OBJECTIVE: To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy. METHODS: The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type. RESULTS: Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume. CONCLUSION The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Neoplasms/radiotherapy* ; Female

Objective:To compare the outcomes of multiple scales, primarily the speech, spatial, and other qualities of hearing scale for parents（SSQ-P）, in children with ipsilateral vs. Contralateral cochleareimplantat ion（CRI）. Methods: A total of 69 children who received cochlear implantation surgery from April 1999 to June 2024 were included. Patients were divided into two groups based on whether the implantation was on the same side. General information such as gender, age, age at initial implantation and reimplantation was collected. The primary caregivers of the children were followed up by telephone using the categories of auditory performance（CAP）, speech intelligibility rating（SIR）, and SSQ-P questionnaires. Statistical methods including stepwise regression, linear regression, and permutation tests were employed to investigate if there were any statistically significant differences in the scores of CAP, SIR, SSQ-P total, SSQ-P speech perception, SSQ-P spatial hearing, and SSQ-P auditory quality dimensions between the ipsilateral and contralateral reimplantation groups. Results:Of the 69 children included, 62 were in the ipsilateral reimplantation group with a mean age of 11.1 years, and 7 were in the contralateral reimplantation group with a mean age of 11.7 years. Statistical analysis showed that patients in the contralateral reimplantation group had significantly lower SSQ-P total scores （P<0.05） and spatial hearing dimension scores （P<0.05） than those in the ipsilateral reimplantation group after controlling for the corresponding confounders. Conclusion:The effect of ipsilateral reimplantation of cochlear implants is superior to that of contralateral reimplantation in terms of overall auditory function and spatial hearing in daily life for children, but the mechanisms require further investigation.
Humans ; Cochlear Implantation ; Child ; Parents ; Speech Perception ; Male ; Cochlear Implants ; Female ; Hearing ; Surveys and Questionnaires ; Speech ; Child, Preschool

Objective:To explore the feasibility and preliminary efficacy of domestic single-port robotic surgical system in the surgical treatment of thyroid cancer. Methods:Thyroid cancer patients who underwent domestic single-port robotic surgery in the Department of Head and Neck Surgery of Sichuan Cancer Hospital from June 2024 to January 2025 were prospectively included. Clinical data, oncological characteristics, and perioperative indicators were systematically collected. Results:A total of 7 patients were included, including 3 males and 4 females, with an age of （34.57±10.26） years. All procedures were successfully completed without conversion to open surgery. Operative time was（180.00±30.41） minutes. Blood loss was（5.00[15.00 ]）mL. Postoperative drainage volume was （167.86±130.95） mL. The postoperative pathological results were all thyroid papillary carcinoma. There were no system failures, no device-related complications and adverse events were observed during the operation and perioperative period. No tumor recurrence or metastasis was observed during the follow-up period. Conclusion:Preliminary data indicate that the domestic single-port robotic surgical system is safe and feasible for the surgical treatment of thyroid cancer, providing a practical basis for subsequent multi-disease, multi-center, and large-sample studies.
Humans ; Thyroid Neoplasms/surgery* ; Robotic Surgical Procedures/instrumentation* ; Male ; Female ; Adult ; Thyroidectomy/methods* ; Operative Time ; Middle Aged ; Prospective Studies

Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.

Objective:To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency.Methods:A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children’s Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein. Results:The probands (Ⅱ 2, Ⅱ 10), their brother (Ⅱ 5) and sons (Ⅲ 1, Ⅲ 8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c. 851T>C (p.Met284Thr) missense variant in exon 5 of the SERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c. 851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+ PM1+ PM5+ PP1+ PP4). Conclusion:The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c. 851 T>C (p.Met284Thr) variant of the SERPINC1 gene may be accountable.

The DNA characterization of Cannabis sativa L.has been one of the key directions of anti-drug research at home and abroad.Previous research mainly focused on the identification of cannabis-species and gender differentiation,and have constructed a number of corresponding composite amplification systems.With the rapid development of high-throughput sequencing technology,the whole genome of C.sativa and the sequences of key enzyme genes for its major physicochemical components have been sequenced successively,and intra-species differentiation studies of C.sativa based on specific molecular markers have gradually emerged.However,due to the high variability of cannabis subspecies-and variety-specific molecular markers,relevant foreign studies failed to provide ideal molecular marker support for the identification of intra-specific distinctions of Cannabis sativa in China.Based on this,this paper comprehensively analyzes the current situation and shortcomings of domestic and international research on intra-specific differentiation of C.sativa,and combines the previous research results of this group to elaborate on how to use high-throughput sequencing technology to solve the problem of the lack of intra-specific molecular markers of C.sativa in China.

