OBJECTIVE: To explore mechanisms of acid-sensing ion channel 1 (ASIC1) mediated lumbar nucleus pulposus cell apoptosis through extracellular-signalregulated protein kinase 5 (ERK5) signaling pathway and mitochondrial dysfunction pathway. METHODS: Totally 34 patients with degenerative lumbar disc herniation (LDH) admitted from January 2020 to December 2022 were collected as research objects, including 21 males and 13 females;aged from 29 to 52 years old with an average of (37.43±4.75) years old;22 patients with grade Ⅱ and 12 patients with grade Ⅳ, according to Pfirrmann grading criteria;15 patients with L_4,5 and 19 patients with L₅S₁. The expression of ASIC1 in nucleus pulposus of LDH patients was measured by immunohistochemical staining. Nucleus pulposus cells were cultured by primary culture method, identified by toluidine blue staining and immunohistochemical staining, and the expression of ASIC1 protein was located by immunofluorescence staining. According to the addition of siRNA-ASIC1, ASIC1 overexpression plasmid, and ERK5 inhibitors, the nucleus pulpocyte was divided into three groups, named as SIRNA-silenced group, overexpression group, and inhibitor group, with 3 patients in each group. Cells of each group were collected at 72 h after intervention, expression of ASIC1, ERK5, BCL-xL/BCL-2-associated Death promoter (Bad), B-cell lymphoma-2 associated X (Bax) and B-cell lymphoblast-2 gene (Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR);intracellular calcium ion levels were detected by calcium ion kit, mitochondrial membrane potential was detected by JC-1 kit, and apoptosis was observed by AV-PI kit. RESULTS: In LDH patients with grade Ⅳ, nucleus pulposus tissue removed during operation revealed poor elasticity, white color and poor ductility, and immunohistochemical results showed increased ASIC1 expression. There was no significant difference in mRNA relative expression of ASIC1 between siRNA silencing group (0.31±0.03) and inhibitor group (0.39±0.05) (P>0.05). The mRNA relative expression level of ERK5 in siRNA silencing group(0.32±0.05) was significantly higher than that in inhibitor group (0.15±0.04)(P<0.05), which suggested ERK5 was the downstream molecule of ASIC1. The mRNA relative expression levels of apoptosis promoting factor Bad and Bax in siRNA silencing group and inhibitor group were lower than those in overexpression group(P<0.05), the relative expression level of anti-apoptosis factor Bcl-2 mRNA was significantly increased (P<0.05). The calcium content in overexpression group was higher than that in siRNA silencing and inhibitor groups (P<0.05), the normal proportion of mitochondrial membrane potential in overexpression group was lower than that in siRNA silencing and inhibitor group (P<0.05), and the apoptosis rate in overexpression group was higher than that in siRNA silencing and inhibitor group (P<0.05). CONCLUSION After the activation of ASIC1 channel protein, calcium ions could enter the cells and act as a second messenger molecule to regulate apoptosis of nucleus pulposus cells by ERK5 signaling pathway and mitochondrial disorder pathway.
Humans ; Acid Sensing Ion Channels/physiology* ; Male ; Female ; Apoptosis ; Middle Aged ; Adult ; Signal Transduction ; Mitogen-Activated Protein Kinase 7/physiology* ; Mitochondrial Diseases/genetics* ; Nucleus Pulposus/metabolism* ; Intervertebral Disc Degeneration/metabolism* ; Mitochondria/metabolism* ; Intervertebral Disc Displacement/genetics*

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective:To develop a preoperative differentiation model for colorectal mucinous adenocarcinoma and non-mucinous adenocarcinoma using a combination of contrast-enhanced CT radiomics and deep learning methods.Methods:This is a retrospective cohort study. Clinical data of colorectal cancer patients confirmed by postoperative pathological examination were retrospectively collected from January 2016 to December 2023 at Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Center 1, n=220) and the First Affiliated Hospital of Bengbu Medical University (Center 2, n=51). Among them, there were 108 patients diagnosed with mucinous adenocarcinoma, including 55 males and 53 females, with an age of (68.4±12.2) years (range: 38 to 96 years); and 163 patients diagnosed with non-mucinous adenocarcinoma, including 96 males and 67 females, with an age of (67.9±11.0) years (range: 43 to 94 years). The cases from Center 1 were divided into a training set ( n=156) and an internal validation set ( n=64) using stratified random sampling in a 7∶3 ratio, and the cases from Center 2 were used as an independent external validation set ( n=51). Three-dimensional tumor volume of interest was manually segmented on venous-phase contrast-enhanced CT images. Radiomics features were extracted using PyRadiomics, and deep learning features were extracted using the ResNet-18 network. The two sets of features were then combined to form a joint feature set. The consistency of manual segmentation was assessed using the intraclass correlation coefficient. Feature dimensionality reduction was performed using the Mann-Whitney U test and the least absolute shrinkage and selection operator regression. Six machine learning algorithms were used to construct models based on radiomics features, deep learning features, and combined features, including support vector machine, logistic regression, random forest, extreme gradient boosting, k-nearest neighbors, and decision tree. The discriminative performance of each model was evaluated using receiver operating characteristic curves, the area under the curve (AUC), DeLong test, and decision curve analysis. Results:After feature selection, 22 features with the most discriminative value were finally retained, among which 12 were traditional radiomics features and 10 were deep learning features. In the internal validation set, the Random Forest algorithm based on the combined features model achieved the best performance (AUC=0.938, 95% CI: 0.875 to 0.984), which was superior to the single-modality radiomics feature model (AUC=0.817, 95% CI: 0.702 to 0.913, P=0.048) and the deep learning feature model (AUC=0.832, 95% CI: 0.727 to 0.926, P=0.087); in the independent external validation set, the Random Forest algorithm with the combined features model maintained the highest discriminative performance (AUC=0.891, 95% CI: 0.791 to 0.969), which was superior to the single-modality radiomics feature model (AUC=0.770, 95% CI: 0.636 to 0.890, P=0.045) and the deep learning feature model (AUC=0.799, 95% CI: 0.652 to 0.911, P=0.169). Conclusion:The combined model based on radiomics and deep learning features from venous-phase enhanced CT demonstrates good performance in the preoperative differentiation of colorectal mucinous from non-mucinous adenocarcinoma.

