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.

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.

Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors

Abstract PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.

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.

Mental Health Status and Influencing Factors of Pediatricians in Guangzhou / 中山大学学报(医学科学版)

ObjectiveTo investigate the mental health of pediatricians in Guangzhou and its influencing factors， and to provide countermeasures for improving the mental health of pediatricians. MethodsA stratified random sampling method was used to randomly select 400 pediatricians in 11 districts of Guangzhou， and they were surveyed using the Symptom Check List（SCL-90） and the Job Stressor Scale. ResultsThe top three job stressors scored by pediatricians in Guangzhou were external environment （3.23±0.59）， workload （3.19±0.56）， and organizational management （2.74±0.55）. All factor scores were higher than those of the clinician group except for career interest， and the difference was statistically significant （P<0.01）. The number of pediatricians with mental health problems was 109， accounting for 27.25%. All factor scores were higher than the physician norm except for anxiety and paranoia. The correlations between each factor of work stressors and each factor of SCL-90 were positive and statistically significant （P<0.05）， except for two pairs of factors， workload and terror as well as external environment and terror. The results of univariate analysis showed statistically significant differences in the mental health scores of pediatricians with different health status， years of work experience， job satisfaction， job stress， and career prospects （P<0.05）. The results of multiple linear regression showed that health status， years of work experience， professional interest， interpersonal relationship， and doctor-patient relationship were influential factors in the mental health of pediatricians （P<0.05）. ConclusionThe mental health of pediatricians in Guangzhou is unsatisfactory， and the factors affecting them are mainly external objective factors such as workload and organizational management.

Progress in the treatment of bladder diverticulum / 中华泌尿外科杂志

Bladder diverticulum is a hernia formed by the protrusion of the mucosa through the weak muscularis propria of the bladder wall. It can be divided into congenital and acquired. Most patients are asymptomatic, and be found by physical examination or incidentally during the diagnosis and treatment of other diseases. The majority of bladder diverticula occur in male patients, mostly due to lower urinary tract obstruction. Severe diverticula may cause recurrent urinary tract infection or even malignant transformation, which requiring surgical treatment.

Prevalence and characteristics of comorbid insomnia and sleep apnea in community population / 中华健康管理学杂志

Objective:To analysis the prevalence and characteristics of comorbid insomnia and sleep disordered breathing (SDB) in community population.Methods:This is a cross-sectional study. Cluster sampling was applied. Community residents in Shantou and Meizhou were investigated during April to May, 2021. Essential information collection, sleep related health investigation, and sleep study were conducted. Insomnia was defined as the insomnia severity index (ISI)≥8. A type Ⅳ wearable intelligent sleep monitor was applied for sleep study. Comorbid insomnia and SDB was defined as both diagnosis of insomnia and SDB. Statistical analysis was conducted by SPSS 25. Prevalence and characteristics of insomnia only, SDB only and comorbid insomnia and SDB were analyzed. Logistic regression was conducted to analyze the relationship between sleep disorders and unrestored sleep, abnormal glucose metabolism, hyperlipidemia, and cardiovascular disease.Results:There were 3 730 residents completed the investigation. The median age was 55.0 (46.0, 63.0) years. The prevalence of insomnia only, SDB only, and comorbid insomnia and SDB were 26.0%, 20.2%, and 10.4% respectively. The incidence of unrestored sleep in insomnia only and comorbid insomnia and SDB were 2.900 times and 3.777 times of that in no insomnia or SDB (both P<0.001); the risk of hyperlipidemia was elevated in insomnia only, SDB only and comorbid insomnia and SDB ( OR=1.553, 1.415, and 1.868; all P<0.05); the risk of cardiovascular disease increased 40.8% in SDB only ( P=0.001), and 42.1% in comorbid insomnia and SDB ( P=0.007), after adjusted by age, sex, body mass index (BMI), smoking, drinking, abnormal glucose metabolism, and hyperlipidemia. Stratified analysis revealed that young female (age<60 years) with normal BMI (<25 kg/m 2) and comorbid insomnia and SDB were associated with higher risk of cardiovascular disease. Female with normal body weight and insomnia only or comorbid insomnia and SDB were associated with higher risk of hyperlipidemia. Conclusions:The prevalence of comorbid insomnia and SDB is high in community population. Patients with comorbid insomnia and SDB present with more significant unrestored sleep, and are correlated with higher risk of hyperlipidemia and cardiovascular diseases.

