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.

Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment / 中华妇产科杂志

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

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.

Environmental and meteorological factors on the risk of lipid-abnormal dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the impact of meteorological factors in different environments in the eastern and western regions of China on the incidence of lipid-abnormal dry eye.METHODS: This is a multicenter retrospective study. From March 1, 2021 to February 28, 2022, all patients with dry eye were selected from the ophthalmology clinic of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine and Friendship Hospital of Xinjiang Yili Kazakh Autonomous Prefecture. General data(gender, age, employment and education)and climate data for outdoor environments(temperature, humidity, air quality index and wind)on the day of the visit were collected. Patients who met the inclusion and exclusion criteria were selected. Single factor, multiple factors and nonlinear model analysis were applied to identify environmental factors of lipid-abnormal dry eye in both regions.RESULTS: There was no significant difference in the incidence of lipid-abnormal dry eye between Nanjing and Yili in different seasons. The incidence of lipid-abnormal dry eye in Yili was significantly higher in all seasons than in Nanjing(P&#x0026;#x003C;0.001). The results of univariate research showed that the factors affecting the incidence of lipid-abnormal dry eye were gender, employment, humidity, air quality, and wind. The results of multivariate Logistic regression analysis showed that humidity, temperature and air quality were statistically significant, and remained significant after adjusting for the three confounding factors of age, gender and employment situation. Nonlinear analysis showed that the probability of lipid-abnormal dry eye increased with the decrease of temperature when the temperature was below 10℃; within the range of 10℃～15℃, the probability of lipid-abnormal dry eye tended to stabilize. When the temperature exceeded 15℃, the probability of lipid-abnormal dry eye increased with the increase of temperature. Humidity was negatively correlated with the onset of lipid-abnormal dry eye. As humidity increased, the probability of lipid-abnormal dry eye decreased.CONCLUSIONS: The risk of lipid-abnormal dry eye in Yili is higher than that in Nanjing throughout the four seasons. Humidity, temperature, air quality and other environmental and meteorological factors can all affect the incidence of lipid-abnormal dry eye.

Research on the driving mechanism of residents′ willingness to participate in tiered medical care based on harmonious management theory / 中华医院管理杂志

Objective:To construct and validate a theoretical model of residents′ willingness to participate in tiered medical care based on harmonious management theory, providing reference for promoting the tiered medical care system and aiding governmental decision-making.Methods:Based on the harmonious management theory and literature review, a model capturing residents′ propensity to engage in tiered medical care was formulated. Using convenience sampling method, a questionnaire survey was conducted on 2 067 residents from 24 communities in Zhejiang province from April to May 2022. Descriptive statistical analysis was conducted on the survey results, and multilevel linear regression and structural equation modeling were used to analyze the driving mechanism of residents′ willingness to participate in tiered medical care.Results:The willingness rate of residents to participate in tiered medical care was 69.7%, which was at an average level. Regression insights highlighted the positive influence of policy support perception ( β=0.170, P<0.01), awareness of management mechanisms ( β=0.093, P<0.01), cognitive attitudes ( β=0.102, P<0.01), and trust levels ( β=0.244, P<0.01) on residents′ participation willingness. In contrast, resource allocation perceptions lacked a significant effect ( β=0.065, P>0.05). The structural equation model revealed that cognitive attitudes played a mediating role in the " policy system perception → participation willingness" and " management mechanism perception → participation willingness" pathways, with effect sizes of 0.030 and 0.039, respectively. Trust levels also mediated these paths, with effect sizes of 0.039 and 0.045, and entirely mediated the " resource allocation perception → participation willingness" path, registering an effect size of 0.053. Conclusions:The harmonious management theory can be used to explain the formation mechanism of residents′ willingness to participate in tiered medical care. The government and medical institutions urgently need to further improve residents′ awareness of tiered medical care, focus on enhancing residents′ trust, and further improve policies and management measures such as financial investment, medical insurance reimbursement, and referral systems.

