Ilizarov bone transport assisted by a 3D printed patient-specific guide plate for treatment of tibial bone defects / 中华创伤骨科杂志

Objective:To evaluate the efficacy of 3D printed patients-specific guide plates in assisting Ilizarov bone transport in the treatment of tibial bone defects.Methods:A retrospective study was conducted to analyze the clinical data of 24 patients with tibial bone defects who had been admitted to Institute of Trauma Orthopedics, The 80th Army Group Hospital of PLA from January 2018 to March 2022. There were 9 males and 15 females with an age of (49.8±6.5) years, and 4 upper tibial defects, 5 middle tibial defects, and 15 lower tibial defects. According to the methods of repairing bone defects, the patients were divided into 2 groups: a 3D printing group of 10 cases where a 3D printed patient-specific guide plate was used to assist Ilizarov bone transport in the treatment of tibial bone defects, and a traditional group of 14 cases where Ilizarov bone transport was performed in a traditional manner. The 2 groups were compared in terms of operation time, frequency of intraoperative fluoroscopy, axial angulation of the tibia at postoperation and the last follow-up, external fixation time (EFT) and external fixation index (EFI). At the last follow-up, healing of bone defects was evaluated according to the criteria of The Association for the Study and Application of the Method of Ilizarov (ASAMI), functional outcomes were evaluated according to the Paley criteria, and needle infection was recorded according to the Paley classification for complications.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (11.3±2.0) months on average after operation. The 3D printing group had significantly shorter operation time [(19.9±2.6) min] and significantly lower frequency of intraoperative fluoroscopy [(3.0±0.8) times] than the traditional group [(38.1±2.2) min and (8.9±1.3) times] (P<0.05), and had significantly better axial angulation of the tibia at postoperation and the last follow-up than the traditional group ( P<0.05). There was no significant difference in EFT or EFI between the 2 groups ( P>0.05), and the last follow-up revealed no significant difference either in bone healing, functional outcomes, or needle infection between the 2 groups ( P>0.05). Conclusion:In the treatment of tibial bone defects, compared with conventional Ilizarov bone transport, the Ilizarov bone transport assisted by a 3D printed patient-specific guide plate demonstrates advantages of shorter operation time, lower intraoperative fluoroscopy, and higher reduction accuracy.

Effectiveness and Safety of Apatinib Plus Programmed Cell Death Protein 1 Blockades for Patients with Treatment-refractory Metastatic Colorectal Cancer:A Retrospective Exploratory Study

This study aimed to investigate the efficacy and safety of apatinib plus programmed cell death protein 1 (PD-1) blockades for patients with metastatic colorectal cancer (CRC) who were refractory to the standard regimens. In this retrospective study, patients with metastatic CRC who received apatinib plus PD-1 blockades in clinical practice were included. The initial dosage of apatinib was 250 mg or 500 mg, and PD-1 blockades were comprised of camrelizumab, sintilimab and pembrolizumab. Efficacy and safety data were collected through the hospital’s electronic medical record system. From October 2018 to March 2022, a total of 43 patients with metastatic CRC were evaluated for efficacy and safety. The results showed an objective response rate of 25.6% (95% CI, 13.5%-41.2%) and a disease control rate of 72.1% (95% CI, 56.3%-84.7%). The median progression-free survival (PFS) of the cohort was 5.8 months (95% CI, 3.81-7.79), and the median overall survival (OS) was 10.3 months (95% CI, 5.75-14.85). The most common adverse reactions were fatigue (76.7%), hypertension (72.1%), diarrhea (62.8%), and hand-foot syndrome (51.2%).Multivariate Cox regression analysis revealed that Eastern Cooperative Oncology Group (ECOG) performance status and location of CRC (left or right-side) were independent factors to predict PFS of patients with metastatic CRC treated with the combination regimen. Consequently, the combination of apatinib and PD-1 blockades demonstrated potential efficacy and acceptable safety for patients with treatment-refractory metastatic CRC. This conclusion should be confirmed in prospective clinical trials subsequently.

Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging / 中华放射肿瘤学杂志

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Secondary metabolites of the endophytic fungus Aspergillus sp.Dq-25 from barnacle / 中国药科大学学报

@#The chemical constituents of solid rice culture of the endophytic fungus Aspergillus sp.Dq-25 from barnacle were isolated and purified by silica gel, Sephadex LH-20, C18 reversed silica gel column chromatography and recrystallization.Their structures were identified by the physical and chemical properties, and by various spectroscopic methods.Six compounds were isolated and identified as: demethyldihydropenicillic acid (1), dihydropenicillic acid (2), penicillic acid (3), fortisterol (4), 22E, 24R-3P, 5a-dihydroxyerogosta-7, 22-diene-6-one (5), and (22E, 24R)-ergosterol-7, 22-diene-3β, 5α, 9α-triol-6-one (6).Compound 1 was a new butyrolactone.MTT method was used to analyze cytotoxicity, and the result showed that compound 3 exhibited inhibitory activity on five cell lines, including K562, HeLa, SGC-7901, A542 and BEL-7402, with IC50 values of 38.0 ~ 105.0 μmol/L.

Application value of donor liver autologous portal venous blood rinse in orthotopic liver trans-plantation / 中华消化外科杂志

Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.

Clinical characteristics and prognosis analysis of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.

Clinical characteristics and prognosis analysis of children with acute lymphoblastic leukemia and TP53 mutation / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and efficacy of children with acute lymphoblastic leukemia (ALL) and TP53 mutation, and to explore the relationship between TP53 mutation and the prognosis of children with ALL.Methods:The clinical data of 141 children with newly diagnosed ALL from November 2016 to December 2019 in Fujian Medical University Union Hospital were collected, and the whole-exome gene assay was performed in bone marrow samples of the children by using next-generation sequencing technology. The clinical characteristics of children with TP53 mutation were retrospectively analyzed, and the Kaplan-Meier method was used to compare the overall survival (OS) and event-free survival (EFS) of children with or without TP53 mutation.Results:Among the 141 children with newly diagnosed ALL, TP53 mutations were detected in 5 children (3.5%), all of which were B-precursor acute lymphoblastic leukemia (B-ALL). No TP53 mutation was detected in T-cell acute lymphoblastic leukemia (T-ALL) children, and TP53 mutation accounted for 4.0% (5/126) of B-ALL children. The types of TP53 mutation were all single nucleotide variants. Five ALL children with TP53 mutation were male, with a median age of 60 months (16- 156 months). At the time of onset, all children had anemia and elevated lactate dehydrogenase, and 4 children had subcutaneous hemorrhage and hyperuricemia. The immunophenotypes of all children were precursor B-cell type, and 4 children had myeloid antigen expression. Among 4 ALL children with TP53 mutation who received standard treatment, 2 cases relapsed, and the recurrence time was 8.9 months and 12.1 months, respectively. The expected 15-month EFS rate and OS rate of ALL children with TP53 mutation were lower than those of ALL children without TP53 mutation (37.5% vs. 97.7%, χ2 = 29.90, P < 0.001; 37.5% vs.98.3%, χ2 = 24.90, P < 0.001). Conclusions:ALL children with TP53 mutation are more commonly found in male and B-cell type, with high early recurrence rate and poor efficacy. TP53 mutation may become a necessary supplement for prognostic assessment.

Anatomical study and clinical application of cross-donor flaps pedicled with peroneal vessels / 中华显微外科杂志

