Femtosecond Laser Maskless Optical Projection Lithography of Cartilage PCM Inspired 3D Protein Matrix to Chondrocyte Phenotype.

Hydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. It is proposed to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) -like scaffolds for the first time, in which the S, M, and L-sized scaffolds are fabricated by femtosecond laser maskless optical projection lithography (FL-MOPL) of bovine serum albumin-glyceryl methacrylate hydrogel. Chondrocytes on the M PCM-like scaffold can maintain round morphology and synthesize extracellular matrix (ECM) to induce regeneration of hyaline cartilage microtissues by geometrical restriction. A series of M PCM-like scaffolds is fabricated with different stiffness and those with a high Young's modulus are more effective in maintaining the chondrocyte phenotype. The proposed PCM-like scaffolds are effective in modulating cartilage formation influenced by pore size, depth, and stiffness, which will pave the way for a better understanding of the geometric cues of mechanotransduction interactions in regulating cell fate and open up new avenues for tissue engineering.

Multipatterned Chondrocytes' Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes' Morphology.

Repairing articular cartilage damage is challenging due to its low regenerative capacity. In vitro, cartilage regeneration is a potential strategy for the functional reconstruction of cartilage defects. A hydrogel is an advanced material for mimicking the extracellular matrix (ECM) due to its hydrophilicity and biocompatibility, which is known as an ideal scaffold for cartilage regeneration. However, chondrocyte culture in vitro tends to dedifferentiate, leading to fibrosis and reduced mechanical properties of the newly formed cartilage tissue. Therefore, it is necessary to understand the mechanism of modulating the chondrocytes' morphology. In this study, we synthesize photo-cross-linkable bovine serum albumin-glycidyl methacrylate (BSA-GMA) with 65% methacrylation. The scaffolds are found to be suitable for chondrocyte growth, which are fabricated by homemade femtosecond laser maskless optical projection lithography (FL-MOPL). The large-area chondrocyte scaffolds have holes with interior angles of triangle (T), quadrilateral (Q), pentagon (P), hexagonal (H), and round (R). The FL-MOPL polymerization mechanism, swelling, degradation, and biocompatibility of the BSA-GMA hydrogel have been investigated. Furthermore, cytoskeleton and nucleus staining reveals that the R-scaffold with larger interior angle is more effective in maintaining chondrocyte morphology and preventing dedifferentiation. The scaffold's ability to maintain the chondrocytes' morphology improves as its shape matches that of the chondrocytes. These results suggest that the BSA-GMA scaffold is a suitable candidate for preventing chondrocyte differentiation and supporting cartilage tissue repair and regeneration. The proposed method for chondrocyte in vitro culture by developing biocompatible materials and flexible fabrication techniques would broaden the potential application of chondrocyte transplants as a viable treatment for cartilage-related diseases.

Synthesis of biocompatible BSA-GMA and two-photon polymerization of 3D hydrogels with free radical type I photoinitiator.

Although the development of three-dimensional (3D) printing technology is growing rapidly in the biomedical field, it remains a challenge to achieve arbitrary 3D structures with high resolution and high efficiency. Protein hydrogels fabricated by two- photon polymerization (TPP) have excellent mechanical properties, high precision, and 3D architecture. However, a large number of the amino acid group in bovine serum albumin (BSA) would be consumed when the protein-based hydrogels use dyes of free radical type II photoinitiators. In this study, we use glycidyl methacrylate (GMA) to modify BSA molecules to obtain a series of BSA-GMA materials, allowing the protein material to be two-photon polymerized with a water-soluble free radical type I photoinitiator. The precisely controllable 3D structure of the BSA-GMA hydrogel was fabricated by adjusting the concentration of the precursor solution, the degree of methacrylation, and the processing parameters of the TPP technique. Importantly, BSA-GMA materials are free of acidic hazardous substances. Meanwhile, the water-soluble initiator lithium phenyl (2,4,6-trimethylbenzoyl) phosphite (LAP) allows TPP on the vinyl group of the GMA chain and thus without consuming its amino acid group. The as-prepared BSA-GMA hydrogel structure exhibits excellent autofluorescence imaging, pH responsiveness, and biocompatibility, which would provide new avenues for potential applications in tissue engineering and biomedical fields to meet specific biological requirements.

