BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Methods: The median sagittal diameter and transverse diameter of the spinal canal from C2 to C7 were measured on CT images. The ratio of the median sagittal diameter to the transverse diameter was calculated. Accordingly, the spinal canal shape of each segment was classified into four, and the specific criteria of lunar phase classification were determined through linear discriminant analysis based on the ratio of the median sagittal diameter to the transverse diameter. The inter-rater reliability of the classification was explored using Kappa coefficients. Finally, the morphology of the different segments of the cervical spinal canal in healthy volunteers was revised and compared. Results: According to the ratio of the median sagittal diameter and the transverse diameter of the cervical spinal canal, the lunar phase classification of the cervical bony spinal canal was determined as follows: full-moon >0.65, 0.55< convex-moon ≤0.65, 0.46≤ quarter-moon ≤0.55, and residual-moon <0.46. The Kappa values of C2–C7 were 0.851, 0.958, 0.823, 0.927, 0.793, and 0.946, and the Kappa value of all C2–C7 segments was 0.854 that mainly presented two forms of full-moon (76.5%) and convex-moon (23.0%). A quarter-moon spinal canal was mainly distributed in C3, C4, C5, and C6; a residual-moon spinal canal was mainly distributed in C4 and C5; and the morphological distribution of C4 and C5 were similar (p>0.05). The frequency of the spinal canal of the residual-moon type was the highest, and the full-moon (6.5%) and residual-moon (7.5%) types of C7 were rare. Conclusions The morphological classification of the cervical spinal canal was established to present anatomical variations. The classification showed good inter-rater reliability.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To investigate the effects of down-regulation of FABP5 (fatty acid binding protein 5) on radiation damage of skin cells, and explore underlying mechanism.Methods:A lentiviral vector with down-regulated FABP5 was constructed to infect human immortalized keratinocytes (HaCaT) cells, and the transfection efficiency was examined. The HaCaT cells were divided into blank control group, FABP5 down-regulation group (FABP5), radiation group (IR), and FABP5 down-regulation combined with radiation group (FABP5+ IR). After 6 MV X-ray radiation, cell proliferation viability was measured by CCK-8 assay, cell migration was detected by scratch assay, apoptosis was analyzed by flow cytometry, radiosensitivity was evaluated by cloning formation assay, and the cellular protein expressions of PARP1, γ-H2AX, AKT and p-AKT were detected by Western blot.Results:FABP5 was successfully knocked-down in both RNA level ( t=25.14, P<0.05) and protein level ( t=20.06, P<0.05). The down-regulation of FABP5 decreased the abilities of cells proliferation ( t=3.55, 5.88, 3.18, P<0.05) and migration ( t=15.44, P<0.05), but increased cell resistance to irradiation with a radiosensitization ratio of 0.782. The apoptosis rate of FABP5+ IR group was significantly lower than IR group (22.05±6.71)% vs. (9.82±1.45)%, t=3.08, P<0.05. The protein levels of PARP1 and γ-H2AX in FABP5+ IR group were also lower than those in the IR group 0.04±0.04, 0.11±0.06, 0.26±0.11, 0.22±0.07, 0.21±0.10, 0.52±0.22, 0.57±0.06, 0.43±0.02( t=2.83, 3.07, 4.50, 5.33, P<0.05), while the protein level of p-Akt in FABP5+ IR group was higher than that in IR group ( t=-16.24—3.02, P<0.05). Conclusions:Down-regulation of FABP5 inhibited cell proliferation and migration, increased radioresistance, and reduced radiation-induced apoptosis and DNA damage of skin cells probably through PI3K/AKT signaling pathway.

