Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Female ; Humans ; Endodermal Sinus Tumor/pathology* ; Adenocarcinoma/pathology* ; Choriocarcinoma/pathology*

There are three types of adipose tissue: white adipose tissue that stores energy, brown adipose tissue that expends energy, and beige adipose tissue which results from the browning of white adipose tissue. Research has established that adipose tissue is vital for energy metabolism. However, the complex regulatory mechanisms limit the development of effective therapeutic strategies for obesity and related metabolic diseases. This review explores the characteristics and functions of adipose tissue types, emphasizing the role of central hypothalamic nuclei in regulating peripheral adipose tissue function Additionally, it provides a summary and comparison of current research on leveraging brown and beige adipose tissue thermogenesis as a treatment for metabolic diseases, offering insights for the advancement of targeted therapies for obesity and related disorders.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

OBJECTIVE: Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury. METHODS: PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments. RESULTS: Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3. CONCLUSION Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Objective: To investigate the clinicopathological characteristics of esophageal carcinoma with gland duct differentiation. Methods: The clinical, morphologic and immunohistochemical (IHC) features of eight cases of esophageal carcinoma with gland duct differentiation diagnosed from 2012 to 2022 at the First Affiliated Hospital of Soochow University were summarized. Results: There were four males and four females, with a mean age of 68.5 (range 59-82) years. Two tumors were located in middle esophagus, five in the lower esophagus, and one in the cardia. The mean diameter was 2.4 cm (range 0.6-4.5 cm). The tumor had a bilayer epithelial structure, including the inner luminal epithelium and the outer basal epithelium. Immunohistochemistry showed that CK7 (8/8) and CK18 (8/8) were positive in the inner epithelium. p40 (8/8), p63 (8/8) and CK5/6 (8/8) were positive in the outer epithelium. SMA, calponin and CD117 were all negative. p53 mutants were found in all eight cases (strong and diffuse positivity in 6/8; complete loss of expression in 2/8). No columnar metaplasia, intestinal metaplasia and ectopic gastric mucosa were observed in the surface squamous epithelium in the cases. The mean follow-up time was 21.5 months (range 5-51 months). Seven patients survived and one patient died 31 months after surgery due to recurrence and liver metastasis. Conclusion: Esophageal carcinoma with esophageal gland duct differentiation is a rare tumor with unique histologic and IHC characteristics.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Esophageal Neoplasms/pathology* ; Epithelium/pathology* ; Metaplasia/metabolism* ; Carcinoma/pathology*

Humans ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Cholangiocarcinoma/pathology* ; Carcinoma, Squamous Cell ; Bile Ducts, Intrahepatic/pathology* ; Bile Duct Neoplasms/pathology*

Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; Biomarkers, Tumor

Humans ; Kidney/pathology*

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
Male ; Female ; Humans ; Prognosis ; Neoplasm Staging ; Retrospective Studies ; Nomograms ; Lymph Nodes/pathology* ; Risk Factors ; Colonic Neoplasms/surgery*