22 nm Resolution Achieved by Femtosecond Laser Two-Photon Polymerization of a Hyaluronic Acid Vinyl Ester Hydrogel.

Three-dimensional (3D) bioinspired hydrogels have played an important role in tissue engineering, owing to their advantage of excellent biocompatibility. Here, the two-photon polymerization (TPP) of a 3D hydrogel with high precision has been investigated, using the precursor with hyaluronic acid vinyl ester (HAVE) as the biocompatibility hydrogel monomer, 3,3'-((((1E,1'E)-(2-oxocyclopentane-1,3-diylidene) bis(methanylylidene)) bis(4,1-phenylene)) bis(methylazanediyl))dipropanoate as the water-soluble initiator, and dl-dithiothreitol (DTT) as the click-chemistry cross-linker. The TPP properties of the HAVE precursors have been comprehensively investigated by adjusting the solubility and the formulation of the photoresist. The feature line width of 22 nm has been obtained at a processing laser threshold of 3.67 mW, and the 3D hydrogel scaffold structures have been fabricated. Furthermore, the average value of Young's modulus is 94 kPa for the 3D hydrogel, and cell biocompatibility has been demonstrated. This study would provide high potential for achieving a 3D hydrogel scaffold with highly precise configuration in tissue engineering and biomedicine.

Analysis of 4 children with DYNC1H1 gene related spinal muscular atrophy with lower extremity predominant 1 / 中华儿科杂志

Objective: To investigate the clinical features and gene variation characteristics of children with dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene associated spinal muscular atrophy with lower extremity predominant (SMALED) 1. Methods: The clinical data of 4 SMALED1 children admitted to Peking University First Hospital from December 2018 to May 2021, who were found to have pathogenic variation of DYNC1H1 gene through genetic testing, except for other genes known to be related to motor retardation, were retrospectively summarized to analyze the phenotype and genotype characteristics. Results: There were 3 males and 1 female. The age of onset was 1 year, 1 day, 1 day and 4 months, respectively. The age of diagnosis was 4 years and 10 months, 9 months, 5 years and 9 months, and 3 years and 1 month, respectively. The clinical manifestations were muscle weakness and muscular atrophy of lower limbs, 2 cases with foot deformity, 1 case with early non progressive joint contracture, 1 case with hip dislocation and 1 case with mental retardation. De novo heterozygous missense variations in DYNC1H1 gene were found in all 4 children. According to the rating of American College of medical genetics and genomics, they were all possible pathogenic and pathogenic variations, with p.R598C, p.P776L, p.Y1109D variations had been reported, and p.I1086R variation had not been reported. Conclusions: For those with unexplained lower limb muscle weakness, muscle atrophy, joint contracture and foot deformity, upper limb motor ability related retention, with or without mental retardation, as well as the motor ability progresses slowly, it is necessary to consider the possibility of SMALED1 and the detection of DYNC1H1 gene when necessary.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Platelet Transfusion Strategies for MASPAT-Matched Platelet Transfusion Failed Patient with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the causes of ineffectiveness of platelet transfusion with monoclonal antibody solid phase platelet antibody test (MASPAT) matching in patients with allogeneic hematopoietic stem cell transplantation and explore the strategies of platelet transfusion.@*METHODS@#A case of donor-specific HLA antibodies (DSA) induced by transfusion which ultimately resulted in transplantation failure and ineffective platelet transfusion with MASPAT matching was selected, and the causes of ineffective platelet transfusion and platelet transfusion strategy were retrospectively analyzed.@*RESULTS@#The 32-year-old female patient was diagnosed as acute myeloid leukemia (high risk) in another hospital with the main symptoms of fever and leukopenia, who should be admitted for hematopoietic stem cell transplantation after remission by chemotherapy. In the course of chemotherapy, DSA was generated due to platelet transfusion, and had HLA gene loci incompatible with the donor of the first transplant, leading to the failure of the first transplant. The patient received platelet transfusion for several times before and after transplantation, and the results showed that the effective rate of MASPAT matched platelet transfusion was only 35.3%. Further analysis showed that the reason for the ineffective platelet transfusion was due to the missed detection of antibodies by MASPAT method. During the second hematopoietic stem cell transplantation, the DSA-negative donor was selected, and the matching platelets but ineffective transfusion during the primary transplantation were avoided. Finally, the patient was successfully transplanted and discharged from hospital.@*CONCLUSIONS@#DSA can cause graft failure or render the graft ineffective. For the platelet transfusion of patients with DSA, the platelet transfusion strategy with matching type only using MASPAT method will miss the detection of antibodies, resulting in invalid platelet transfusion.

