Progress in Chimeric Antigen Receptor-Modified Natural Killer Cells for Multiple Myeloma / 中国医学科学院学报

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Advances in Modeling of Multiple Myeloma in Mice / 中国医学科学院学报

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Townes-Brocks syndrome caused by de novo mutation in spalt-like transcription factor 1 gene: a case report and literature review / 中华围产医学杂志

Objective:To summarize the clinical features and gene variations in children with Townes-Brocks syndrome (TBS).Methods:The clinical data of a female infant diagnosed with TBS caused by human spalt-like transcription factor 1 ( SALL1) gene mutation in Gansu Maternal and Child Health Hospital in May 2022 were analyzed retrospectively. Relevant articles up to July 2022 were retrieved from several databases including CNKI, VIP, Wanfang, Chinese Medical Journal Network and PubMed with the terms of " SALL1 gene" and "Townes-Brocks syndrome". Patients diagnosed with TBS caused by SALL1 gene mutation were retrieved and the clinical phenotype-genotype correlations in patients with TBS caused by frameshift mutation in SALL1 gene were analyzed and summarized. Descriptive statistical analysis was applied. Results:(1) Clinical data: The index patient was a 40-day-old girl exhibiting major clinical manifestations of polycystic kidney dysplasia, congenital external ear deformity, preaxial polydactyly and recto-perineal fistula. Whole exome sequencing and Sanger sequencing revealed a heterozygous variation of c.420delC (p.S141fs*42) in the SALL1 gene, while the same gene was found to be wild type in her parents and sister. The variant was predicted to be pathogenic (PVS1+PS2+PM2). (2) Literature review retrieved 161 cases of TBS, of which 71 were attributable to a frameshift mutation in SALL1 gene. Clinical phenotypes of the 71 cases and the index case were summarized. TBS was mainly characterized by external ear, hand and anal deformities, sometimes accompanied by hearing loss, abnormal kidney development and foot deformity. A small number of affected cases presented with rare clinical phenotypes such as abnormal eyes, hypothyroidism and abnormal development. At present, the human gene mutation database records 110 variations in the SALL1 gene, with a majority located in exon 2. The most common mutation type was frameshift variation, accounting for 52%, followed by missense variation and nonsense variation. Conclusion:TBS should be considered in children with ear, hand and anal malformations, accompanied by renal dysfunction and hearing loss, and genetic testing is recommended for timely diagnosis.

Genetic analysis of a child with Pitt-Hopkins syndrome due to a novel variant of TCF4 gene derived from low percentage maternal mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a child with Pitt-Hopkins syndrome.@*METHODS@#A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. Karyotype analysis was also carried out for the child, and her mother was subjected to ultra-deep sequencing and prenatal diagnosis upon her subsequent pregnancy.@*RESULTS@#The clinical manifestations of the proband included facial dysmorphism, Simian crease, and mental retardation. Genetic testing revealed that he has carried a heterozygous c.1762C>T (p.Arg588Cys) variant of the TCF4 gene, for which both parents had a wild-type. The variant was unreported previously and was rated as likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Ultra-deep sequencing indicated that the variant has a proportion of 2.63% in the mother, suggesting the presence of low percentage mosaicism. Prenatal diagnosis of amniotic fluid sample suggested that the fetus did not carry the same variant.@*CONCLUSION@#The heterozygous c.1762C>T variant of the TCF4 gene probably underlay the disease in this child and has derived from the low percentage mosaicism in his mother.

Rapid health technology assessment of Aidi injection combined with first-line chemotherapy for non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the effectiveness， safety and economics of Aidi injection combined with first-line chemotherapy for non-small cell lung cancer （NSCLC）， and to provide evidence-based reference for clinical drug use and decision. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang databases， VIP and Health Technology Assessment （HTA） related websites， HTA reports， systematic evaluation/meta-analysis and economic evaluations about Aidi injection combined with first-line chemotherapy for NSCLC were collected from the inception to Aug. 2022. After data extraction and quality evaluation， descriptive analysis was performed for the results of included studies. RESULTS A total of 16 pieces of literature were included， involving 1 piece of systematic review， 13 pieces of meta-analysis， 2 pieces of pharmacoeconomic studies. Compared with first-line chemotherapy， Aidi injection combined with first-line chemotherapy could improve response rate and disease control rate， prolonged survival time， improved survival quality， reduced the incidence of nausea and vomiting， leukocytopenia and thrombocytopenia， and improved immune function， but had controversial effects on liver and kidney function. With the payment threshold set by 3 times the national per capita GDP in 2019， Aidi injection combined with first-line chemotherapy had a more economical probability. CONCLUSIONS Aidi injection combined with first-line chemotherapy for NSCLC has good efficacy and safety， and has certain economic benefits. However， given the limited pharmacoeconomic studies included， the economic conclusions obtained need to be carefully interpreted.

