARGs, a comprehensive study on the spatial and temporal distribution of ARGs in the estuarine sediments is needed. In the present study, six ARGs were determined in sediments taken along the Yangtze Estuary temporally and spatially. The sulfonamides, tetracyclines and fluoroquinolones resistance genes including sul1, sul2, tetA, tetW, aac(6')-Ib, and qnrS, were ubiquitous, and the average abundances of most ARGs showed significant seasonal differences, with relative low abundances in winter and high abundances in summer. Moreover, the relative high abundances of ARGs were found at Shidongkou (SDK) and Wusongkou (WSK), which indicated that the effluents from the wastewater treatment plant upstream and inland river discharge could influence the abundance of ARGs in sediments. The positive correlation between intI1 and sul1 implied intI1 may be related to the occurrence and propagation of sulfonamides resistance genes. Correlation analysis and redundancy discriminant analysis showed that antibiotic concentrations had no significant correlation to their corresponding ARGs, while the total extractable metal, especially the bioavailable metals, as well as other environmental factors including temperature, clay, total organic carbon and total nitrogen, could regulate the occurrence and distribution of ARGs temporally and spatially. Our findings suggested the comprehensive effects of multiple pressures on the distribution of ARGs in the sediments, providing new insight into the distribution and dissemination of ARGs in estuarine sediments, spatially and temporally., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ubiquitous in the aquatic environment, sulphate-reducing bacteria (SRB) are considered one of the dominant microorganisms involved in the degradation of sulphate. This study focused on the spatial and temporal distributions of SRB in the Scirpus triquter rhizosphere sediments with a comparison to non-rhizosphere sediments and evaluated the implication of SRB to the bioavailability of metals in the Yangtze Estuary. The results showed that taking dsrB as the target gene, SRB abundances in rhizosphere sediments were significantly higher than those in non-rhizosphere sediments (P<0.01). SRB abundances were relatively higher in April and January than other seasons. Moreover, redundancy discriminate analysis (RDA) results indicated that sulphate, pH and TOC were the major environmental factors affecting the SRB abundance in rhizosphere sediments. The concentrations of most metals were significantly related to SRB abundance, and sulphide concentrations showed a significantly positive correlation to metal concentrations, indicating metal sulphide/metal associated sulphide could be regulated by SRB. Furthermore, electron microscope analysis found that nano-sized metal sulphide particles were ubiquitous in rhizosphere sediments and could be further taken up by plants. This study provides new insights into the immobilization and removal of heavy metals and the ecological value of the sulphate-reducing bacteria in the Yangtze Estuary., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Biofilms are ubiquitous throughout aquatic environments and they are thought to promote the acquisition and dissemination of antibiotic resistant genes (ARGs). This study focused on the occurrence and distribution of five types of ARG in naturally-occurring biofilms, in comparison to associated sediment and water samples, from the Yangtze Estuary, which borders the meta-city of Shanghai, China. The detection frequency and abundances of most ARGs showed the following order: biofilm > sediment > water, which can be attributed to a high level of antibiotics and metals that can accelerate the generation and propagation of ARGs in biofilms. Most of ARG abundances were contributed by extracellular DNA (eDNA) in biofilm and sediment samples. ARGs (sul1, sul2, tetA and tetW) in eDNA were significantly correlated with TOC in both biofilm and sediment samples. Furthermore, both intracellular DNA-associated ARGs per gram of microbial biomass carbon (MBC) and eDNA-associated ARGs per gram of non-MBC and were higher in biofilms than sediments, and the partitioning coefficients of ARGs in eDNA between biofilm and water were higher than those between sediment and water. Our results provide new insight for evaluating the occurrence and abundance of ARGs in aquatic environments, confirming that biofilms are a significant sink for ARGs in the estuarine environment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This study was designed to investigate the characteristics of bacterial communities in intertidal sediments along the Yangtze Estuary and their responses to environmental factors. The results showed that bacterial abundance was significantly correlated with salinity, SO 4 2- and total organic carbon, while bacterial diversity was significantly correlated with SO 4 2- and total nitrogen. At different taxonomic levels, both the dominant taxa and their abundances varied among the eight samples, with Proteobacteria being the most dominant phylum in general. Cluster analysis revealed that the bacterial community structure was influenced by river runoff and sewerage discharge. Moreover, SO 4 2- , salinity and total phosphorus were the vital environmental factors that influenced the bacterial community structure. Quantitative PCR and sequencing of sulphate-reducing bacteria indicated that the sulphate reduction process occurs frequently in intertidal sediments. These findings are important to understand the microbial ecology and biogeochemical cycles in estuarine environments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD - . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD - with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