Objective:Anatomical study of the cross-donor flap pedicled with the peroneal artery and the discussion of the effect of clinical application, so as to describe a new method for the repair of large-area soft tissue defects in the foot and ankle.Methods:From June 2016 to August 2019, 12 specimens of adult lower limbs were studied. The popliteal arteries were perfused with perchloroethylene-ethyl acetate-lead oxide and red perchloroethylene-ethyl acetate. The origin, number, outer diameter, course and distribution of perforating branches of the peroneal artery were anatomically observed. The source, distribution and anastomosis of the skin nutrient vessels in the posterolateral area of the calf were also studied. Relationship of the blood supply between the peroneal arteries and veins and the nutritional vessels of the sural nerve were observed. In 9 patients, the peroneal artery and vein were designed as the pedicle of cross-donor flap in the repair of large soft tissue defects of foot and ankle. The patients were entered follow-up through outpatient visits and telephone interviews.Results:Among the 12 adult specimens of lower limbs, there were 65 perforating branches from the peroneal artery, 4-7 branches on each side, with an average of (5.41±1.00) branches. The diameter of the penetrating deep fascia was(1.07±0.36) mm. The perforator branches were mostly distributed in 3 sections of 4.0-11.0 cm, 16.0-21.0 cm and 24.0-27.0 cm away from the lateral malleolus, accounting for 48%, 24% and 17% of the total number of perforators, respectively. The outer diameters of the perforator vessels were (0.92±0.26)(0.56-1.68) mm, (1.32±0.38)(0.60-2.14) mm, and (0.98±0.28)(0.62-1.36) mm. The length of the pedicle of the perforator vessels were (3.91±0.96)(2.15-5.78) cm, (5.34±0.50)(4.01-5.85) cm, and (3.31±1.15)(2.16-5.66) cm. The perforating branches in the 3 sections appeared constantly. The diameter of the vessels was≥0.5 mm with an average length of at(4.19±1.16)(2.15-5.85) cm. The vascular network of the flap in the posterolateral area of the calf was mainly composed of subdermal vascular network and deep fascial vascular network. The deep fascia vascular network in the posterolateral area of the calf had 3 obvious longitudinal chains, including the medial sural neurotrophic vascular chain, the small saphenous vein-sural nerve communicating branch vascular chain and the lateral sural neurotrophic vascular chain, which took the nutrient blood supply from the perforating branches of the peroneal artery also formed a longitudinal and transverse anastomosis between the perforating branches of the peroneal artery. In the clinical trials performed on 9 patients, all soft tissue defects of foot and ankle were repaired. The composite tissue flap survived without infection or necrosis. The follow-up was lasted for 12 months to 3 years. The postoperative function and the donor site appearance were good and the patients walked normally. According to the American Orthopaedic Foot and Ankle Association(AOFAS) foot scoring standard, the function of affected feet were evaluated. Five patients were excellent and 4 were good.Conclusion:The cross-donor flaps pedicled with peroneal arteries and veins has sufficient blood supply and a large area. It provides a method for the repair of large-area soft tissue defects in the foot and ankle.

Clinical features and prognosis of B-cell acute lymphoblastic leukemia children with intrachromosomal amplification of chromosome 21 / 白血病·淋巴瘤

Objective:To investigate the clinical features and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) children with intrachromosomal amplification of chromosome 21 (iAMP21).Methods:The data of 233 children diagnosed with B-ALL who received chemotherapy according to Chinese Children Cancer Group (CCCG) - acute lymphoblastic leukemia -2015 (CCCG-ALL-2015) protocol in the Affiliated Union Hospital of Fujian Medical University from January 2019 to December 2020 were retrospectively analyzed. These patients were divided into iAMP21 group and non-iAMP21 group according to whether iAMP21 was positive in the bone marrow fluid of children before chemotherapy based on ETV6-RUNX1 probe fluorescence in situ hybridization. Children in iAMP21 group received CCCG-ALL-2015 intermediate-risk group regimen induction chemotherapy, while children in non-iAMP21 group received different intensities of chemotherapy according to the clinical risk classification. The clinicopathological characteristics of patients were compared in both groups, the therapeutic efficacy and prognosis of B-ALL children with iAMP21 was analyzed.Results:iAMP21 was found in 5 (2.1%) of 233 B-ALL children. The median hemoglobin concentration in iAMP21 group was higher than that in non-iAMP21 group [99 g/L (71-148 g/L) vs. 74 g/L (30-156 g/L); U = 268.50, P = 0.043]; there were 4 cases (80%) with bone pain in iAMP21 group (5 cases) and 53 cases (23.2%) with bone pain in non-iAMP21 group (228 cases),and the difference in the osteoarticular pain incidence of both groups was statistically significant ( χ2 = 8.53, P = 0.017). There were no significant differences in the proportion of patients with different gender, age, white blood cell counts, platelet counts, hepatosplenomegaly between the two groups (all P > 0.05). Among 5 children with iAMP21, 1 patient was detected with high CRLF2 expression and 1 patient with IKZF1 1-8 exon loss of heterozygosity. The above mentioned two children with iAMP21, whose minimal residual disease (MRD) were still positive after consolidation therapy, and then they received chimeric antigen receptor T-cell treatment and hematopoietic stem cell transplantation. MRD of the other 3 children with iAMP21 turned negative after induction therapy. Up to the last follow-up in October 2021, 5 patients with iAMP21 had disease-free survival. Conclusions:The incidence of B-ALL children with iAMP21 is about 2%. These patients are prone to osteoarticular pain and have relatively mild anemia. The curative effect of some children is still poor after active treatment,which needs to be further clarified with more samples.

