BACKGROUND:Crosslinked sodium hyaluronate gel has good mechanical property,biocompatibility,and biodegradability,and can be used as an isolated protective material in tumor radiation therapy to protect endangered organs from damage caused by excess radiation dose. OBJECTIVE:To investigate the safety and efficacy of crosslinked sodium hyaluronate gel in reducing the dose of radiation to dangerous organs during brachytherapy. METHODS:A total of 16 specific pathogen-free Kunming mice of the same age and similar body weight were selected as experimental subjects and divided into experimental group and control group by the random number table method,with 8 mice in each group.125I seeds were implanted subcutaneously in the back of mice in the experimental group,and then crosslinked sodium hyaluronate gel was injected around the radioactive particles.Only 125I seeds were implanted subcutaneously in the back of mice in the control group.After injection,the distance between the radioactive particles and the epidermis was measured by spiral CT scan,and the surface radiation dose was measured by radiation dosimeter.Within 10 weeks after injection,the growth state,survival rate,skin radiation damage,and gel retention of mice were observed. RESULTS AND CONCLUSION:(1)Spiral CT scan showed that the implanted gel was relatively concentrated and created an effective distance between the radioactive seeds and the epidermis.The body surface radiation dose of the experimental group was significantly lower than that of the control group(P<0.01).(2)During the experimental observation period,mice in both groups survived;mice in the control group showed obvious irritability and other unstable behavior in the late experimental period,and some mice in the experimental group showed similar behavior.The daily food intake of mice in the two groups had no significant change,and the body mass showed the same increasing trend.After implantation of radioactive seeds,the two groups of mice showed different degrees of radioactive skin injury.From day 23 after injection to the end of the experiment,the skin radiation injury score of the experimental group was lower than that of the control group(P<0.01).At week 10 after implantation,6 mice in the experimental group had no obvious gel residue under their skin,and 2 mice had a very small amount of scattered gel-like samples under their skin.(3)Therefore,the crosslinked sodium hyaluronate injection technique can increase the space between the radioactive target area of 125I seeds and the organ at risk outside the target through physical space occupying,which can effectively reduce the dose of the organ at risk,and play a role in the isolation and protection of the organ at risk.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective: To investigate the expression level of signal transducer and activator of transcription 4(STAT4) in lung adenocarcinoma(LUAD), and to analyze its impact on the proliferation, invasion, and migration abilities of LUAD cells. Methods: Gene expression omnibus data base(GEO),human protein atlas(HPA) and Kaplan-Meier Plotter databases were used to explore the expression of STAT4 in LUAD and its effect on the survival of patients with LUAD. Stable LUAD cell lines with STAT4 knockdown were constructed using lentiviral packaging technology, and the knockdown efficiency of STAT4 was assessed via RT-qPCR. The effects of STAT4 on LUAD cell proliferation were evaluated using CCK-8 assays and colony formation assays, while the impacts on cell migration and invasion were assessed through wound healing assays and Transwell assays. Results: STAT4 was lowly expressed in LUAD, and its low expression was unfavorable to the survival of LUAD patients. After STAT4 was knocked down in LUAD, the proliferation, invasion and migration abilities of lung adenocarcinoma cells were enhanced. Conclusion STAT4 is a prognostic marker in LUAD which significantly inhibits the proliferation, invasion, and migration abilities of LUAD cells. STAT4 is expected to become a new therapeutic target for LUAD.

The prevalence of food allergy is increasing worldwide and seriously affects the living quality of patients and their families. Egg allergy is one of the commonest forms of food allergy. The traditional regimen is to delay the introduction of eggs to infant complementary foods, which is not able to reduce the prevalence of egg allergies and causes negative effects on infants′ physical and psychological conditions. Oral tolerance therapy is an approach to establish immune tolerance by the active suppression of specific immune responses to antigens in the gastrointestinal tract. The development of oral tolerance through early introduction of eggs to infant complementary has proven effective in randomized controlled trials, which has been incorporated into infant feeding guidelines in many countries. This article focuses on the mechanism, efficacy and safety of oral tolerance induction in the prevention of egg allergy.

Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

AIM To explore the effects of Rosa roxburghii Radix on ulcerative colitis(UC)in rats based on pyroptosis and neutrophil extracellular traps(NETs).METHODS Rats were randomly divided into the normal group and the model group.The successfully established UC rat models by trinitrobenzene sulfonic acid(TNBS)/ethanol enema were then randomly divided into the model group,the sulfasalazine group(0.3 g/kg)and the low,medium and high dose R.roxburghii Radix groups(2,4,8 g/kg),followed by dosing of corresponding drugs by gavage.21 days later,the rats had their disease activity index(DAI)score calculated;their pathological changes of colon tissue observed by HE staining;their levels of serum interleukin(IL)-18,IL-1β and myeloperoxidase(MPO)detected by ELISA;and their protein expressions of NE,MPO,NLRP3,caspase-1 and GSDMD in colon tissue detected by Western blot and immunohistochemistry.RESULTS Compared with the normal group,the model group displayed increased DAI score(P＜0.01),increased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and increased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.01).Compared with the model group,the groups intervened with sulfasalazine,or medium,or high dose R.roxburghii Radix demonstrated with decreased DAI scores(P＜0.05,P＜0.01),decreased serum levels of IL-1β,IL-18 and MPO(P＜0.01),and decreased protein expressions of NE,MPO,caspase-1,NLRP3 and GSDMD in colon tissue(P＜0.05,P＜0.01).CONCLUSION R.roxburghii Radix may alleviate the inflammatory reaction in a rat model of UC and improve its pathological injury of colon via regulating pyroptosis and NETs.

