Augmented antitumor immune responses of HER2-targeted pyroptotic induction by long-lasting recombinant immunopyroptotins.

Pyroptosis is a well-documented form of programmed cell death caused by the gasdermin-driven perforation of cell membranes. Selective induction of pyroptosis in tumor cells represents a promising antitumor strategy to enhance the efficacy of immunotherapy. In this study, we established a recombinant protein-based immunopyroptotin strategy that led to the intratumoral induction of pyroptosis for HER2-directed therapy. Long-lasting immunopyroptotins were constructed by sequentially fusing the humanized anti-HER2 single-chain antibody P1h3, albumin-binding peptide (ABD035 or dAb7h8), cathepsin B-cleavable peptide B2, endosome-disruptive peptide E5C3, and active pyroptotic effector gasdermin D-N fragment (GN). After purification, we evaluated the cytotoxicity and antitumor immune responses primarily induced by the immunopyroptotins in HER2-overexpressing breast cancer cells. The resulting ABD035-immunoGN and dAb7h8-immunoGN showed improved in vitro cytotoxicity in HER2-overexpressing cancer cells compared with that in the immunotBid that we previously generated to induce tumor cell apoptosis. The binding of long-lasting immunopyroptotins to albumin increased the half-life by approximately 7-fold in nude mice. The enhanced antitumor efficacy of long-lasting immunopyroptotins was confirmed in both N87 tumor-bearing T cell-deficient mice and 4T1-hHER2 bilateral tumor-bearing immunocompetent mice. Immunopyroptotin treatment elicited systemic antitumor immune responses involving CD8+ T cells and mature dendritic cells and upregulated the expression of proinflammatory cytokines, leading to sustained remission of non-injected distant tumors. This study extends the repertoire of antibody-based therapeutics through the tumor-targeted delivery of a constitutively active pore-forming gasdermin-N fragment, which shows great potential for pyroptosis-based antitumor therapy.

[Heat-sensitive moxibustion combined with tropisetron hydrochloride for chemotherapy-induced nausea and vomiting: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy of heat-sensitive moxibustion combined with tropisetron hydrochloride and tropisetron hydrochloride alone in the treatment of chemotherapy-induced nausea and vomiting (CINV). METHODS: Sixty CINV patients were randomly divided into an observation group and a control group, 30 cases in each group.The control group was treated with tropisetron hydrochloride. On the basis of the treatment in the control group, heat-sensitive acupoints were explored at Zhongwan (CV 12), Shenque (CV 8), Qihai (CV 6), Guanyuan (CV 4), Shangwan (CV 13), Xiawan (CV 10), Jianli (CV 11) and bilateral Zusanli (ST 36), Neiguan (PC 6), Tianshu (ST 25), Liangmen (ST 21) areas in the observation group，and heat-sensitive moxibustion was applied at heat-sensitive acupoints. The treatment started from the day of chemotherapy in both groups, once a day for 7 days. The occurrence and severity of nausea and vomiting after chemotherapy were recorded after each treatment on the 1st to 7th days of chemotherapy in the two groups, the complete remission rate was evaluated. The KPS score, quality of life scale score before and after treatment and incidence of myelosuppression were compared between the two groups. RESULTS: On the 2nd to 4th days of chemotherapy, the incidence and severity of nausea and vomiting in the observation group were lower than those in the control group (P<0.05), the complete remission rates of nausea and vomiting were higher than those in the control group (P<0.05). After treatment, the KPS score in the observation group was higher than those before treatment and in the control group (P<0.05). After treatment, the scores of emotional function and overall health status in the observation group were higher than those before treatment and in the control group (P<0.05), the scores of fatigue, pain, insomnia, loss of appetite and diarrhea were lower than those before treatment and in the control group (P<0.05). The incidence of myelosuppression in the observation group was 20.0% (6/30), which was lower than 46.7% (14/30) in the control group (P<0.05). CONCLUSION: Heat-sensitive moxibustion combined with tropisetron hydrochloride can effectively reduce nausea and vomiting after chemotherapy in patients with malignant tumor, improve the quality of life, relieve the myelosuppression caused by chemotherapy drugs.

Establishment of XRD fourier fingerprint identification method of realgar decoction pieces and its anti-tumor activity in tumor-in-situ transplanted mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control. AIM OF THE STUDY: The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed. MATERIALS AND METHODS: Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed. RESULT: The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits. CONCLUSION: The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

Impact of body mass index at diagnosis on outcomes of pediatric acute leukemia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.

Inflammatory Myofibroblastic Tumor of the Sciatic Nerve Mimicking Lumbar Disc Herniation: A Diagnostic Challenge.

