Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.

Objective:To explore the real experience of patients with diffuse large B-cell lymphoma in clinical trials of chimeric antigen receptor T (CAR-T) cell therapy, providing reference for clinical practice.Methods:This study was descriptive qualitative research. From January to December 2024, 15 patients with diffuse large B-cell lymphoma who completed a clinical trial of CAR-T cell therapy in Ward of Biological Immunotherapy of the First Affiliated Hospital of Zhengzhou University were selected by purposive sampling method for semi-structured interviews. The data was analyzed by content analysis method.Results:The experience of patients with diffuse large B-cell lymphoma participating in the clinical trial of CAR-T cell therapy were summarized into three themes and 12 sub-themes, namely, the pre-enrollment situation and attitude towards the clinical trial: survival from adversity (caught in the dilemma of treatment, grasping the last hope, survival desire overcoming fear, active psychological construction), social support and power source in the clinical trial: support network (unnoticeable personal strength, multi-dimensional family support system, professional medical support system, weak peer support system), and experience and feeling after CAR-T cell therapy: positive experience driven by efficacy (satisfaction with treatment effectiveness and clinical trials, pleased with reduced adverse reactions, increased confidence in treating diseases, adverse reactions were not scary) .Conclusions:Patients with diffuse large B-cell lymphoma have an overall positive experience during clinical trials of CAR-T cell therapy, but the negatives should not be ignored. Healthcare professionals should strengthen the health education of clinical trials, assist patients to improve the social support network, make up for the short board of patient support, alleviate the adverse reactions of patients, and then increase the enthusiasm of patients to participate in clinical trials.

Objective:To explore the real experience of patients with diffuse large B-cell lymphoma in clinical trials of chimeric antigen receptor T (CAR-T) cell therapy, providing reference for clinical practice.Methods:This study was descriptive qualitative research. From January to December 2024, 15 patients with diffuse large B-cell lymphoma who completed a clinical trial of CAR-T cell therapy in Ward of Biological Immunotherapy of the First Affiliated Hospital of Zhengzhou University were selected by purposive sampling method for semi-structured interviews. The data was analyzed by content analysis method.Results:The experience of patients with diffuse large B-cell lymphoma participating in the clinical trial of CAR-T cell therapy were summarized into three themes and 12 sub-themes, namely, the pre-enrollment situation and attitude towards the clinical trial: survival from adversity (caught in the dilemma of treatment, grasping the last hope, survival desire overcoming fear, active psychological construction), social support and power source in the clinical trial: support network (unnoticeable personal strength, multi-dimensional family support system, professional medical support system, weak peer support system), and experience and feeling after CAR-T cell therapy: positive experience driven by efficacy (satisfaction with treatment effectiveness and clinical trials, pleased with reduced adverse reactions, increased confidence in treating diseases, adverse reactions were not scary) .Conclusions:Patients with diffuse large B-cell lymphoma have an overall positive experience during clinical trials of CAR-T cell therapy, but the negatives should not be ignored. Healthcare professionals should strengthen the health education of clinical trials, assist patients to improve the social support network, make up for the short board of patient support, alleviate the adverse reactions of patients, and then increase the enthusiasm of patients to participate in clinical trials.