A "4D" systemic view on meridian essence: Substantial, functional, chronological and cultural attributes / 中西医结合学报

The term Jingluo, translated as meridian or channel, is a core component of traditional Chinese medicine (TCM) and has played a fundamental role in guiding the clinical practice of acupuncture for thousands of years. However, the essence of the meridian remains elusive and is a source of both confusion and debate for researchers. In this study, a "4D" systemic view on the essence of the meridian, namely substantial, functional, chronological, and cultural dimensions, was proposed based on a review of the ancient medical classics, recent research developments, and results from clinical practice. Previous studies have primarily focused on the substantial dimension of the meridian system, with scant interpretation about its functional domain. Neither systemic data nor evaluations have been adequately documented. Additionally, a limited but increasing number of studies have focused on the chronological and cultural dimensions. More investigations that embody the holistic concept of TCM and integrate the systemic modes and advanced techniques with dominant diseases of TCM need to be performed to obtain a more comprehensive understanding of the essence of meridians. The goal of this study is to yield useful information in understanding the essence of meridians and provide a reference and perspective for further research.

Construction and application of virtual simulation experimental teaching platform of nursing / 中华医学教育探索杂志

Virtual simulation experimental teaching is a major component of nursing education reform in colleges and universities, which makes space-unlimited cyber-learning and self-learning into reality and is helpful in the development of students' critical thinking and clinical nursing decision-making ability. Based on the "5E learning cycle" model, we have set up an experimental teaching system, and constructed a virtual simulation experimental platform of nursing, which comprises basic experimental skills, clinical experimental skills, comprehensive virtual simulation projects and training system of clinical thinking. The platform combines online learning and offline learning, virtual simulation and physical simulation together, and narrowes the gap between theoretical teaching and clinical practice. This platform has promoted the development of nursing skills, clinical thinking and comprehensive abilities for nursing students and been also ready for the design and development of virtual simulation experimental teaching projects in the future.

A comparative analysis of the mastery of nursing knowledge for patients with deterioration between Chinese and Australian nursing students / 中华医学教育探索杂志

Objective To investigate the mastery of nursing knowledge for diabetic patients with disease deterioration between Chinese and Australian nursing students and possible influencing factors,and to provide a reference for improving nursing teaching method in China.Methods From May to June,2016,a self-designed online knowledge questionnaire was used to investigate the mastery of clinical emergency knowledge among the third-grade nursing students in Chongqing Medical University in China and Hinders University in South Australia.A total of 303 questionnaires were collected,among which 243 valid questionnaires (164 from Chinese students and 79 from Australian students) were included in statistical analysis,with an effective collection rate of 80.20％.SPSS 19.0 software was used for statistical analysis,and the paired t-test or the chi-square test was used for data comparison.Results Australian nursing students had a significantly higher score of clinical emergency knowledge than their Chinese counterparts (t=4.115,P=0.000).Compared with the low-score group (score ＜12),the high-score group (score ≥ 12) had a significantly higher proportion of students with a family/medical history of diabetes,clinical experience in diabetes care,or self-learning as the main method (P＜0.05).As for learning method,Australian nursing students tended to use online self-learning (60 students,75.95％) and do assignments (56 students,70.89％) and participate in class discussion (51 students,64.56％),while Chinese students tended to receive theoretical teaching (138 students,84.15％),consult clinical teachers (138 students,84.15％),and receive simulation/experimental teaching (123 students,75.00％).Conclusion Chinese nursing students have lower degrees of willingness for self-learning and mastery of knowledge for disease deterioration than Australian nursing students.Focus on specialized practice,development of online teaching,and cultivation of the awareness and ability for self-learning may help to improve the mastery of clinical emergency knowledge among nursing students.

A Highly Sensitive Electrochemical Biosensor for Detection of Adenosine Triphosphate Based on Space Block / 分析化学

In this work,a highly sensitive electrochemical biosensor for the detection of trace adenosine triphosphate (ATP) was proposed.The biosensor was based on porous anodic alumina (PAA) and SiO2 nanoparticles combining with several oligonucleotides to construct sandwich structure.It was characterized by scanning electron microscopy,fluorescence microscopy,differential pulse voltammetry and electrochemical impedance spectroscopy,which conformed to the reliability of the biosensor fabrication and the feasibility of the detection.In the presence of ATP,the sandwich structures could be destroyed.The variation of the current was directly corresponding to the amount of the ATP.The application of SiO2nanoparticles could effectively reduce the background and increase the sensitivity of the biosensor.The calibration curve of ATP was obtained in the range of 0.025-0.900 nmol/L with the detection limit of 13 pmol/L (S/N=3).Also,the biosensor exhibited a good specificity.Besides,the sensor was constructed easily and possessed excellent regeneration ability.The proposed biosensor was applied in detection of real sample such as mice blood.Therefore,the proposed ATP-sensing biosensor could be expected to be applied in clinical,pharmaceutical and environmental detection.

Progress of corneal biomechanical measurements and applications in clinic / 国际眼科杂志(Guoji Yanke Zazhi)

· Cornea is an important part ofhuman's refractive system.Corneal biomechanics plays an important role in corneal ectasia and related diseases.The corneal biomechanics measured in vitro and in vivo and its clinical application in system diseases and elastic corneal disease,glaucoma,myopic are reviewed in this literature summary.