[Clinical Analysis of Mitoxantrone Liposome in the Treatment of Children with High-Risk Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia (AML). METHODS: The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group, and the children with high-risk AML who received idarubicin regimen were enrolled as controls, and their clinical data were analyzed. Time to bone marrow recovery, the complete remission rate of bone marrow cytology, the clearance rate of minimal residual disease, and treatment-related adverse reactions were compared between the two groups. RESULTS: The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day), granulocytes(18 vs 24 day), platelets(17 vs 24 day), and hemoglobin(20 vs 26 day) compared with those treated with idarubicin, there were statistical differences (P <0.05). The effective rate and MRD turning negative rate in the observation group were 90.9% and 72.7%, respectively, while those in the control group were 94.1% and 76.4%, with no statistical difference (P >0.05). The overall response rate of the two groups of patients was similar. CONCLUSION: The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML, but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

[Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases)].

OBJECTIVE: To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL). METHODS: The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed. RESULTS: Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ï¼»(3.92-470)×109/Lï¼½ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%. CONCLUSION: B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Transgenerational hormesis and sublethal effects of five key insecticides for controlling Spodoptera frugiperda on its endoparasitoid Cotesia marginiventris.

BACKGROUND: The endoparasitoid Cotesia marginiventris (Cresson) is a promising biological control agent of the fall armyworm (FAW) Spodoptera frugiperda (Smith). Because the application of insecticides is one of the prime choices in pest management, we evaluated the sublethal and transgenerational effects of the five key insecticides-chlorantraniliprole, emamectin benzoate, spinetoram, Bacillus thuringiensis (Bt), and Mamestra brassicae nucleopolyhedrovirus (MbNPV)-on the parasitoid. RESULTS: Exposure to five insecticides at a concentration causing 10% mortality (LC10 ) caused hormetic effects in the parent generation (F0 ) by increasing the parasitism and reducing the immature duration. Interestingly, the hormetic response was also observed in the offspring generation indirectly exposed to the insecticides. Furthermore, insecticides increased the parasitism rate by 6.32-14.73% in the F1 generation, which was similar to that of the F0 generation (3.96-11.81%) compared with the control. No significant adverse effect was observed on the number of emerged parasitoids of the F1 and F2 generations. However, insecticides had a detrimental impact on body size and fecundity in the F1 and F2 generations, which showed a small body size with shorter hind tibiae and a significant reduction in the female ratio compared with the control; the exception was that chlorantraniliprole significantly improved the female ratio in the F2 generation. CONCLUSIONS: Five insecticides at LC10 induced transgenerational hormetic and sublethal effects on C. marginiventris. Our results provide a scientific basis for a better understanding of the long-term impacts of insecticides at sublethal doses on parasitoids, facilitating the development of improved integrated pest management programs for FAW control. © 2023 Society of Chemical Industry.

Biomechanical evaluation of a novel atlas polyaxial transverse connecting screw system, an in vitro human cadaveric study.

PURPOSE: To introduce a novel transverse connecting screw system, and to evaluate the biomechanical stability of the novel screw system using human cadaveric specimens. METHODS: Six fresh-frozen cadaveric upper cervical spines were used in our study. Every specimen was tested under 5 conditions: intact group; unstable group; C1 to C2 screw rod system group; C1 to C2 + crosslink system group; atlas polyaxial transverse connecting screw (APTCS) system. RESULTS: Compared with the intact state, C1 to C2 screw rod system, C1 to C2 + CL system and APTCS showed statistically decrease range of motion in all directions except for the unstable group under posterior extension direction (P < .05). APTCS group has the least range of motion in all directions (P < .001). CONCLUSION: The APTCS system was able to restore stability to the atlantoaxial joint. APTCS system has the advantages of easy installation, convenient bone grafting, and strong biomechanical strength.

Three-dimensional ultrasound-based radiomics nomogram for the prediction of extrathyroidal extension features in papillary thyroid cancer.