Objective:To investigate the diagnostic efficacy of MRI-based or CT-based measurements and the combined evaluation methods for preoperative bone quality assessment in patients with cervical degenerative diseases.Methods:Patients who underwent spine surgery for cervical degenerative diseases at the Department of Orthopedics, Huashan Hospital, Fudan University from September 2020 to March 2022 with available preoperative X-ray, CT, MRI and dule energy X-Ray absorptiometry (DEXA) data were included in this study. Vertebral bone quality score (VBQ) based on MRI T1-weightedimages and CT Hounsfiled unit (HU) values of the cervical spine were measured, and a combined diagnostic formula based on the binary logistic regression was constructed. The patients were divided into normal bone mass (T≥-1.0) and osteopenia/osteoporosis groups (T<-1.0). The student's t-test and Chi-square test were performed for comparisons between groups. The Pearson correlation coefficient was also used to investigate the correlation between DEXA-T scores, cervical VBQ and CT HU values. In addition, receiver operating characteristic curve (ROC) were plotted to explore the diagnostic efficacy of VBQ, CT HU and their combined diagnosis. Meanwhile, the corresponding sensitivity and specificity were obtained. Results:A total of 71 patients were included in this study (17 in the normal group and 54 in the osteopenia/osteoporosis group). The student's t-test showed that VBQ (2.90±0.70 vs. 3.83±0.83, t=4.23, P<0.001) and CT HU values (370.26±85.38 vs. 295.20±67.96, t=3.73, P=0.002) were significantly different between the two groups. The area under the ROC curve (AUC) for VBQ and CT values of the cervical spine were 0.81 and 0.75, respectively, and the AUC for the combined diagnostic value constructed on the basis of both was 0.85. Applying VBQ scores alone had a diagnostic sensitivity of 80% and a specificity of 70%, and the combined diagnosis with VBQ and CT HU had a sensitivity of 90% and a specificity of 75%. Person correlation analysis showed a significant correlation between DEXA T value, cervical VBQ value and CT HU value. The detailed formula was: DEXA T score=-0.63×cervical VBQ+0.64 ( r=-0.55, P<0.001), CT HU value=-40.20×cervical VBQ+458.40 ( r=-0.45, P<0.001), DEXA T score=0.006×CT HU-3.47 ( r=0.45, P<0.001). Conclusion:This study confirmed the feasibility of using cervical VBQ values, CT HU values and combined diagnostics for preoperative bone density screening in patients with degenerative cervical spine diseases. This method allows surgeons to perform an initial preoperative bone density screening based on the patient's existing imaging data, and thus could aid in confirming the indication and scheme of surgery. The method could be a powerful tool for preoperative bone density assessment screening in patients with cervical degenerative diseases.

【Objective:】 To understand the current situation and influencing factors of ethical knowledge, attitude, and practice (KAP) among clinical researchers, enhance their ethical awareness, and improve the quality of clinical researches. 【Methods:】 A self-designed questionnaire was used to conduct a convenient sampling survey of medical staff who have participated in clinical study. 【Results:】 A total of 6,021 subjects were investigated, with males accounting for 28.46% and females accounting for 71.53%. The average age of them was (37.47±11.46) years old. The total score of ethics and the mean scores of the three dimensions of knowledge, attitude and practice were (70.62±12.99), (59.63±12.50), (79.55±19.62) and (74.92±18.29), respectively. Multiple linear regression analysis showed that researchers with male, tertiary hospitals, doctors, ethics-related part-time jobs, postgraduate education, associate senior title or above, and training experience scored higher (P<0.05). 【Conclusion:】 Ethical attitudes have a significant mediating effect between knowledge and practice, accounting for 62.72% of the total effect. Researchers recognize the importance of ethics, but it is urgent to strengthen their knowledge learning and practical application.

Objective:To explore the risk factors of oral fungal infection in patients with severe hepatitis, and the prevention role of nystatin oral care combined with precision health education on oral fungal infection.Methods:A total of 150 patients with severe hepatitis who were hospitalized for diagnosis and treatment in the First Affiliated Hospital of Zhengzhou University from February 2018 to February 2020 were selected as the research objects. According to the random number table method, they were divided into the observation group (given nystatin oral care combined with precision health education intervention) and the control group (given routine oral care combined with precision health education intervention), 75 cases in each group. The incidence of oral fungal infections in the two groups after the intervention were compared.Results:The fungal infection rate in the observation group at 1 week, 2 weeks and 4 weeks after intervention were 2.67% (2/75), 4.00% (3/75), 8.00% (6/75), which were significantly lower than 12.00% (9/75), 18.67% (14/75), 25.33% (19/75) in the control group ( χ2=4.81, 8.03, 8.11, all P<0.05). Four weeks after the intervention, among the 6 patients with fungal infection in the observation group, there were 5 cases of oral leukoplakia and foreign body sensation in the pharynx, and 1 patient with oral leukoplakia; among the 19 patients with fungal infection in the control group, all had oral mucosal leukoplakia. There were 17 cases of leukoplakia and pharyngeal foreign body sensation, and 2 cases of oral leukoplakia. Conclusions:Nystatin oral care combined with precision health education is of great significance in patients with severe hepatitis, and can effectively reduce the incidence of oral fungal infections.

