Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation / 中华血液学杂志

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Research progress of retinal microscopic changes after extraocular muscle surgery / 国际眼科杂志(Guoji Yanke Zazhi)

As a primary treatment for strabismus, extraocular muscle surgery can achieve the purpose of correcting the eye position, improving the appearance and reconstructing the third-level visual function. Previous studies have found that the vascular density(VD)and thickness of retina increased in the early stage after extraocular muscle surgery, where multiple mechanisms involved. In recent years, with the appearance of detection means such as optical coherence tomography angiography(OCTA), our quantitative understanding of retinal microscopic changes and their mechanisms brought about by traditional extraocular muscle surgery has become more and more profound. The increase of retinal VD in the early postoperative period may be closely related to the recovery of postoperative visual function. However, the related studies are few, and the association between microscopic changes and visual function after extraocular muscle surgery and its mechanism need to be further clarified. This article will review the microscopic changes of retina and their mechanisms after extraocular muscle surgery from multiple perspectives to improve our understanding of the relationship between the mechanism of its influence and visual function, with a view to provide references for the choice of extraocular muscle surgery scheme and related clinical research.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Distribution and Drug Sensitivity Analysis of Pathogenic Bacteria Isolated from Patients in Hematology Department / 中国实验血液学杂志

OBJECTIVE@#To investigate the distribution and drug sensitivity of pathogenic bacteria isolated from patients in hematology department, in order to provide evidence for rational use of antibiotics in clinic.@*METHODS@#The distribution of pathogenic bacteria and drug sensitivity data of patients in the hematology department of The First Affiliated Hospital of Nanjing Medical University from 2015 to 2020 were retrospectively analyzed, and the pathogens isolated from different specimen types were compared.@*RESULTS@#A total of 2 029 strains of pathogenic bacteria were isolated from 1 501 patients in the hematology department from 2015 to 2020, and 62.2% of which were Gram-negative bacilli, mainly Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii. Gram-positive coccus accounted for 18.8%, mainly Coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus. Fungi (17.4%) were mainly candida. The 2 029 strains were mainly isolated from respiratory tract (35.1%), blood (31.8%) and urine (19.2%) specimens. Gram-negative bacilli were the main pathogenic bacteria in different specimen types (>60%). K. pneumoniae, S. maltophilia and A. baumannii were the most common pathogens in respiratory specimens, E. coli, CoNS, K. pneumoniae and P. aeruginosa were common in blood samples, and E. coli and Enterococcus were most common in urine samples. Enterobacteriaceae had the highest susceptibility to amikacin and carbapenems (>90.0%), followed by piperacillin/tazobactam. P. aeruginosa strains had high sensitivity to antibiotics except aztreonam (<50.0%). The susceptibility of A. baumannii to multiple antibiotics was less than 70.0%. The antimicrobial resistance rates of E. coli and K. pneumoniae in respiratory tract specimens were higher than those in blood specimens and urine specimens.@*CONCLUSION@#Gram-negative bacilli are the main pathogenic bacteria isolated from patients in hematology department. The distribution of pathogens is different in different types of specimens, and the sensitivity of each strain to antibiotics is different. The rational use of antibiotics should be based on different parts of infection to prevent the occurrence of drug resistance.

Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Development and Evaluation of Biocontrol Agents Against Panax ginseng Root Rot / 中国实验方剂学杂志

ObjectiveTo develop safe and effective microbial agents against Panax ginseng root rot. MethodP. notoginseng endophytes were screened in plate confrontation tests， followed by morphological and molecular biological identification of antagonistic strains， optimization of strain fermentation conditions in a single factor test， and determination of optimal carriers and auxiliary agents of the microbial agent and their ratio using response surface methodology for formulating the production process. The prevention and control effects of the microbial agent were verified in the confrontation and pot culture experiments. ResultThe plate confrontation test yielded a strain named Fusarium pseudoanthophilum with significant resistance to root rot， and its antibacterial rate was 53.33%. According to the single factor test， the fermentation conditions of F. pseudoanthophilum were determined to be fermentation time 60 h， fermentation temperature 26 ℃， speed 120 r·min-1， and pH 6.5. The response surface optimization results showed that the number of viable bacteria reached the maximum （5.23×109 cfu·g-1） when the peat was 60.00 g， sodium carboxymethylcellulose 3.50 g， and sodium alginate 4.76 g. The influences of carriers and auxiliary agents on the number of viable bacteria were sorted by degree in a descending order as follows： peat>sodium carboxymethylcellulose >sodium alginate. The confrontation test results showed that when the microbial agent concentration was greater than 1.00 g·L-1， it had a significant inhibitory effect on the root rot pathogen F. oxysporum and the inhibitory rate was more than 42.3%. As demonstrated by the pot culture experiment， the inoculation of biocontrol agent for 28 d significantly reduced the incidence （66.99%） of root rot in P. ginseng seedlings and disease index （61.69%） and increased their leaf length （33.04%） and fresh weight （34.48%）. ConclusionF. pseudoanthophilum inoculant is efficient in preventing and controlling the root rot， making it worthy of further development and utilization.