Purpose: To develop and validate a three-dimensional ultrasound (3D US) radiomics nomogram for the preoperative prediction of extrathyroidal extension (ETE) in papillary thyroid cancer (PTC). Methods: This retrospective study included 168 patients with surgically proven PTC (non-ETE, n = 90; ETE, n = 78) who were divided into training (n = 117) and validation (n = 51) cohorts by a random stratified sampling strategy. The regions of interest (ROIs) were obtained manually from 3D US images. A larger number of radiomic features were automatically extracted. Finally, a nomogram was built, incorporating the radiomics scores and selected clinical predictors. Receiver operating characteristic (ROC) curves were performed to validate the capability of the nomogram on both the training and validation sets. The nomogram models were compared with conventional US models. The DeLong test was adopted to compare different ROC curves. Results: The area under the receiver operating characteristic curve (AUC) of the radiologist was 0.67 [95% confidence interval (CI), 0.580-0.757] in the training cohort and 0.62 (95% CI, 0.467-0.746) in the validation cohort. Sixteen features from 3D US images were used to build the radiomics signature. The radiomics nomogram, which incorporated the radiomics signature, tumor location, and tumor size showed good calibration and discrimination in the training cohort (AUC, 0.810; 95% CI, 0.727-0.876) and the validation cohort (AUC, 0.798; 95% CI, 0.662-0.897). The result suggested that the diagnostic efficiency of the 3D US-based radiomics nomogram was better than that of the radiologist and it had a favorable discriminate performance with a higher AUC (DeLong test: p < 0.05). Conclusions: The 3D US-based radiomics signature nomogram, a noninvasive preoperative prediction method that incorporates tumor location and tumor size, presented more advantages over radiologist-reported ETE statuses for PTC.

Advanced Messaging Intervention for Medication Adherence and Clinical Outcomes Among Patients With Cancer: Randomized Controlled Trial.

BACKGROUND: Medication adherence is crucial for improving clinical outcomes in the treatment of patients with cancer. The lack of adherence and adverse drug reactions can reduce the effectiveness of cancer therapy including the quality of life. The commonly used intervention methods for medication adherence continue to evolve, and the age of fifth-generation (5G) messaging has arrived. OBJECTIVE: In this study, we conducted a prospective, pilot randomized controlled trial to evaluate the effect of 5G messaging on medication adherence and clinical outcomes among patients with cancer in China. METHODS: The research population was patients with nonsmall cell lung cancer undergoing pemetrexed chemotherapy who require regular folic acid (FA) and vitamin B12 supplements. The intervention and control groups were assigned to 5G messaging and second-generation (2G) messaging, respectively. The patients' medication adherence and quality of life were assessed at baseline and 1-month and 3-month time points. Moreover, the chemotherapy-related hematologic or nonhematologic toxicities, as well as the serum levels of FA and vitamin B12, were measured. RESULTS: Of the 567 patients assessed for eligibility between January and May 2021, a total of 154 (27.2%) patients were included. Overall, 80 were randomized to the control group and 74 to the intervention group. The odds of adherence in the 5G messaging intervention group were significantly higher than the control group at the 1-month (62/69, 90% vs 56/74, 76%; adjusted odds ratio 2.67, 95% CI 1.02-7.71) and 3-month (50/60, 83% vs 48/64, 75%; adjusted odds ratio 2.36, 95% CI 1.00-5.23) time points. Correspondingly, the FA and vitamin B12 serum levels of patients in the 5G messaging group were higher than those of the control group. Regarding hematologic toxicities, only the incidence of leukopenia in the intervention group was lower than that in the control group (25/80, 31% in the control group vs 12/74, 16% in the intervention group; P=.04). There were no differences in nonhematologic toxicities and quality of life between the 2 groups. CONCLUSIONS: In summary, we conclude that compared with conventional 2G text-based messaging, a 5G messaging intervention can better improve medication adherence and clinical outcome among patients with cancer. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200058188; https://www.chictr.org.cn/showproj.html?proj=164489.

pH/enzyme dual sensitive Gegenqinlian pellets coated with Bletilla striata polysaccharide membranes for the treatment of ulcerative colitis.

