Efficacy and safety of concurrent chemoradiotherapy with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma: A multi-center propensity-score matched study.

BACKGROUND: Elderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC). METHODS: From January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed. RESULTS: After PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0-58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects. CONCLUSIONS: Our findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer.

BACKGROUND: Several studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. METHODS: Pooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. RESULTS: The median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). CONCLUSION: The differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.

Jianpi Jiedu Recipe Inhibits Proliferation through Reactive Oxygen Species-Induced Incomplete Autophagy and Reduces PD-L1 Expression in Colon Cancer.

BACKGROUND: Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. METHODOLOGY: CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. The RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. The xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. RESULTS: JPJDR has an excellent inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly, and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1. Meanwhile, JPJDR can exert an excellent therapeutic effect in xenograft tumor mice. CONCLUSION: JPJDR is a low-toxicity and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.

Radiotherapy with S-1 for the treatment of esophageal squamous cell carcinoma 75 years or older.

OBJECTIVE: Explore the efficacy and safety of involved-field irradiation (IFI) combined with S-1 as definitive concurrent chemoradiotherapy (dCRT) for locally advanced elderly esophageal squamous cell carcinoma (ESCC), under the premise of intensity-modulated radiotherapy (IMRT). METHODS: We designed a prospective single-arm phase II study. The study enrolled 91 patients aged 75 to 92 years. Eligible participants had histologically confirmed squamous cell carcinoma, stage II to IV disease based on the 8th edition of the American Joint Committee on Cancer (AJCC). All elderly patients (EPs) received dCRT with S-1. which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions or 50.4 Gy delivered in 28 fractions. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression-free survival (PFS), local control rate (LCR), and safety. RESULTS: From July 2017 to July 2021, we enrolled EPs with ESCC who were treated at the Jiangsu Cancer hospital. As of August 1, 2023, the median follow-up of surviving EPs was 31.4 months (IQR: 25.2 to 72.6 months). 83 patients (91.2%) completed the whole course of treatment. The 2-year OS rate was 59.2%, and the PFS rate was 43.7%. The most common grade 1 to 2 adverse effects (AEs) were radiation esophagitis (79.1%), and then were radiation pneumonia (46.2%). Anemia (41.8%) was the most common of grade 1 to 2 hematologic toxicity. The incidence of grade 3 or above AEs was 24.2%, and the incidence of leukopenia was the highest (11.0%). There was not one death due to treatment-related toxicity. In a subgroup analysis of radiotherapy doses, we found no statistically significant differences in PFS (P = 0.465) and OS (P = 0.345) in EPs with ESCC who received 50.4 Gy and 61.2 Gy, and that patients in the 50.4 Gy group had lower dermatitis (P = 0.045) and anemia (P = 0.004). CONCLUSIONS: IF-IMRT combined with S-1 is a promising regimen for elderly ESCC. And the radiotherapy dose of 50.4 Gy remains the standard dose for EPs with ESCC undergoing CCRT.

Perioperative Transcutaneous Electrical Acupoint Stimulation Reduces Postoperative Pain in Patients Undergoing Thoracoscopic Surgery: A Randomized Controlled Trial.

Objectives: This study aimed to determine the effects of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain management in patients undergoing thoracic surgery. Methods: In the prospective, randomized, controlled study, a total of 84 patients undergoing video-assisted thoracoscopic surgery (VATS) were randomly allocated to the TEAS group (Group T) or control group (Group C). Patients in the Group T received TEAS at Neiguan (PC6) and Hegu (LI4) acupoints for 30 min before anesthesia induction and 30 min after thoracoscopic surgery. Patients in the Group C received the same placement of electrodes but without electrical stimulation. The numeric rating scale (NRS) pain score, remifentanil consumption, demand for rescue analgesics and incidence of postoperative nausea and vomiting (PONV), patient satisfaction, and the levels of plasma ß-endorphin (EP) and IL-6 were recorded. Results: Patients in the Group T had significantly lower NRS pain scores at 6 h, 12 h, 24 h, and 48 h after surgery than those in the Group C. Compared with Group C, patients in Group T had lower remifentanil consumption during operation, lower demand for rescue analgesics and lower rate of PONV within 24 h after surgery. Patients in Group T also had lower IL-6 content, higher ß-EP content and higher satisfaction degree than those in the Group C. Conclusions: Perioperative TEAS significantly decreased postoperative pain and rescued analgesia requirements and the incidence of PONV in patients undergoing thoracoscopic surgery, with a higher patient satisfaction. This trial is registered with ChiCTR2100051841.

