Enantioselective Nickel-Catalyzed Denitrogenative Transannulation En Route to N-N Atropisomers.

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

Gene Expression Array Analyses Predict Proto-Oncogene Expression During Perineural Invasion in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma is the tumor type with the highest incidence of perineural invasion. This study tries to identify the differentially expressed genes regulated between pancreatic ductal adenocarcinoma tissues with perineural invasion and without perineural invasion. MATERIALS AND METHODS: The GSE102238 profile was downloaded. Gene function and pathway analysis were subsequently conducted. A protein-protein interaction network was constructed to search for hub genes. Both univariate Cox analysis and multivariate Cox analysis were calculated to identify prognostic factors. Quantitative real-time polymerase chain reaction (RT-PCR) and overall survival analysis of hub genes were used to verify. RESULTS: Our study identified 242 differentially expressed genes including 68 upregulated differentially expressed genes and 174 downregulated differentially expressed genes, which were involved in important functions and pathways. Nine relevant core genes using protein-protein interaction analysis as well as nestin (NES)/vascular endothlial growth factor (VEGF) signaling pathway which is highly related to the pathological process of perineural invasion in pancreatic ductal adenocarcinoma were also discovered. The differentiation was identified as an independent prognostic factor (P < .05) after multivariate Cox analysis. Three upregulated genes (JUP, CALM1, and NES) and 6 downregulated genes (EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3) were validated by quantitative RT-PCR and they all had markedly worse overall survival (P < .05). CONCLUSION: This analysis showed that 9 core genes including JUP, CALM1, NES, EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3, as well as NES/VEGF signaling pathway, have a relationship with the development process of perineural invasion in pancreatic ductal adenocarcinoma. Cox analysis and overall survival analysis suggested differentiation as an independent prognostic factor and key roles for these 9 hub genes in perineural invasion prognosis in pancreatic ductal adenocarcinoma.

Chemotherapy alone versus chemotherapy plus 125I brachytherapy for the second-line treatment of locally recurrent cervical cancer after/with radical treatment: A propensity score analysis.

Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.

Pseudo-capsulated Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization.

RATIONALE AND OBJECTIVES: The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. MATERIALS AND METHODS: A total of 196 cases with single pHCC (diameter >5 cm) receiving initial HAIC (n = 92) and TACE (n = 104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. RESULTS: The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P = .267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P = .003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P = .046; ORR, 35.6% vs. 21.7%; P = .033). The nomogram model showed high predictive accuracy and significant discrimination. CONCLUSION: TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.

Clinical Application of Ureteroscope-Assisted Laparoscopic Surgery for Prostatic Utricle in Children.

Purpose: To investigate the use of ureteroscope-assisted laparoscopic surgery (UALS) in treating symptomatic prostatic utricle (PU) in children. Materials and Methods: Data on surgically treated cases of PU at the Department of Urology in Hunan Children's Hospital between September 2014 and September 2022 were retrospectively collected and analyzed. The diagnosis was confirmed by cystourethroscopy followed by ureteroscopy, and PU was excised by ureteroscope-assisted laparoscopy. Results: A total of 21 patients with PU were enrolled in this study. The median age of the patients at surgery was 8.1 (4.6-11.5) years. Karyotyping was available for 15 children: 13 (86.7%) were 46XY, 1 (6.7%) was 45X/46XY, and 1 (6.7%) was 45X/46XY/47XYY. The median length of the PU was 5.0 (4.1-7.1) cm. Nineteen patients underwent only ureteroscope-assisted laparoscopic excision, whereas 2 also had a perineal incision. All excisions were successfully performed. The median intraoperative blood loss was 25.0 (20.0-37.5) mL. The median hospital stay and follow-up durations were 18.0 (14.5-25.0) days and 24.0 (13.5-49.0) months, respectively. The patients reported no postoperative clinical symptoms. Conclusion: UALS allows for accurate patient positioning and thorough exposure of the anatomical structures, and it is a safe, effective, and minimally invasive treatment for PU in children.

