BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.

OBJECTIVE: To investigate the effectiveness of spring ligament repair combined with subtalar arthroereisis (STA) and the Kidner procedure for treating children's flexible flatfoot with painful accessory navicular. METHODS: A retrospective analysis was conducted on clinical data from 45 children (45 feet) aged 7-14 years with flexible flatfoot and painful accessory navicular who met the selection criteria and were treated between February 2018 and May 2022. Among them, 23 cases (23 feet) were treated with spring ligament repair combined with STA and Kidner procedure (observation group), while 22 cases (22 feet) received STA with Kidner procedure alone (control group). Comparison of baseline data between the two groups including gender, age, affected side, preoperative visual analogue scale (VAS) score, American Orthopaedic Foot & Ankle Society (AOFAS) score, talonavicular coverage angle (TCA), talus-first metatarsal angle (T1MT), talus-second metatarsal angle (T2MT), talus first plantar angle (Meary angle), calcaneal inclination angle (Pitch angle) showed no significant differences ( P>0.05). The following parameters were recorded and compared between the two groups: operation time, intraoperative blood loss, incision length, hospital stay, time to full weight-bearing, and complication rates. Foot pain and functional recovery were assessed using the VAS score and AOFAS score preoperatively and at last follow-up. Radiographic measurements including TCA, T1MT, T2MT, Meary angle, and Pitch angle were analyzed by comparing preoperative to last follow-up values. RESULTS: Both groups of patients successfully completed the surgery without any procedure-related complications such as vascular, neural, or tendon injury. The operation time in the observation group was significantly longer than that in the control group ( P<0.05). There was no significant difference between the two groups in terms of intraoperative blood loss, incision length, hospital stay, or time to full weight-bearing ( P>0.05). All patients were followed up 23-47 months (mean, 33.7 months). In the control group, 1 patient experienced discomfort during walking, attributed to screw irritation in the sinus tarsi, which resolved after 2-3 months of rehabilitation. None of the remaining patients developed complications such as sinus tarsi screw loosening, peroneal tendon contracture, or wound infection. At last follow-up, the observation group showed significantly better improvements in radiographic parameters (TCA, T1MT, T2MT, Meary angle, Pitch angle) and greater reductions in VAS and AOFAS scores compared to the control group ( P<0.05). CONCLUSION The combined procedure of spring ligament repair, STA, and Kidner procedure for children's flexible flatfoot with painful accessory navicular demonstrates significant improvements in foot appearance, arch collapse correction, and pain relief. This technique offers technical simplicity, minimal intraoperative complications, and satisfactory clinical outcomes.
Humans ; Flatfoot/surgery* ; Child ; Retrospective Studies ; Adolescent ; Male ; Female ; Treatment Outcome ; Tarsal Bones/abnormalities* ; Subtalar Joint/surgery* ; Ligaments, Articular/surgery* ; Orthopedic Procedures/methods* ; Foot Diseases

Objective To measure the range of cervical spine mobility in flight trainees and analyze its correlation with flight task performance.Methods A total of 55 participants were enrolled(30 in the experimental group,25 in the control group).An independently developed AI-based digital cervical spine function assessment system was used to measure rotational ranges in yaw,pitch,and roll directions,with comparative analysis performed against contralateral rotation.A subjective scoring scale was designed,and flight instructors of the experimental group were invited to provide performance ratings to explore the relationship between cervical mobility and flight task performance.Results Significant differences were observed between the experimental and control groups in left rotation(P<0.01),right rotation(P<0.05),and flexion(P<0.05).Within the experimental group,significant differences were found between left and right rotation(P<0.01)and between flexion and extension(P<0.01).Correlation analysis between flight performance scores and cervical mobility revealed a significant association between situational awareness and yaw range(r=-0.415,P<0.05).Conclusion The experimental group exhibited significant differences in certain cervical mobility parameters compared to the control group,suggesting that occupational characteristics may influence cervical mobility.The correlation between yaw range and situational awareness implies a potential link between head-neck yaw capability and vestibular-visual system functions,though further validation is required.

Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

Objective:To investigate the effect of Jaceosidin on immune escape of colorectal cancer(CRC)cells by regulating cyclic guanosine monophosphate-adenylate synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:Human CRC cells HCT116 were cultured in vitro and grouped into control group,Jaceosidin-L group(25 μmol/L),Jaceosidin-M group(50 μmol/L),Jaceosidin-H group(100 μmol/L),activator group[100 μmol/L Jaceosidin+10 μmol/L cGAS activator manganese chloride(MnCl2·4H2O)],and inhibitor group(100 μmol/L Jaceosidin+1 μmol/L cGAS inhibitor RU.521);CCK-8 method was applied to de-tect the proliferation of HCT116 cells;flow cytometry was applied to detect apoptosis of HCT116 cells;HCT116 cells were co-cultured with NK cell to detect NK cell killing activity;ELISA was applied to detect the levels of IFN-γ and Granzyme B in the supernatant of co cultured cells;Western blot and qRT-PCR were applied to detect the expression of cGAS-STING signaling pathway and apoptosis related factors.Results:Compared with the control group,the A450 value and Bcl-2 expression of HCT116 cells in the Jaceosidin-L,Ja-ceosidin-M,and Jaceosidin-H groups were obviously reduced,the apoptosis rate,and the expression of cGAS,STING and Bax were obviously increased,and were dose-dependent(P<0.05);compared with the control co culture group,the levels of IFN-γ and Gran-zyme B,and NK cell killing activity in the supernatant of the Jaceosidin-L,Jaceosidin-M,and Jaceosidin-H co culture groups were significantly increased,in a dose-dependent manner(P<0.05);cGAS activator MnCl2·4H2O enhanced the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis,cGAS inhibitor RU.521 weakened the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis.Conclusion:Jaceosidin inhibits HCT116 cell proliferation,immune escape,and promotes cell apoptosis by activating cGAS-STING signaling pathway.

Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.

Objective:To investigate the effect of Jaceosidin on immune escape of colorectal cancer(CRC)cells by regulating cyclic guanosine monophosphate-adenylate synthase(cGAS)-stimulator of interferon gene(STING)signal pathway.Methods:Human CRC cells HCT116 were cultured in vitro and grouped into control group,Jaceosidin-L group(25 μmol/L),Jaceosidin-M group(50 μmol/L),Jaceosidin-H group(100 μmol/L),activator group[100 μmol/L Jaceosidin+10 μmol/L cGAS activator manganese chloride(MnCl2·4H2O)],and inhibitor group(100 μmol/L Jaceosidin+1 μmol/L cGAS inhibitor RU.521);CCK-8 method was applied to de-tect the proliferation of HCT116 cells;flow cytometry was applied to detect apoptosis of HCT116 cells;HCT116 cells were co-cultured with NK cell to detect NK cell killing activity;ELISA was applied to detect the levels of IFN-γ and Granzyme B in the supernatant of co cultured cells;Western blot and qRT-PCR were applied to detect the expression of cGAS-STING signaling pathway and apoptosis related factors.Results:Compared with the control group,the A450 value and Bcl-2 expression of HCT116 cells in the Jaceosidin-L,Ja-ceosidin-M,and Jaceosidin-H groups were obviously reduced,the apoptosis rate,and the expression of cGAS,STING and Bax were obviously increased,and were dose-dependent(P<0.05);compared with the control co culture group,the levels of IFN-γ and Gran-zyme B,and NK cell killing activity in the supernatant of the Jaceosidin-L,Jaceosidin-M,and Jaceosidin-H co culture groups were significantly increased,in a dose-dependent manner(P<0.05);cGAS activator MnCl2·4H2O enhanced the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis,cGAS inhibitor RU.521 weakened the inhibitory effects of high-dose Jaceosidin on HCT116 cell proliferation,immune escape,and the promoting effect on cell apoptosis.Conclusion:Jaceosidin inhibits HCT116 cell proliferation,immune escape,and promotes cell apoptosis by activating cGAS-STING signaling pathway.

Cancer stands as a significant global public health challenge,and cancer screening serves as a pivotal strategy for reducing its mortality.Presently,only a limited number of cancer types have appropriate screening methods available.Traditional single-cancer screen-ing approaches are fraught with limitations,including invasiveness,low accuracy,and poor patient compliance.Multi-cancer early detection(MCED)leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA,cell-free RNA,proteins,and metabolites in blood and other bodily fluids.This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage,showcasing immense potential for improving existing can-cer screening strategies.This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED,biomarker selection and detection technologies,the criteria for cancer type selection,research design and clinical utility evaluation,as well as implementation path-ways.The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED,thereby facilitating the continuous optimization of cancer screening strategies.