Drug clinical trial is a method of experimental epidemiology to evaluate the effectiveness and safety of medicines.This article introduced the types and design thought of innovation in drug clinical trial design,and provided methodological reference for related researches.Adaptive design is a complex and innovative clinical trial design,which can be divided into group sequential design,sample size re-estimation,seamless trial,enrichment design and master protocol design(basket trial,umbrella trial,platform trial,etc.)according to the purpose of adaptability.The adaptive design has greater adjustment flexibility,which overcomes the shortcomings of conventional clinical trials to a certain extent,then improves the validity of the trial results and the strength of the evidence.The design innovation and remodeling of drug clinical trials will provide more powerful evidence-based evidence for the realization of precision medicine.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective To explore the application of goal-directed fluid therapy based on pulse pressure variation rate(PPV)combined with low central venous pressure(LCVP)technique in liver surgery.Methods A total of 86 patients who underwent liver lobe/segment resection in our hospital from January 2022 to December 2023 were included,and randomly divided into two groups by random sequence method.Patients in the conventional group were treated with LCVP technique,while patients in the test group were given PPV goal-directed intervention on the basis of the conventional group.The surgical indicators,hemodynamic indicators,cognitive function,adverse reactions and recovery of gastrointestinal function of patients in the two groups were compared.Results There was no statistically significant difference in the operation time,Pringle maneuver time,first postoperative exhausting time or first postoperative defecation time of patients between the two groups(P>0.05).However,the intraoperative blood loss,intraoperative fluid infusion volume and hospital stay of patients in the test group were all less/shorter than those in the conventional group(P<0.05).Compared with the time point of T0,patients in the two groups showed increased heart rate(HR)but decreased mean arterial pressure(MAP)and central venous pressure(CVP)at time points of T1 and T2(P<0.05).There was no statistically significant difference in the HR or MAP of patients between the two groups at time points of T0,T1,T2 and T3(P>0.05).At time points of T1 and T2,the CVP of patients in the test group was lower than that in the conventional group(P<0.05).One day after operation,the mini-mental state examination(MMSE)score of patients in the test group was higher than that in the conventional group(P<0.05).The MMSE scores 7 days after operation of patients in the two groups were higher than those 1 day after operation(P<0.05).Patients in the test group had a lower total incidence of adverse reactions and a shorter recovery time of gastrointestinal function than those in the conventional group(P<0.05).Conclusion The goal-directed fluid therapy based on PPV combined with LCVP technique has a good application effect in liver surgery,which can reduce intraoperative blood loss and fluid infusion volume of patients,shorten hospital stay,increase hemodynamic stability,improve postoperative cognitive dysfunction,and promote the recovery of gastrointestinal function,with a relatively high treatment safety.

Given the lack of annotations for key lung organs and tissues in existing public datasets,this study collected 863 cases of chest CT scan images and constructed the first comprehensive dataset containing annotations of pulmonary vessels,airways,and nodules using a semi-automated method that combines computer vision algorithms with manual corrections by radiologists.On this basis,a lung nodule segmentation model based on multi-task learning is proposed.By incorporating annotations of pulmonary vessels(pulmonary arteries and veins)and the trachea to enhance model's ability to learn lung features,the proposed model reduces the false discovery rate in lung nodule detection,and improves generalization ability.Additionally,the use of larger image patches further optimizes model performance.The trained VAAN_128 model achieves the best performance,with a Dice coefficient of 0.694 and a false discovery rate of 0.210 for lung nodule segmentation.Moreover,it simultaneously provides accurate segmentation results of pulmonary vessels and the trachea,assisting in the formulation of more precise diagnosis and treatment plans.Based on the VAAN_128 model,a software system for navigation and localization in biopsy procedures is developed.In clinical practice,this system can assist physicians in accurately locating lung nodules,distinguishing critical tissues,and improving preoperative planning efficiency.This provides precise and efficient technical support for early diagnosis and disease monitoring of lung diseases,and is of great significance for path planning in clinical navigation system and future lung imaging research.

Objective:To investigate the clinical value of dynamic AI ultrasonic intelligent assisted diagnosis system for preoperative evaluation of thyroid nodules with diameter ≤1.0 cm.Methods:From Apr. 1, 2023, to Dec. 30, 2023, 742 thyroid nodules with diameter ≤1.0 cm were removed from 532 patients with thyroid nodule disease who received surgical treatment in the Department of Thyroid (hernia) of the First Medical Center of the Chinese People’s Liberation Army General Hospital. Among them, 423 were d≤0.5 cm. 319 cases (235 males and 507 females) with 0.5