Mutational spectrum and its prognostic significance in childhood acute lymphoblastic leukemia based on next-generation sequencing technology / 中华血液学杂志

Objective: This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia (ALL) . Methods: Targeted exome by next-generation sequencing (NGS) technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019. Correlation of genetic features and clinical features and outcomes was analyzed. Results: Among the 141 pediatric patients with ALL, 160 somatic mutations were detected in 83 patients (58.9% ) , including 37 grade Ⅰ mutations and 123 grade Ⅱ mutations. Single nucleotide variation was the most common type of mutation. KRAS was the most common mutant gene (12.5% ) , followed by NOTCH1 (11.9% ) , and NRAS (10.6% ) . RAS pathway (KRAS, FLT3, PTPN11) , PAX5 and TP53 mutations were only detected, and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found, and NOTCH1 mutation was mainly detected in T-ALL. The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL (4.16±1.33 vs 2.04±0.92, P=0.004) . The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation. There were no statistically significant differences in sex, age, newly diagnosed white blood cell count, minimal or measurable residual disease monitoring results, expected 3-year event-free survival (EFS) and overall survival (OS) between the two groups (P>0.05) . On the other hand, the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group (P=0.021 and 0.000, respectively) . Among the patients without fusion gene, the EFS of children with grade I mutation was significantly lower than children without grade I mutation (85.5% vs 100.0% , P=0.039) . Among children with B-ALL, the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation (37.5% vs 91.2% , P<0.001) . Conclusion: Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis. Therefore, targeted exome by NGS can be used as an important supplement to the traditional morphology, immunology, cytogenetics, and molecular biology classification.

Thoracoumbilical flap combined with random abdominal flap in repair of large-area soft tissue defects of calf in children / 中华显微外科杂志

Objective:To investigate the clinical effect of thoracoumbilical flap combined with random abdominal flap in repair of large-area soft tissue defects of calf in children.Methods:The clinical data of 16 children with large-area soft tissue defects of calf treated with thoracoumbilical flap combined with abdominal random flap from January 2004 to December 2007 in PLA Trauma Orthopaedic Research Institute, 80th Group Military Hospital of the PLA were retrospectively analysed. There were 7 boys and 9 girls aged 8 to 14(11.3 in average) years old. Six cases were crushed by heavy objects, 6 crushed by wheels, 3 by thermal press and 1 by machine strangulation. After thorough debridement, the wound area ranged from 16.0 cm×9.0 cm to 38.0 cm×15.0 cm. Four cases were treated after 3-10 hours of injury by emergency surgery. Twelve cases received surgeries 0-11 days after hospital admission and wound being stabilised. Doppler ultrasound was used to locate the perforating vessels according to the location, size and shape of the wound. Thoracoumbilical flap combined with abdominal random flap were designed and harvested to repair the wound. The sizes of flaps were 18.0 cm×11.0 cm-40.0 cm×16.0 cm. All patients entered follow-up at the outpatient clinic or through WeChat interviews. The appearance, texture of the flap and limb recovery were checked and recorded.Results:After surgery, all of 16 flaps survived, of which 12 flaps had phase-one healing, 3 flaps had small area of necrosis at the edge, which healed after repeated dressing changes and 1 flap developed vascular comproise, and survived after surgical exploration. The donor sites healed in phase-one. All 16 children had 6 months to16 years of follow-up, with an average of 20.7 months. The colour of the flaps was normal with soft texture. The motor function of calf was satisfactory. According to Punor functional evaluation criteria, 12 cases were in excellent and 4 in good.Conclusion:The thoracoumbilical flap combined with abdominal random flap features a reasonable design, strong blood supply and repair of a large area. It is a reliable method for repairing large area soft tissue defects in the calf of children.