Gegen Qinlian Decoction, derived from Zhang Zhongjing's Treatise on Typhoid Fever, has been widely used in the treatment of various common diseases, frequently-occurring diseases and difficult and complicated diseases, such as ulcerative colitis. In this study, Bletilla striata polysaccharide (BSP) was innovatively used as a film coating material to prepare Gegen Qinlian pellets with dual sensitivity of pH enzyme for the treatment of ulcerative colitis. BSP has the ability to repair the inflamed colon mucosa and can produce synergistic effects, while avoiding the adverse therapeutic effects caused by the early release of drugs from a single pH-sensitive pellets in the small intestine. The prepared pellets have a uniform particle size, good roundness, a particle size range from 0.8 mm to 1.0 mm, and a particle yield is 85.6 %. The results of in vitro release showed that ES-BSP pellets hardly released drugs in the pH range of 1.2-6.8. However, in the colon mimic fluid containing specific enzymes, the drug release was significantly accelerated, demonstrating the sensitivity of the pellets to pH enzymes. In vivo and ex vivo fluorescence imaging of small animals showed that Gegen Qinlian pellets with dual sensitivity of pH enzyme remained longer in the colon compared with pH-sensitive pellets. In vivo pharmacodynamics study showed that the Gegen Qinlian pellets with dual sensitivity of pH enzyme had a better therapeutic effect in the rat model of the ulcerative colon than the commercially available Gegenqinlian pellets in the control group.

[Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry].

OBJECTIVE: To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM). METHODS: The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed. RESULTS: Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status. CONCLUSION: Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Development and Validation of a Radiomics Model Based on 3-Dimensional Endoanal Rectal Ultrasound of Rectal Cancer for Predicting Lymph Node Metastasis.

BACKGROUND: Development of a radiomics model for predicting lymph node metastasis status in rectal cancer patients based on 3-dimensional endoanal rectal ultrasound images. METHODS: This study retrospectively included 79 patients (41 with lymph node metastasis positive and 38 with lymph node metastasis negative) diagnosed with rectal cancer in our hospital from January 2018 to February 2022. The tumor's region of interest is first delineated by radiologists, from which radiomics features are extracted. Radiomics features were then selected by independent samples t-test, correlation coefficient analysis between features, and least absolute shrinkage and regression with selection operator. Finally, a multilayer neural network model is developed using the selected radiomics features, and nested cross-validation is performed on it. These models were validated by assessing their diagnostic performance and comparing the areas under the curve and recall rate curve in the test set. RESULTS: The areas under the curve of radiologist was 0.662 and the F1 score was 0.632. Thirty-four radiomics features were significantly associated with lymph node metastasis (P < .05), and 10 features were finally selected for developing multilayer neural network models. The areas under the curve of the multilayer neural network models were 0.787, 0.761, 0.853, and the mean areas under the curve was 0.800. The F1 scores of the multilayer neural network models were 0.738, 0.740, and 0.818, and the mean F1 score was 0.771. CONCLUSIONS: Radiomics models based on 3-dimensional endoanal rectal ultrasound can be used to identify lymph node metastasis status in rectal cancer patient with good diagnostic performance.

Influence of continuous renal replacement therapy on the plasma concentration of tigecycline in patients with septic shock: A prospective observational study.

Objective: The influence of continuous renal replacement therapy (CRRT) on the steady-state plasma concentration of high-dose tigecycline was investigated in septic shock patients to provide references for drug dosing. Methods: In this prospective observational study, 17 septic shock patients presenting with severe infections needing a broad-spectrum antibiotic therapy with high-dose tigecycline (100 mg per 12 h) in the intensive care unit were included and divided into CRRT group (n = 6) or non-CRRT group (n = 11). The blood samples were collected and plasma drug concentration was determined by SHIMADZU LC-20A and SHIMADZU LCMS 8040. The steady-state plasma concentration was compared between groups using unpaired t-test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model. Results: Peak concentration (Cmax) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 ± 143.84 vs. 406.29 ± 108.00 ng/mL, p-value: 0.129). Trough concentration (Cmin) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 ± 41.91 vs. 174.79 ± 33.15 ng/mL, p-value: 0.000, adjusted p-value: 0.000). In safety, Cmin was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, Cmin of all patients in CRRT group was lower than 474.8 ng/mL. Conclusion: The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only Cmin shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2000037475.

