Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Objective To develop and validate a model to predict the risk of radiation-induced lung injury (RILI) and assess its clinical feasibility. Methods Clinical data from 125 patients with non-small cell lung cancer (NSCLC) were included in the study. The patients were divided into training group (88 cases) and validation group (38 cases). Key predictive factors were identified using univariate and multivariate logistic regression analyses combined with least absolute shrinkage and selection operator (LASSO) regression. A predictive model was constructed and evaluated using a nomogram, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results The key variables identified by the model were tumor volume (P = 0.017), Eastern Cooperative Oncology Group performance status score (P = 0.035), 95% of the minimum dose to the target volume (P = 0.028), percentage of bilateral lung volume receiving 20 Gy of radiation (P < 0.001), and neutrophil-to-lymphocyte ratio (P = 0.021). The ROC curve showed that the areas under the curve (AUC) for the model in the training and validation groups were 0.987 and 0.992, respectively, indicating good predictive ability. The calibration curve and decision curve further confirmed the accuracy and clinical practicability of the model. Conclusion The predictive model proposed in this study can accurately assess the risk of developing RILI in patients with NSCLC who have undergone radiotherapy, demonstrating its potential value in clinical practice.

OBJECTIVE: To investigate the feasibility and effectiveness of precise-guided temporary fixation assistive devices in assisting the main nail guide pin placement and precise temporary fixation in proximal femoral nail antirotation (PFNA) internal fixation of femoral intertrochanteric fractures. METHODS: A prospective randomized controlled study was conducted to analyze the clinical data of 60 patients with femoral intertrochanteric fractures over 65 years old who met the selection criteria between January 2020 and June 2022 and were treated with PFNA internal fixation. The patients were randomly divided into the trial group (auxiliary device guided main nail guide pin placement and temporary fixation) and the control group (conventional treatment), with 30 cases in each group. There was no significant difference in baseline data such as gender, age, cause of injury, time from injury to operation, fracture side, AO/Orthopaedic Trauma Association (AO/OTA) classification, and combined medical diseases between the two groups ( P>0.05). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, intraoperative blood loss, and perioperative blood transfusion were recorded and compared between the two groups. The quality of fracture reduction was evaluated by CHANG Shimin et al criteria. Harris score was used to evaluate the hip function at 1 year after operation. RESULTS: In the trial group, 2 temporary fixation needles were successfully placed 2-5 times, including 2 times in 13 cases (43.3%), 3 times in 8 cases (26.7%), 4 times in 7 cases (23.3%), and 5 times in 2 cases (6.7%). The operation time, times of main nail guide pin placement, intraoperative fluoroscopy frequency, and intraoperative blood loss in the trial group were significantly less than those in the control group, and the reduction quality score was significantly better than that in the control group ( P<0.05). There was no significant difference in perioperative blood transfusion between the two groups ( P>0.05). All patients were followed up 12-19 months (mean, 15 months). There was no complication such as incision infection, deep vein thrombosis, or internal fixation loosening. At 1 year after operation, the Harris score of the affected hip joint in the trial group was significantly higher than that in the control group ( P<0.05). CONCLUSION The technique of main nail guide pin placement and temporary fixation under the guidance of auxiliary devices in PFNA internal fixation can achieve faster insertion of the main nail guide pin, accurate temporary fixation to maintain reduction, and avoid the subsequent operation space, so as to improve the effectiveness.