A patient with Owren disease requires pancreatic surgery: A case report.

RATIONALE: Coagulation factor V deficiency is rare, and perioperative management of patients with this condition is particularly important, especially during major abdominal surgery. We present a case of a patient with pancreatic duct stones combined with coagulation factor V deficiency. We share our perioperative management experience. PATIENT CONCERNS: A 31-year-old man presented with recurrent upper abdominal pain for 2 years. DIAGNOSES: The diagnosis of pancreatic duct stones in the patient has been established through abdominal computed tomography and magnetic resonance imaging examinations. The diagnosis of factor V deficiency was initially identified through coagulation function tests, revealing significant prolongation of both aPTT and PT. Subsequent testing of coagulation factors and inhibitors demonstrated that the patient has a deficiency in coagulation factor V. Finally, genetic testing revealed that the factor V deficiency in this case is hereditary. INTERVENTIONS: The patient underwent a partial resection of the pancreatic head, and FFP was infused 1 hour before surgery. 600 mL of FFP was instilled 1 hour before the start of surgery along with 10 U of cryoprecipitate. and 600 ml of FFP were added during surgery. Postoperative treatment included intermittent FFP supplemental infusion in the first 5 days after surgery while monitoring the coagulation function. OUTCOMES: The patient underwent a successful surgery without any abnormal bleeding or oozing during the procedure. The postoperative recovery was smooth, with no abnormal bleeding. LESSONS: Patients with a deficiency of coagulation factor V are not contraindicated for surgery. Appropriate Fresh Frozen Plasma (FFP) replacement therapy can ensure the safe conduct of the surgical procedure. For patients with abnormal blood coagulation function, we recommend testing for coagulation factors and inhibitors, as well as performing genetic testing for abnormal coagulation factors, which can provide guidance on marriage and childbirth.

Dual-Modality Imaging-Guided Manganese-Based Nanotransformer for Enhanced Gas-Photothermal Therapy Combined Immunotherapeutic Strategy Against Triple-Negative Breast Cancer.

Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.

A multitask deep learning radiomics model for predicting the macrotrabecular-massive subtype and prognosis of hepatocellular carcinoma after hepatic arterial infusion chemotherapy.

BACKGROUND: The macrotrabecular-massive (MTM) is a special subtype of hepatocellular carcinoma (HCC), which has commonly a dismal prognosis. This study aimed to develop a multitask deep learning radiomics (MDLR) model for predicting MTM and HCC patients' prognosis after hepatic arterial infusion chemotherapy (HAIC). METHODS: From June 2018 to March 2020, 158 eligible patients with HCC who underwent surgery were retrospectively enrolled in MTM related cohorts, and 752 HCC patients who underwent HAIC were included in HAIC related cohorts during the same period. DLR features were extracted from dual-phase (arterial phase and venous phase) contrast-enhanced computed tomography (CECT) of the entire liver region. Then, an MDLR model was used for the simultaneous prediction of the MTM subtype and patient prognosis after HAIC. The MDLR model for prognostic risk stratification incorporated DLR signatures, clinical variables and MTM subtype. FINDINGS: The predictive performance of the DLR model for the MTM subtype was 0.968 in the training cohort [TC], 0.912 in the internal test cohort [ITC] and 0.773 in the external test cohort [ETC], respectively. Multivariable analysis identified portal vein tumor thrombus (PVTT) (p = 0.012), HAIC response (p < 0.001), HAIC sessions (p < 0.001) and MTM subtype (p < 0.001) as indicators of poor prognosis. After incorporating DLR signatures, the MDLR model yielded the best performance among all models (AUC, 0.855 in the TC, 0.805 in the ITC and 0.792 in the ETC). With these variables, the MDLR model provided two risk strata for overall survival (OS) in the TC: low risk (5-year OS, 44.9%) and high risk (5-year OS, 4.9%). INTERPRETATION: A tool based on MDLR was developed to consider that the MTM is an important prognosis factor for HCC patients. MDLR showed outstanding performance for the prognostic risk stratification of HCC patients who underwent HAIC and may help physicians with therapeutic decision making and surveillance strategy selection in clinical practice.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

Chronic stress promotes colorectal cancer progression by enhancing glycolysis through ß2-AR/CREB1 signal pathway.