Inflammatory myofibroblastic tumors (IMTs), which involve the proliferation of fibroblastic-myofibroblastic cells mixed with inflammatory infiltrates, are exceedingly rare in the extremities. There are no reported IMTs involving the sciatic nerve. This type of involvement may cause entrapment of the sciatic nerve, whose symptoms may mimic lumbar disc herniation (LDH), especially when it occurs in patients with lumbar degenerative disc disease. We describe the case of a 40-year-old male with lumbar degenerative disc disease accompanied by IMT involving the sciatic nerve whose symptoms mimicked LDH and posed a diagnostic challenge. We showed the course of the disease as well as the systematic imaging manifestations of IMTs involving the sciatic nerve and discussed their therapeutic management.

BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Oxygen vacancy-rich nickel oxide nanoplatforms for enhanced photothermal and chemodynamic therapy combat methicillin-resistant Staphylococcus aureus.

Bacterial infections pose a global concern due to high fatality rates, particularly with the rise of drug-resistant bacteria and biofilm formation. There is an urgent need for innovative strategies to combat this issue. A study on chemodynamic therapy (CDT) using nanozymes in conjunction with photothermal therapy (PTT) has displayed potential in addressing drug-resistant bacterial infections. However, the effectiveness of this combined approach is limited by inadequate light absorption. This work suggests the NiOx nanoparticles enriched with oxygen vacancies enhance CDT and PTT to overcome this challenge. The presence of oxygen vacancies in NiOx can reduce the energy gap between its valence band and conduction band, facilitating oxygen adsorption. NiOx has exhibited notable antibacterial properties and complete eradication of biofilms in both laboratory and animal trials. In animal abscess models, NiOx demonstrated antibacterial and anti-inflammatory effects in the initial stages, while also promoting wound healing and tissue regeneration by influencing immune factors and encouraging collagen deposition and neovascularization. With positive biosafety and biocompatibility profiles, the oxygen vacancy-enhanced CDT and PTT therapy proposed in this article hold promise for effective sterilization, deep biofilm removal, and treatment of infections caused by drug-resistant bacteria. STATEMENT OF SIGNIFICANCE: This study constructs oxygen vacancies NiOx nanoparticles (NiOx NPs) to improve the efficacy of photothermal therapy and chemodynamic therapy. The presence of oxygen vacancies in NiOx NPs helps bridge the energy gap between its valence band and conduction band, facilitating oxygen adsorption and improving catalytic efficiency. In both in vivo and in vitro antibacterial experiments, NiOx NPs demonstrate effective antibacterial and anti-inflammatory properties. Furthermore, it aids in wound healing and tissue regeneration by modulating immune factors, collagen deposition, and angiogenesis. This approach presents a promising collaborative strategy for utilizing nickel-based defective nanomaterials in combating deep drug-resistant bacterial infections.

AQP8 Modulates Mitochondrial H2O2 Transport to Influence Glioma Proliferation.

BACKGROUND: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. MATERIALS AND METHODS: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. RESULT: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. CONCLUSIONS: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.

Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma.

BACKGROUND: Obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC) and may influence its outcomes. However, after diagnosis of HCC, like other malignancies, the obesity paradox may exist where higher body mass index (BMI) may in fact confer a survival benefit. This is frequently observed in patients with advanced HCC and cirrhosis, who often present late with advanced tumor features and cancer related weight loss. AIM: To explore the relationship between BMI and survival in patients with cirrhosis and HCC. METHODS: This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers. Patient and tumor characteristics were extracted manually from medical records of each institutions' cancer registries. Patients were stratified according to BMI classes: < 25 kg/m2 (lean), 25-29.9 kg/m2 (overweight), and > 30 kg/m2 (obese). Patient and tumor characteristics were compared according to BMI classification. We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria. A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC. RESULTS: A total of 2548 patients with HCC were included in the analysis of which 11.2% (n = 286) were classified as non-cirrhotic. The three main BMI categories: Lean (n = 754), overweight (n = 861), and obese (n = 933) represented 29.6%, 33.8%, and 36.6% of the total population overall. Within each BMI class, the non-cirrhotic patients accounted for 15% (n = 100), 12% (n = 94), and 11% (n = 92), respectively. Underweight patients with a BMI < 18.5 kg/m2 (n = 52) were included in the lean cohort. Of the obese cohort, 42% (n = 396) had a BMI ≥ 35 kg/m2. Out of 2262 patients with cirrhosis and HCC, 654 (29%) were lean, 767 (34%) were overweight, and 841 (37%) were obese. The three BMI classes did not differ by age, MELD, or Child-Pugh class. Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients (71%, 62%, 49%, P < 0.001). Lean patients had significantly larger tumors compared to the other two BMI classes (5.1 vs 4.2 vs 4.2 cm, P < 0.001), were more likely outside Milan (56% vs 48% vs 47%, P < 0.001), and less likely to undergo transplantation (9% vs 18% vs 18%, P < 0.001). While both tumor size (P < 0.0001) and elevated alpha fetoprotein (P < 0.0001) were associated with worse survival by regression analysis, lean BMI was not (P = 0.36). CONCLUSION: Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria, reflecting cancer related cachexia from delayed diagnosis. Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit, but not overweight or obese BMI classifications.