Research on the harmonious driving mechanism of doctors′ collaboration willingness and behavior in the tiered diagnosis and treatment system / 中华医院管理杂志

Objective:To explore the driving mechanisms of doctors′ collaborative willingness and behavior in the tiered diagnosis and treatment system, in order to provide reference for promoting the construction of the tiered diagnosis and treatment system.Methods:Based on the harmonious management theory, a theoretical framework for the driving mechanisms of doctors′ collaborative behavior in the tiered diagnosis and treatment system was developed. Through random sampling, a questionnaire survey was conducted among doctors from 40 medical institutions in five prefecture-level cities in Zhejiang province between April and May 2022. The t-test, variance analysis, and non-parametric tests were employed to analyze the differences in collaborative willingness and behavior among doctors based on various demographic characteristics. The structural equation model and stratified linear regression were used to assess the impact of collaborative factors (professional environment and work expectations) and harmonious factors (perception of policy support and perception of management mechanism) on doctors′ collaboration willingness and behavior. Results:A total of 1 959 doctors participated in the survey. Doctors′ collaborative behavior scored 2.13±1.12, indicating a slightly below-average level, whereas their willingness to collaborate scored 3.88±0.79, falling between neutral and somewhat willing. Significant differences in collaborative behavior scores were observed based on the medical institution′s ranking, age, years of experience, monthly average income, and professional titles ( P<0.05). Both collaborative and harmonious factors directly influenced the doctors′ willingness to collaborate, with standardized path coefficients of 0.428 and 0.139, respectively. Similarly, these factors directly impacted their collaborative behavior, with standardized path coefficients of 0.104 and 0.366. The perceptions of policy support and management mechanisms demonstrated a significant positive moderating effect on the relationship between doctors′ collaborative willingness and behavior, with effect values of 0.047 and 0.043 respectively ( P<0.05). Conclusions:The collaborative and harmonious elements serve as positive drivers for collaboration among doctors in the tiered diagnosis and treatment system at both the cognitive and behavioral levels. Enhancing and optimizing policy support and management mechanisms can facilitate the transition from intention to actual collaborative actions among doctors from different levels of medical institutions.

Theoretical exploration and research pathways of the harmonious symbiotic mechanism in the tiered medical treatment system / 中华医院管理杂志

The tiered medical treatment system stands as a cornerstone in the deepening reforms of China′s medical and health sectors, playing a crucial role in building a healthy China. Exploring the harmonious coexistence mechanism of multiple entities on the supply and demand sides of the tiered diagnosis and treatment system, and promoting the formation of a scientific and reasonable tiered diagnosis and treatment order, has become an urgent public proposition that needs to be answered and has significant social impact. Addressing the challenges in China′s tiered medical treatment system, particularly its need for a more systematic, comprehensive, and collaborative approach, this study is informed by a thorough literature review. Based on the harmonious management and symbiosis theories, the authors proposed a theoretical concept and future research path for the formation of a harmonious symbiotic mechanism in the tiered diagnosis and treatment system, in order to pave the way for exploring the harmonious symbiotic mechanism in the tiered diagnosis and treatment system.

Gait Analysis of Hip Disarticulation Amputees Based on Kinematic Parameters and Plantar Pressure Measurement / 医用生物力学

Objective To analyze the gait characteristics of hip disarticulation amputees, and analyze the reasons for their differences from normal gait, so as to assist clinical diagnosis and evaluation. Methods Through the portable human motion capture device and plantar pressure analysis system, the kinematics and plantar pressure information of 5 hip amputees were collected and compared with 15 healthy volunteers in control group. Gait differences between the amputees and normal subjects and between the affected leg side and the healthy leg side of the amputees were compared. Results The proportion of double-support period for hip amuptees was higher than that of normal gait. Step length, step time, loading response period, mid support period, pre-swing period, proportion of the swing period for the affected leg side and healthy leg side of hip amputees showed significant differences with those of control group. The relative symmetry index of the gait for hip amputees was 0.60±0.05. Compared with the affected leg side, the support period of the healthy leg side was extended, the step length was shortened, the ground reaction force was greater than that of the affected leg side, and the center of pressure trajectory shifted to the affected leg side. Conclusions The gait of hip amputees is significantly different from that of normal people. Hip amputees have weak walking ability, poor gait symmetry, and they lack of continuity in the body’s center of gravity. The results provide experimental basis and theoretical analysis for the design of mechanical structure and control system of novel hip prosthesis.