Effect and molecular mechanism research of Astragalus membranaceus on inhibiting intestinal absorption of six alkaloids of Aconitum carmichaelii in spleen deficiency rats / 中草药·英文版

Objective: To investigate the effect and the mechanism of Astragalus membranaceus (Huangqi in Chinese, HQ) extract on the intestinal absorption of six alkaloids of Aconitum carmichaelii (Fuzi in Chinese, FZ) in rats with spleen deficiency and provide novel insights into the application of HQ on modulating intestinal barrier. Methods: Four-week-old male Sprague-Dawley rats were fed with Xiaochengqi Decoction to induce the spleen deficiency model for 40 d. Single-pass intestinal perfusion model were used to study the effects of HQ extract on the absorption of alkaloids. Protein expression and mRNA levels of MRP2 and BCRP and tight junction proteins (TJ, including Claudin-1, Occludin and ZO-1) were measured using Western blot and real-time PCR, respectively. The location and expression of TJ protein was also investigated by the immunofluorescence method. Results: Compared with the normal group, the protein expression of MRP2, BCRP and TJ proteins in the model group were significantly down-regulated. After oral administration of HQ, the alkaloid absorption in intestinal villi was inhibited, MRP2, BCRP and TJ proteins were up-regulated, the green fluorescence staining of Claudin-1, Occludin, and ZO-1 was enhanced, and a thick layer of mucus was deposited on the surface of the epithelium of the intestinal cavity. Conclusion: HQ as an intestinal barrier modulator improves the physiological changes of the intestinal environment of spleen deficiency to reduce the absorption of toxic components, leading to a decrease in the absorption of drug-like molecules.

Effects of m 6A methylase METTL14 mediated long-chain non-coding RNA EIF3J-AS1 on the migration and invasion of cholangiocarcinoma cells / 中华胰腺病杂志

Objective:To investigate the effects of methyltransferase-like protein 14 (METTL14)-mediated long-chain non-coding RNA EIF3J antisense RNA1 (Inc EIF3J-AS1) on the migration and invasion of cholangiocarcinoma cells and its mechanism.Methods:From September 2017 to December 2018, 10 pairs of cholangiocarcinoma and adjacent normal tissues were collected from the First Affiliated Hospital of Naval Medical University, which were surgically resected and pathologically confirmed. The expression of METTL14 mRNA and Inc EIF3J-AS1 in cholangiocarcinoma tissues was detected by fluorescence quantitative PCR, and the protein expression of METTL14 was detected by Western blotting. Cholangiocarcinoma cell lines HUCCTI and RBE were divided into control group and METTL14 or Inc EIF3J-AS1 knockdown group. The corresponding normal lentivirus was transfected in the control group, and METTL14 or Inc EIF3J-AS1 knockdown group was transfected with lentivirus that interfered with the expression of METTL14 or Inc EIF3J-AS1, respectively. Transwell assay was used to detect the ability of cell migration and invasion, and Western blotting was used to detect the expression of epidermal growth factor receptor (EGFR) and AKT protein.Results:The expressions of METTL14 mRNA and lnc EIF3J-AS1 in cholangiocarcinoma tissues were significantly higher than those in adjacent normal tissues (0.075±0.012 vs 0.031±0.006, 0.140±0.032 vs 0.064±0.012), and there was a positive correlation between expression of METTL4 mRNA and expression of lnc EIF3J-AS1 ( r=0.883, P=0.0007). The expression of METTL14 protein in cholangiocarcinoma tissues was higher than that in adjacent normal tissues (0.354±0.131 vs 0.187±0.183). Compared with the control group, the expression of lnc EIF3J-AS1 was significantly lower in METTL14 or Inc EIF3J-AS1 knockdown group (0.217±0.020 vs 1.000±0.052, 0.149±0.066 vs 1.000±0.045). The migration and invasion ability of cell lines HUCCTI and RBE decreased significantly in lnc EIF3J-AS1 knockout group (5.00±0.58 vs 23.33±0.33, 20.33±0.67 vs 70.67±0.33; 12.00±0.58 vs 25.00±2.52, 22.33±0.89 vs 43.67±0.33). The expression of EGFR and p-AKT/AKT protein were also significantly decreased (0.109±0.015 vs 1.000±0.018, 0.226±0.036 vs 1.000±0.051; 0.118±0.052 vs 1.000±0.069, 0.132±0.098 vs 1.000±0.023). The above differences were statistically significant (all P<0.05). Conclusions:Abnormal expression of lnc EIF3J-AS1 in cholangiocarcinoma mediated by METTL14 can promote tumor cell migration and invasion.