Efficacy, safety, and survival of neoadjuvant immunotherapy plus chemotherapy in locally advanced esophageal squamous cell carcinoma: A real-world retrospective study.

BACKGROUND: This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months. METHODS: From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital. RESULTS: A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection. CONCLUSIONS: Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.

Multimodal integration of radiology and pathology signatures for distinguishing between aldosterone-producing adenomas and nonfunctional adrenal adenomas.

OBJECTIVE: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). METHODS: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. RESULTS: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000). CONCLUSION: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.

Cadmium promoted LPS-induced inflammation through TLR4/IκBα/NFκ-B signaling by increasing ROS-mediated incomplete autophagy.

Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.

Arthroscopic wafer procedure versus ulnar shortening osteotomy for ulnar impaction syndrome: a systematic review and meta-analysis.

PURPOSE: This study aimed to systematically compare the efficacy and safety of arthroscopic wafer procedure (AWP) versus ulnar shortening osteotomy (USO) for ulnar impaction syndrome (UIS) treatment. METHODS: All the studies included in this meta-analysis compared the efficacy of AWP to USO for UIS and were acquired through a comprehensive search across multiple databases. The meta-analysis was performed by calculating the effect sizes with the Cochrane Collaboration's RevMan 5.4 software. RESULTS: A total of 8 articles were included in this analysis, comprising 148 cases in the AWP group and 163 cases in the USO group. The pooled estimates indicated no significant differences in combined Darrow's Criteria or Modified Mayo Wrist Score, Modified Mayo Wrist Score, DASH scores, grip strength, VAS score, and postoperative ulnar variation. On the other hand, the patients in the AWP group exhibited fewer complications (OR = 0.17, 95%CI 0.05-0.54, P = 0.003) and a lower reoperation rate (OR = 0.12, 95%CI 0.05-0.28, P < 0.00001) than those in the USO group. CONCLUSIONS: The two surgical techniques were both effective in treating UIS but the AWP group showed fewer complications and a lower reoperation rate. Therefore, AWP may present a superior alternative for UIS treatment.

The first dorsal metacarpal artery flaps versus reverse homodigital dorsal flaps for thumb reconstruction: a systematic review and meta-analysis.

PURPOSE: This review was performed to systematically compare the effectiveness and safety of the first dorsal metacarpal artery flaps (FDMAF) and reverse homodigital dorsal flaps (RHDF) for thumb reconstruction. METHODS: All literatures, which compared FDMAF versus RHDF for thumb reconstruction, were acquired through a comprehensive search in multiple databases from inception until 31st August 2022. A meta-analysis was performed using the Cochrane Collaboration's RevMan 5.4 software. RESULTS: A total of 19 articles were retrieved, comprising 396 patients in the FDMAF group and 423 patients in the RHDF group. The pooled estimates suggested that there were no significant differences in venous congestion, complications about flap necrosis and reduced range of motion (ROM) of thumb, static 2-point discrimination (S-2PD) between the two groups. On the other hand, patients in the RHDF group had less vascular crisis (odds ratio [OR] = 3.15, 95%CI, 1.31-7.56), complications about poor cortical reorientation (OR = 440.02, 95%CI, 91.97-2105.27) and higher satisfaction rate (OR = 0.56, 95% CI, 0.33-0.96) than those in the FDMAF group. CONCLUSIONS: The two surgical procedures were both safe and reliable since no significant differences were found in flap necrosis between the two groups. However, the patients in the RHDF group had less complications about vascular crisis, poor cortical reorientation and higher satisfaction rate. Accordingly, we thought RHDF may be more superior for thumb reconstruction than FDMAF.

From ferroptosis to cuproptosis, and calcicoptosis, to find more novel metals-mediated distinct form of regulated cell death.

Regulated cell death (RCD), also known as programmed cell death (PCD), plays a critical role in various biological processes, such as tissue injury/repair, development, and homeostasis. Dysregulation of RCD pathways can lead to the development of many human diseases, such as cancer, neurodegenerative disorders, and cardiovascular diseases. Maintaining proper metal ion homeostasis is critical for human health. However, imbalances in metal levels within cells can result in cytotoxicity and cell death, leading to a variety of diseases and health problems. In recent years, new types of metal overload-induced cell death have been identified, including ferroptosis, cuproptosis, and calcicoptosis. This has prompted us to examine the three defined metal-dependent cell death types, and discuss other metals-induced ferroptosis, cuproptosis, and disrupted Ca2+ homeostasis, as well as the roles of Zn2+ in metals' homeostasis and related RCD. We have reviewed the connection between metals-induced RCD and various diseases, as well as the underlying mechanisms. We believe that further research in this area will lead to the discovery of novel types of metal-dependent RCD, a better understanding of the underlying mechanisms, and the development of new therapeutic strategies for human diseases.