[Clinical Analysis of Salvage Treatment of Glucocorticoid Resistant Graft-Versus-Host Disease with Vedolizumab in Children].

OBJECTIVE: To investigate the efficacy and safety of VDZ (Vedolizumab) in the salvage treatment of glucocorticoid resistance to gastrointestinal graft-versus-host disease (GR-GI GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 5 patients with refractory GI GVHD who received allo-HSCT in Wuhan Children's Hospital from December 2020 to December 2021 were retrospectively analyzed with VDZ salvage therapy. RESULTS: Among the 5 children with refractory GI GVHD, there were 1 male and 4 female, including 2 cases of extremely severe aplastic anemia, 1 case of acute myeloid leukemia (M2, high-risk), 1 case of fanconi anemia and 1 case of myelodysplastic syndrome. The median age of transplant recipients was 54.4 (12-164) months. The median treatment time from transplantation to VDZ was 1.4 (0.6-6.8) months. On average, 3.5 (2-5) doses of VDZ were received. After receiving treatment, 2 patients achieved a complete response (CR), 2 patients achieved a very good partial response (VGPR), 1 patient was non-responsive (NR) after a short-term partial response (PR). Compared with that before VDZ treatment, the amount of diarrhea, stool color, blood and traits of the children after medication were effectively improved. The median follow-up time was 9.3 (7.23-12.83) months. No disseminated or severe bacterial/fungal infections occurred during VDZ treatment and follow-up, and 2 children died of leukemia recurrence and pulmonary bronchiolitis obliterans. CONCLUSION: VDZ salvage treatment of refractory GI GVHD in children has obvious short-term efficacy and good safety.

Stentless at ostium: a novel approach for treating ostial left anterior descending or left circumflex coronary artery lesions with drug-coated balloons.

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

[Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine].

OBJECTIVE: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. METHODS: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. RESULTS: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. CONCLUSION: 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

[Clinical Study of Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Children].

OBJECTIVE: To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors. METHODS: The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method. RESULTS: Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543). CONCLUSION: Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.

Robust Optimal Control Design for Performance Enhancement of PWM Voltage Source Inverter.

PWM (pulse-width modulation) voltage source inverters are used in a wide range of AC power systems where the output voltage must be controlled to follow a sinusoidal reference waveform. In order to achieve precision and fast-tracking control, restrictive sliding mode control (RSMC) provides a fast system state convergence time. However, the RSMC still suffers from the chattering problem, which leads to high harmonic distortion and slow response of the inverter output state. Furthermore, the load of the inverter may be severe load changing and the control parameters become difficult to adjust, worsening the adaptability to achieve the desired control of the inverter output. In this paper, a robust optimal control design comprised of an enhanced restrictive sliding mode control (ERSMC) and density particle swarm optimization (DPSO) algorithm is proposed, and then applied to PWM voltage source inverters. The ERSMC not only has finite time convergence but also provides chatter elimination. The DPSO is highly adaptable for acquiring the control parameters of the ERSMC and finding the best solution in the global domain. The proposed controller is realized for the actual PWM voltage source inverter controlled by a TI DSP-based development platform, so that the inverter output voltage has fast dynamic response and satisfactory steady-state behavior despite high load changing and non-linear disturbances.

Reliability and repeatability of a modified thoracolumbar spine injury classification scoring system.