Colorectal cancer (CRC) is a common malignancy worldwide, and chronic stress has been considered as a significant risk factor for CRC. However, the role of chronic stress in CRC progression is unclear. The present study showed that pre-exposure to chronic stress facilitated CRC tumor growth in mice, and epinephrine promoted CRC cell proliferation in vitro. Metabolomics analysis revealed that chronic stress reshaped metabolic pathways to enhance glycolysis. Additional studies have shown that stress enhanced the expression levels of glycolytic-associated enzymes, including GLUT1, HK2 and PFKP. Mechanistically, chronic stress activated the ß2-AR/PKA/CREB1 pathway, as a result, phosphorylated CREB1 transcriptional induced glycolytic enzymes expression. Furthermore, stress-induced cell proliferation and tumor growth could be reversed by administration of glycolysis inhibitor 2-deoxyglucose (2-DG) and ß2-AR antagonist ICI118,551, respectively. Altogether, these findings define novel insights into the stress-induced epinephrine-mediated CRC progression from the point of view of tumor energy metabolism reprogramming and provide a perspective on targeting glycolysis as a potential approach in stress-associated CRC treatment.

Preoperative prediction model for macrotrabecular-massive hepatocellular carcinoma based on contrast-enhanced CT and clinical characteristics: a retrospective study.

Objective: To investigate the predictive value of contrast-enhanced computed tomography (CECT) imaging features and clinical factors in identifying the macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) preoperatively. Methods: This retrospective study included 101 consecutive patients with pathology-proven HCC (35 MTM subtype vs. 66 non-MTM subtype) who underwent liver surgery and preoperative CECT scans from January 2017 to November 2021. The imaging features were evaluated by two board-certified abdominal radiologists independently. The clinical characteristics and imaging findings were compared between the MTM and non-MTM subtypes. Univariate and multivariate logistic regression analyses were performed to investigate the association of clinical-radiological variables and MTM-HCCs and develop a predictive model. Subgroup analysis was also performed in BCLC 0-A stage patients. Receiver operating characteristic (ROC) curves analysis was used to determine the optimal cutoff values and the area under the curve (AUC) was employed to evaluate predictive performance. Results: Intratumor hypoenhancement (odds ratio [OR] = 2.724; 95% confidence interval [CI]: 1.033, 7.467; p = .045), tumors without enhancing capsules (OR = 3.274; 95% CI: 1.209, 9.755; p = .03), high serum alpha-fetoprotein (AFP) (≥ 228 ng/mL, OR = 4.101; 95% CI: 1.523, 11.722; p = .006) and high hemoglobin (≥ 130.5 g/L; OR = 3.943; 95% CI: 1.466, 11.710; p = .009) were independent predictors for MTM-HCCs. The clinical-radiologic (CR) model showed the best predictive performance, achieving an AUC of 0.793, sensitivity of 62.9% and specificity of 81.8%. The CR model also effectively identify MTM-HCCs in early-stage (BCLC 0-A stage) patients. Conclusion: Combining CECT imaging features and clinical characteristics is an effective method for preoperatively identifying MTM-HCCs, even in early-stage patients. The CR model has high predictive performance and could potentially help guide decision-making regarding aggressive therapies in MTM-HCC patients.

Combined chemo-immuno-photothermal therapy based on ursolic acid/astragaloside IV-loaded hyaluronic acid-modified polydopamine nanomedicine inhibiting the growth and metastasis of non-small cell lung cancer.