Atherosclerosis(As)is a chronic inflammatory disease caused by lipid deposition.Panvascular disea-ses,which are mainly caused by As,have gradually attracted the attention of many scholars,and their main pathological features are vascular lesions.Vitamin D plays an important role in anti-As in panvascular diseases.It is involved in the regulation of renin-angiotensin system(RAS),endothelial cell injury,immune response,neutrophil extracellular traps(NET)regulation,apoptosis and autophagy,and is a new target in panvascular diseases research.Traditional Chinese Medicine(TCM)has certain advantages in the prevention and treatment of panvascular diseases.Among them,single herbs,active ingredients and compound prescriptions can regulate vitamin D-related metabolism,and have unique scientific value for the prevention and treatment of As.This article mainly discusses the role of vitamin D in multiple pathological links of panvascular diseases and related Chinese medicine interventions,aiming to provide effective ideas for the prevention and treatment of panvascular diseases from the perspective of vitamin D.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

The prevalence of food allergy is increasing worldwide and seriously affects the living quality of patients and their families. Egg allergy is one of the commonest forms of food allergy. The traditional regimen is to delay the introduction of eggs to infant complementary foods, which is not able to reduce the prevalence of egg allergies and causes negative effects on infants′ physical and psychological conditions. Oral tolerance therapy is an approach to establish immune tolerance by the active suppression of specific immune responses to antigens in the gastrointestinal tract. The development of oral tolerance through early introduction of eggs to infant complementary has proven effective in randomized controlled trials, which has been incorporated into infant feeding guidelines in many countries. This article focuses on the mechanism, efficacy and safety of oral tolerance induction in the prevention of egg allergy.

Objective:To analyze the clinical manifestations, gene mutation characteristics and treatment effects of patients with GATOR1 complex-related epilepsy, and to explore the diagnosis and treatment of this disease.Methods:The medical history, electroencephalogram, brain imaging, genetic test results, treatment and follow-up data of patients with GATOR1 complex-related epilepsy who attended the Children′s Hospital Affiliated to Capital Institute of Pediatrics, Beijing Tsinghua Changgung Hospital, and Shanghai Deji Hospital from May 2017 to July 2022 were retrospectively analyzed.Results:A total of 16 patients with GATOR1 complex-related epilepsy were collected, including 7 males and 9 females. The age of onset of epilepsy was from 2 months to 14 years. Ten cases had focal seizures only, 2 cases had generalized seizures only, and 4 cases had coexistence of focal seizures and generalized seizures, of which generalized seizures included generalized tonic-clonic seizure, spastic seizure, and myoclonic seizure. Among the 16 patients, 2 had infantile spasms, 3 had familial focal epilepsy with variable focus, and 1 had sleep related hyperkinetic epilepsy. Electroencephalogram intervals suggested multiple brain areas discharge or diffuse discharge. A total of 13 DEPDC5 gene mutation sites, 1 NPRL2 gene mutation site, and 2 NPRL3 gene mutation sites were found; 4 sites of DEPDC5 gene were reported sites, the rest were unreported; all mutations had pathogenic significance; 8 cases had nonsense mutation, 1 case had large fragment deletion, 4 cases had frameshift mutation, 1 case had integer mutation, 2 cases had splicing mutation; 13 cases′ mutation was inherited from parents, 2 cases had new mutation, and 1 case had unverified mutation. Magnetic resonance imaging (MRI) showed 5 of the 16 patients were normal, and 11 had abnormal cerebral cortex structure, manifested as bottom-of-sulcus focal cortical dysplasia (FCD), abnormal formation of sulci and (or) gyri with or without ill-defined gray-white matter and malformation of cortical dysplasia of the bilateral brain. Seven patients underwent stereotactic electroencephalogram (SEEG) monitoring, and the SEEG showed low-amplitude fast rhythm at the beginning in 6 patients, of whom 5 cases started from the frontal lobe, and 1 case started from the parietal lobe. Eight patients were only treated with drugs, 1 with single-drug therapy and the rest with multi-drug combination therapy. Eight patients underwent surgery. Among them, 5 patients with DEPDC5 gene mutation underwent epileptogenic cortex excising after SEEG monitoring, and postoperative pathological examinations showed FCDⅡ, FCDⅢ or non-specific changes; 1 patient was waiting for surgery. One patient with NPRL3 gene mutation underwent epileptogenic foci resection and postoperative pathological examinations showed FCDⅡa; the other patient with NPRL3 gene mutation underwent radiofrequency thermocoagulation after SEEG monitoring. Follow-up showed that 3 patients were seizure-free with drug treatment, and 4 patients had fewer seizures after drug treatment. Six cases underwent epileptic foci resection. Five of them were assisted by SEEG to locate the epileptic foci before surgery and were seizure-free after the operation, but the range of surgical resection was wider than the abnormal range shown by MRI; whereas 1 case who was not assisted by SEEG showed no improvement. There was still 1 case who underwent SEEG-guided radiofrequency thermocoagulation and had no improvement after operation. Conclusions:GATOR1 complex-related epilepsy mostly manifests as focal seizures. SEEG shows that seizures originate from the frontal lobe more often, and cortical developmental abnormalities are often found. DEPDC5 gene mutations are the most common ones, mostly inherited from parents, with high incomplete penetrance rate. Therefore, genetic testing is recommended for non-acquired brain structural abnormalities. For those who are refractory to drugs, a radical cure can be obtained by resection of the epileptogenic foci after preoperative evaluation.