Clinical application and research progress of 225Ac for tumor targeted therapy / 中华核医学与分子影像杂志

In recent years, the application of alpha particle-based nuclide targeted therapy in tumors has shown great potential. 225Ac is a nuclide that can be used for alpha radionuclide targeted therapy which has been studied at home and abroad. A number of preclinical and clinical trials have been carried out, and some achievements have been obtained. This article summarizes the current research status of several malignant tumors, and analyzes the challenges and progress faced by 225Ac in radionuclide targeted therapy.

Efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the efficacy and safety of laparoscopic surgery in treatment of recurrent hepatocellular carcinoma.Methods:The clinical data of 58 patients with recurrent hepatocellular carcinoma who underwent surgical treatment from January 2010 to January 2018 at Hunan Provincial People’s Hospital were retrospectively analyzed. There were 50 males and 8 females, ranging in age from 28 to 78 (53.0±10.8) years old. Patients were divided into laparoscopic group ( n=27) and laparotomy group ( n=31) according to different surgical procedures. The differences in operative time, intraoperative blood loss, hospital stay, postoperative anal exhaustion time, postoperative complications and prognosis between the two groups were compared. Results:The intraoperative blood loss of laparoscopy group and laparotomy group were 100.0(50.0, 400.0) ml vs 300.0(100.0, 500.0) ml, the postoperative anal exhaustion time were (2.7±0.6) d vs (3.3±0.6) d, the hospital stay were (14.8±3.8) d vs (21.4±6.3) d, and these differences were statistically significant (all P<0.05). The operative time of the two groups were (243.4±27.2) min vs (217.5±34.7) min, with no statistical significance ( t=0.59, P=0.344). There were no significant differences between the two groups in postoperative complications (bile leakage, abdominal infection, hemorrhage, pleural effusion and hepatic encephalopathy) (all P>0.05); thetumor free survival, 1-year, and 3-year overall survival rates of the two groups were also not significantly different (both P>0.05). Conclusion:Laparoscopic surgery is safe and effective in the treatment of recurrent hepatocellular carcinoma, and its prognosis is similar to laparotomy, its complications are not significantly increased, which is worthy of promotion in clinic.

Clinical application differences between TW3-Carpal and TW3-RUS based artificial intelligence-assisted bone age assessment system: a real-world pilot study / 中华放射学杂志