Combining chemotherapy and immunotherapy is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis. However, platinum-based chemotherapeutics and immune checkpoint blockade-based cancer immunotherapy have toxic side effects and limitations. Ursolic acid (UA) and astragaloside IV (AS-IV) are natural compounds with anticancer activity sourced from Traditional Chinese medicine (TCM). However, their poor water solubilities and targeted deletions limit their medicinal value. In this study, we fabricated hyaluronic acid (HA)-modified UA/(AS-IV)-loaded polydopamine (PDA) nanomedicine (UA/(AS-IV)@PDA-HA) with a high yield at a low cost via simple synthesis. This represents a novel multifunctional nanomedicine that combines chemotherapy, photothermal therapy (PTT), and immunotherapy with an active tumor-targeting ability. The as-prepared nanomedicine not only increased the aqueous solubilities of UA and AS-IV, but also improved their active targeting abilities. HA binds specifically to the overexpressed cluster of differentiation 44 (CD44) on the surface of most cancer cells, thereby improving drug targeting. While evaluating the anticancer effect of UA/(AS-IV)@PDA-HA in vitro and in vivo, the PDA nanodelivery system significantly improved UA-mediated cytotoxicity and anti-metastatic ability against NSCLC cells. In addition, the system also improved the AS-IV-mediated self-immune response of tumor-related antigens, which further inhibited the growth and distant metastasis of NSCLC. Further, PDA nanomaterial-mediated PTT inhibited tumor growth substantially. UA/(AS-IV)@PDA-HA not only significantly eradicated the primary tumor but also strongly inhibited the distant metastasis of NSCLC in vitro and in vivo. Thus, it has immense potential for development as an efficient anti-metastatic agent for NSCLC.

Development and validation of prognostic nomograms for large hepatocellular carcinoma after HAIC.

Background and aims: Hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen (oxaliplatin plus fluorouracil and leucovorin) is a promising option for large hepatocellular carcinoma (HCC). However, post-HAIC prognosis can vary in different patients due to tumor heterogeneity. Herein, we established two nomogram models to assess the survival prognosis of patients after HAIC combination therapy. Methods: A total of 1082 HCC patients who underwent initial HAIC were enrolled between February 2014 and December 2021. We built two nomogram models for survival prediction: the preoperative nomogram (pre-HAICN) using preoperative clinical data and the postoperative nomogram (post-HAICN) based on pre-HAICN and combination therapy. The two nomogram models were internally validated in one hospital and externally validated in four hospitals. A multivariate Cox proportional hazards model was used to identify risk factors for overall survival (OS). The performance outcomes of all models were compared by area under the receiver operating characteristic curve (AUC) analysis with the DeLong test. Results: Multivariable analysis identified larger tumor size, vascular invasion, metastasis, high albumin-bilirubin grade, and high alpha-fetoprotein as indicators for poor prognosis. With these variables, the pre-HAICN provided three risk strata for OS in the training cohort: low risk (5-year OS, 44.9%), middle risk (5-year OS, 20.6%), and high risk (5-year OS, 4.9%). The discrimination of the three strata was improved significantly in the post-HAICN, which included the above-mentioned factors and number of sessions, combination with immune checkpoint inhibitors, tyrosine kinase inhibitors, and local therapy (AUC, 0.802 versus 0.811, p < 0.001). Conclusions: The nomogram models are essential to identify patients with large HCC suitable for treatment with HAIC combination therapy and may potentially benefit personalized decision-making. Lay summary: Hepatic arterial infusion chemotherapy (HAIC) provides sustained higher concentrations of chemotherapy agents in large hepatocellular carcinoma (HCC) by hepatic intra-arterial, result in better objective response outperformed the intravenous administration. HAIC is significantly correlated with favorable survival outcome and obtains extensive support in the effective and safe treatment of intermediate advanced-stage HCC. In view of the high heterogeneity of HCC, there is no consensus regarding the optimal tool for risk stratification before HAIC alone or HAIC combined with tyrosine kinase inhibitors or immune checkpoint inhibitors treatment in HCC. In this large collaboration, we established two nomogram models to estimate the prognosis and evaluate the survival benefits with different HAIC combination therapy. It could help physicians in decision-making before HAIC and comprehensive treatment for large HCC patients in clinical practice and future trials.