Comparison of effects of conservative treatment and percutaneous kyphoplasty on paravertebral muscle degeneration in patients with osteoporotic compression vertebral fractures / 中华骨科杂志

Objective:To compare effects of conservative treatment and percutaneous kyphoplasty on paravertebral muscle degeneration in patients with osteoporotic compression vertebral fractures.Methods:A retrospective case control analysis was conducted on 286 cases of osteoporotic compression vertebral fractures from January 2017 to December 2019. There were 54 males and 232 females, with a mean age of 67.7 (range, 52-90 years). According to the treatment, the patients were divided in to conservative treatment group (134 patients) and percutaneous kyphoplasty treatment group (152 patients). The pre-operation and post-operation of paravertebral muscle cross-sectional area (CSA) and fatty infiltration (FI% ) , bed rest time, visual analogue scale (VAS), Oswestry disability index (ODI), the sagittal view Cobb angle, and the anterior column height of fractured vertebra were compared between these two groups.Results:The two groups had no significant difference in CSA and FI% of paravertebral muscle in each plane of the intervertebral discs of the L 3-4、L 4-5 and L 5S 1. The CSA of multifidus in each plane of the intervertebral discs three months after operation were 6.56±1.26 cm 2, 6.87±1.31 cm 2, and 7.14±1.29 cm 2; the CSA of erector were 12.39±2.16 cm 2, 14.72±2.67 cm 2, and 16.45±3.09 cm 2; the CSA of psoas major were 7.05±1.52 cm 2, 8.12±1.75 cm 2, and 8.68±1.66 cm 2, which all were larger than those in conservative treatment group and showed significant difference between two groups ( P<0.05). However, the two groups had no significant difference in FI% of paravertebral muscle three months after operation. The CSA of multifidus in each plane of the intervertebral discs one year after operation were 6.43±1.23 cm 2, 6.62±1.42 cm 2, and 7.06±1.32 cm 2; the CSA of erector were 12.02±2.08 cm 2, 14.53±2.76 cm 2, and 16.39±2.84 cm 2; the CSA of psoas major were 6.98±1.47 cm 2, 8.01±1.59 cm 2, and 8.37±1.72 cm 2, which all were larger than those in conservative treatment group and showed significant difference between two groups ( P<0.05). The FI% of multifidus in each plane of the intervertebral discs one year after operation were 31.40%±5.84% , 32.54%±6.64% , and 33.26%±7.16% ; the FI% of erector were 22.64%±3.47% , 23.08%±3.72% , and 23.84%±3.99% ; the FI% of psoas major were 9.23%±2.20% , 9.72%±2.54% , and 10.98%±2.43% , which all were less than those in conservative treatment group and showed significant difference between two groups ( P<0.05). Two groups had significant difference in bed rest time as (9.21±2.52) d vs. (40.32±9.79) d ( t=37.79, P<0.001). The VAS, ODI score at the time of the first day after treatment and the last follow-up of the surgical treatment group were all significantly lower than those of conservative treatment group ( P<0.05). The operation could effectively improve the kyphosis deformity and reduce the loss the anterior column height of fractured vertebra compared with conservative treatment ( P<0.05). Conclusion:There exists paravertebral muscle degeneration of varying degrees during the course of the osteoporotic compression vertebral fractures. Compared to conservative treatment, percutaneous kyphoplasty treatment can not only significantly relieve pain in the short term, improve quality of patient's life, but also significantly delay the degeneration of paravertebral muscle.

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% .

Comparison of minimally invasive reduction through a bone tunnel combined with Jail screwing and posterolateral locking plating for simple posterolateral tibial plateau fractures / 中华创伤骨科杂志