Objective:To investigate the differences between Tanner-Whitehouse (TW)3-Carpal and TW3-RUS(radius, ulna and short bone)-based artificial intelligence (AI)-assisted bone age assessment system using real world data.Methods:The image data of 262 children who received X-ray examination of left wrist in the Affiliated Children′s Hospital, Capital Institute of Pediatrics from July to September 2021 were retrospectively collected. The AI bone age assistant methods based on TW3-RUS and TW3-Carpal criteria were used to obtain the bone age results, respectively. Two senior pediatric radiologists evaluated the bone age on the basis of TW3-RUS and TW3-Carpal criteria, and the averaged values of two reviewers was calculated and taken as the gold standard reference. The cases were stratified into six age groups at 3-year intervals according to the gold standard reference, including 1-3 ( n=10), 4-6 ( n=35), 7-9 ( n=70), 10-12 ( n=118), 13-15 ( n=27) and 16-18 ( n=2) years old groups. Intraclass correlation coefficient (ICC) was used to evaluate the consistency between AI results and the gold standard bone age results. Pearson correlation method was used to measure the reliability between AI results and the gold standard results. The difference of bone age results between using TW3-RUS and TW3-Carpal criteria in different age groups was compared using paired t-test. Results:As for the whole sample, the results based on TW3-RUS criteria were 8.9±3.1 years old for AI assessment and 8.7±2.9 years old for the golden standard reference, with the ICC of 0.983; and the results based on TW3-Carpal criteria were 8.7±3.0 years old for AI and 8.8±2.8 years old for the golden standard reference, with the ICC of 0.976. Positive correlation were found in both TW3-RUS ( r=0.985, P<0.001) and TW3-Carpal criteria groups ( r=0.978, P<0.001). There were significant differences between TW3-RUS and TW3-Carpal at age groups of 7-9( t=-3.36, P=0.001), 10-12( t=-1.77, P=0.046), and 13-15 years old ( t=1.84, P=0.040). The bone age assessment using TW3-RUS and TW3-Carpal criteria were both in good agreement with the gold standard reference in age group of 4-6 years old (ICC=0.929 and 0.940), as well as in age group of 7-9 years old (ICC=0.882 and 0.927, respectively), with the results using TW3-Carpal criteria were slightly higher. As for the age groups of 10-12 and 13-15 years old, the method using TW3-RUS criteria showed excellent agreement with the gold standard reference (ICC=0.962 and 0.963, respectively), which were better than the performance of method using TW3-Carpal criteria (ICC=0.744 and 0.605, respectively). Conclusions:AI-assisted bone age system based TW3-Carpal and TW3-RUS criteria both show good reliability and accuracy in the bone age measurements. The AI method based TW3-Carpal criteria shows better performance in age group of 4-9 years old, while the method based on TW3-RUS criteria may be better for children of age 10-15 years old.

Effect of echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation on the Lown classification in patients with hypertrophic obstructive cardiomyopathy / 中华超声影像学杂志

Objective:To investigate the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) guided by echocardiography on the Lown classification of ventricular arrhythmias in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:A total of 85 patients with HOCM who received PIMSRA treatment at Xijing Hospital of Air Force Military Medical University from May 2017 to October 2019 were retrospectively selected. All patients underwent 24-hour Holter examinations before and 1 year after PIMSRA to obtain parameters related to Lown classification. The changes in Lown grades after PIMSRA were analyzed. The patients were divided into improved group and unimproved group according to whether there was significant improvement in Lowen′s grades, and the difference of the parameters related were compared. The influencing factors of the changes in Lown classification were analyzed.Results:Compared with before PIMSRA, there was a significant improvement in the Lown classification after PIMSRA ( P=0.001). The patients with Lown grade Ⅰ increased significantly ( P=0.001), and the patients with grade Ⅲ decreased significantly ( P=0.005). There were no significant changes in patients with Lown grades 0, Ⅱ, and Ⅳ (all P>0.05). The proportion of patients with family history of hypertrophic cardiomyopathy (HCM), the baseline Lown classes, the reduction rate of the maximum left ventricular wall thickness and the reduction rate of the provocative left ventricular outflow tract gradient (LVOTG) were higher in the improved group than the unimproved group (all P<0.05). Multivariate Logistic regression results showed that HCM family history ( OR=3.95, 95% CI=1.34-11.64, P=0.013), baseline Lown classes ( OR=2.01, 95% CI=1.25-3.22, P=0.004) and the reduction rate of the provocative LVOTG gradient ( OR=1.02, 95% CI=1.00-1.04, P=0.041) were independent factors of postoperative Lown classification improvement. Conclusions:The Lown classes of HOCM patients after PIMSRA is significantly improved.HCM family history, the baseline Lown classes, and the reduction rate of postoperative provocative LVOTG are independent influencing factors for the improvement of Lown grade.