Humans ; Bone Nails ; Male ; Female ; Hip Fractures/surgery* ; Fracture Fixation, Intramedullary/instrumentation* ; Aged ; Prospective Studies ; Operative Time ; Treatment Outcome ; Fracture Fixation, Internal/instrumentation* ; Aged, 80 and over

BACKGROUND:Previously,a SENP1 gene-silenced human alveolar epithelial cell line was successfully constructed in vitro,and the role of SENP1 in hyperoxic lung injury was investigated at the cellular level.OBJECTIVE:To construct a mouse model of alveolar type II epithelial cell-specific knockout of SENP1 gene based on the Cre-loxP recombinase system.METHODS:SENP1flox/-mice were self-crossed to obtain SENP1flox/flox and SENP1flox/-mice;Sftpc-Cre+/+mice were crossed with wild-type mice to obtain more Sftpc-Cre+/-mice.Sftpc-Cre+/+or offspring Sftpc-Cre+/-mice were crossed with SENP1flox/-or offspring SENP1flox/flox mice to obtain SENP1flox/-Sftpc-Cre+/-double heterozygous mice.SENP1flox/-Sftpc-Cre+/-mice were then crossed with SENP1flox/flox mice to obtain SENP1flox/floxSftpc-Cre+/-mice.The genomic DNA was extracted by tail clipping and amplified by PCR.The amplified product was subjected to agarose gel electrophoresis to determine the mouse genotypes.Lung tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were subjected to immunofluorescence double-labelling and western blot assay to verify the knockdown effect of SENP1 gene.Heart,liver,lung and kidney tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were stained with hematoxylin-eosin to observe the histomorphology of each organ in the two groups of mice.RESULTS AND CONCLUSION:SENP1flox/floxSftpc-Cre+/-mice were correctly screened by agarose gel electrophoresis.Immunofluorescence double-labeling experiments showed that the mean fluorescence intensity of SENP1 was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with that of SENP1flox/flox mice(P<0.01)and no significant co-localization of SENP1 and Sftpc was observed(P<0.01).Western blot results showed that SENP1 protein expression was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with SENP1flox/flox mice(P<0.001).Hematoxylin-eosin staining showed no significant alterations in the histomorphology of heart,liver,lung and kidney tissues in SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice.This study successfully constructed alveolar type II epithelial cell-specific knockout SENP1 gene mice using the Cre-loxP recombinase system,which provides a good tool for the subsequent study of the role of SENP1 gene in lung diseases such as bronchopulmonary dysplasia and idiopathic pulmonary fibrosis,in which alveolar type II epithelial cells are the main damage cells.

Objective:A prognosis prediction model for pancreatic cancer was constructed based on multi-scale radiomics combined with deep learning, and the prediction effect of the model was evaluated.Methods:A retrospective analysis was conducted on the clinical data of 215 patients who underwent radical resection of pancreatic cancer at the First Affiliated Hospital of Naval Medical University from January 2017 to December 2017. Among them, 134 were male and 81 were female, with an age of (61.9±9.2) years. Patients were randomly divided into the training set ( n=151) and the test set ( n=64) in a ratio of 7: 3. Habitat features, peritumoral radiomics features, 3D radiomics features, and 2.5D deep learning features were extracted from preoperative CT images respectively. After feature screening, a survival prediction model was constructed using the CoxBoost machine learning algorithm that integrated the Boosting algorithm and the Cox proportional hazards model. The performance of the model was evaluated using the area under the time-dependent receiver operating characteristic curve and the consistency index. The clinical benefits of the model were evaluated using decision curve analysis. The survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used for the comparison of survivals between groups. Results:The LASSO, random forest and extreme gradient boosting models were each used to screen out the top 10 most important features and take the union, ultimately obtaining 20 radiomics features for modeling. In the training set and test set, the consistency index of the CoxBoost model in predicting overall survival was 0.717 (95% CI: 0.669-0.765) and 0.688 (95% CI: 0.610-0.766), respectively, and the area under the curve for predicting overall survival at 1, 2, and 3 years after surgery was 0.830 (95% CI: 0.752-0.898), 0.753 (95% CI: 0.665-0.833), 0.828 (95% CI: 0.735-0.908) and 0.690 (95% CI: 0.549-0.824), 0.780 (95% CI: 0.649-0.887 and 0.793 (95% CI: 0.660-0.897), respectively. The area under the curve for predicting long-term survival after surgery (≥40 months) was above 0.8. Based on the optimal cutoff value of -0.19 for the predicted value of the CoxBoost model calculated by the R package " survminer", the patients were divided into high-risk (predicted value >-0.19) and low-risk (predicted