Effects of leptin on proliferation and differentiation of hypoxic rat retinal progenitor cells in vitro / 南方医科大学学报

OBJECTIVE@#To investigate the the effects of leptin on the proliferation, differentiation and PTEN expression of rat retinal progenitor cells (RPCs) cultured under hypoxic condition.@*METHODS@#SD rat RPCs were cultured in normoxic conditions or exposed to hypoxia in the presence of 0, 0.3, 1.0, 3.0, 10, and 30 nmol/L leptin for 12, 48 and 72 h, and the cell viability was assessed using cell counting kit 8 (CCK 8) assay. The RPCs in primary culture were divided into control group, hypoxia group, and hypoxia+leptin group, and after 48 h of culture, the cell medium was replaced with differentiation medium and the cells were further cultured for 6 days. Immunofluorescence staining was employed to detect the cells positive for β-tubulin III and GFAP, and Western blotting was used to examine the expression of PTEN at 48 h of cell culture.@*RESULTS@#The first generation of RPCs showed suspended growth in the medium with abundant and bright cellular plasma and formed mulberry like cell spheres after 2 days of culture. Treatment with low-dose leptin (below 3.0 nmol/L) for 48 h obviously improved the viability of RPCs cultured in hypoxia, while at high concentrations (above 10 nmol/L), leptin significantly suppressed the cell viability (P < 0.05). The cells treated with 3.0 nmol/L leptin for 48 h showed the highest viability (P < 0.05). After treatment with 3.0 nmol/L leptin for 48 h, the cells with hypoxic exposure showed similar GFAP and β-tubulin Ⅲ positivity with the control cells (P>0.05), but exhibited an obvious down-regulation of PTEN protein expression compared with the control cells (P < 0.05).@*CONCLUSION@#In rat RPCs with hypoxic exposure, treatment with low dose leptin can promote the cell proliferation and suppress cellular PTEN protein expression without causing significant effects on cell differentiation.

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation / 中华医学杂志(英文版)

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Risk factors associated with osteoporosis and fracture in psoriatic arthritis / 中华医学杂志(英文版)

BACKGROUND@#Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.@*METHODS@#A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.@*RESULTS@#Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm2, P  = 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm2, P  = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = -0.503, -0.580, -0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = -0.521, -0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026-1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214-1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002-1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012-44.180, P < 0.05) were risk factors for fracture in the multivariate model.@*CONCLUSIONS@#Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.

Benefit of ultrasound in the phenotype recognition of psoriatic arthritis / 北京大学学报(医学版)

OBJECTIVE@#To explore the difference in phenotype recognition of PsA patients in two clinical scenarios, physical examination with and without ultrasound assessment.@*METHODS@#PsA patients who visited the rheumatology and clinical immunology department of Peking University First Hospital between January 2010 and October 2020, with complete data of clinical and ultrasound assessment were enrolled. The phenotypes were first identified based on physical examination only, and then combined with enthesitis and dactylitis shown on power doppler and gray-scale ultrasound. The phenotype groupings without and with ultrasound assessment were presented with Wayne diagram. The distributions of different clinical phenotypes were compared by using χ2 test or Fisher's exact test. The differences of clinical phenotypes with and without ultrasound assessment were compared by using Wilcoxon signed rank test.@*RESULTS@#A total of 227 patients with PsA were enrolled with one or more clinical domains. Physical examination revealed that psoriasis was in 209 (92.1%, 209/227) patients, nail involvement in 98 (43.2%, 98/227) patients, peripheral arthritis in 219 (96.5%, 219/227) patients, axial involvement in 25 (11.0%, 25/227) patients, dactylitis in 80 (35.2%, 80/227) patients, and enthesitis in 18 (7.9%, 18/227) patients. Besides 18 patients with clinical enthesitis, ultrasound scan revealed acute enthesitis in 80 patients, with hypoechogenicity (55 cases), tendon thickening (62 cases), and presence of Doppler signals (48 cases). Similarly, dactylitis on ultrasound was found in 18 patients besides those patients with clinical dactylitis. Compared with the phenotypes recognized based on physical examination only, the additional ultrasound assessment revealed that the most common phenotypes, peripheral arthritis was significantly less frequently recognized (49.8% vs. 27.8%, P < 0.001), however on the other hand, the proportion of the patients with peripheral arthritis and enthesitis was significantly increased (4.4% vs. 18.1%, P < 0.001). The phenotype of peripheral arthritis combined with enthesitis, and dactylitis was also dramatically increased (1.8% vs. 17.6%, P < 0.001).@*CONCLUSION@#Ultrasound is a useful tool to identify enthesitis and dactylitis. With the aid of ultrasound assessment, rheumatologists can better identify the lesions of PsA, accurately identify the phenotypes, and further guide the subsequent treatment.

Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study / 中华心血管病杂志

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.

Beneficial effects and related mechanism of hawthorn leaves flavonoids on cardiac function in rats with acute myocardial infarction / 中华心血管病杂志

Objective: To explore the effect and related regulatory mechanism of hawthorn leaf flavonoids (FHL) on cardiac function in rats with acute myocardial infarction (AMI). Methods: Sixty SPF male Sprague-Dawley rats (9-week-old, weighing 300-350 g) were used in this study. Ten rats were assigned to sham operation group, and the remaining 50 rats were used to establish the AMI model with coronary artery ligation method, AMI was successfully established in 36 rats. AMI rats were randomly divided into AMI group and FHL low-, medium-, and high-dose groups (n=9 for each group). Rats received intraperitoneal injection (10 ml·kg-1·day-1) with physiological saline and FHL solution with concentrations of 0.3, 0.6, and 1.2 mg/ml, respectively for 4 consecutive weeks. Echocardiography was performed at the end of experiments. Left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic anterior wall thickness (LAWD), left ventricular ejection fraction (LVEF) and left ventricular end diastolic pressure (LVEDP) were measured. Then the rats were sacrificed under deep anesthesia, and the left ventricular anterior wall tissue was used for pathological examinations by hematoxylin-eosin (HE) staining. Other myocardial tissue was used for in situ terminal transferase labeling (TUNEL) staining, and the apoptosis rate of cardiomyocytes was calculated. The myocardial cell apoptosis rate, the mRNA, and protein expressions of phosphatidylinositol 3β-kinase (PI3K), protein kinase B (Akt), glycogen synthetase kinase-3 (GSK3β), cyclin D1 and the protein expressions of p-Akt and p-GSK3β were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot respectively. Results: Compared with sham operation group, the LVEDD and LVEDP of the rats in AMI group and FHL low-, medium-and high-dose groups were increased, and the LAWD and LVEF were reduced (all P<0.05). Compared with AMI group, LVEDD and LVEDP were reduced, and LAWD and LVEF were increased in FHL low-, medium-and high-dose groups (all P<0.05). LVEDD and LVEDP decreased, and LAWD and LVEF increased in proportion to the increase of FHL dose (all P<0.05). LVEDD and LAWD values were similar between FHL low-dose and medium-dose groups (both P>0.05). HE staining results evidenced necrotic myocardial tissue, together with disordered arrangement of myocardial fibers, and a large number of inflammatory cells infiltrated in the myocardial tissue in AMI group. The myocardial damage of rats in FHL low-, medium-, and high-dose groups was less than that of AMI group. The myocardial fibers were arranged neatly, but there were still partial breaks and a small amount of inflammatory cell infiltration in the myocardial tissue and there were scattered islands of normal myocardial tissue in the infarct area of these groups. Among them, myocardial damage was the least in FHL high-dose group. The results of TUNEL staining showed that compared with AMI group, the apoptosis rate of myocardial cells was significantly reduced in FHL low-, medium-, and high-dose groups (all P<0.001), but was still higher than that in sham operation group (all P<0.001). Myocardial cell apoptosis rate decreased in proportion with increasing FHL dose (P<0.05). The RT-qPCR results showed that compared with AMI group, the expression levels of PI3K and cyclin D1 mRNA were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and PI3K and cyclin D1 mRNA expression levels increased with the increase dose of FHL (P<0.05). Western blot results showed that compared with AMI group, the expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 were significantly upregulated in the myocardial tissue of rats in FHL low-, medium-, and high-dose groups, but still lower than those in sham operation group (all P<0.05), and the protein expression levels of PI3K, p-Akt, p-GSK3β, and cyclin D1 increased in proportion with the increase dose of FHL (all P<0.05). Conclusion: FHL can effectively improve cardiac function in rats with AMI, and the beneficial effects may be partly mediated through activating PI3K/GSK3β/cyclin D1 signaling pathway.