Purpose: On the basis of the Thoracolumbar Injury Classification and Severity Score (TLICS), an modified TLICS classification system was presented, its reliability and repeatability were assessed, and the factors influencing classification consistency were examined. Methods: Five spinal surgeons were chosen at random. The clinical data of 120 patients with thoracolumbar fractures admitted to the Department of Spine Surgery, Ningbo Sixth Hospital from December 2019 to June 2021 were categorized using the modified TLICS system. After 6 weeks, disrupt the order of data again. Using unweighted Cohen's kappa coefficients, the consistency of the modified TLICS system was assessed in five aspects: neurofunctional status, disc injury status, fracture morphology, posterior ligament complex (PLC) integrity, and treatment plan. Results: In terms of reliability, the average kappa values for the subclasses of the modified TLICS system (neurofunctional status and disc injury status) were 0.920 and 0.815, respectively, reaching the category of complete confidence. Fracture morphology and treatment plan had average kappa values of 0.670 and 0.660, respectively, which were basically reliable. The average kappa value of PLC integrity was 0.453, which belonged to the category of moderate confidence. The average kappa coefficients of each subcategory (neurological status, disc injury status) had excellent consistency, and the kappa values were 0.936 and 0.879, respectively, which belonged to the completely credible category. The kappa values of fracture morphology and treatment plan repeatability were 0.772 and 0.749, respectively, reaching the basic credibility category. PLC integrity repeatability kappa value is low, 0.561, to moderate credibility category. Conclusion: The modified TLICS system is intuitive and straightforward to understand. The examination of thoracolumbar fracture injuries is more exhaustive and precise, with excellent reliability and repeatability. The examination of neurological status and disc injury status is quite reliable and consistent. The consistency of fracture morphology is slightly poor, which is basically credible; the PLC integrity consistency is poor, reaching a reliability level of moderate, which may be associated with the subjectivity of clinical evaluation of PLC.

Lead Exposure in Developmental Ages Promotes Aß Accumulation by Disturbing Aß Transportation in Blood-Cerebrospinal Fluid Barrier/Blood-Brain Barriers and Impairing Aß Clearance in the Liver.

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aß) generation in the brain. However, the potential effect of lead exposure on Aß transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aß clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1ß in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aß transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aß1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aß endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aß deposition in BCSFB and BBB and impairs Aß clearance in the liver, which would ultimately disturb Aß transportation via choroid plexus/brain microvessels and facilitate Aß deposition in the brain.

Chemical approach to generating long-term self-renewing pMN progenitors from human embryonic stem cells.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders.

Comprehensive analysis of N6 -methyladenosine-related long non-coding RNAs for prognosis prediction in liver hepatocellular carcinoma.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a lethal cancer. This study aimed to identify the N6 -methyladenosine (m6 A)-targeted long non-coding RNA (lncRNA) related to LIHC prognosis and to develop an m6 A-targeted lncRNA model for prognosis prediction in LIHC. METHODS: The expression matrix of mRNA and lncRNA was obtained, and differentially expressed (DE) mRNAs and lncRNAs between tumor and normal samples were identified. Univariate Cox and pathway enrichment analyses were performed on the m6 A-targeted lncRNAs and the LIHC prognosis-related m6 A-targeted lncRNAs. Prognostic analysis, immune infiltration, and gene DE analyses were performed on LIHC subgroups, which were obtained from unsupervised clustering analysis. Additionally, a multi-factor Cox analysis was used to construct a prognostic risk model based on the lncRNAs from the LASSO Cox model. Univariate and multivariate Cox analyses were used to assess prognostic independence. RESULTS: A total of 5031 significant DEmRNAs and 292 significant DElncRNAs were screened, and 72 LIHC-specific m6 A-targeted binding lncRNAs were screened. Moreover, a total of 29 LIHC prognosis-related m6 A-targeted lncRNAs were obtained and enriched in cytoskeletal, spliceosome, and cell cycle pathways. An 11-m6 A-lncRNA prognostic model was constructed and verified; the top 10 lncRNAs included LINC00152, RP6-65G23.3, RP11-620J15.3, RP11-290F5.1, RP11-147L13.13, RP11-923I11.6, AC092171.4, KB-1460A1.5, LINC00339, and RP11-119D9.1. Additionally, the two LIHC subgroups, Cluster 1 and Cluster 2, showed significant differences in the immune microenvironment, m6 A enzyme genes, and prognosis of LIHC. CONCLUSION: The m6 A-lncRNA prognostic model accurately and effectively predicted the prognostic survival of LIHC. Immune cells, immune checkpoints (ICs), and m6 A enzyme genes could act as novel therapeutic targets for LIHC.