Objective:To study the preoperative predictors for lower extremity intermuscular venous thrombosis (IMVT) in patients with thoracolumbar fracture.Methods:A retrospective study was conducted to analyze the 421 spinal fracture patients who had been admitted to Department of Spinal Surgery, The Fourth Hospital of Wuhan from November 2023 to October 2024. The cohort included 110 males and 311 females, aged from 16 to 89 years. They were stratified into a thrombosis group (26 cases) and a control group (395 cases) based on the presence or absence of lower extremity IMVT. Univariate analysis was performed of the following variables: gender, age, body mass index, multisegmental spinal fractures, fracture location, Caprini thrombosis risk score, visual analogue scale (VAS) pain score, D-dimer level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen, coagulation factor activity assay, fibrinogen level, estimated fibrinolytic ratio, clotting time, 30-minute fibrinolytic ratio, coagulation comprehensive index, clot mechanical strength, platelet function, and fibrin generation rate. The variables with a significance level of P<0.05 in the univariate analysis were further analyzed using multivariate logistic regression to identify the independent risk factors for lower extremity IMVT. The predictive efficacy of these factors was evaluated using receiver operating characteristic (ROC) curve analysis. Results:Comparisons between the 2 groups showed that age, multisegmental spinal fractures, Caprini thrombotic risk score, and D-dimer level were variables with P<0.05. Binary logistic regression analysis of the above variables showed that a high Caprini thrombotic risk score, a high D-dimer level, and multisegmental spinal fractures were independent risk factors for preoperative lower extremity IMVT ( P<0.05). The ROC plot suggested an optimal cutoff point: a Caprini thrombotic risk score of 5 and a D-dimer level of 2.57 mg/L. Combination of Caprini thrombotic risk score, D-dimer level, and multisegmental spinal fractures demonstrated a sensitivity of 88.5%, a specificity of 71.9%, and an area under the curve (AUC) of 0.881 for diagnosis of lower extremity IMVT. Conclusions:The Caprini thrombosis risk score and presence of multisegmental spinal fractures are critical indicators for the preoperative risk of lower extremity IMVT in patients with thoracolumbar fracture. For individuals with a low Caprini thrombosis risk score, a D-dimer test is necessary in combination to determine the necessity of color Doppler ultrasound examination.

Objective: To investigate the symptoms of depression and anxiety and their influencing factors in adolescents undergoing facial scar plasty, so as to provide insights into psychological interventions among them. Methods: The patients with facial scars who were 14 to 25 years old and admitted to the Department of Plastic Surgery, Hospital of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College were selected. General information and scar condition were collected through questionnaire surveys. Symptoms of depression and anxiety were assessed using the Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS). The patients who scored 50 points and over in both SDS and SAS were identified as having depression and anxiety symptoms. Factors affecting depression and anxiety symptoms were identified using a multivariable logistic regression model. Results: A total of 108 adolescents undergoing facial scar plasty were surveyed, with a mean age of (19.16±2.03) years. There were 50 boys (46.30%) and 58 girls (53.70%). Depression and anxiety symptoms were detected in 62 cases, accounting for 57.41%. Multivariable logistic regression analysis showed that girls (OR=1.547, 95%CI: 1.072-2.231), unhealthy diet (OR=1.428, 95%CI: 1.120-1.820), high scores of pain (OR=1.677, 95%CI: 1.120-2.511) and high scores of scar severity (OR=1.629, 95%CI: 1.112-2.387) were associated with increased risks of depression and anxiety symptoms in adolescents undergoing facial scar plasty, while high scores of social support (OR=0.569, 95%CI: 0.348-0.931) and high scores of resilience (OR=0.465, 95%CI: 0.252-0.858) were associated with decreased risks. Conclusion Depression and anxiety symptoms are relatively prevalent in adolescents undergoing facial scar plasty, and are influenced by gender, diet, pain degree, scar severity, social support and resilience.

Objective To evaluate the effects of triple therapy combined with betahistine on cerebral blood circulation and cutaneous sympathetic response (SSR) in patients with residual dizziness after reposition of benign paroxysmal positional vertigo. Methods A total of 196 patients with residual dizziness after reposition of benign paroxysmal positional vertigo were randomly divided into two groups, with 98 cases in each group. Control group was treated with betahistine, while experimental group was treated with betahistine and triple therapy (compound manipulation, transcranial magnetic stimulation and specific body position), and both groups were treated for 2 courses of treatment, with 7 days as a course of treatment. Efficacy, duration of residual dizziness, the scores of the Dizziness Handicap Inventory (DHI), the Visual Analogue Scale (VAS), the Activity Balance Confidence (ABC), the Hamilton Anxiety Scale (HAMA) and the Vestibular Symptom Index (VSI) before treatment and after the course of the treatment, SSR, and values of mean blood flow velocity (V_m) of cerebral vertebral artery (VA) and basilar artery (BA) were compared between the two groups. Results The duration of residual dizziness in the experimental group was (10.25±3.74) days, which was significantly shorter than (15.26±2.98) days in the control group (P < 0.001); the total treatment effective rate of the experimental group was 93.88%, which was significantly higher than 79.59% of the control group (P < 0.05). At the end of the course, the scores of the three dimensions of the DHI in the experimental group were significantly lower than those in the control group (P < 0.05). At the end of the course, the VAS, the HAMA and the VSI scores in the experimental group were significantly lower than those in the control group, while the ABC score was significantly higher than that in the control group (P < 0.05). At the end of the course, the SSR amplitude value in the experimental group was significantly lower than that in the control group, while the SSR latency value was significantly higher than that in the control group (P < 0.05). At the end of the course, the values of V_m of VA and BA in the experimental group were significantly higher than those in the control group (P < 0.05). Conclusion The combination of triple therapy and betahistine has a definite therapeutic effect on residual dizziness after reposition of benign paroxysmal positional vertigo, which can alleviate dizziness and vestibular symptoms, enhance activity balance confidence, relieve anxiety degree, and improve SSR and cerebral blood circulation.