Clinical Features and Prognosis of Acute Lymphoblastic Leukemia Children with P2RY8-CRLF2 Gene Rearrangement / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement.@*METHODS@#A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification.@*RESULTS@#Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×10@*CONCLUSION@#The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.

Clinical Effect and Safety of CCLG-ALL 2008 (high risk group) Protocol in the Treatment of Childhood Mixed Phenotype Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL).@*METHODS@#The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy.@*RESULTS@#One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033).@*CONCLUSION@#The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.

Quality changes of Gardeniae Fructus Praeparatus processed by different frying methods: a color-component correlation analysis / 中国中药杂志

The chromatic values of the broken-fried and single-fried Gardeniae Fructus Praeparatus(GFP) were measured by the color analyzer to analyze the color variation rule, and the contents of 10 main components were determined by ultra-high performance liquid chromatography(UPLC). The multivariate statistical analysis, Pearson correlation analysis, and discriminant analysis were conducted to investigate the color and components of GFP samples. The experimental results revealed that L~*, a~*, b~*, and E~*ab decreased continuously during processing, and the color of samples gradually deepened. The trend and range of chromatic values during broken-frying and single-frying processes were basically identical. Gardenoside, crocin-Ⅰ(C-Ⅰ), and crocin-Ⅱ(C-Ⅱ) showed an obviously downward trend, while the contents of geniposidic acid and 5-hydroxymethylfurfural(5-HMF) increased significantly. Shanzhiside, deacetyl-asperulosidic acid methyl ester, and geniposide(G2) showed a downward trend. Scandoside methyl ester rose first and fell later. Genipin-1-O-gentiobioside(G1) went through a decrease-increase-decrease trend. The change trends of component contents during broken-frying and single-frying processes were generally consistent, but the change range was different. Among all the components, scandoside methyl ester and G1 showed obvious change. Because of different stir-frying time, the change rate of each component content in the process of broken-frying was higher than that in single-frying process. Additionally, geniposidic acid, gardenoside, scandoside methyl ester, C-Ⅰ, C-Ⅱ, and 5-HMF exhibited a higher correlation with apparent color. On the basis of above findings, the discriminant function of two frying processes was established, which could be applied to the discrimination of broken-fried and single-fried samples. This study analyzed the dynamic quality change rule of GFP during broken-frying and single-frying processes based on color-component correlation analysis, and found the two methods showed consistent change trend, yet with slight difference in the quality of samples. This study can provide data support for the processing of GFP.

Model-informed drug development for immune checkpoint inhibitors / 药学学报

With a deepening understanding of cancer treatment, immune checkpoint inhibitors are recognized widely as a novel fundamental remedy for various malignancies with effectiveness and safety. With the development of pharmacometrics, model-informed drug development (MIDD) has emerged to accelerate the process of clinical research for new drugs and improve the accuracy of decision-making in new drug research, especially for immune checkpoint inhibitors. As a typical illustration, the research development of pembrolizumab is presented in this review to highlight the application of MIDD, which may provide a reference for the development of other new antitumor drugs.

Primary central nervous system anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in children: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical features and prognosis of primary central nervous system (CNS) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) in children.Methods:The clinical data of a child with primary CNS ALK-positive ALCL in Fujian Medical University Union Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:The child went to other hospitals with headache and fever as the main symptoms. Head magnetic resonance imaging showed a right cerebellar mass, and there was no evidence of lymphoma infiltration outside the CNS before surgery. Later, cerebellar tumor resection was performed. After the surgery, through pathological examination, the child was diagnosed as ALK-positive ALCL, but did not receive chemotherapy in time. The child transferred to Fujian Medical University Union Hospital on the 27th day after surgery, and the tumor had spread to bone marrow, testis, vertebrae, etc., and the peripheral blood NPM-ALK fusion gene was positive. The child received 2 courses of chemotherapy and achieved complete remission, but eventually died of chemotherapy complications.Conclusions:Primary CNS ALK-positive ALCL is rare and easy to be misdiagnosed. The disease progresses quickly, and the overall prognosis is poor. Timely biopsy for diagnosis and early comprehensive treatment based on chemotherapy may improve the prognosis of patients.

