Clinical and Genetic Study on 48 Children with Short Stature of Unknown Etiology / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

Evidence-based evaluation of the global cancer-associated thromboembolism risk assessment tools / 中国药房

OBJECTIVE To evaluate the global cancer-associated thromboembolism risk assessment tools based on evidence- based methods， and to provide methodological reference and evidence-based basis for constructing a specific tool in China. METHODS A comprehensive search was conducted on 6 databases， including CNKI， Wanfang data， VIP， CBM， PubMed， and Embase， as well as on the websites of NCCN， ASCO， ESMO and so on with a deadline of June 30， 2022. Furthermore， a supplementary search was conducted in January 2023. The essential characteristics and methodological quality of included risk assessment tools were described and analyzed qualitatively， focusing on comparing each assessment stratification ability. RESULTS Totally 14 risk assessment tools were included in the study， with a sample size of 208-18 956 cases and an average age distribution of 53.1-74.0 years. The applicable population included outpatient cancer student@sina.com patients， lymphoma patients， and multiple myeloma patients，etc. The common predictive factors were body mass index， venous thromboembolism history， and tumor site. All tools had undergone methodological validation， with 9 presented in a weighted scoring format. Only seven tools were used simultaneously for specificity， sensitivity， negative predictive value （NPV）， positive predictive value （PPV） and area under the curve （AUC） or C statistical analysis. CONCLUSIONS The risk of bias in constructing existing tools is high， and the heterogeneity of tool validation results is significant. The overall methodological quality must be improved， and its risk stratification ability must also be investigated. There are still certain limitations in clinical practice in China.

Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Role of Macrophage Activation and Polarization in Myocardial Fibrosis and Intervention of Traditional Chinese Medicine / 中国实验方剂学杂志

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

Neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating SIRT1/NF-κB signaling pathway / 中国药房

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 （SIRT1）/nuclear factor-κB （NF-κB） signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group， sodium aescinate low-dose group （1.8 mg/kg）， sodium aescinate high-dose group （3.6 mg/kg）， sodium aescinate+EX527 （sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg） group， with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally， once a day， for 21 consecutive days. Twenty-four hours after the end of the last administration， the motor and cognitive functions of rats were detected， and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine （DA） in the nigrostriatal and the expression levels of tyrosine hydroxylase （TH） and α-synuclein （α-Syn） in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 （IL-6）， IL-18]， anti-inflammatory factor （IL-10）， and the expression levels of SIRT1， phosphorylated NF-κB p65 （p-NF-κB p65） and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group， the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group； the number of rotations， escape latency， the expression levels of α-Syn in substantia nigra， the levels of serum pro-inflammatory factors， the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly （P＜0.05）； the target quadrant residence time， the content of DA in nigrostriatal， the expression level of TH in substantia nigra， the serum level of anti-inflammatory factor， and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened （P＜0.05）. Compared with model group， the damage degrees of neuron in sodium aescinate groups were alleviated， and the quantitative indicators were significantly improved， which were more significant in the high-dose group （P＜0.05）； EX527 could reverse the improvement effect of high-dose sodium aescinate （P＜0.05）. CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1， thereby reducing the neuroinflammation of rats with Parkinson’s disease， improving the motor and cognitive dysfunctions， and finally playing a neuroprotective role.

Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Transient change in the binocular visual function after femtosecond laser-assisted in situ keratomileusis for myopia patients

Purpose: The goal of this study was to compare the difference in binocular visual function for high and low?moderate myopes before and after femtosecond laser?assisted in situ keratomileusis (FS?LASIK). Methods: Thirty?three subjects (17 males and 16 females) were divided into two groups according to their preoperative refractive errors in spherical equivalent (SE): low?moderate myopia group (SE ??6.00 D) and high myopia group (SE <?6.00 D). The binocular visual function including accommodative amplitude (AA), accommodative facility (AF), positive and negative relative accommodation (PRA and NRA, respectively), horizontal phoria measurement, positive and negative fusion vergence, accommodative–convergence over accommodation (AC/A) ratio, and stereopsis were assessed with the best?corrected vision before patients received FS?LASIK and 7 and 30 days after the surgery. Repeated measures analysis of variance (ANOVA) was applied to study the change in binocular visual function. Results: The AF values in both groups were significantly reduced after 7 days of FS?LASIK (baseline vs. day 7 (mean): high myopia group: 7.85 vs. 5.62 cpm, repeated ANOVA, P = 0.01; low?moderate myopia group: 5.95 vs. 4.40 cpm, repeated ANOVA, P = 0.04). This change returned to the baseline level 30 days after the operation. In addition, the horizontal phoria values in both groups were significantly reduced for both distant (P = 0.019 and P = 0.001, respectively) and near (P = 0.003 and P = 0.049, respectively) 7 days after the operation, but they rebound to preoperative state after 30 days. Conclusion: A transient change in binocular visual function was noticed after 7 days of FS?LASIK operation, which could cause symptoms of asthenopia. Our data showed all the binocular visual functions returned to baseline level after 30 days of operation.