value <-0.19) groups. In both the training set and the test set, the survival of patients in the low-risk group was better than that in the high-risk group (training set: χ2=39.01, P<0.001; test set: χ2=12.34, P<0.001). The median survival period of patients in the high-risk group was lower than that in the low-risk group (training set: 15.80 vs 34.07 months; test set: 16.87 vs 43.07; months). Decision curve analysis shows that patients obtain survival benefit when the threshold probability of the training set is greater than 0.25 and that of the test set is greater than 0.45. Conclusion:The CoxBoost model has a good predictive ability for the overall survival of pancreatic cancer patients after surgery and can effectively screen out patient subgroups that may significantly benefit from surgical treatment.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Objective To investigate the effect of different radiotherapy doses on the prognosis of patients with stage cT1-4N0M0 esophageal squamous cell carcinoma(ESCC)who received radical radio(chemo)therapy categorized into subgroups with different tumor local factors.Methods A retrospective analysis was conducted on 256 patients with clinically nonmetastatic esophageal squamous cell carcinoma.The optimal cutoff for tumor local factors was determined.The relationship between latest treatment efficacy and tumor local factors was analyzed,and independent indicators affecting patient overall survival(OS)were examined using multivariate analysis.The subgroup analysis was performed to determine the correlation between selected factors and radiation therapy doses.Results The shorter the X-ray length of esophageal tumor lesion and the smaller the lesion canal wall thickness and gross tumor volume(GTV),the better the latest treatment efficacy of the patients(χ2=9.066,10.310,15.661,respectively,P=0.011,0.006,P＜0.001).Multivariate analysis results showed that GTV(P＜0.001),radiation dose(P=0.038),and latest treatment efficacy(P＜0.001)were independent predictors of the patients'OS,and the latter two were also independent predictors of the patients'progression-free survival(PFS)(P=0.033,＜0.001).Subgroup analysis further showed that high doses of radiotherapy(over 60 Gy)resulted in good OS(χ2=5.040,4.588,5.400,P=0.025,0.032,0.020)and PFS(χ2=6.089,4.353,6.459,P=0.014,0.037,0.011)in the subgroup with maximum wall thickness below 3.7 cm,with esophageal lesions with GTV below 37.34 cm3,or not receiving simultaneous chemotherapy.Conclusion Local tumor factors are important prognostic factors of ESCC patients treated with radical radio(chemo)therapy.Patients with thin lesion walls and small tumor volumes may greatly benefit from high doses of radiation(over 60 Gy).

Objective:To characterize fine motor function in middle-aged and elderly individuals utilizing a novel wearable inertial motion capture device.Additionally, it seeks to investigate the relationship between fine motor deficits and overall cognitive function, as well as various cognitive dimensions.Methods:Participants aged 50 years and older were recruited between November 2022 and April 2023.The Montreal Cognitive Assessment Scale(MoCA)was employed to evaluate the cognitive function of the subjects, and a radar chart was utilized to illustrate the extent of impairment across different cognitive dimensions.An independent computerized fine motor evaluation system was developed using the motion capture technology of a novel wearable microelectromechanical system(MEMS)inertial sensor, enabling a quantitative assessment of fine motor skills.The differences in fine motor function characteristics between the two groups were compared.Spearman's correlation analysis and multivariate logistic regression were conducted to examine the relationship between fine motor deficits and cognitive dysfunction.Results:A total of 289 participants were recruited, among whom 140(48.4%)were classified into the cognitive impairment group.The mean MoCA scores for the cognitive impairment group and the non-cognitive impairment group were 22.2 ± 2.79 and 27.7 ± 1.19, respectively( P<0.001).The electronic assessment of fine motor function revealed that the motion parameters of hand function in the cognitive impairment group were significantly poorer across all three numerical evaluation tasks.Spearman's correlation analysis demonstrated a robust correlation between deficits in fine motor function and cognitive dysfunction.Furthermore, in the multiple logistic regression model, after adjusting for potential confounding factors including age, gender, and education level, a significant association between cognitive dysfunction and fine motor dysfunction persisted. Conclusions:A novel wearable motion capture technology was employed to facilitate the digital assessment of fine motor function.The findings revealed a significant correlation between deficits in fine motor function and cognitive dysfunction among middle-aged and elderly populations.