Objective:To compare the clinical effects of minimally invasive reduction through a bone tunnel combined with Jail screwing and those of posterolateral locking plating in the treatment of simple posterolateral tibial plateau fractures.Methods:A retrospective analysis was conducted of the data of 48 patients who had been operatively treated and completely followed up at Department of Orthopedics, Suqian Hospital of Nanjing Drum Tower Hospital Group for simple posterolateral tibial plateau fractures from October 2016 to October 2020. There were 26 males and 22 females, aged from 35 to 68 years. They were divided into a minimally invasive group (25 cases subjected to minimally invasive reduction through a bone tunnel combined with Jail screwing) and an incision group (23 cases subjected to posterolateral locking plating) according to their surgical methods. The operation time, incision length, intraoperative blood loss, fracture healing time, cumulative fluoroscopy time, hospital stay and posterior inclination angles of the tibial plateau and Hospital for Special Surgery (HSS) knee function scores at 1, 3, 6, 9, and 12 months after operation were compared between the 2 groups. Complications in the 2 groups of patients were recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The 48 patients were followed up for 12 to 36 months (average 16.5 months). The minimally invasive group was significantly better than the incision group in operation time [(42.6±9.1) min versus (65.7±11.5) min], incision length [(4.0±0.4) cm versus (15.0±1.5) cm], intraoperative blood loss[(22.6±5.8) mL versus (31.5±8.8) mL], hospital stay [(7.6±1.4) d versus (11.1±2.4) d], and HSS score one month after operation [(84.8±1.9) points versus (72.9±4.1) points], but the cumulative fluoroscopy time in the incision group [(4.1±1.4) s]was significantly less than that in the minimally invasive group [(22.3±4.2) s] ( P<0.05). There were no significant differences in fracture healing time, HSS scores at 3, 6, 9, or 12 months after operation, or posterior inclination angle of the tibial plateau between the 2 groups ( P>0.05). There were no such complications as wound infection, vascular injury, internal fixation failure, nonunion or malunion of fractures in either of the 2 groups. Two cases in the incision group presented with symptoms of common peroneal nerve injury but recovered 3 months after operation. Conclusions:Although both minimally invasive reduction through a bone tunnel combined with Jail screwing and posterolateral locking plating can achieve satisfactory outcomes in the treatment of simple posterolateral tibial plateau fractures, the minimally invasive technique is preferable because it shows the advantages of a smaller incision, less bleeding, shorter operation time, a lower operation risk, quicker postoperative recovery and shorter hospital stay.

Exploration of multi-faceted model in plant biology teaching / 生物工程学报

Plant biology is a basic course for students majoring in biological science. Under the guidance of developmental biology, we have constructed a comprehensive, systematic and dynamic new curriculum system for plant biology. There are still some problems existing in the current curriculum teaching mode, e.g. the students do not listen carefully to the lecture due to single classroom teaching mode, the mismatch between theoretical and experimental courses in terms of content and timing, the incomplete understanding on plants and the difficulty of integrating learning and practicing due to insufficient field practices. In view of these problems, a series of new teaching strategies for bioscience major of Harbin Institute of Technology were proposed and implemented. The combination of lectures and high quality massive open online courses (MOOC) were used for theoretical study, to which the flipped classroom was added. In addition, the theoretical study and the experiment work were combined. Moreover, the plant cognitive practices were carried out in the campus and the botanical garden in early spring, late spring and summer, respectively. Satisfactory results were achieved after two rounds of teaching practice, which fulfilled the education requirements and laid foundations for students to continue follow-up basic and professional courses.

Qiling Tongluo Prescription Improves Renal Injury in Rats with Idiopathic Membranous Nephropathy by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Qiling Tongluo prescription against idiopathic membranous nephropathy （IMN） in rats based on Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-κB （TLR4/MyD88/NF-κB） signaling pathway. MethodSixty male SD rats were randomly divided into the normal group， model group， benazepril hydrochloride （10 mg·kg-1） group， and low-，medium-， and high-dose （6.48， 12.95， and 25.9 g·kg-1） Qiling Tongluo prescription groups. The IMN rat model was established by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After the model was successfully prepared， the rats were gavaged with the corresponding drugs， once a day， for four consecutive weeks. After the treatment， the pathological changes in rat kidneys were observed by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-silver metheramine （PASM） staining， followed by the detection of 24 h urinary total protein （24 h UTP）， plasma albumin （ALB）， total serum protein （TP）， serum creatinine （SCr）， urea nitrogen （BUN）， and uric acid （UA） levels. The levels of interleukin-1β （IL-1β） and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of TLR4， MyD88， and NF-κB in the kidney tissue were assayed by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry （IHC）， and Western blot. ResultCompared with the normal group， the model group exhibited elevated 24 h UTP and serum SCr， BUN， UA， IL-1β， and IL-6 （P<0.05， P<0.01）， decreased ALB and TP （P<0.01）， up-regulated TLR4， MyD88， and NF-κB p65 mRNA and protein expression in kidney tissue （P<0.05， P<0.01）， obvious inflammation， disordered glomerular structure with enlarged volume， irregularly thickened basement membrane， inflammatory cell infiltration in the renal interstitium， reduced renal tubular epithelial cells due to shedding and apoptosis， and some vacuolar degeneration. Compared with the model group， benazepril hydrochloride and Qiling Tongluo prescription at the high dose remarkably lowered the serum SCr and UA （P<0.05） and increased ALB and TP （P<0.05）. Benazepril hydrochloride and Qiling Tongluo prescription at the low， medium， and high doses down-regulated the 24 h UTP， serum IL-1β and IL-6 levels， and renal TLR4， MyD88， and NF-κB p65 mRNA and protein expression to varying degrees （P<0.05， P<0.01）， alleviated IMN inflammatory reaction， glomerular swelling， and volume increase， slightly dilated glomerular capillaries， proliferated mesangial matrix， and relieved pathological and morphological damages in rat kidney， with inflammatory cell infiltration occasionally observed. ConclusionQiling Tongluo prescription may reduce the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to inhibit the inflammatory response in IMN rats， ameliorate proteinuria and kidney damage， and protect kidney function.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron / 中国天然药物