Isokinetic kneel muscle strength characteristics in high jump athletes / Características da força muscular isocinética na articulação do joelho em atletas de salto em altura / Características de la fuerza muscular isocinética en la articulación de la rodilla en atletas de salto de altura

ABSTRACT Introduction: Vertical jump is inherent to the practice of high jump and demands great capacity of force generation and work of the knee muscles, especially the quadriceps muscle. Due to this demand, imbalances between the extensor and flexor knee muscles may be present, leading to an overload of the musculotendinous structures of the knee joint. Therefore, it is necessary to establish the characteristics of isokinetic muscle strength in the knee joint of these athletes. Objective: This study aimed to analyze the biomechanical properties of the knee flexor and extensor muscles in high jump athletes. Methods: Ten high jumpers volunteered for the experiment. They were divided into experimental and control groups. Both groups performed basic strength training. The experimental group added isokinetic knee muscle training based on this training. Statistical analyses were performed on the training data of the two groups of athletes using relevant mathematical statistics. Results: The high jump consists of four phases being respectively the approach run, the jump itself (impulsion, elevation, transposition), and the fall. The strength of the ankle joint dorsiflexion and plantar flexors was significantly increased in the experimental group of athletes. In contrast, the strength of the plantar flexors in the control group was significantly increased. Statistical differences were found between the two groups (P<0.05). Conclusion: The isokinetic knee joint strength training mode can improve the leg support strength of jumpers. This paper suggests that high jump athletes can further adopt this lower limb strength training method. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O salto vertical é inerente à prática do salto em altura e demanda grande capacidade de geração de força e trabalho da muscular do joelho, principalmente do músculo quadríceps. Devido a esta demanda, desequilíbrios entre os músculos extensores e flexores podem estar presentes, levando à sobrecarga das estruturas musculotendíneas da articulação do joelho. Sendo assim, torna-se necessário o estabelecimento das características da força muscular isocinética na articulação do joelho desses atletas. Objetivo: Este estudo teve como objetivo analisar as propriedades biomecânicas dos músculos flexores e extensores do joelho nos atletas de salto em altura. Métodos: Dez saltadores voluntariaram-se para o experimento. Eles foram divididos em grupos experimentais e grupos de controle. Ambos os grupos realizaram o treinamento básico de força. O grupo experimental adicionou treinamento muscular isocinético do joelho baseado neste treinamento. Foram realizadas análises estatísticas sobre os dados de treinamento dos dois grupos de atletas, utilizando estatísticas matemáticas pertinentes. Resultados: O salto em altura consiste de quatro fases, sendo respectivamente a corrida de aproximação, o salto em si (impulsão, elevação, transposição) e a queda. A força da dorsiflexão da articulação do tornozelo e dos flexores plantares foi significativamente aumentada no grupo experimental de atletas. Em contraste, somente a força dos flexores plantares no grupo de controle foi significativamente aumentada. Foram encontradas diferenças estatísticas entre os dois grupos (P<0,05). Conclusão: O modo de treinamento de força isocinética da articulação do joelho pode melhorar a força de apoio nas pernas dos saltadores. Este artigo sugere que os atletas de salto em altura podem adotar mais este método para o treinamento de força para membros inferiores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El salto vertical es inherente a la práctica del salto de altura y exige una gran capacidad de generación de fuerza y trabajo de los músculos de la rodilla, principalmente del cuádriceps. Debido a esta demanda, puede haber desequilibrios entre los músculos extensores y flexores, lo que lleva a la sobrecarga de las estructuras musculotendinosas de la articulación de la rodilla. Por lo tanto, es necesario establecer las características de la fuerza muscular isocinética en la articulación de la rodilla de estos atletas. Objetivo: El propósito de este estudio fue analizar las propiedades biomecánicas de los músculos flexores y extensores de la rodilla en atletas de salto de altura. Métodos: Diez saltadores de altura se ofrecieron como voluntarios para el experimento. Se dividieron en grupos experimentales y de control. Ambos grupos realizaron un entrenamiento de fuerza básico. El grupo experimental añadió un entrenamiento muscular isocinético de la rodilla basado en este entrenamiento. Se realizaron análisis estadísticos de los datos de entrenamiento de los dos grupos de atletas utilizando las estadísticas matemáticas pertinentes. Resultados: El salto de altura consta de cuatro fases, que son respectivamente la carrera de aproximación, el salto propiamente dicho (impulsión, elevación, transposición) y la caída. La fuerza de la dorsiflexión de la articulación del tobillo y de los flexores plantares aumentó significativamente en el grupo experimental de atletas. Por el contrario, sólo aumentó significativamente la fuerza de los flexores plantares en el grupo de control. Se encontraron diferencias estadísticas entre los dos grupos (P<0,05). Conclusión: El modo de entrenamiento isocinético de la fuerza de la articulación de la rodilla puede mejorar la fuerza de apoyo de la pierna en los saltadores. Este artículo sugiere que los atletas de salto de altura pueden adoptar este método para el entrenamiento de la fuerza de las extremidades inferiores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid

Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

CT radiomics for prediction of microvascular invasion in hepatocellular carcinoma: A systematic review and meta-analysis

Abstract The power of computed tomography (CT) radiomics for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) demonstrated in current research is variable. This systematic review and meta-analysis aim to evaluate the value of CT radiomics for MVI prediction in HCC, and to investigate the methodologic quality in the workflow of radiomics research. Databases of PubMed, Embase, Web of Science, and Cochrane Library were systematically searched. The methodologic quality of included studies was assessed. Validation data from studies with Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) statement type 2a or above were extracted for meta-analysis. Eleven studies were included, among which nine were eligible for meta-analysis. Radiomics quality scores of the enrolled eleven studies varied from 6 to 17, accounting for 16.7%-47.2% of the total points, with an average score of 14. Pooled sensitivity, specificity, and Area Under the summary receiver operator Characteristic Curve (AUC) were 0.82 (95% CI 0.77-0.86), 0.79 (95% CI 0.75-0.83), and 0.87 (95% CI 0.84-0.91) for the predictive performance of CT radiomics, respectively. Meta-regression and subgroup analyses showed radiomics model based on 3D tumor segmentation, and deep learning model achieved superior performances compared to 2D segmentation and non-deep learning model, respectively (AUC: 0.93 vs. 0.83, and 0.97 vs. 0.83, respectively). This study proves that CT radiomics could predict MVI in HCC. The heterogeneity of the included studies precludes a definition of the role of CT radiomics in predicting MVI, but methodology warrants uniformization in the radiology community regarding radiomics in HCC.

Neuroblastoma with superficial soft tissue mass as the first symptom: case reports with atypical ultrasonic image and literature review

Neuroblastoma is one of the most common tumors in children. Cases where an isolated soft-tissue metastasis mass is the initial symptom are rare, with only four such cases reported to date. We describe the imaging findings of ten cases of neuroblastoma patients in our hospital with superficial soft tissue mass (SSTM) as the primary symptom. The main ultrasound finding of SSTM was hypoechoic masses or scattered speck-like hyperechoic masses. However, when this type of SSTM is caused by soft tissue metastasis, the location is often atypical, and ultrasound findings are difficult to distinguish from other benign diseases. Therefore, this research should remind clinicians to recognize atypical presentations of this common childhood malignant tumor. Radiologists should also consider the possibility of neuroblastoma when finding this type of SSTM with atypical ultrasound features.

Three-dimensional finite element analysis of cement flow in abutment margin-crown platform switching / 北京大学学报(医学版)