Objective:To evaluate the long-term efficacy of liposuction combined with lymphaticovenous anastomosis (LVA) in the treatment of secondary lymphedema in lower extremity and analyse the factors that affect therapeutic outcomes.Methods:A retrospective analysis was conducted on the clinical data of 172 patients who were treated in the Department of Lymphatic Surgery, Capital Medical University Affiliated Beijing Shijitan Hospital for secondary lymphedema in lower extremity, between January 2019 and December 2021. The cohort comprised 170 females and 2 males, with a median age of 55 years. The primary diseases were: 99 patients with cervical cancer, 47 with endometrial cancer, 1 with penile cacer and 25 with other malignant tumours. All patients received liposuction to aspirate subcutaneous adipose tissue and LVA anastomosis of the inguinal lymphatic vessels with the great saphenous vein and its branches. Postoperative follow-ups were performed at outpatient clinic, telephone interview and questionnaire survey to acquire immediate status of the patients at the time. Following variables were included the follow-up: gender, age, body mass index (BMI), duration, hypertension, diabetes, the type of primary disease, history of surgery, history of lymph node dissection, history of radiotherapy or chemotherapy, extracellular water ratio (ECW%) in the affected limb, preoperative history of erysipelas, preoperative percentage difference in circumference of bilateral proximal toes, dorsal feet, ankles, distal third of legs, middle legs, proximal third of legs, knees, distal third of thighs, mid thighs, proximal third of thighs and groins. Additional parameters included duration of liposuction, intraoperative blood loss, adipose tissue content, number of lymphatic vessels anastomosed in LVA, postoperative daily standing time, postoperative history of erysipelas, and usage of compression garment. Univariate and multivariate analyses were performed using SPSS 26.0 software, with P <0.05 considered statistically significant. Results:A complete remission was defined as less than 10.0% in the percentage of bilateral limb volume difference during follow-up. There were 112 patients with complete remission. After excluded confounding factors through univariate analysis, multivariate analysis had revealed following independent risk factors: ECW% of affected limb ( P<0.01), postoperative standing duration >6 hours/day ( P=0.021), postoperative history of erysipelas ( P=0.016), regular use of compression garment ( P=0.013), and percentage difference of circumference at bilateral proximal toes ( P=0.038). Among the remaining 60 patients, 32 patients achieved effective remission which was defined as less than 20.0% in the swelling volume expansion ratio. Conclusion:Liposuction combined with LVA can relieve secondary lymphedema of lower extremity for majority of patients. ECW% of affected limb, postoperative standing duration >6 hours/day, postoperative history of erysipelas, irregular use of elastic socks, and percentage difference in circumference at bilateral proximal toes are the independent risk factors that affect the prognosis.

Objective:To observe the color Doppler flow imaging (CDFI) features of vitreoretinal lymphoma (VRL).Methods:Retrospective case series. From January 2022 to December 2024, 71 eyes of 42 patients diagnosed with VRL at the Eye Center of Beijing Tongren Hospital were enrolled. Among them, 17 were male and 25 female; 29 had bilateral and 13 unilateral involvement. Age ranged 17-78 years (median 59 years). Eleven cases had histopathologic confirmation and 31 were clinically diagnosed. All patients underwent CDFI and optical coherence tomography (OCT). CDFI findings were analyzed, noting the presence or absence of vitreous opacities (centrifugal distribution), posterior vitreous detachment (PVD), retinal detachment, and retinal elevated lesions. With Doppler overlay, blood flow within retinal lesions was assessed. The χ 2 test was used to compare the detection rates of retinal lesions by CDFI and OCT, while Cohen’s Kappa assessed agreement in identifying the depth of lymphoma cell infiltration. Results:Among 71 eyes, vitreous opacity occurred in 66 eyes (93.0%, 66/71), of which 40 eyes (60.6%, 40/66) showed centrifugal opacity. 58 eyes (81.7%, 58/71) had posterior vitreous detachment. Retinal detachment occurred in 7 eyes (9.9%, 7/71). Retinal occupying lesions occurred in 23 eyes (32.4%, 23/61), of which 15 eyes (65.2%, 15/23) showed blood flow signals on the surface of the lesions but no blood flow signals inside the lesions by CDFI, and OCT showed that tumor cells gathered under the retinal pigment epithelium. CDFI showed blood flow signals inside the lesions in 8 eyes (34.8%, 8/23), and OCT showed that tumor cells gathered between retinal neuroepithelial layers. The lesion detection rate of OCT (69.6%, 16/23) was significantly lower than that of CDFI (100.0%, 23/23) ( χ 2= 6.066, P=0.014). OCT and CDFI showed perfect agreement in determining the depth of tumor cell infiltration (Kappa=1.0). Conclusions:The ultrasonographic manifestations of VRL include vitreous opacity, PVD, and some retinal occupying lesions. Vitreous opacity often presents a characteristic centrifugal distribution. By observing whether there is blood flow signal in retinopathy using Doppler, the level of lymphoma cell infiltration can be suggested.