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Preliminary Study on Screening and Identification of Lewis a Antigen Mimic Epitope in Alpaca Phage Display Nanobody Library / 中国实验血液学杂志

OBJECTIVE@#To establish a new method for synthesizing Lewis blood group antigens, that is, the mimotopes of Lewis blood group antigens were screened by using an alpaca phage display nanobody library.@*METHODS@#We selected mimotopes of the Lewis a (lea) antigen by affinity panning of an alpaca phage display nanobody library using a monoclonal anti-lea antibody. Enzyme-linked immunosorbent assay (ELISA) was used to test the affinity of the positive clones for the monoclonal anti-lea antibody, and the high-affinity positive clones were selected for sequencing and synthesis. Finally, the sensitivity, specificity and reactivity of the synthesized lea mimotope in clinical samples were verified by ELISA.@*RESULTS@#A total of 96 phage clones were randomly selected, and 24 were positive. Fourteen positive clones with the highest affinity were selected for sequencing. The result showed that there were 5 different sequences, among which 3 sequences with the highest frequency, largest difference and highest affinity were selected for expression and synthesis. The sensitivity and specificity of lea mimic antigen by ELISA showed that, the minimum detection limit of gel microcolumn assay (GMA) and ELISA method were 25 times different, and the lea mimic antigen had no cross reacted with the other five unrelated monoclonal antibodies(P<0.001). Finally, 30 clinical plasma samples were analyzed. The mean absorbance of the 15 positive plasma samples was significantly higher than that of the 15 negative plasma samples (P=0.02). However, the positive signal values of the clinical samples were much lower than those of the monoclonal antibodies.@*CONCLUSION@#A new method of screening lea mimic antigen by using alpaca phage nanoantibody library has been established, which is expected to realize the screening of lea mimotopes, thus realizing the application of high-sensitivity detection methods such as ELISA and chemiluminescence in blood group antibody identification.