OBJECTIVE@#To analyze the cement flow in the abutment margin-crown platform switching structure by using the three-dimensional finite element analysis, in order to prove that whether the abutment margin-crown platform switching structure can reduce the inflow depth of cement in the implantation adhesive retention.@*METHODS@#By using ANSYS 19.0 software, two models were created, including the one with regular margin and crown (Model one, the traditional group), and the other one with abutment margin-crown platform switching structure (Model two, the platform switching group). Both abutments of the two models were wrapped by gingiva, and the depth of the abutment margins was 1.5 mm submucosal. Two-way fluid structure coupling calculations were produced in two models by using ANSYS 19.0 software. In the two models, the same amount of cement were put between the inner side of the crowns and the abutments. The process of cementing the crown to the abutment was simulated when the crown was 0.6 mm above the abutment. The crown was falling at a constant speed in the whole process spending 0.1 s. Then we observed the cement flow outside the crowns at the time of 0.025 s, 0.05 s, 0.075 s, 0.1 s, and measured the depth of cement over the margins at the time of 0.1 s.@*RESULTS@#At the time of 0 s, 0.025 s, 0.05 s, the cements in the two models were all above the abutment margins. At the time of 0.075 s, in Model one, the gingiva was squeezed by the cement and became deformed, and then a gap was formed between the gingiva and the abutment into which the cement started to flow. In Model two, because of the narrow neck of the crown, the cement flowed out from the gingival as it was pressed by the upward counterforce from the gingival and the abutment margin. At the time of 0.1 s, in Model one, the cement continued to flow deep inside with the gravity force and pressure, and the depth of the cement over the margin was 1 mm. In Model two, the cement continued to flow out from the gingival at the time of 0.075 s, and the depth of the cement over the margin was 0 mm.@*CONCLUSION@#When the abutment was wrapped by the gingiva, the inflow depth of cement in the implantation adhesive retention can be reduced in the abutment margin-crown platform switching structure.

Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection / 中华肝脏病杂志

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Analysis of Key Points of Technical Review of Traditional Chinese Medicine Fumigation Treatment Device / 中国医疗器械杂志

Traditional Chinese medicine fumigation device is the carrier of traditional Chinese medicine fumigation treatment. In recent years, with the rapid development of new technology and new materials, the development of fumigation device changes with each passing day, and a variety of new products continue to emerge. However, at present, the lack of corresponding evaluation norms, resulting in some difficulties in the registration, marketing, quality control, evaluation scale and other aspects of the product. Some products have many disadvantages in clinical use. From the perspective of technical review, this paper elaborates and analyzes the main concerns in technical review, such as product structure, main risks, performance requirements, clinical evaluation, etc., in order to provide a basis for the design, development, production, registration, use and post-marketing supervision of the devices.

Establishment of a reporter system for estimating activation of human hepatic stellate cells based on COL1A1 promoter and enhanced green fluorescent protein / 北京大学学报(医学版)

OBJECTIVE@#To establish a visual reporting system for evaluating the activity of collagen Ⅰ α 1 chain (COL1A1) gene promoter in immortalized human hepatic stellate cells, so as to estimate the activation status of the cells and provide a new cell model for the screening and study of anti-hepatic fibrosis drugs.@*METHODS@#The promoter sequence of human COL1A1 was amplified from the genomic DNA of human hepatocarcinoma cell line HepG2. Based on the pLVX-AcGFP1-N1 plasmid, the recombinant plasmid pLVX-COL1A1-enhanced green fluorescent protein (EGFP) was constructed, in which the enhanced green fluorescent protein gene expression was regulated by the COL1A1 promoter. The monoclonal cell line was acquired by stably transfecting pLVX-COL1A1-EGFP into the immortalized human hepatic stellate cell line LX-2 by the lentivirus packaging system and screening. The cell line was treated with transforming growth factor-β1 (TGF-β1) or co-treated with TGF-β1 and drugs with potential anti-hepatic fibrosis effects. The EGFP fluorescence intensity in cells was analyzed by the fluorescence microscope and ImageJ 1.49 software using a semi-quantitative method. The COL1A1 and EGFP mRNA were detected by reverse transcription real-time quantitative PCR (RT-qPCR), and corresponding proteins were detected by Western blot.@*RESULTS@#The recombinant plasmid pLVX-COL1A1-EGFP with the expression of EGFP regulated by COL1A1 promoter was successfully constructed. Kozak sequence was added to enhance the expression of EGFP, which was identified by double digestion and sequencing. The LX-2 monoclonal cell line LX-2-CE stably transfected with pLVX-COL1A1-EGFP was obtained. After co-treatment with TGF-β1 and 5 μmol/L dihydrotanshinone Ⅰ with potential anti-hepatic fibrosis effect for 24 h, the total fluorescence intensity and the average fluorescence intensity of LX-2-CE were lower than those in TGF-β1 single treatment group (P < 0.05), the intracellular mRNA and protein levels of COL1A1 and EGFP were also lower than those in the TGF-β1 single treatment group (P < 0.05).@*CONCLUSION@#A reporter system for estimating activation of hepatic stellate cells based on COL1A1 promoter regulated EGFP expression is successfully constructed, which could visually report the changes in COL1A1 expression, one of the activation-related markers of hepatic stellate cells, in vitro. It provides a new cell model for the screening and study of anti-hepatic fibrosis drugs.