Objective:To investigate the correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment disease (ASDis) after lumbar fusion operation.Methods:A retrospective study was conducted among 195 patients who underwent posterior lumbar fusion again for ASDis at this institution from January 2014 to December 2020, including 29 patients with ASDis whose initial surgical fusion segment was L 4,5. According to Roussouly's staging, there were 5 cases of type I, 9 cases of type II, 10 cases of type III, and 5 cases of type IV. Another 29 cases were selected from patients without ASDis after lumbar fusion as a control group. The control group was paired 1∶1 with the ASDis group according to gender, fusion segment, and Roussouly typing of the lumbar spine. The cross-sectional area (CSA) and fat infiltration (FI) of paravertebral muscle, facet joint angle (F-J) and pedicle facet (P-F) angle before the first (second) operation were measured and compared between the two groups. Then logistic regression analysis was used to determine the predictors of ASDis after posterior lumbar fusion. Finally, the receiver operation characteristic (ROC) curve was described, and the area under the curve (AUC) and cut-off point were calculated. At the same time, the paraspinal muscle atrophy before the second operation in ASDis group was measured. Results:The average follow-up time of 98 patients was 59.25±6.38 months (range, 49-73 months). The average body mass index (BMI) of ASDis group was 24.76±3.64 kg/m 2, which was higher than that in control group (22.24±2.92 kg/m 2) ( t=2.481, P=0.041). The average CSA and relative cross-sectional area (rCSA) of paraspinal muscle in ASDis group were 3 214.32± 421.15 mm 2 and 1.69±0.36 respectively, which were less than 3 978.91±459.87 mm 2 and 2.26±0.29 in control group ( t=10.22, P=0.012; t=9.47, P=0.038). The FI degree of paraspinal muscle in ASDis group (21.95%±5.89%) was significantly higher than that in control group (14.64%±7.11%) ( t=7.32, P=0.002). The F-J angle in ASDis group was 35.06°±3.45°, which was less than 38.39°±4.67° in control group ( t=4.76, P=0.027). The P-F angle in ASDis group was 117.39°±8.13°, which was greater than 111.32°±4.78° in control group ( t=5.25, P=0.031). Multivariate logistic regression analysis showed that higher BMI ( OR=1.34, P=0.038), smaller rCSA of paraspinal muscle ( OR=0.02, P=0.017) and higher FI of paraspinal muscle ( OR=1.58, P=0.032) were the risk factors of postoperative ASDis. The ROC curve showed that the AUC of BMI was 0.680 and the cut-off point was 22.58 kg/m 2; The AUC of the FI of paraspinal muscle was 0.716 and the cut-off point was 15.69%; The AUC of rCSA of paraspinal muscle was 0.227 and the cut-off point was 1.92. For ASDis patients, the paraspinal muscle before the second operation had a higher degree of FI (25.47%±6.59% vs. 21.95%±5.89%, t=3.99, P=0.042) and a smaller rCSA (1.52±0.28 vs. 1.69±0.36, t=3.85, P=0.038) than that before the first operation. The difference between the FI degree of paraspinal muscle before the second operation and the first operation was negatively correlated with the occurrence time of ASDis ( r=-0.53, P=0.039) , and the difference of rCSA was positively correlated with the occurrence time of ASDis ( r=0.64, P=0.043) . Conclusion:When BMI >22.58 kg/m 2, FI of paraspinal muscle >15.69%, and rCSA of paraspinal muscle <1.92, it suggests that ASDis is more likely to occur after operation. And the more obvious paraspinal muscle atrophy after the first operation, the earlier ASDis may occur. Morphological changes of facet joints cannot be used as an index to predict the occurrence of ASDis.