Research on planting area and industrial development strategy of Tibetan medicine / 中国中药杂志

Appropriate producing areas can guarantee the quality of Tibetan medicine, but research on the suitable ecological factors and suitable producing areas of Tibetan medicinal plants is scarce. This paper used the Geographic Information System for Global Medicinal Plants(GMPGIS) to analyze the ecological suitability of Tibetan medicinal plants nationwide. For the first time, the range of ecological factors and main soil types of Tibetan medicinal plants were extracted, such as the average annual temperature-19.4-24.2 ℃, annual average precipitation 17-4 088 mm, annual average sunshine 124.2-171.6 W·m~(-2). The main soil types were black calcareous soil, thin layer soil, chestnut soil and so on. Based on 337 sampling points, the largest ecological similarity area of Tibetan medicine across the country was obtained through ecological similarity analysis. In addition to Tibet and Qinghai provinces and Tibetan Autonomous Prefectures in Sichuan, Gansu, and Yunnan provinces, Jiuquan city and Linxia county in Gansu province, Panzhihua and Ya'an in Sichuan province, and Xinjiang, Inner Mongolia, and Shanxi provinces also had larger suitable cultivation areas. In addition, by analyzing the current situation of Tibetan medicine industry, the research pointed out that there were some problems such as unreasonable development and utilization of resources, lack of standards and norms, weak basic research and imperfect industrial system, and made corresponding countermeasures for sustainable development of resources, formulation of standards and specifications, promotion of medicine through science and technology, expansion of domestic and foreign markets, etc. This study provided the basis for guiding the rational layout of production bases, introduction and breeding of plant Tibetan medicine nationwide, laying the foundation for the scientific and standardized production of high-quality Tibetan medicine, clarifying the development direction of Tibetan medicine industry, and providing ideas for the development strategy of Tibetan medicine and other national medicine industry.

Mechanism of Xuanfei Baidu Tang in treatment of COVID-19 based on network pharmacology / 中国中药杂志

The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.

Research progress of anterior segment ischemia after extraocular muscle surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#Anterior segment ischemia(ASI)is a rare but serious complication after extraocular muscle surgery. Due to its complex clinical manifestations, it is easy to be misdiagnosed. If not treated in time, it may lead to blindness such as vision loss. This paper mainly reviews the concept, clinical manifestations, pathogenesis, risk factors, diagnosis and treatments of ASI after extraocular muscle surgery, so as to improve people's understanding of ASI and minimize or avoid the occurrence of ASI in clinical work.

Ecological Suitability Analysis of Production Areas and Industrial Development Strategy of Dai Medicine / 中国实验方剂学杂志

The suitable production area can guarantee the quality of Dai medicine， but the research on the suitable ecological factors and suitable production area of plant Dai medicine is relatively scarce at present. In this study， gmpgis was used to analyze the ecological suitability of Dai medicine in China. For the first time， the range of ecological factors and main soil types in the main distribution areas of Dai medicine were extracted， such as annual average temperature of 8.6-23.7 ℃， annual average precipitation of 1212-1881 mm， annual average sunshine of 149.7-157.4 W·m-2， the main soil types are strong eluvial soil， alluvial soil， high activity strong acid soil， etc. Based on 179 sampling points， through the analysis of ecological similarity， the largest ecological similarity area of plant Dai medicine in the world was obtained， mainly including China， Brazil， the United States， Myanmar， Laos and other countries. In China， it is mainly concentrated in the West and south of Yunnan， including Xishuangbanna Dai Autonomous Prefecture， Dehong Dai Jingpo Autonomous Prefecture， Pu'er City， Baoshan City and Lincang City， which are suitable for cultivation. In addition， by analyzing the current situation of Dai medicine industry， this paper summarizes the problems such as the lack of talents， the decreasing of Dai medicine resources， the limitation of cultural heritage， and the weakness of scientific research， and puts forward strategies such as training high-quality talents of Dai medicine， the investigation and protection of Dai medicine resources， promoting the collection and arrangement of Dai medicine data and ancient books， and strengthening the basic and applied research of Dai medicine Enter the development of Dai medicine. This study provides a basis for guiding the rational layout， introduction and breeding of plant Dai medicine production base， and lays a foundation for the scientific and standardized production of high-quality Dai medicine.