Objective To evaluate the influence of the wearing position of dosimeters outside lead aprons on effective dose estimation for interventional radiology workers, analyze the differences between single and double dosimeter methods in effective dose estimation, and provide a reference for the personal dose monitoring of interventional radiology workers. Methods This study employed a combined approach of on-site monitoring and Monte Carlo simulation to evaluate the impact of the wearing position of dosimeters outside lead aprons on effective dose estimation, as well as the differences between effective doses measured using single and double dosimeters. Interventional radiology workers wore dosimeters at three positions: the neck outside the lead collar, the left chest outside the lead apron, and inside the lead apron. Effective doses were estimated using the single and double dosimeter methods specified in GBZ 128-2019 Specifications for individual monitoring of occupational external exposure, and the impact of different wearing positions on the estimation results was compared. Geant4 Monte Carlo simulations were used to model dose distributions at the neck outside the lead collar and at the left chest outside the lead apron for operators performing cardiovascular interventions under tube voltages of 70, 80, 90, and 100 kVp and exposure angles of posteroanterior (PA), anteroposterior (AP), and left anterior oblique 45° (LAO45°) positions. The study assessed the impact of dosimeter wearing position on effective dose estimation. Results Monte Carlo simulations demonstrated that neck doses consistently exceeded left chest doses across different tube voltages and exposure angles, with neck-to-chest dose ratios of 0.80-0.90. Under identical tube voltage conditions, AP showed the highest doses, followed by LAO45°, and PA demonstrated the lowest doses. The single and double dosimeter methods exhibited consistent patterns in effective dose estimation. Single dosimeter method generally yielded higher effective doses with relative deviations of 9.9% to 83%, though these deviations decreased under high tube voltages. Field monitoring data indicated that most interventional radiology workers maintained relative deviations between single and double dosimeter calculations below 6%, with neck-to-chest dose ratios of 0.95-1.1. The estimation patterns remained consistent across both methods, though single dosimeter method showed slightly higher results. Conclusion Under PA, AP, or LAO45°, the doses at the neck consistently exceeded those at the left chest. Therefore, when wearing lead protective equipment, the dosimeter should be properly positioned at the neck outside the lead collar to accurately reflect the radiation doses of surgeons. Some interventional radiology workers improperly positioned the dosimeter (intended at the neck outside the lead collar) at the left chest outside the lead apron, and this may result in an underestimation of the effective dose.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective:To develop a preoperative differentiation model for colorectal mucinous adenocarcinoma and non-mucinous adenocarcinoma using a combination of contrast-enhanced CT radiomics and deep learning methods.Methods:This is a retrospective cohort study. Clinical data of colorectal cancer patients confirmed by postoperative pathological examination were retrospectively collected from January 2016 to December 2023 at Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Center 1, n=220) and the First Affiliated Hospital of Bengbu Medical University (Center 2, n=51). Among them, there were 108 patients diagnosed with mucinous adenocarcinoma, including 55 males and 53 females, with an age of (68.4±12.2) years (range: 38 to 96 years); and 163 patients diagnosed with non-mucinous adenocarcinoma, including 96 males and 67 females, with an age of (67.9±11.0) years (range: 43 to 94 years). The cases from Center 1 were divided into a training set ( n=156) and an internal validation set ( n=64) using stratified random sampling in a 7∶3 ratio, and the cases from Center 2 were used as an independent external validation set ( n=51). Three-dimensional tumor volume of interest was manually segmented on venous-phase contrast-enhanced CT images. Radiomics features were extracted using PyRadiomics, and deep learning features were extracted using the ResNet-18 network. The two sets of features were then combined to form a joint feature set. The consistency of manual segmentation was assessed using the intraclass correlation coefficient. Feature dimensionality reduction was performed using the Mann-Whitney U test and the least absolute shrinkage and selection operator regression. Six machine learning algorithms were used to construct models based on radiomics features, deep learning features, and combined features, including support vector machine, logistic regression, random forest, extreme gradient boosting, k-nearest neighbors, and decision tree. The discriminative performance of each model was evaluated using receiver operating characteristic curves, the area under the curve (AUC), DeLong test, and decision curve analysis. Results:After feature selection, 22 features with the most discriminative value were finally retained, among which 12 were traditional radiomics features and 10 were deep learning features. In the internal validation set, the Random Forest algorithm based on the combined features model achieved the best performance (AUC=0.938, 95% CI: 0.875 to 0.984), which was superior to the single-modality radiomics feature model (AUC=0.817, 95% CI: 0.702 to 0.913, P=0.048) and the deep learning feature model (AUC=0.832, 95% CI: 0.727 to 0.926, P=0.087); in the independent external validation set, the Random Forest algorithm with the combined features model maintained the highest discriminative performance (AUC=0.891, 95% CI: 0.791 to 0.969), which was superior to the single-modality radiomics feature model (AUC=0.770, 95% CI: 0.636 to 0.890, P=0.045) and the deep learning feature model (AUC=0.799, 95% CI: 0.652 to 0.911, P=0.169). Conclusion:The combined model based on radiomics and deep learning features from venous-phase enhanced CT demonstrates good performance in the preoperative differentiation of colorectal mucinous from non-mucinous adenocarcinoma.