Objective To explore the myopia control effect of orthokeratology(OK)lenses and build a prediction model of myopia control effect based on random forest and Logistic regression,so as to provide a basis for further impro-ving adolescent vision.Methods A total of 289 patients who wore OK lenses after seeing an ophthalmologist in Shiji-azhuang People's Hospital from January to June 2019 were selected as the OK lens group,and a total of 289 patients who wore framed glasses during the same period were selected as the framed glass group.After 2 and 4 years of wearing,the in-crease in axial length(AL)of the patients was observed.The patients were divided into a well-controlled myopia group and a poorly-controlled myopia group according to the changes in AL of the eyes after wearing OK lenses for 4 years.The fac-tors influencing the myopia control effect were analyzed based on random forest and Logistic regression,and a nomogram prediction model was constructed.The performance of the model was evaluated using the receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results After 2 and 4 years,the diopter increase and AL increase of patients wearing OK lenses were lower than those of patients wearing framed glasses(all P＜0.001).There were no significant changes in corneal endothelial cell parameters and central corneal thickness at the thinnest point before,2 years and 4 years after wearing between the two groups(all P＞0.05).The random forest model showed that basic AL,daily wear time,correct eye health behavior,pupil diameter,daily outdoor activity time,homework time after school,and daily sleep time were the top 7 variables in importance ranking.Logistic regression analysis showed that home-work time after school was a risk factor for poor myopia control in OK lens wearers,while basic AL,pupil diameter,daily wear time,correct eye health behavior,daily outdoor activity time,and daily sleep time were protective factors for myopia control.The ROC curve,calibration curve,and DCA suggested that the nomogram prediction model constructed based on random forest and Logistic regression analysis had good accuracy,consistency and clinical effectiveness.Conclusion OK lens shows good myopia control effect,has little effect on corneal endothelial cells and corneal thickness,and demon-strates high safety.Homework time after school,basic AL,pupil diameter,daily wear time,correct eye health behavior,daily outdoor activity time,and daily sleep time are influencing factors of myopia control.Strengthening the construction of a prediction model is helpful in identifying high-risk groups with poor myopia control and guiding clinical interventions in time.

Acute respimtory distress syndrome(ARDS)is an acute diffuse inflammatory lung injury caused by various internal and external lung injury factors.It has complex pathogenesis,rapid onset and high mortality,which seriously endangers human life and health.Pulmonary fibrosis is one of the important pathologic processes of ARDS occurrence and development,and it is also an important cause of death in ARDS patients.To a certain extent,the severity of pulmonary fibrosis in ARDS is determined by the dynamic balance of macrophage-fibroblast interactions.Therefore,this article aims to review the interaction mechanism of macrophage-fibroblasts in the pro-cess of ARDS pulmonary fibrosis,and provide new methods and ideas for the diagnosis and treatment of ARDS pul-monary fibrosis.

AIM:This study aims to investigate the impact of nobiletin(NOB)on the gut microbiota and short-chain fatty acids(SCFAs)in high-fat diet-induced obese rats.METHODS:A total of 22 SD rats were randomly di-vided into the control(CON)group and high-fat diet(HFD)group.The HFD induced obesity,upon successful modeling,the rats were further divided into the HFD and NOB group,each group consisting of 6 rats.The NOB group received nobi-letin solution(100 mg·kg-1·d-1)via gavage for 21 consecutive days.Body weight was measured bi-daily,and hematoxylin-eosin(HE)staining was employed to observe pathological changes in adipose tissue and liver.Serum lipid levels were as-sessed using an auto-biochemical analyzer.Analysis of the gut microbiota was performed using 16S ribosomal RNA(rRNA)sequencing,while high-performance liquid chromatography mass spectrometry(LC-MS)was used to determine SCFAs levels in rat feces.RESULTS:Compared with CON group,HFD-fed demonstrated a substantial increase in body weight(P<0.01),accompanied by an augmentation in adipocyte diameter and the presence of hepatic cell vacuolization,indicative of cellular steatosis and inflammation.Moreover,there was a notable elevation in TG and TC levels(P<0.05).At the phylum level,the HFD rats exhibited an altered composition,characterized by an increase in Firmicutes and a con-current decrease in Bacteroidetes.At the genus level,Bacteroides,Lactobacillus and Blautia experienced a significant de-crease,while Colidextribacter showed an increase.Notably,there was a substantial reduction in the expression of propion-ic acid and butyric acid.In comparison to the HFD group,rats administered with NOB demonstrated a marked decrease in body weight(P<0.05),a reduction in adipocyte diameter,and an amelioration in hepatic cell vacuolization and cellular steatosis.Furthermore,TG and TC levels exhibited a significant decrease(P<0.05).At the phylum level,Firmicutes de-creased,and Bacteroidetes increased.At the genus level,Bacteroides,Lactobacillus and Blautia exhibited a significant in-crease,while Colidextribacter displayed a decrease.Additionally,there was an up-regulation of propionic acid and butyric acid levels in the NOB group.CONCLUSION:Nobiletin,through its multifaceted actions,demonstrates a potential anti-obesity effect by effectively reducing body weight in obese rats.This includes the regulation of gut microbiota structure,modulation of SCFAs content,and enhancement of lipid metabolism.