Clinical observation of azacitidine combined with CAG regimen in reinduction treatment of pediatric relapsed/refractory acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of azacitidine combined with CAG (cytarabine + aclacinomycin + granulocyte colony-stimulating factor) regimen in reinduction treatment of pediatric relapsed/refractory acute myeloid leukemia (AML) patients.Methods:The clinical data of 3 pediatric patients with relapsed/refractory AML treated with azacitidine combined with CAG regimen reinduction in Fujian Medical University Union Hospital between November 2018 and October 2019 were retrospectively analyzed, and the efficacy, prognosis and adverse reactions were also analyzed.Results:Among 3 patients, 2 cases were relapsed AML (relapse time began 18 months and 8 months after treatment started, respectively), and 1 case was refractory AML (cannot achieve complete remission after 2 courses of standard chemotherapy). After 2 courses of azacitidine combined with CAG regimen reinduction, 2 cases achieved complete remission, and 1 case achieved partial remission. And then they all underwent hematopoietic stem cell transplantation (HSCT) and had leukemia-free survival after 16-21 months follow-up (time from the first azacitidine combined with CAG reinduction). Except for hematological adverse reactions and infection, azacitidine did not increase other adverse effects.Conclusions:Azacitidine combined with CAG regimen in reinduction treatment of pediatric relapsed/refractory AML has a higher remission rate and safety, and patients undergoing timely bridging HSCT may have a good prognosis.

Investigation of Potential Pharmacodynamic Substances and Mechanism of Gardeniae Fructus in Treatment of Ischemic Stroke Based on HPLC-Q-TOF-MS/MS and Network Pharmacology / 中国实验方剂学杂志

Objective:Combined with high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） and network pharmacology， to predict the target and potential mechanism of Gardeniae Fructus in the treatment of cerebral ischemia. Method:HPLC-Q-TOF-MS/MS was used to identify the chemical constituents of Gardeniae Fructus according to the retention time， relative molecular weight， secondary mass spectrometry fragmentation and other information of chromatographic peaks， and combined with literature data. The targets of main active ingredients in Gardeniae Fructus were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and SwissTargetPrediction database. The potential targets of Gardeniae Fructus against cerebral ischemia were obtained through Online Mendelian Inheritance in Man （OMIM）， GeneCards and Kyoto Encyclopedia of Genes and Genomes （KEGG）. Gene ontology （GO） function enrichment and KEGG pathway analysis of potential targets were analyzed with the DAVID 6.8. Cytoscape 3.6.0 software was used to construct the network of active components-targets-pathways. At last， Discovery Studio 2016 software was applied in the molecular docking verification between the key active ingredients and potential protein targets. Result:A total of 40 chemical constituents in Gardeniae Fructus were identified， including iridoids， diterpenoid pigments， organic acids， monoterpenoids and other components. According to the main active ingredients， 208 potential targets were predicted， 560 disease targets related to cerebral ischemia were retrieved， 59 key targets were selected by mapping component targets with disease targets. These targets could act on key target proteins such as tumor necrosis factor （TNF）， Caspase-3 （CASP3） and CASP8， and participate in the regulation of TNF， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， hypoxia inducible factor 1 （HIF-1） and other signal pathways. Molecular docking results showed that geniposide could interact with targets of prostaglandin G/H synthase 2 （PTGS2）， TNF<italic> </italic>and nuclear transcription factor-<italic>κ</italic>B p65 （RELA）， crocin Ⅰ could interact with interleukin-2 （IL-2）. Conclusion:Geniposide， crocin Ⅰ and other ingredients in Gardeniae Fructus can play a role of anti-inflammatory and inhibiting apoptosis to prevent or treat cerebral ischemic diseases by up-regulating protein expression level of RELA and IL-2， down-regulating protein expression level of TNF， CASP8， CASP3 and matrix metalloproteinase 2 （MMP2）， and regulating TNF， PI3K/Akt and HIF-1 signaling pathways.