Abnormal Amygdala Subregion Functional Connectivity in Patients with Crohn's Disease with or without Anxiety and Depression.

Objective: The aim of this study was to explore the resting-state functional connectivity (rsFC) of amygdala subregions in healthy controls (HCs) and in patients with Crohn's disease (CD) both with and without anxiety or depression. Materials and Methods: A total of 33 patients with CD and with anxiety or depression (CDad group), 31 patients with CD but without anxiety or depression (CDnad group), and 29 age-, sex-, and education level-matched HCs underwent functional magnetic resonance imaging. rsFC analysis was used to analyze the FC between the amygdala subregions and other areas of the brain. Results: Compared with the HC group, the CDad group demonstrated decreased rsFC between the right laterobasal subregion and the left hippocampus (P < .001) and right middle frontal gyrus (P < .001) and between the left superficial subregion and the left insula (P < .001). Compared with the HC group, the CDnad group demonstrated decreased rsFC between the left centromedial subregion and the left insula (P < .001). Compared with the CDnad group, the CDad group demonstrated decreased rsFC between the left centromedial subregion and the right precuneus (P < .001) and postcentral gyrus (P < .001), between the right laterobasal subregion and the left hippocampus (P < .001), and between the left superficial subregion and the right middle frontal gyrus (P < .001). Conclusions: There are significant FC changes in the amygdala subregions in patients with CD. These changes may be related to the disease itself or to the symptoms of anxiety and depression.

Sensory re-education after free neurovascular toe pulp flap for digital pulp reconstruction.

PURPOSE: To evaluate the effectiveness of a sensory re-education (SR) program after free neurovascular toe pulp flap for finger or thumb pulp defect reconstruction. METHODS: From January 2015 to January 2020, 49 patients with finger or thumb pulp defects treated with free fibular side flaps of the great toe or tibial side flaps of the second toe were recruited. The patients were randomly divided into two groups one month after surgery. The training group received the SR program, and the control group underwent the traditional rehabilitation program. Clinical evaluation included Semmes-Weinstein Monofilament (SWM) tests, static two-point discrimination (2-PD), and sensibility grading, measured at 1, 3, 6, 9, and 12 months postoperatively. RESULTS: A total of 42 patients completed the follow-up, including 22 (16 males) patients in the training group and 20 patients (12 males) in the control group. Compared with 1 month after the operation, significant improvements in sensory recovery were observed at 3, 6, 9, and 12 months postoperatively in both groups. In addition, earlier sensory recovery was seen in the SR group compared to the control group, showing significant differences at 3 and 6 months but not at 9 and 12 months postoperatively. CONCLUSION: Although SR seemed to accelerate preliminary sensory recovery after free neurovascular toe pulp flaps for digital defect reconstruction, the program should be reconsidered as it offers no significant improvement over the control group at later follow-up stages.

Inhibiting stanniocalcin 2 reduces sunitinib resistance of Caki-1 renal cancer cells under hypoxia condition.

Background: Our previous study has suggested that blocking stanniocalcin 2 (STC2) could reduce sunitinib resistance in clear cell renal cell carcinoma (ccRCC) under normoxia. The hypoxia is a particularly important environment for RCC occurrence and development, as well as sunitinib resistance. The authors proposed that STC2 also plays important roles in RCC sunitinib resistance under hypoxia conditions. Methods: The ccRCC Caki-1 cells were treated within the hypoxia conditions. Real-time quantitative PCR and Western blotting were applied to detect the STC2 expression in ccRCC Caki-1 cells. STC2-neutralizing antibodies, STC2 siRNA, and the recombinant human STC2 (rhSTC2) were used to identify targeting regulation on STC2 in modulating sunitinib resistance, proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. In addition, autophagy flux and the lysosomal acidic environment were investigated by Western blotting and fluorescence staining, and the accumulation of sunitinib in cells was observed with the addition of STC2-neutralizing antibodies and autophagy modulators. Results: Under hypoxia conditions, sunitinib disrupted the lysosomal acidic environment and accumulated in Caki-1 cells. Hypoxia-induced the STC2 mRNA and protein levels in Caki-1 cells. STC2-neutralizing antibodies and STC2 siRNA effectively aggravated sunitinib-reduced cell viability and proliferation, which were reversed by rhSTC2. In addition, sunitinib promoted EMT, migration, and invasion, which were reduced by STC2-neutralizing antibodies. Conclusion: Inhibiting STC2 could reduce the sunitinib resistance of ccRCC cells under hypoxia conditions.