Study on quality standard for rice-fired Glehnia littoralis / 中国药房

OBJECTIVE To establish a quality standard for rice-fired Glehnia littoralis . METHODS Appearance observation ， powder microscopic identification and thin-layer chromatography （TLC）identification were performed for the samples of rice-fired G. littoralis decoction piece. According to the relevant methods stated in 2020 edition of Chinese Pharmacopoeia （part Ⅳ），the contents of moisture ，total ash ，acid-insoluble ash ，water-soluble extract and acid-soluble extract were determined. The contents of psoralen，zanthoxylin，bergapten，imperatorin and isoimperatorin were determined by high performance liquid chromatography （HPLC）. RESULTS The rice-fired G. littoralis decoction pieces were round-like small segments ，slightly rough ，yellow（peeled） or dark yellowish brown （with peel ），special gas and slightly sweet taste. The powder was yellowish white. Under the microscope ， secretions and secretory cells ，ducts，gelatinized starch granules ，ray cells ，parenchyma cells ，etc. could be seen. TLC showed the spots developed clearly. In the chromatogram of the test sample ，there was the same blue fluorescent spot at the corresponding position of the chromatogram of isoimperatorin control sample. The moisture ，total ash ，acid-insoluble ash ，water-soluble extract and ethanol-soluble extract from 9 batches of samples were 5.82％-6.27％，3.19％-3.59％，0.21％-0.27％，24.91％-30.30％ and 20.66％ -25.83％ ，respectively. The linear range of psoralen ，zanthotoxin，bergapten，imperatorin and isoimperatorin were 0.240-2.400，0.320-3.200，0.224-2.240，0.292-2.920，0.208-2.080 µg/mL（all r＞0.999 0）. Limits of quantitation were 0.032 0， 0.030 0，0325 0，0.032 0，0.045 0 µg，respectively. Limits of detection were 0.100 8，0.089 6，0.071 5，0.090 0，0.132 0 µg， respectively. RSDs of prescision ，stability（24 h）and reprodu- cibility tests were less than 3％. Average recoveries were 100.56％ （RSD＝1.36％ ，n＝6），100.73％（RSD＝2.25％ ，n＝6）， 100.36％（RSD＝0.98％，n＝6），98.24％（RSD＝0.40％，n＝6） E-mail：853063968@qq.com and 99.40％（RSD＝0.35％，n＝6），respectively. The contents of above five components were 5.85-13.31，8.63-33.38，6.23- E-mail：shixiaofeng2005@sina.com 15.25，6.12-12.98，5.52-10.77 µg/g，respectively. The total contents were 34.20-83.47 µg/g. CONCLUSIONS It is preliminarily proposed that the moisture ，total ash and acid-insoluble ash should not exceed 7.30％，4.10％，0.30％. The water-soluble extract and ethanol-soluble extract are no less than 21.00％ and 18.00％，respectively. The total content of coumarin should not be less than 52.03 µg/g（with peel ）and 26.34 μg/g（peeled）. Established quality standard can be used for the quality control of rice-fired G. littoralis .

Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy.

Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity. Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor, compared with monotherapy. Here, we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1, and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1. P-Lipo increases intratumoral drug accumulation and promotes DC maturation, and thereby facilitates adaptive immune responses against tumor growth. The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ, and the reduced CD4+Foxp3+ regulatory T cells (Tregs). Collectively, the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.

Analysis of reasons of insufficient blood collected in Guangzhou during 2018~2020 / 中国输血杂志

【Objective】 To retrospectively analyze the reasons of insufficient blood collected, to provide evidences for further taking targeted measures, to reduce the discard of insufficient whole blood and prevent the loss of blood donors. 【Methods】 Calculate the total number of whole blood donors and the number of whole blood donors donating insufficient blood during 2018~2020 annually in Guangzhou Blood Center Information System, and the data was analyzed in SPSS (22.0) software for χ2test and linear trend test. 【Results】 During 2018~2020, the incidence of insufficient blood collected was 0.066 4%(531/799 439), and the incidence of insufficient blood collected because of poor blood flow, needle-sickness and other reasons were 0.048 7%(389/799 439), 0.010 6%(85/799 439) and 0.007 1%(57/799 439). Furthermore, the incidence of insufficient blood collected of the three above reasons had statistically significant difference between the years respectively (P<0.05), meanwhile the incidence of insufficient blood collected because of poor blood flow was in a general rising trend significantly (0.036 3%<0.038 2%<0.072 7%, P<0.05). 【Conclusion】 The incidence of insufficient blood collected because of poor blood flow was in the rising trend and further precautions should be considered. Under the normalization of the novel corona-virus pneumonia (COVID-19), the professional knowledge of epidemic prevention and control should be learned and trained, in addition the puncture technique, the ability of offering psychological care and dealing with adverse events during blood collection should be also improved among nurses continually, so as to provide high quality services for blood donors.

Research Advance on Preparation Technology and Application of Virus-inactivated Lyophilized Plasma---Review / 中国实验血液学杂志

Lyophilized plasma has a certain advantage in emergency situation, such as war wound treatment. However, lyophilized plasma has two major problems, plasma pathogen pollution and mass loss after lyophilized. Studies have shown that plasma pathogen inactivation technology targeting pathogen envelope or nucleic acid can ensure its safety, and adding citric acid and glycine to plasma can effectively maintain pH and protein activity of plasma after reconstitution. At present, there are three kinds of lyophilized plasma products on the market abroad, but none for China. Therefore, understanding the research progress of lyophilized plasma may contribute to the development of similar products in China.

