Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Immunotherapy has achieved relatively satisfactory results in the treatment of non-small cell lung cancer (NSCLC), but not all patients can benefit from immunotherapy. Peripheral blood-based markers are easily accessible and can be monitored dynamically. Peripheral blood tumor cell-related markers (circulating tumor DNA, circulating tumor cells, peripheral blood tumor mutation load, exosomes, etc.), as well as immune and inflammatory markers (T-lymphocyte subpopulations, hematology-associated ratios, C-reactive protein, etc.) have demonstrated great potential in immunotherapy efficacy prediction, prognosis evaluation, and dynamic monitoring.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To observe the changes in choroidal morphology and blood perfusion in patients with macular edema secondary to retinal vein occlusion (RVO) after intravitreal injections of ranibizumab.Methods:A cohort study was performed.A total of 157 patients (157 eyes) with macular edema secondary to monocular acute retinal vein occlusion (RVO) were enrolled in the Third People's Hospital of Dalian from January 2022 to March 2023.There were 66 cases (66 eyes) with central retinal vein occlusion (CRVO) and 91 cases (91 eyes) with branch retinal vein occlusion (BRVO).All patients were treated with 3+ pro re nata (PRN) regimen of ranibizumab.Before and 1 month after each injection, the central retinal thickness of the macula was measured by optical coherence tomography (OCT).Clear images of the choroid were obtained using the OCT enhanced depth scan mode.Subfoveal choroidal thickness (SFCT), the nasal choroidal thickness at 1 500 μm of macula (CT N1.5 mm), the temporal choroidal thickness at 1 500 μm of macula (CT T1.5 mm) were measured and mean macular thickness (CT Mean) was calculated.Binarization of choroidal images processed by ImageJ software was used to analyze luminal area (LA), stromal area (SA) and total choroidal area (TCA), and choroidal vascularity index (CVI) was calculated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Dalian (No.2023-145-001).Results:SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI of RVO eyes were higher than those of the contralateral eyes and the differences were statistically significant (all P<0.01).CT Mean in CRVO group was (326.99±64.92)μm, which was higher than (299.80±73.08)μm in BRVO group, with a statistically significant difference ( t=2.41, P=0.02).Baseline CVI values in CRVO group and BRVO group were (72.50±5.62)% and (72.33±5.85)%, respectively, with no significant difference ( t=0.187, P=0.85).In eyes with RVO, CRVO and BRVO, SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI after every injection were lower than the baseline and the differences were statistically significant (all P<0.05).In eyes with CRVO, there was no significant difference in LA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with BRVO, there was no significant difference in SA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with RVO, CRVO and BRVO, there was no significant difference in SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA, TCA and CVI between second and third injections (all P>0.05). Conclusions:After intravitreal injection of ranibizumab, the choroidal thickness becomes thinner and CVI decreases in eyes with macular edema secondary to RVO, and remain relatively stable after the second injection.

Objective:To observe the changes in choroidal morphology and blood perfusion in patients with macular edema secondary to retinal vein occlusion (RVO) after intravitreal injections of ranibizumab.Methods:A cohort study was performed.A total of 157 patients (157 eyes) with macular edema secondary to monocular acute retinal vein occlusion (RVO) were enrolled in the Third People's Hospital of Dalian from January 2022 to March 2023.There were 66 cases (66 eyes) with central retinal vein occlusion (CRVO) and 91 cases (91 eyes) with branch retinal vein occlusion (BRVO).All patients were treated with 3+ pro re nata (PRN) regimen of ranibizumab.Before and 1 month after each injection, the central retinal thickness of the macula was measured by optical coherence tomography (OCT).Clear images of the choroid were obtained using the OCT enhanced depth scan mode.Subfoveal choroidal thickness (SFCT), the nasal choroidal thickness at 1 500 μm of macula (CT N1.5 mm), the temporal choroidal thickness at 1 500 μm of macula (CT T1.5 mm) were measured and mean macular thickness (CT Mean) was calculated.Binarization of choroidal images processed by ImageJ software was used to analyze luminal area (LA), stromal area (SA) and total choroidal area (TCA), and choroidal vascularity index (CVI) was calculated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of the Third People's Hospital of Dalian (No.2023-145-001).Results:SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI of RVO eyes were higher than those of the contralateral eyes and the differences were statistically significant (all P<0.01).CT Mean in CRVO group was (326.99±64.92)μm, which was higher than (299.80±73.08)μm in BRVO group, with a statistically significant difference ( t=2.41, P=0.02).Baseline CVI values in CRVO group and BRVO group were (72.50±5.62)% and (72.33±5.85)%, respectively, with no significant difference ( t=0.187, P=0.85).In eyes with RVO, CRVO and BRVO, SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA, SA, TCA and CVI after every injection were lower than the baseline and the differences were statistically significant (all P<0.05).In eyes with CRVO, there was no significant difference in LA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with BRVO, there was no significant difference in SA and CVI between first and second injections (both P>0.05), and SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, LA and TCA after second injection were lower than those after first injection with statistically significant differences (all P<0.05).In eyes with RVO, CRVO and BRVO, there was no significant difference in SFCT, CT T1.5 mm, CT N1.5 mm, CT Mean, SA, TCA and CVI between second and third injections (all P>0.05). Conclusions:After intravitreal injection of ranibizumab, the choroidal thickness becomes thinner and CVI decreases in eyes with macular edema secondary to RVO, and remain relatively stable after the second injection.

Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Child ; Child, Preschool ; Humans ; Male ; Cafe-au-Lait Spots ; Computational Biology ; Genetic Testing ; Genomics ; Intellectual Disability/genetics* ; Mutation

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To survey and supervise the risk of infection control and radiation safety in the radiological diagnostic workplace for COVID-19, and provide data support for the safety protection of radiographers and related staff.Methods:4 emergency hospitals for COVID-19 including 2 makeshift hospitals, module hospital and brick pattern hospital in Hubei province were performed for testing and evaluation of imaging performance and radiological protection for the 8 new installed CT scanners and places according to the national standards of WS 519-2019 and GBZ 130-2013. The infection control safety factors such as the layout of the equipment room were monitored and investigated. Two COVID-19 designated hospitals including general hospital and infectious disease specialized hospital were selected to carry out field investigation and sampling of environmental biological samples for 4 CT rooms. Then the samples were detected for the nucleic acid of novel coronavirus. The results of radiodiagnostic workplace overall arrangement, infection prevention and the nucleic acid testing were analyzed, and the biological safety reliability and risk point were evaluated.Results:The indicators of imaging performance and radiation protection for 8 CT scanners in emergency hospitals could meet the requirements of national standards.Each of 2 makeshift hospitals had 3 CT rooms with the area of 38.8 m 2 and 4 mm Pb equivalent thickness of protective shielding. The CT rooms in module hospital and brick pattern hospital were 20.0 m 2, and 35.8 m 2 in areas, with 4 mm Pb equivalent and 3 mm Pb equivalent thickness of protection shielding, respectively. The 8 radiological diagnostic workplaces of the emergency hospitals were designed and constructed based on " three zones with two passage ways" . The result of the nucleic acid test indicated that the positive samples were found at the multiple sites such as scanning bed, internal of gantry and ground touched by patients in CT scanning room. The areas such as console panel and ground were risked of pollution by the virus infected hands and feet of radiographers. In addition, the similar positive samples were found in the areas in scanning room with no touch of patients, such as observation window and air outlet. Conclusions:8 CT scanners and rooms in 4 emergency hospitals basically meet the requirements of imaging performance and radiation protection. The disinfection of COVID-19 radiodiagnostic workplace should be standardized.