A follow-up study of percutaneous intramyocardial septal radiofrequency ablation in the treatment of obstructive hypertrophic cardiomyopathy with mild septal hypertrophy / 中华超声影像学杂志

Objective:To evaluate the clinical efficacy of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in the treatment of obstructive hypertrophic cardiomyopathy (HOCM) with mild septal hypertrophy.Methods:Forty-five HOCM patients with mild septal hypertrophy (the maximal left ventricular wall thickness is 15-19 mm) who were treated with PIMSRA between November 2016 to February 2021 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled, and their clinical datas were collected and analyzed. The clinical symptoms and NYHA functional class before operation, 6 months and 1 year after operation were collected. Interventricular septum thickness, left ventricular outflow tract pressure gradient, left ventricular outflow tract diameter, mitral regurgitation, left ventricular systolic and diastolic function were evaluated by transthoracic echocardiography before operation, 6 months and 1 year after operation, intraoperative complications were monitored and recorded. Postoperative arrhythmias were monitored by routine 12 lead ECG and 24-hour ambulatory ECG.Results:All patients successfully completed PIMSRA procedure.No clinical adverse events such as death, bleeding and stroke occurred during and around the operation.No left bundle branch block, complete atrioventricular block and malignant arrhythmia occurred after the operation. All patients did not need permanent pacemaker implantation.NYHA functional class and clinical symptoms of patients were significantly improved after 6 months compared with values before operation (all P<0.001, respectively), it remained stable for 1 year after operation; Anterior interventricular septum, posterior interventricular septum, maximal left ventricular wall thickness all significantly decreased (all P<0.001, respectively), left ventricular outflow tract diameter widened ( P<0.001), continuous improvement 1 year after operation; left ventricular outflow tract gradient and provoked left ventricular outflow tract gradient all significantly decreased, mitral regurgitation decreased and SAM classification reduced after 6 months compared with values before operation (all P<0.001, respectively); left ventricular end-diastolic diameter widened and left atrial diameter decreased (all P<0.001, respectively), it remained stable for 1 year after operation. Left atrial volume index decreased ( P<0.001), with continuous improvement 1 year after operation; The ratio of early diastolic mitral valve velocity to early diastolic mitral annulus velocity (E/e′) decreased ( P=0.001), it remained stable for 1 year after operation. There were no significant differences in left ventricular end diastolic volume, left ventricular end systolic volume and left ventricular ejection fraction among the three groups (all P>0.05). Conclusions:PIMSRA is effective in the treatment of obstructive hypertrophic cardiomyopathy with mild ventricular septal hypertrophy.

Novel biomarkers combination in the application of discriminating active tuberculosis and latent tuberculosis infection / 中华传染病杂志

