Purpose: Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Materials and Methods: Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. Results: All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. Conclusion CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

OBJECTIVE: To evaluate the safety and efficacy of catheter-directed thrombolysis (CDT) versus systemic thrombolysis (ST) in the treatment of pulmonary embolism (PE). METHODS: The Cochrane Library, PubMed, and Embase databases were searched to collect the literature on the comparison of the results of CDT and ST in the treatment of PE from the beginning of their records to May 2020, and meta-analysis was performed by STATA software (version 15.1). Using standardized data-collection forms, the authors screened the studies and independently extracted data, and assessed the quality of the studies using the Newcastle-Ottawa Scale for cohort studies. Cohort studies that examined the following results were included in the current study: in-hospital mortality, all-cause bleeding rate, gastrointestinal bleeding rate, intracranial hemorrhage rate, the incidence of shock, and hospital length of stay. RESULTS: A total of eight articles, with 13,242 participants, involving 3962 participants in the CDT group and 9280 participants in the ST group were included. CDT compared with ST in the treatment of PE can significantly affect in-hospital mortality rate [odds ratio (OR) = 0.41, 95% CI: 0.30-0.56, P < 0.05], all-cause bleeding rate (OR = 1.20, 95% CI: 1.04-1.39, P = 0.012), gastrointestinal bleeding rate (OR = 1.43, 95% CI: 1.13-1.81, P = 0.003), the incidence of shock (OR = 0.46, 95% CI: 0.37-0.57, P < 0.05), and hospital length of stay [standard mean difference (SMD) = 0.16, 95% CI: 0.07-0.25, P < 0.05]. However, there was no significant effect on intracranial hemorrhage rate in patients with PE (OR = 0.70, 95% CI: 0.47-1.03, P = 0.070). CONCLUSIONS CDT is a viable alternative to ST in the treatment of PE, as it can significantly reduce in-hospital mortality rate, all-cause bleeding rate, gastrointestinal bleeding rate, and incidence of shock. However, CDT may prolong hospital length of stay to a certain extent. Further research is needed to evaluate the safety and efficacy of CDT and ST in the treatment of acute PE and other clinical outcomes.

Objective:To investigate whether the presynaptic dopamine neuronal depletion in different striatal subregions predicts future development of wearing-off (WO) in Parkinson′s disease (PD) patients.Methods:A retrospective longitudinal study included 57 PD patients who were referred to the Department of Neurology of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2020, and completed 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane dopamine transporter (DAT) positron emission tomography scans at the initial evaluation and received dopaminergic drugs for at least 12 months during follow-up. The time of starting dopaminergic drug treatment and the occurrence of WO were recorded. After adjusting for clinical related factors, the predictive value of DAT uptake and related parameters in striatal subregions for WO was evaluated by Cox proportional hazards model. Results:During a median follow-up period of 23 months, 10 patients (18.18%) developed WO. Patients with WO exhibited less DAT uptake in the caudate nucleus and anterior putamen nucleus (0.66±0.52 vs 1.08±0.42, t=2.76, P=0.008 and 0.66±0.20 vs 0.87±0.28, t=2.27, P=0.027 respectively), especially in these subregions contralateral to the less-affected side of the body, compared to those without WO. Cox proportional hazard models revealed that after adjusting for gender, age, course of disease, baseline Unified Parkinson′s Disease Rating Scale Ⅲ score and increment of levodopa equivalent dosage, the lower the DAT uptake of the caudate ipsilateral to the less-affected side of the body ( HR=0.20, 95% CI 0.07-0.63, P=0.006), as well as the lower the DAT uptake of the caudate nucleus and posterior putamen nucleus ( HR=0.28, 95% CI 0.11-0.69, P=0.006 and HR=0.08, 95% CI 0.01-0.64, P=0.018 respectively) and the higher the ratio of putamen/caudate contralateral to the less-affected side of the body ( HR=2.33, 95% CI 1.02-5.33, P=0.045), the higher the risk of WO. Conclusion:The presynaptic dopamine neuronal loss, particularly bilateral caudate nucleus dopaminergic depletion at the early stage, has predictive value of development of WO in PD.