Objective:To analyze the perioperative risks and prognosis in patients with differentiated thyroid cancer (DTC) complicated by Graves' disease (GD) .Methods:Clinical data of 880 DTC patients who underwent radical thyroidectomy at the Department of General Surgery, the First Medical Center of Chinese PLA General Hospital between Jan. 2016 and Dec. 2022 was retrospectively collected. The cohort included 119 DTC patients with GD (hyperthyroid group) and 761 DTC patients with normal thyroid function without GD (normal group) . Use propensity score matching (PSM) was used to obtain cohorts with balanced baseline characteristics between the hyperthyroid and normal groups. Perioperative risks and prognos were compared between the two groups.Results:For perioperative risk comparison, after 1∶2 matching, 116 patients were included in the hyperthyroid group and 232 patients in the normal group. The operation time was longer in the hyperthyroid group compared to normal group ([107.26±30.27]min vs. [96.45±32.51]min, P=0.003) . There were no statistical differences between the two groups in intraoperative blood loss, postoperative drainage volume or postoperative hospital stay ( P>0.05) . There were no statistical difference in the incidence of complications such as temporary or permanent hypoparathyroidism, temporary or permanent recurrent laryngeal nerve injury, and lymphatic leakage between the two groups. For prognostic comparison, after 1∶2 matching, 117 cases were included in the hyperthyroid group and 234 cases in the normal group. During follow-up period, 16 patients experienced DTC recurrence, including 5 cases in the hyperthyroid group and 11 cases in the normal group. There was no statistical difference in reccurence-free survival rates between the two groups (5-year RFS: 95.7% vs. 95.3%, P=0.907) . Multivariate Cox regression analysis revealed GD was not the risk factor for DTC recurrence. Conclusions:With standardized and adequate preoperative preparation, the perioperative risks of DTC patients complicated by GD were not increased compared to patients without GD. Additionally, GD does not increase the risk of postoperative tumor recurrence in DTC patients.

Objective Investigate the clinical efficacy and application value of gasless trans-subclavian approach endoscopic surgery(GTAES)for the treatment of primary hyperparathyroidism(PHPT).Methods 55 PHPT patients who underwent unilateral parathyroid adenoma resection from January 2023 to October 2024 were absorbed.Based on surgical approaches,31 patients were divided into the traditional low-collar arc incision open surgery group(open group)and 24 patients were divided into gasless trans-subclavian approach endoscopic surgery group(endoscopic group).The perioperative data,anterior neck function recovery,and incision healing were compared between two groups.Results There were no significant differences in operation time,intraoperative blood loss,postoperative drainage volume and postoperative hospital stay between the two groups(P＞0.05).The preoperative blood calcium levels of the endoscopic group and the open group were(2.68±0.10)mmol/L and(2.63±0.16)mmol/L,respectively.The blood calcium levels on the first day after surgery were(2.39±0.12)mmol/L and(2.36±0.16)mmol/L,respectively.Preoperative parathyroid hormone(PTH)was 27.55(110.05,155.75)pg/ml in endoscopic group and 137.00(107.00,210.30)pg/ml in open group,respectively.PTH on the first day after surgery was 18.98(12.64,23.53)pg/ml and 13.85(7.36,23.23)pg/ml,respectively.Blood calcium and PTH in each group 1 day after surgery decreased compared with that before surgery,and the difference was statistically significant(P＜0.05).There were no postoperative complications such as hoarseness,bleeding and incision infection in both groups.Postoperative hand and foot numbness:5 cases(20.8％)in endoscopic group and 8 patients(25.8％)in the open group,there was no significant difference between the two groups(P=0.667).There was no significant difference in the score of neck pain 3 days after surgery between the two groups(P＞0.05).The score of swallowing tension[(1.92±1.06)points compared with(2.77±1.38)points,P=0.015]and the score of anterior neck discomfort[(1.63±0.88)points compared with(2.35±1.33)points,P=0.018]in the endoscopic group one month after surgery were better than those in the open group.There was no significant difference in the score of neck scar scale between the two groups 3 months after surgery(P＞0.05).VAS score of incision satisfaction was(9.08±0.88)in endoscopic group and(8.19±1.30)in open group,and the endoscopic group was better than the open group,the difference was statistically significant(P=0.004).Conclusion For PHPT patients caused by unilateral parathyroid adenoma confirmed through preoperative localization examination,GTAES is a safe and effective surgical approach,which offers unique advantages in intraoperative lesion identification,cosmetic outcomes of the incision,and preservation of anterior neck function,providing a new surgical option for PHPT patients.

Given the lack of annotations for key lung organs and tissues in existing public datasets,this study collected 863 cases of chest CT scan images and constructed the first comprehensive dataset containing annotations of pulmonary vessels,airways,and nodules using a semi-automated method that combines computer vision algorithms with manual corrections by radiologists.On this basis,a lung nodule segmentation model based on multi-task learning is proposed.By incorporating annotations of pulmonary vessels(pulmonary arteries and veins)and the trachea to enhance model's ability to learn lung features,the proposed model reduces the false discovery rate in lung nodule detection,and improves generalization ability.Additionally,the use of larger image patches further optimizes model performance.The trained VAAN_128 model achieves the best performance,with a Dice coefficient of 0.694 and a false discovery rate of 0.210 for lung nodule segmentation.Moreover,it simultaneously provides accurate segmentation results of pulmonary vessels and the trachea,assisting in the formulation of more precise diagnosis and treatment plans.Based on the VAAN_128 model,a software system for navigation and localization in biopsy procedures is developed.In clinical practice,this system can assist physicians in accurately locating lung nodules,distinguishing critical tissues,and improving preoperative planning efficiency.This provides precise and efficient technical support for early diagnosis and disease monitoring of lung diseases,and is of great significance for path planning in clinical navigation system and future lung imaging research.