It has been proposed by Basic Questions On Proper Therapies for Different Diseases Geographically （《素问·异法方宜论篇》） that "wei （痿） diseases should be treated by Daoyin （导引）". Furthermore， it is clarified that the indications of Daoyin are those conditions related to spleen and dampness caused by dampness pathogen， excessive food intake and less exercise， and mainly manifested as heavy limbs， fatigue and flaccidity， which is similar to the metabolic imbalance in the early stage of glucose or lipid metabolism disorder in modern medicine. Based on modern clinical and basic research evidence， Daoyin can inhibit the response of inflammation， alleviate oxidative stress， regulate intestinal microbiota， and modulate gene expression to improve metabolic abnormalities， and this will provide ideas for researches on the indications of Daoyin.

BACKGROUND: Progressive lipid loss of adipose tissue is a major feature of cancer-associated cachexia. In addition to systemic immune/inflammatory effects in response to tumor progression, tumor-secreted cachectic ligands also play essential roles in tumor-induced lipid loss. However, the mechanisms of tumor-adipose tissue interaction in lipid homeostasis are not fully understood. METHODS: The yki -gut tumors were induced in fruit flies. Lipid metabolic assays were performed to investigate the lipolysis level of different types of insulin-like growth factor binding protein-3 (IGFBP-3) treated cells. Immunoblotting was used to display phenotypes of tumor cells and adipocytes. Quantitative polymerase chain reaction (qPCR) analysis was carried out to examine the gene expression levels such as Acc1 , Acly , and Fasn et al . RESULTS: In this study, it was revealed that tumor-derived IGFBP-3 was an important ligand directly causing lipid loss in matured adipocytes. IGFBP-3, which is highly expressed in cachectic tumor cells, antagonized insulin/IGF-like signaling (IIS) and impaired the balance between lipolysis and lipogenesis in 3T3-L1 adipocytes. Conditioned medium from cachectic tumor cells, such as Capan-1 and C26 cells, contained excessive IGFBP-3 that potently induced lipolysis in adipocytes. Notably, neutralization of IGFBP-3 by neutralizing antibody in the conditioned medium of cachectic tumor cells significantly alleviated the lipolytic effect and restored lipid storage in adipocytes. Furthermore, cachectic tumor cells were resistant to IGFBP-3 inhibition of IIS, ensuring their escape from IGFBP-3-associated growth suppression. Finally, cachectic tumor-derived ImpL2, the IGFBP-3 homolog, also impaired lipid homeostasis of host cells in an established cancer-cachexia model in Drosophila . Most importantly, IGFBP-3 was highly expressed in cancer tissues in pancreatic and colorectal cancer patients, especially higher in the sera of cachectic cancer patients than non-cachexia cancer patients. CONCLUSION Our study demonstrates that tumor-derived IGFBP-3 plays a critical role in cachexia-associated lipid loss and could be a biomarker for diagnosis of cachexia in cancer patients.
Humans ; Insulin-Like Growth Factor Binding Protein 3/metabolism* ; Culture Media, Conditioned/pharmacology* ; Cachexia/pathology* ; Gastrointestinal Neoplasms ; Somatomedins/metabolism* ; Insulins/metabolism* ; Lipids

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.

Insulin-like growth factor-1 receptor (IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers. However, targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings. Here, we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I. The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A. In response to ligands, IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250, opening the middle loop (Leu130‒Cys141) to the RING domain of MEX3A through the conformational changes of βarr2. The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I. The assay of the mutants βarr2^Y64A and βarr2^Y250A further confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A. The truncated-βarr2 and the peptide ATQAIRIF, which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes, thus blocking the IGF-1R-triggered RIG-I degradation. Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway. Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I. In summary, we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.