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed．The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Core Binding Factors ; Disease-Free Survival ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Prognosis ; Remission Induction ; Retrospective Studies

Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Breast Neoplasms/drug therapy* ; Cell Line ; Cell Line, Tumor ; Cyclophosphamide/pharmacology* ; Ginkgo biloba/chemistry* ; Mammary Neoplasms, Animal/drug therapy* ; Mice ; Plant Extracts/administration & dosage*

OBJECTIVE: To explore the applicability of integration between three-dimensional (3D) facial and dental data to evaluate the nasolabial morphology variation before and after the cross-arch fixed restoration of the maxillary implant-supported prostheses. METHODS: Twelve patients (4 women and 8 men), mean age (54.82±5.50) years (from 45 to 62 years) referred to the Department of Oral Implan-tology, Peking University School and Hospital of Stomatology, were selected and diagnosed with edentulous maxilla. For all the patients, 4 to 6 implants were inserted into the maxilla. Six months later, the final cross-arch fixed prostheses were delivered. The 3D facial images were collected before and after the final restoration. The 3D data of prostheses were also captured. All the 3D data were registered and measured in the same coordinate system. Then the displacement of all the landmarks [cheilion left (CHL), cheilion right (CHR), crista philtri left (CPHL), crista philtri right (CPHR), labrale supe-rius (LS), subnasale (SN), stomion (STO), upper incisor (UI), upper flange border of the prostheses (F-point, F)], and the variation of the distances between these landmarks (SN-LS, CPHR-CPHL, CHR-CHL, LS-STO) were analyzed and compared. RESULTS: The consistency test among three measurements of the length of F-SN indicated that the integration method of the dental prostheses and soft tissue had the good repetitiveness, ICC=0.983 (95%CI: 0.957-0.995). After wearing the final cross-arch maxillary implant-supported prostheses, all the landmarks on the soft tissue moved forward. The nasal base area changed minimally, and the shift of SN in the sagittal direction was only (0.61±0.44) mm. But the sagittal shift of LS was (3.12±1.38) mm. In the vertical direction, SN, LS, CPHL, and CPHR moved upward. But STO, CHL, and CHR moved downward a little. Except for the slight decrease of the length of philtrum (SN-LS), the length of CHL-CHR, CPHL-CPHR, and the height of upper lip were increased together (P < 0.01). In the direction of Z axis, the strong correlations were found not only between the movements of SN and F (r=0.904 3) but also between the movements of LS and UI (r=0.958 4). CONCLUSION The integration method of 3D facial and dental data showed good repetitiveness. And the strong correlations between the landmarks of prostheses and nasolabial soft tissue in the sagittal direction were found by this new method.
Female ; Humans ; Incisor ; Lip ; Male ; Maxilla/surgery* ; Middle Aged ; Mouth, Edentulous ; Prostheses and Implants

BACKGROUND: Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma (PBL) is a rare entity of diffuse large B-cell lymphoma (DLBCL). The clinicopathological features of and optimal treatment for HIV-negative PBL remain largely unknown. METHODS: To gain insight into this distinct lymphoma, we summarized the clinicopathologic characteristics of 8 unpublished HIV-negative PBLs and performed a comprehensive review of 394 published cases. RESULTS: Of the 8 unpublished PBLs, the median patient age was 53.0 years. Four patients presented with stage IV disease. All 8 patients showed a plasma cell-like immunophenotype. Of the six patients who received anthracycline-based chemotherapy, including two who received bortezomib, three patients achieved a continuous complete response, two patients died due to disease progression, and one patient was lost to follow-up. The other two patients achieved continuous complete response after receiving chemotherapy combined with radiotherapy and surgery. Of the 402 patients, the majority were male, with a mean age of 58.0 years. EBV infection was detected in 55.7% of the patients. The median survival times of the patients who received CHOP or CHOP-like regimens and intensive regimens were not reached and 23.0 months, respectively, and the intensive regimen did not improve the survival outcome (P=0.981). Multivariate analysis showed that EBER remained the only independent factor affecting overall survival (OS). CONCLUSION HIV-negative PBL is a distinct entity with a predilection for elderly and immunosuppressed individuals. Intensive chemotherapy had no apparent survival benefits over the CHOP regimen in terms of OS; the prognosis of this disease is poor with current chemotherapy methods, and treatment remains a challenge.

【Objective】 To study the mutation characteristics of Tyrosine hydroxyls（TH） gene in a pedigree with dopa-responsive dystonia（DRD）. 【Methods】 Extraction of genomic DNA from peripheral blood of a proband and his parents and two sisters using high- throughput sequencing （NGS） method were detected on 256 known pathogenicity genes associated with dystonia and dyskinesia.【Results】Mutations on tyrosine hydroxylase（TH）gene in the exon 14 and exon 9 were detected in the proband and his eldest sister in this pedigree. They had a complex heterozygosity of c.1481C > T（p.Thr494Met）and c.943G >A（p.Gly315Ser），and one heterozygous mutation was carried by parents respectively. The mutation was not detected in his second sister and 50 people with normal phenotype controls. 【Conclusion】 The mutations of TH gene c. 1481C > T（p.Thr494Met）and c. 943G > A（p.Gly315Ser）led to the gene abnormality in DRD family，and a new mutation of TH gene was found，which expanded the relationship between DRD genotype and clinical phenotype. It is vital that early accurate diagnosis and treatment of DRD is the key to improve prognosis.