The clinical value of 123I-metaiodobenzylguanidine myocardial imaging in the diagnosis of dementia with Lewy bodies / 生物医学工程学杂志

Metaiodobenzylguanidine (MIBG) is an analog of norepinephrine that accumulates in sympathetic nerve endings soon after intravenous administration. The degree of accumulation reflects the uptake, storage and release of transmitters by noradrenergic neurons. Myocardial imaging with 123I labeled MIBG ( 123I-MIBG) can be used to estimate the extent of local myocardial sympathetic nerve damage, which has been widely used in the diagnosis and treatment of various heart diseases. In recent years, numerous studies have been carried out on the application of 123I-MIBG in the diagnosis of degenerative diseases of the nervous system (such as Parkinson's disease and dementia of Lewy body), and have made some achievements. The purpose of this review is to summarize the current clinical application of 123I-MIBG myocardial imaging in the diagnosis of dementia with Lewy bodies, the problems in imaging technology and the possible research directions in the future, so as to provide valuable reference information for clinicians to reasonably and accurately apply this technology in the early diagnosis and discrimination of dementia.

Study on the relationship between serum cytokines levels after chimeric antigen receptor (CAR)-T cell immunotherapy and the prognosis of bridged allogeneic hematopoietic stem cell transplantation in acute B lymphoblastic leukemia patients / 中华检验医学杂志

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Proposal for risk control of thoracic surgery during the COVID-19 pandemic / 中华胸心血管外科杂志

With the change of COVID-19 prevention and control strategy in China, the number of COVID-19 cases has increased significantly recently, which has also brought new challenges to the perioperative risk control of thoracic surgery. This paper puts forward several suggestions, aiming to standardize the preoperative screening and evaluation during the COVID-19 period, strictly grasp the indications and timing of surgery, optimize the medical management process, individualize surgical decision-making, and minimize the risk of COVID-19 infection to surgery.

Expression and role of angiopoietin-like protein 4 signaling pathway in rats with adenine- induced chronic kidney disease / 中华肾脏病杂志

Objective:To observe the expression of angiopoietin-like protein 4 (ANGPTL4) signaling pathway in adenine-induced chronic kidney disease (CKD) rat model, and to explore the role of this pathway in renal fibrosis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into control group (saline, intragastric administration, n=15) and CKD group (250 mg·kg -1·d -1 2.5% adenine, intragastric administration, n=21). At the end of the 1st, 2nd and 4th week, 5 rats were randomly selected from each group. Renal function and 24-hour urinary protein quantity were measured. HE and Masson staining were used to observe the pathological changes of kidneys. Immunohistochemistry and real-time PCR were used to detect renal protein and mRNA expressions of hypoxia-inducible factor-1α (HIF-1α), ANGPTL4, bone morphogenetic protein 7 (BMP7), Smad1, α-smooth muscle actin (α-SMA) and type Ⅰ collagen (Col-Ⅰ). Pearson correlation analysis was used to analyze the correlation between the different indicators. Results:(1) Compared with the control group, the expression levels of serum creatinine and blood urea nitrogen in CKD group were higher at each time point, and the expression levels of 24-hour urinary protein quantity were higher at the end of the 2nd and 4th week (all P < 0.05). (2) HE and Masson staining showed that there were obvious renal structural disorders and collagen fiber deposition at each time point in CKD group compared with the control group, which got worse with time. (3) The results of immunohistochemistry and real-time PCR showed that compared with the control group, the protein and mRNA expression levels of ANGPTL4, α-SMA and Col-Ⅰ were higher, while the protein and mRNA expression levels of BMP7 and Smad1 were lower at the end of the 1st, 2nd and 4th week, and the protein and mRNA expression levels of HIF-1α were higher at the end of 2nd and 4th week in CKD group (all P < 0.05). (4) Correlation analysis results showed that HIF-1α and ANGPTL4 mRNA expression were positively correlated with α-SMA mRNA ( r=0.919, P < 0.001; r=0.757, P < 0.001), and also positively correlated with Col-Ⅰ mRNA ( r=0.925, P < 0.001; r=0.777, P < 0.001). HIF-1α mRNA expression was positively correlated with ANGPTL4 mRNA ( r=0.766, P < 0.001). There were significant negative correlations between HIF-1α, ANGPTL4 mRNA and BMP7 mRNA ( r=-0.652, P < 0.001; r=-0.741, P < 0.001). Conclusions:ANGPTL4 signaling pathway may be activated in adenine-induced CKD rat model, and involved in the renal fibrosis process of CKD.