ROS-responsive self-activatable photosensitizing agent for photodynamic-immunotherapy of cancer.

Photodynamic therapy (PDT), as a non-invasive and spatiotemporally controllable modality, exhibits great potential in cancer treatment. However, the efficiency of reactive oxygen species (ROS) production was restricted to the hydrophobic characteristics and aggregation-caused quenching (ACQ) of photosensitizers. Herein, we designed a ROS self-activatable nano system (denoted as PTKPa) based on poly(thioketal) conjugated with photosensitizers (PSs) pheophorbide A (Ppa) on the polymer side chains for suppressing ACQ and enhancing PDT. The process of self-activation is that ROS, which is derived from laser irradiated PTKPa, as an activating agent accelerates poly(thioketal) cleavage with the release of Ppa from PTKPa. This in turn generates abundant ROS, accelerates degradation of the remaining PTKPa and amplifies the efficacy of PDT with more tremendous ROS generated. Moreover, these abundant ROS can amplify PDT-induced oxidative stress, cause irreversible damage to tumor cells and achieve immunogenic cell death (ICD), thereby boosting the efficacy of photodynamic-immunotherapy. These findings provide new insights into ROS self-activatable strategy for enhancing cancer photodynamic- immunotherapy. STATEMENT OF SIGNIFICANCE: This work described an approach to utilize ROS-responsive self-activatable poly(thioketal) conjugated with pheophorbide A (Ppa) for suppressing aggregation-caused quenching (ACQ) and enhancing photodynamic-immunotherapy. The ROS, generated from the conjugated Ppa upon 660nm laser irradiation, as a triggering agent which initiates the release of Ppa with poly(thioketal) degradation. That in turn generates abundant ROS and facilitates degradation of the remaining PTKPa, resulting in oxidative stress to tumor cells and achieving immunogenic cell death (ICD). This work provides a promising solution to improve tumor photodynamic therapeutic effects.

Efficacy of press needle on immune function and quality of life in female breast cancer patients after radical mastectomy: study protocol for a randomized controlled trial.

Radical mastectomy may lead to suppression of cellular immune function in patients with malignant tumors, and affect the quality of life (QOL) of patients. Immune suppression is a common cause of complications and adverse reactions in adjuvant therapy after radical mastectomy of breast cancer. Currently, there are few proven effective treatments for immune suppression. Therefore, it's necessary to develop a new treatment method. Press needle is widely used in clinical practice. However, there have been relatively few studies that evaluate the effects of press needle on postoperative immune function. The aim of the present study is to assess the effects of press needle on immune function and QOL in female breast cancer patients undergoing radical mastectomy. This study will be a single-center, randomized and single-blinded trial. Totally 78 eligible patients will be randomized in a ratio of 1:1 to the press needle group or the sham press needle group. During the treatment phase, patients will undergo five times weekly of verum press needle or sham press needle for 2 weeks. The primary outcome measures will be the peripheral blood levels of CD8+, CD4+, CD3+, and CD4+/CD8+ T cells. The secondary outcome measures will be the changes of patients' QOL, evaluated by the Karnofsky Performance Scale score and the EORTC core quality of life questionnaire (EORTC QLQ-C30). Furthermore, 5-year survival rate and recurrence rate will be evaluated. Safety and adverse events will be assessed at each visit. The results of this on-going study will provide clinical evidence for the effects and safety of press needle on immune function and QOL in patients after breast cancer resection compared with sham press needle. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000040100. Registered on 21 November 2020.

Development and validation of a prognostic model based on a single-cell RNA-seq in Wilms tumor in children.