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 μmol·L-1.

Research progress and trend analysis of medical insurance governance in China based on CNKI database / 中华医院管理杂志

Objective:To analyze the research hot topics, knowledge evolution context, potential frontier trends and future breakthrough directions in the field of medical security governance in China.Methods:Subject term retrieval was used to study the literatures related to medical security governance published by CNKI from January 2009 to December 2021. CiteSpace V software was used to draw the keyword co-occurrence network, time zone map, cluster map, and emergent word graph, and to visually analyze and predict the frontier hotspots and evolution trends in the field of medical security governance.Results:A total of 793 literatures were retrieved. The cooperation network among medical security governance research institutions in China needed to be strengthened; the mainstream of research focused on basic research on medical insurance system design, research on medical security governance paths and methods, and empirical research combined with the era background or policy hotspots.Conclusions:There are some problems in the current rerearch on medical security governance, such as imperfect theoretical construction, research content to be expanded, insufficient communication and cooperation, etc. Future research hotspots tend to be innovation of the goal, structure and path of medical security governance, application of big data in the field of medical security governance, and research on crisis response and challenges of medical security governance under public health emergencies. Future research should strengthen multi-cooperation to jointly tackle key problems, pay attention to the cross-integration of disciplines, develop localized medical security governance innovation systems and mechanisms, and enrich problem-oriented empirical research.

Research progress on role of Hippo pathway in bone repair / 中华骨科杂志

The initiation and operation of the tissue repair program between the broken ends after fracture is very important for fracture healing, which goes through three intertwined and gradual evolution stages: hematoma inflammatory organization stage, primitive callus formation stage and callus remodeling stage. It is completed by a variety of tissues, cells and cytokines in the bone marrow cavity. In the study of the mechanism of fracture healing, it is found that there are many signal pathways and molecules regulating bone repair, including bone formation, bone remodeling and neovascularization. At the cellular level, it regulates osteoblasts, chondrocytes, osteoclasts and endothelial cells. Hippo signaling pathway is a signal pathway that maintains the size of organs and the balance between cell proliferation and apoptosis, and also plays an important role in maintaining bone homeostasis and bone metabolism. In the process of regulating bone development and repair, it regulates the physiological activities of cells in microenvironment through protein kinase cascade reaction and transcriptional coactivator. The upstream and downstream effectors of Hippo signal pathway directly or indirectly regulate the proliferation, differentiation and apoptosis of bone metabolic cells, and the interaction with Wnt signal pathway, Notch signal pathway and other important pathways related to bone repair show that Hippo signal pathway plays an important role in the regulation of fracture healing and may become a new target to promote fracture healing. This article reviews the regulatory mechanism of Hippo signaling pathway and its regulatory role in the process of fracture healing, and looks forward to the research prospect of promoting bone healing by using it as a target.

Elimination of hepatitis B virus infection in children: experience and challenge in China / 中华医学杂志(英文版)

Chronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to 2 × 105 U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.