Unilateral vertebroplasty and kyphoplasty by digital subtraction angiography for the treatment of osteoporotic vertebral compression fractures / 中国骨伤

OBJECTIVE@#To explore the methods and efficacy of unilateral extra-pedicle precision puncture percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty(PKP) by digital subtraction angiography (DSA) for the treatment of osteoporotic vertebral compression fractures (OVCFs).@*METHODS@#The clinical data of 68 patients with osteoporotic vertebral compression fractures treated from August 2015 to December 2018 were retrospectively analyzed. There were 20 males and 48 females, aged 56 to 90(73.5±8.0) years, 40 cases of double segments, 28 cases of three segments, a total of 168 vertebrae. All the patients were performed PVP orPKP through unilateral extra pedicle precision puncture under the guidance of DSA. The vertebrae were distributed in T@*RESULTS@#All the punctures were successful in 68 patients. All the puncture needles reached the midline of vertebral body, and the bone cement was well dispersed in the vertebral body with symmetrical distribution. The operation time was 35 to 60 (41.6±3.2) minutes, and there was no puncture complications. The injection volume of bone cement was 3 to 5 (3.6±0.5) ml in each vertebra. There were 8 cases of bone cement leakage, with a leakage rate of 11.76%. All 68 patients were followed up from 12 to 27 (14.3±3.5) months in the study. VAS score and ODI at 3 days after surgery and at final follow-up time were significantly improved (@*CONCLUSION@#PVP or PKP under the guidance of DSA via a unilateral extrapedicular approach with precision puncture can effectively relieve pain, restore vertebral body height and spinal function, which is a safe, fast and effective method in the treatment of osteoporotic vertebral compression fractures.

Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors / 中华胃肠外科杂志

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/β-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.

Analysis of bone mineral density and bone metabolism in elderly hip fracture patients of different genders / 中华老年医学杂志

Objective@#To understand changes and characteristics of bone mineral density(BMD)and early-stage bone turnover biochemical markers in elderly hip fracture patients of different genders.@*Methods@#This was a retrospective cohort study.A total of 1 161 elderly patients with hip fractures hospitalized in Beijing Jishuitan Hospital from May 2015 to December 2017 were enrolled.Based on gender, patients were divided into the female group(n=831)and the male group(n=330). Clinical data, BMD, serum type I procollagen amino terminal propeptide(P1NP), and 25-hydroxyvitamin D3 [25-(OH)VD3], type I collagen cross-linked carboxy terminal peptide beta degradation products(β-CTX), osteocalcin(OC)and parathyroid hormone(PTH)were measured and compared between the two groups.@*Results@#Of the 1 161 elderly patients with hip fractures, 831 were female and 330 were male.The BMD of the lumbar vertebrae and the total hip in the female and male groups showed that 30.4%(353/1 161)and 6.8%(79/1 161)had T≥-1.0 SD respectively; 36.6%(425/1 161)and 44.7%(519/1 161)had -2.5 SD<T<-1.0 SD; and 33.0%(383/1 161)and 48.5%(563/1 161)had T≤-2.5 SD respectively.The sensitivity of the hip BMD T value was better than that of lumbar vertebrae(P<0.05). Female BMD was significantly lower than that of male BMD(P<0.05). The BMD T values, which were significantly related to age, were recorded at the femoral neck and the total hip(femoral neck was better than total hip)for males and at total hip(the total hip T value is the most strongly related index)for females; (2)In the early stage of elderly hip fractures, 25-(OH)VD3 was significantly lower than normal, and bone resorption and bone formation indexes were not significantly increased(P>0.05). The levels of tP1NP, β-CTX, OC and PTH in females were higher than those in males, and the level of 25-(OH)VD3 was lower than that in males(all P<0.05). As the T value decreased, β-CTX and OC increased and 25-(OH)VD3 decreased accordingly(all P<0.05).@*Conclusions@#With the increase of age, the BMD T value in elderly patients with hip fractures shows a downward trend, but its decline in women is faster and earlier.Overall, the BMD T value is not sensitive enough for osteoporosis diagnosis or hip fracture prediction in the elderly, especially in men.In the early stage of fractures, the bone turnover biochemical markers show varying degrees of change, and bone resorption and bone formation are both reduced.The significance of OC, β-CTX and VD levels in early bone metabolic abnormalities requires further study.