Objective: To explore the clinical efficacy and safety of modified Huqianwan in treatment of rheumatoid arthritis (RA) liver-kidney Yin deficiency syndrome, and investigate its possible mechanism. Method: A total of 184 patients with RA liver-kidney Yin deficiency syndrome were randomly divided into Chinese medicine group (62 cases), western medicine group (57 cases) and integrated Chinese and western medicine group (65 cases) according to the digital table method. The patients in Chinese medicine group were treated with Huqianwan; the patients in western medicine group were treated with methotrexate tablets and leflunomide tablets; and the patients in integrated Chinese and western medicine group received Huqianwan+methotrexate tablets and leflunomide tablets,with a treatment course of 12 weeks in all groups. The pain visual analog scale (VAS), swelling and tenderness scores of 28 joints (DAS28), average hands grip strength, morning stiffness time and liver-kidney Yin deficiency syndrome differentiation of traditional Chinese medicine (TCM) syndrome score were compared between groups before and after treatment. The changes of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulin (Ig) G, tumor necrosis factor-alpha (TNF-α) and rheumatoid factor (RF) were detected in all groups after treatment. Clinical efficacy, and incidence of adverse reactions such as gastrointestinal response, liver injury, leukopenia, serum glutamate oxaloacetic aminotransferase (GOT) and platelet (PLT) level changes were compared between the groups, so as to investigate the efficiency and safety of the different medicines. Result: After 12 weeks of treatment, the total clinical effective rate was 79.0%, 80.7%, and 92.3% respectively in Chinese medicine group, western medicine group, and integrated Chinese and western medicine group; the integrated Chinese and western medicine group was significantly better than the Chinese medicine group and western medicine group (P<0.01), but there was no difference between the Chinese medicine group and western medicine group. Every treatment group can effectively improve liver and kidney Yin deficiency syndrome in RA patients (P<0.05), and the effect in integrated Chinese and western medicine group was superior to that in Chinese medicine group (P<0.05); the effect in Chinese medicine group was superior to that in western medicine group (P<0.05). The incidence of adverse reactions was Chinese medicine group (1.61%, 1/62)Conclusion: The efficacy in treating RA liver and kidney Yin deficiency syndrome shows no significant difference between modified Huqianwan and methotrexate tablets+leflunomide tablets. In the treatment of RA liver and kidney Yin deficiency syndrome, Huqianwan has fewer adverse reactions. Huqianwan combined with methotrexate tablets+leflunomide tablets is superior to that in methotrexate tablets+leflunomide tablets in treatment of RA liver-kidney Yin deficiency syndrome.

The purpose of current study is to investigate the metabolic profile of a triptolide derivative (5R)-5-hydroxytriptolide in vitro. (5R)-5-Hydroxytriptolide was incubated with the hepatocytes of human, monkey, dog, rat or mouse, respectively. Compared with inactivated hepatocytes, four metabolites were identified in hepatocytes from all five species: oxidative ring-opening metabolite (M1), glutathione-conjugating metabolite (M2), and monooxidative combined with glutathione-conjugating metabolites (M3-1 and M3-2), respectively. In human or rat liver microsomes, seven metabolites of (5R)-5-hydroxytriptolide were found, dehydrogenated metabolite (M4) and monooxidative metabolites (M5-1–M5-6), respectively. Reference standards for the metabolites were obtained either through chemical semisynthesis or biotransformation through rat primary hepatocytes. The structures of five metabolites were confirmed, which were 12,13-epoxy ring-opening metabolite M1, 12-glutathione-conjugating metabolite M2, (16S)-, (2R)- and (19R)-monohydroxylated metabolites M5-1, M5-4, and M5-5, respectively. In vitro activity assay revealed that only (2R)-hydroxylated metabolite exhibited weak immunosuppressive activity with less than one-tenth the activity of its parent drug, and a significant decrease in toxicity was observed. It is suggested that (5R)-5-hydroxytriptolide might undergo metabolic inactivation and detoxification in vivo.