Comparative Study on the Efficacy of Precise Radiotherapy in Lymphatic Drainage Area of Esophageal Cancer between Preventive Radiation and Invasive Field Radiation.

To investigate the efficacy of precise radiation therapy for lymphatic drainage area prevention (ENI) and invasive field irradiation (IFI) in patients with esophageal cancer undergoing radical radiotherapy. A retrospective analysis was conducted on 96 esophageal cancer patients admitted to our hospital from March 2018 to March 2021 who underwent radical radiotherapy. Among them, 48 patients who received precise radiation therapy to prevent radiation in the lymphatic drainage area were included in the ENI group, and 48 patients who received field irradiation were included in the IFI group. Compare and analyze the total clinical response rate, local control rate within 3 years after treatment, survival rate, and incidence of adverse reactions after radiotherapy between two groups of patients. There was no statistically significant difference in the total clinical response rate between the ENI group and the IFI group after radiotherapy (P > .05). There was no statistically significant difference in local control rate and survival rate between the ENI group and the IFI group within 3 years of treatment (P > .05). The incidence of postoperative complications in the ENI group was significantly higher than that in the IFI group, with a statistically significant difference (P < .05). When giving radical radiotherapy to esophageal cancer patients, the clinical total effective rate, survival rate, and local control rate of involving field irradiation are equivalent to the preventive radiation effect of precise radiotherapy for lymphatic drainage area. Besides, involving field irradiation can reduce the incidence of adverse reactions in patients after radiotherapy, which has high clinical value.

Development and Validation of a Radiomics Nomogram for Liver Metastases Originating from Gastric and Colorectal Cancer.

The origin of metastatic liver tumours (arising from gastric or colorectal sources) is closely linked to treatment choices and survival prospects. However, in some instances, the primary lesion remains elusive even after an exhaustive diagnostic investigation. Consequently, we have devised and validated a radiomics nomogram for ascertaining the primary origin of liver metastases stemming from gastric cancer (GCLMs) and colorectal cancer (CCLMs). This retrospective study encompassed patients diagnosed with either GCLMs or CCLMs, comprising a total of 277 GCLM cases and 278 CCLM cases. Radiomic characteristics were derived from venous phase computed tomography (CT) scans, and a radiomics signature (RS) was computed. Multivariable regression analysis demonstrated that gender (OR = 3.457; 95% CI: 2.102-5.684; p < 0.001), haemoglobin levels (OR = 0.976; 95% CI: 0.967-0.986; p < 0.001), carcinoembryonic antigen (CEA) levels (OR = 0.500; 95% CI: 0.307-0.814; p = 0.005), and RS (OR = 2.147; 95% CI: 1.127-4.091; p = 0.020) exhibited independent associations with GCLMs as compared to CCLMs. The nomogram, combining RS with clinical variables, demonstrated strong discriminatory power in both the training (AUC = 0.71) and validation (AUC = 0.78) cohorts. The calibration curve, decision curve analysis, and clinical impact curves revealed the clinical utility of this nomogram and substantiated its enhanced diagnostic performance.

A nomogram based on CT texture features to predict the response of patients with advanced pancreatic cancer treated with chemotherapy.

OBJECTIVE: This study aimed to evaluate the predictive value of computed tomography (CT) texture features in the treatment response of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy. METHODS: This study enrolled 84 patients with APC treated with first-line chemotherapy and conducted texture analysis on primary pancreatic tumors. 59 patients and 25 were randomly assigned to the training and validation cohorts at a ratio of 7:3. The treatment response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). The patients were divided into progressive and non-progressive groups. The least absolute shrinkage selection operator (LASSO) was applied for feature selection in the training cohort and a radiomics signature (RS) was calculated. A nomogram was developed based on a multivariate logistic regression model incorporating the RS and carbohydrate antigen 19-9 (CA19-9), and was internally validated using the C-index and calibration plot. We performed the decision curve analysis (DCA) and clinical impact curve analysis to reflect the clinical utility of the nomogram. The nomogram was further externally confirmed in the validation cohort. RESULTS: The multivariate logistic regression analysis indicated that the RS and CA19-9 were independent predictors (P < 0.05), and a trend was found for chemotherapy between progressive and non-progressive groups. The nomogram incorporating RS, CA19-9 and chemotherapy showed favorable discriminative ability in the training (C-index = 0.802) and validation (C-index = 0.920) cohorts. The nomogram demonstrated favorable clinical utility. CONCLUSION: The RS of significant texture features was significantly associated with the early treatment effect of patients with APC treated with chemotherapy. Based on the RS, CA19-9 and chemotherapy, the nomogram provided a promising way to predict chemotherapeutic effects for APC patients.