Analysis of bone mineral density and bone metabolism in elderly hip fracture patients of different genders / 中华老年医学杂志

Objective To understand changes and characteristics of bone mineral density(BMD)and early-stage bone turnover biochemical markers in elderly hip fracture patients of different genders.Methods This was a retrospective cohort study.A total of 1 161 elderly patients with hip fractures hospitalized in Beijing Jishuitan Hospital from May 2015 to December 2017 were enrolled.Based on gender,patients were divided into the female group (n =831) and the male group (n =330).Clinical data,BMD,serum type Ⅰ procollagen amino terminal propeptide(P1NP),and 25-hydroxyvitamin D3 [25-(OH) VD3],type Ⅰ collagen cross linked carboxy terminal peptide beta degradation products (β-CTX),osteocalcin(OC)and parathyroid hormone(PTH)were measured and compared between the two groups.Results Of the 1 161 elderly patients with hip fractures,831 were female and 330 were male.The BMD of the lumbar vertebrae and the total hip in the female and male groups showed that 30.4％(353/1 161)and 6.8％(79/1 161)had T≥-1.0 SD respectively;36.6％ (425/1 161)and 44.7％(519/1 161)had-2.5 SD＜T＜-1.0 SD;and 33.0％(383/1 161)and 48.5％(563/1 161)had T≤-2.5 SD respectively.The sensitivity of the hip BMD T value was better than that of lumbar vertebrae(P＜0.05).Female BMD was significantly lower than that of male BMD(P＜0.05).The BMD T values,which were significantly related to age,were recorded at the femoral neck and the total hip(femoral neck was better than total hip)for males and at total hip(the total hip T value is the most strongly related index) for females;(2) In the early stage of elderly hip fractures,25-(OH) VD3 was significantly lower than normal,and bone resorption and bone formation indexes were not significantly increased(P＞0.05).The levels of tP1NP,β-CTX,OC and PTH in females were higher than those in males,and the level of 25-(OH)VD3 was lower than that in males(all P ＜ 0.05).As the T value decreased,β-CTX and OC increased and 25-(OH)VD3 decreased accordingly (all P ＜ 0.05).Conclusions With the increase of age,the BMD T value in elderly patients with hip fractures shows a downward trend,but its decline in women is faster and earlier.Overall,the BMD T value is not sensitive enough for osteoporosis diagnosis or hip fracture prediction in the elderly,especially in men.In the early stage of fractures,the bone turnover biochemical markers show varying degrees of change,and bone resorption and bone formation are both reduced.The significance of OC,β-CTX and VD levels in early bone metabolic abnormalities requires further study.

Overview of recent advances in liposomal nanoparticle-based cancer immunotherapy.

The clinical performance of conventional cancer therapy approaches (surgery, radiotherapy, and chemotherapy) has been challenged by tumor metastasis and recurrence that is mainly responsible for cancer-caused mortalities. The cancer immunotherapy is being emerged nowadays as a promising therapeutic modality in order to achieve a highly efficient therapeutic performance while circumventing tumor metastasis and relapse. Liposomal nanoparticles (NPs) may serve as an ideal platform for systemic delivery of the immune modulators. In this review, we summarize the cutting-edge progresses in liposomal NPs for cancer immunotherapy, with focus on dendritic cells, T cells, tumor cells, natural killer cells, and macrophages. The review highlights the major challenges and provides a perspective regarding the clinical translation of liposomal nanoparticle-based immunotherapy.

Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia / 中华血液学杂志

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion: The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.