Objective:To evaluate the expressions of three biomarkers combination of CD27, CD38 and human leucocyte antigen (HLA)-DR in the application of discrminating active tuberculosis (ATB) and latent tuberculosis infection (LTBI).Methods:Sixty cases of ATB and 44 cases of LTBI were enrolled from March 2021 to February 2022 in Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital. Freshly isolated peripheral blood mononuclear cells (PBMC) from patients were stimulated with 6 kDa early secretory antigenic target/culture filtrate protein 10 peptide pools. The expressions of CD27, CD38 and HLA-DR on Mycobacterium tuberculosis-specific CD4 + T lymphocytes were evaluated by polychromatic flow cytometry. Mann-Whitney U test was used for statistical analysis. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the diagnostic value of biomarkers in discriminating ATB and LTBI. Results:The frequencies of CD27 -, CD38 +, HLA-DR +, CD27 -CD38 +, CD27 -HLA-DR + and CD38 + HLA-DR + in ATB group were all higher than those in LTBI group, and the differences were all statistically significant ( U=26.00, 451.00, 384.00, 8.00, 7.00 and 184.00, respectively, all P<0.001). The AUROC of CD27 -CD4 + interferon-γ(IFN-γ) + T lymphocytes was 0.71 with a cut-off value of 52.31%, with the sensitivity of 50.00% and specificity of 87.20%. The AUROC of CD38 + CD4 + IFN-γ + T lymphocytes was 0.82 with a cut-off value of 30.25%, with the sensitivity of 73.40% and specificity of 89.70%. The AUROC of HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.85 with a cut-off value of 36.60%, with the sensitivity of 66.00% and specificity of 94.90%. The AUROC of CD27 -CD38 + CD4 + IFN-γ + T lymphocytes was 0.80 with a cut-off value of 8.82%, with the sensitivity of 90.60% and specificity of 61.50%. The AUROC of CD27 -HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.83 with a cut-off value of 18.62%, with the sensitivity of 75.00% and specificity of 79.50%. The AUROC of CD38 + HLA-DR + CD4 + IFN-γ + T lymphocytes was 0.93 with a cut-off value of 22.35%, with the sensitivity of 79.70% and specificity of 100.00%. Conclusions:The expressions of CD27 -, CD38 + and HLA-DR + in Mycobacterium tuberculosis-specific CD4 + T lymphocytes are higher in ATB group compared to LTBI group. ATB and LTBI could be well discriminated by detecting the expressions of CD27, CD38 and HLA-DR on CD4 + IFN-γ + T lymphocytes with flow cytometry.

Abnormal topology of cortical thickness covariance network and altered functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华行为医学与脑科学杂志

Objective:To explore the changes in topological attributes of structural covariance network based on cortical thickness and the brain functional activities in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis by graph theory and functional connectivity (FC) analyses, and to investigate whether these changes were correlated to cognitive impairment.Methods:A total of 33 patients with anti-NMDAR encephalitis from Department of Neurology of the First Affiliated Hospital of Guangxi Medical University(patient group) and 35 healthy controls(control group) with matched gender, age, and education were included from July 2018 to November 2021.All subjects received cognitive function assessments, structural and functional magnetic resonance imaging scans.Structural covariance networks were constructed in the two groups based on cortical thickness values and topological characteristics of networks were computed.A non-parametric permutation test which repeated 1 000 times was used to compare the characteristics of the networks between the two groups.Brain regions with abnormal topology were defined as region of interest(ROI), and FC values in global brain level were calculated.SPM 12 and RESTplus were used to identify the brain regions with significant differences in FC values between the two groups.Finally, Spearman correlation analysis between FC values of significant brain regions and cognitive scores were performed by SPSS 24.0.Results:The cognitive score of patients with anti-NMDAR encephalitis (27.0(23.5, 28.0)) was lower than that in control group(29.0(27.0, 30.0)) ( Z=-3.029, P=0.002). Graph theory analysis found that the patients showed significantly increased clustering coefficients ( P=0.004) and decreased global efficiency ( P=0.004) compared with healthy controls.Moreover, the nodal efficiency of left ventral posterior cingulate cortex (vPCC) and right dorsal posterior cingulate cortex (dPCC), as well as the nodal degree centrality of left vPCC and left polar planum of superior temporal gyrus (ppSTG) in patient group were significantly decreased ( P<0.05, FDR corrected) compared with control group.FC analysis showed the increased FC values between left vPCC and posterior cerebellum (MNI: x=6, y=-66, z=-21), as well as between left ppSTG and anterior cerebellum (MNI: x=6, y=-54, z=-12) (GRF corrected, voxel level P<0.001, cluster level P<0.05) in patient grooup.The FC values between left vPCC and posterior cerebellum were negatively correlated with the cognitive scores ( r=-0.403, P=0.020). Conclusion:Patients with anti-NMDAR encephalitis show abnormal topology of structural covariance network based on cortical thickness and altered FC values, some of which are correlated to cognition and may be the underlying neural mechanism of cognitive impairment in patients with anti-NMDAR encephalitis.