In this study, the 16S rRNA-based Illumina MiSeq sequencing was used to investigate the bacterial community structure and composition of intertidal biofilm taken along the Yangtze Estuary. The results showed that 680,721 valid sequences of seven samples were assigned to 147,239 operational taxonomic units, which belonged to 49 phyla, 246 family and 314 genera. Compared to other studies on water and sediments in the study area, biofilms showed highest index of bacterial diversity and abundances. At different taxonomic levels, both dominant taxa and their abundances varied among the seven samples, with Proteobacteria as the dominant phylum in general. Principal component analysis and cluster analysis revealed that bacterial communities at WSK differed from those at other sampling sites. Salinity, dissolved oxygen, pH and nutrients were the vital environmental factors to influence the bacterial community structure of biofilms. These results may provide a new insight into the microbial ecology in estuarine environments., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) . Methods: Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively. Results: With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95% CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95% CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95% CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT ( P =0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS ( P =0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor. Conclusions: Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.

Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: ①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95% CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95% CI 50.6%-75.2%) vs 88.9% (95% CI 76.6%-100.0%) , P <0.001], higher relapse[11.4% (95% CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P =0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P =0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P =0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [ HR =4.565 (95% CI 2.918-9.482) , P <0.001], relapse [ HR =5.854 (95% CI 1.538-22.288) , P =0.010] and NRM [ HR =3.379 (95% CI 1.361-8.391) , P =0.009] after allo-HSCT in CR(1)-AML. Conclusion: MRD positive pre-conditioning was the only negative impact factor for patients with CR(1)-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR(1)-AML after allo-HSCT.

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR(1), 72 cases in CR(2)) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) ( P =0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34(+) cell number and transfused CD3(+) cell number. DFS was significant lower in primary AML than that in secondary AML ( P =0.006) and also lower in MRD positive than that in MRD negative ( P =0.003) . The accumulative relapse was significant higher in CR(2) compared to that in CR(1) ( P =0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML ( P =0.004) and also higher in MRD positive compared to that in MRD negative ( P =0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion: Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR(1) and CR(2) patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

Chemical and topological parameters have been widely used for predicting the phase selection in high-entropy alloys (HEAs). Nevertheless, previous studies could be faulted due to the small number of available data points, the negligence of kinetic effects, and the insensitivity to small compositional changes. Here in this work, 92 TiZrHfM, TiZrHfMM, TiZrHfMMM (M = Fe, Cr, V, Nb, Al, Ag, Cu, Ni) HEAs were prepared by melt spinning, to build a reliable and sufficiently large material database to inspect the robustness of previously established parameters. Modification of atomic radii by considering the change of local electronic environment in alloys, was critically found out to be superior in distinguishing the formation of amorphous and crystalline alloys, when compared to using atomic radii of pure elements in topological parameters. Moreover, crystal structures of alloying element were found to play an important role in the amorphous phase formation, which was then attributed to how alloying hexagonal-close-packed elements and face-centered-cubic or body-centered-cubic elements can affect the mixing enthalpy. Findings from this work not only provide parametric studies for HEAs with new and important perspectives, but also reveal possibly a hidden connection among some important concepts in various fields.