Artificial Intelligence and Big Data Technologies in the Construction of Surgical Risk Prediction Model for Patients with Coronary Artery Bypass Grafting.

The objective of this work was to predict the risk of mortality rate in patients with coronary artery bypass grafting (CABG) based on the risk prediction model of CABG using artificial intelligence (AI) and big data technologies. The clinical data of 2,364 patients undergoing CABG in our hospital from January 2019 to August 2021 were collected in this work. Based on AI and big data technology, business requirement analysis, system requirement analysis, complication prediction module, big data mining technology, and model building are carried out, respectively; the successful CABG risk prediction system includes case feature analysis service, risk warning service, and case retrieval service. The commonly used precision, recall, and F1-score were adopted to evaluate the quality of the gradient-boosted tree (GBT) model. The analysis proved that the GBT model was the best in terms of precision, F1-score, and area under the receiver operating characteristic curve (ROC). According to the CABG risk prediction model, 1,382 patients had a score of <0, 463 patients had a score of 0 ≤ score ≤ 2, 252 patients had a score of 2 < score ≤ 5, and 267 patients had a score of >5, which were stratified into four groups: A, B, C, and D. The actual number of in-hospital deaths was 25, and the in-hospital mortality rate was 1.05%. The mortality rate predicted by the CABG risk prediction model was 2.67 ± 1.82% (95% confidential interval (CI) (2.87-2.98)), which was higher than the actual value. The CABG risk prediction model showed the credible results only in group B with AUC = 0.763 > 0.7. In group B, 3 patients actually died, the actual mortality rate was 0.33%, and the predicted mortality rate was 0.96 ± 0.78 (95% CI (0.82-0.87)), which overestimated the mortality rate of patients in group B. It successfully constructed a CABG risk prediction model based on the AI and big data technologies, which would overestimate the mortality of patients with intermediate risk, and it is suitable for different types of heart diseases through continuous research and development and innovation, and provides clinical guidance value.

Cadmium-induced stress: a close look at the relationship between autophagy and apoptosis.

Stress is acknowledged as one of the major factors responsible for autophagy induction, a tightly regulated process that acts as a pro-death or pro-survival mechanism within cells. Cadmium (Cd), a toxic heavy metal, induces apoptosis and autophagy in cells after exposure to low concentrations. This is due to Cd's ability to induce oxidative stress in cells and tissues by overproducing reactive oxygen species. Several proteins have been found to mediate the process of autophagy but aspects of their specific roles and targets remain undefined. Though LC3-II and p62 have traditionally been used as biomarkers that define autophagy, recent findings have revealed some limitations to LC3-II because it can be accumulated in cells in an autophagy-independent manner, whereas p62 remains a good determinant of the process. In addition to LC3-II and p62, recent studies have suggested that a new member of the autophagy protein family, the vacuole membrane protein 1 (VMP1), is essential in driving autophagy and could be an important biomarker for detecting the initiation and progression of autophagy. This review therefore focuses on current trends in autophagy biomarkers, the effect of Cd on the expression of LC3-II, p62, VMP1, and Beclin-1 and their relation and inter-regulatory roles in autophagy and apoptosis, pharmacological importance, and the mechanisms involved.

Cadmium induced immunosuppression through TLR-IκBα-NFκB signaling by promoting autophagic degradation.

Environmental and occupational exposure to cadmium (Cd) poses a serious threat to human health. Recent studies indicate that Cd perturbs the immune system and increases the risk of pathogenicity and mortality of bacterial or virus infection. However, the underlying mechanism of Cd-modulated immune responses remains unclear. In this study, we aim to investigate the role of Cd in the immune function of mouse spleen tissues and its primary T cells with Concanavalin A (ConA, a well-known T cell mitogen) activation condition, and elucidate the molecular mechanism. The results showed that Cd exposure inhibited ConA-induced the expressions of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in mouse spleen tissues. Furthermore, the transcriptomic profile by RNA-sequence reveals that: (1) Cd exposure can alter immune system process; (2) Cd may affect the NFκB signaling pathway. Both in vitro and in vivo results showed that Cd exposure reduced ConA-activated toll-like receptor 9 (TLR9)-IκBα-NFκB signaling, and the expressions of TLR9, TNF-α and IFN-γ, which were effectively reversed by autophagy-lysosomal inhibitors. All these results confirmedly demonstrated that, by promoting the autophagy-lysosomal degradation of TLR9, Cd suppressed immune response under ConA activation condition. This study provides insight on the mechanism of Cd immunnotoxicity, which might contribute to the prevention of Cd toxicity in the future.