To analyze the heterogeneity between different cell types in pediatric Wilms tumor (WT) tissue, and identify the differentially expressed genes (DEGs) of malignant tumor cells, thereby establishing a prognostic model. The single-cell sequencing data of pediatric WT tissues were downloaded from the public database. Data filtration and normalization, principal component analysis, and T-distributed stochastic neighbor embedding cluster analysis were performed using the Seurat package of R language. Cells were divided into different clusters, malignant tumor cells were extracted, and DEGs were obtained. Then, the pseudo-time trajectory analysis was performed. Prognostic biomarkers were determined by univariate and multivariate COX regression analyses and LASSO regression analysis. Kaplan-Meier survival analysis and receiver operator characteristic curve analysis were performed. Combined with the prognostic biomarkers and clinical characteristics, a nomogram was generated to predict WT prognosis. The prognostic power was validated in the external datasets. Cells in the WT tissue were divided into 10 clusters. Three prognostic biomarkers that affected the survival time of patients were screened from 215 DEGs in malignant tumor cells, and a nomogram was constructed using the three genes and clinical characteristics. The area under the curve (AUC) values of 3- and 5-year disease-free survival were 0.756 and 0.734, respectively. In the external validation dataset, the AUC value of this nomogram model was 0.826. Based on the single-cell RNA-seq, we recognized cell clusters in the WT tissue of children, identified prognostic biomarkers in malignant tumor cells, and established a comprehensive prognostic model. Our findings might provide new ideas and methods for the diagnosis and treatment of WT.

Testicular regression syndrome: A retrospective analysis of clinical and histopathological features in 570 cases.

This study aimed to analyze the clinical features and pathological findings of the largest reported case series of testicular regression syndrome (TRS). Data, including age, affected side, color Doppler ultrasound results, surgical methods, intraoperative conditions, and pathological examinations, of children with unilateral TRS who were treated in our center from December 2012 to November 2021 were retrospectively analyzed. A total of 570 patients were included in this study. The mean age at surgery was 38 (range, 5-193) months. There were 457 cases (80.2%) of left TRS. Preoperative color Doppler ultrasonography found nubbins in 172 cases (30.2%). The long diameter of the contralateral testis was 17.11 (±4.22) mm, and the volume was 0.81 (±1.15) ml. The long diameter was ≥1.6 cm in 62.0% of the patients (240/387) aged ≤3 years. Laparoscopy was performed as the initial surgical step in 513 cases, of which 96.7% of the children had closed internal rings. One or more lesions of fibrosis, hemosiderin, and calcification were found in 92.4% (474/513) of the excised remnants. Germ cells were present in 16 cases (3.1%). In conclusion, TRS is more common on the left side and is usually accompanied by a closed internal ring and compensatory hypertrophy of the contralateral testis. Germ cells are only present in cases where the spermatic vessels enters the internal ring. We recommend that further exploration and excision of the remnants may not be applicable in cases where only the vas deferens has entered the internal ring.

Ginsenosides in cancer: A focus on the regulation of cell metabolism.

Metabolic alterations play a key role in promoting tumor initiation and progression, leading to extensive tumor heterogeneity and adaptability. Thus, targeting abnormal metabolic processes is a promising novel approach for cancer treatment. Numerous pharmacological studies have indicated that many traditional Chinese medicines possess remarkable antitumor activities. Ginsenosides, the main bioactive ingredients of Panax and other types of ginseng, exert beneficial antitumor effects, in addition to the anti-inflammation, anti-oxidant, and anti-fatigue effects. Recently, considerable attention has been paid to the regulation of cancer cell metabolism by ginsenosides. Here, we summarize the structural characteristics and classification of ginsenosides, their antitumor mechanisms, recent progress and the achievements of ginsenoside research in modulating cancer cell metabolism, including the diverse metabolic processes and their regulatory processes, as well as the opportunities and challenges of strategies targeting metabolic vulnerabilities. This review provides novel perspectives on the potential applications of ginsenosides that exert antitumor effects by reshaping cancer metabolism.