Objective: To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance., Methods: A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used., Results: All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%)., Conclusion: These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

Objective: To investigate the mothod and therapeutic efficacy of total hip anthroplasties (THA) for osteoarthritis secondary to Crowe type IV developmental dysplasia of hip in adults., Methods: From May 2006 to December 2013, THA was performed on 15 adult patients (17 hips) with Growe type IV acetabular dysplasia, including 13 females and 2 males, with a mean age of 30.9 years old (22 to 58 years old) and an average preoperative Harris score of (34.0 ± 6.5) points. Traction of the affected limb was not performed before surgery. After extensive release and lengthening of soft tissues, sub-trochanteric osteotomy of the femur was performed, hip joint center was rebuilt and the abduction function was restored., Results: The patients were followed up with a mean period of 33 months (ranged from 6 months to 5 years). The postoperative Harris score was 85.0 ± 7.3,higher than the preoperative score. The extended length of limb ranged from 1.6 to 5.4 cm, with a mean of (3.42 ± 0.65) cm. The shortening and malformation of the affected limb were corrected in the most patients,with the difference in length of the two legs less than 1.5 cm. After surgery, 1 patient experienced partial sciatic nerve injury, which was largely recovered after 3 months of conservative treatment. One patient experienced complete sciatic nerve injury, which was partially recovered after 6 months of conservative treatment; a foot-drop varus deformity was formed in the distal end of the affected limb, which was improved after tendon transposition and transplantation. Joint pain was relieved, and the joint function was restored significantly. Over the follow-up period, no severe complications such as dislocation, infection, prosthesis loosening, or subsiding occurred., Conclusion: Satisfactory efficacy can be achieved for adult Growe type IV acetabular dysplasia associated with osteoarthritis by THA, with proper soft tissue release and lengthening, sub-trochanteric osteotomy of femur, joint functional restoration, appropriate choice of prosthesis, and careful protection of nerves and vessels.

The aim of the present study was to explore the effect of epigenetic modification of class II transactivator (CIITA) methylation on histocompatibility complex (MHC) class II expression and the immune evasion of leukemia HL-60 cells. HL-60 cells were treated with various concentrations of 5-aza-2'deoxycytidine (5-Aza-CdR) and 0.5 µmol/l suberoylanilide hydroxamic acid (SAHA) for 24 h and then stimulated by interferon γ (IFN-γ) for 48 h. The mRNA levels of MHC class I, II and co-stimulatory molecules were quantified by reverse transcription polymerase chain reaction (RT-PCR). The levels of CIITA protein were determined by western blot analysis, and the CpG island methylation ratios in the CIITA promoter IV (CIITApIV) were analyzed by bisulfite-sequencing PCR (BSP). MHC I as well as the co-stimulatory molecules CD40 and CD80 were significantly increased following treatment with 5-Aza-CdR + SAHA + IFN-γ (epigenetic groups) compared with those in the control group and IFN-γ group (P<0.05). The expression of MHC class II and CIITA was restored and increased in an 5-Aza-CdR concentration-dependent manner in the three epigenetic groups. The results of the BSP assay showed that the methylation rate of CIITApIV CpG sites decreased with the treatment of epigenetic modification and negatively correlated to the 5-Aza-CdR concentration. This demonstrated that the negative expression of CIITA protein was the key reason for the loss of MHC II expression in HL-60 cells. The results of the present study may help to illustrate the mechanism of immune evasion in HL-60 cells.

The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway., (Copyright © 2015 the American Physiological Society.)

Common practice of establishing occlusal vertical dimension by adopting traditional method for patients with long-term pathological conditions has left the results much less than desired, since the degree of pathological condition for each patient varies from one patient to another, and traditional methods to determine vertical dimension are mostly intended for normal patients. Ideally, the occlusal vertical dimension should be dictated by, and conformed to patient's comfort range for the physiological accommodation to each patient's condition. This article describes a method of a double checking system for occlusion determination by increasing vertical dimension of occlusion (VDO) by 1/2 mm each week to find the most comfort zone and beyond for patient, and then to gradually decrease ½ mm of the VDO each week to the original VDO to double check the comfort zone for the patient. During the process, Bi-Digital O-Ring Test was employed to corroborate, to determine, and to individualize the occlusal vertical dimension for patients with pathological abnormalities. Traditional methods of vertical dimension determination were merely used as a guiding reference in our treatment of those patients. Patient's comfort and discomfort were carefully recorded, compared and studied before the denture prosthesis was fabricated.