Augmented Mitochondrial Transfer Involved in Astrocytic PSPH Attenuates Cognitive Dysfunction in db/db Mice.

Diabetes-associated cognitive dysfunction (DACD) has ascended to become the second leading cause of mortality among diabetic patients. Phosphoserine phosphatase (PSPH), a pivotal rate-limiting enzyme in L-serine biosynthesis, has been documented to instigate the insulin signaling pathway through dephosphorylation. Concomitantly, CD38, acting as a mediator in mitochondrial transfer, is activated by the insulin pathway. Given that we have demonstrated the beneficial effects of exogenous mitochondrial supplementation on DACD, we further hypothesized whether astrocytic PSPH could contribute to improving DACD by promoting astrocytic mitochondrial transfer into neurons. In the Morris Water Maze (MWM) test, our results demonstrated that overexpression of PSPH in astrocytes alleviated DACD in db/db mice. Astrocyte specific-stimulated by PSPH lentivirus/ adenovirus promoted the spine density both in vivo and in vitro. Mechanistically, astrocytic PSPH amplified the expression of CD38 via initiation of the insulin signaling pathway, thereby promoting astrocytic mitochondria transfer into neurons. In summation, this comprehensive study delineated the pivotal role of astrocytic PSPH in alleviating DACD and expounded upon its intricate cellular mechanism involving mitochondrial transfer. These findings propose that the specific up-regulation of astrocytic PSPH holds promise as a discerning therapeutic modality for DACD.

Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment: A phase 2 clinical trial (BG01-1801).

Background: Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), but acquired resistance presents challenges. The aim of this open-label, multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone, a novel genetically engineered epothilone analog and microtubule-stabilizing agent, as a third- or later-line treatment for locally advanced or metastatic NSCLC. Methods: Patients who had failed standard second-line treatment (including platinum-containing chemotherapy or targeted therapy) received utidelone (40 mg/m2 via intravenous injection daily, day 1-5) every 21 days. The primary endpoint was the objective response rate (ORR). Secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: From March 12, 2019 to January 18, 2021, 26 pretreated patients with locally advanced or metastatic NSCLC (100% of patients had received prior platinum and 65.4% patients had received prior taxane treatment) were enrolled (80.8% of patients had adenocarcinoma). At baseline, nine (34.6%) patients had received second-line treatment, 10 (38.5%) patients had received third-line treatment, and seven (26.9%) patients had received fourth- or later-line treatment. By the data cut-off date of August 10, 2021, the median follow-up was 7.49 months (range, 1.4-26.7 months). The ORR was 15.4% (95% confidence interval [CI], 4.4%-34.9%) in the intention-to-treat (ITT) cohort (N = 26) and 19.0% (95% CI, 5.4%-41.9%) in the per-protocol (PP) cohort (N = 21). The disease control rate was 69.2% (95% CI, 48.2%-85.7%) and 81.0% (95% CI, 58.1%-94.6%) in the ITT and PP cohorts, respectively. The median DoR was 4.1 months (95% CI, 3.1-5.1 months) in the ITT cohort. The median PFS was 4.37 months (95% CI, 2.50-5.29 months) in the ITT cohort and 4.37 months (95% CI, 2.50-9.76 months) in the PP cohort. The median OS was not reached, and the 12-month OS rate was 69% (95% CI, 45.1%-84.1%). Grade 3/4 treatment-emergent adverse events occurred in 38.5% of patients, and the most common was peripheral neuropathy (23.1%, all Grade 3), which was manageable with dose modifications. Conclusions: In this clinical trial, utidelone showed promising efficacy and had a manageable safety profile. Further clinical studies are warranted to confirm its role in NSCLC treatment. Trial registration: No.NCT03693547; https://classic.clinicaltrials.gov.

[Neonatal cervical chondromesenchymal hamartoma: a case report and literature review].

Cartilage mesenchyme hamartoma originates from the mesoderm and contains a blend of interstitium and cartilage, which is mostly benign tumor and is a non-neoplastic cartilage lesion with self-limiting hyperplasia. This article reports a infant with cervical chondromesenchymal hamartoma in the neck, the main clinical manifestations of which are asphyxia and acute respiratory distress, and the imaging features are often similar to those of malignant tumors.Radical resection operation under general anesthesia is the main treatment method, and the postoperative pathological diagnosis was cartilage mesenchyme, and immunohistochemistry showed Catenin（-）,MDM2（+）,CDK4（-）,H3K36M（+）,Myogenin （-）,SMA （-）.The clinical characteristics and diagnosis and treatment process of this case are reported and related literature is reviewed.

Fruit but not vegetable consumption is beneficial for low prevalence of colorectal polyps in a high-risk population: findings from a Chinese Lanxi Pre-colorectal Cancer Cohort study.

PURPOSE: The available evidence regarding the role of fruit and vegetable consumption in the development of colorectal polyps remains inconclusive, and there is a lack of data on different histopathologic features of polyps. We aimed to evaluate the associations of fruit and vegetable consumption with the prevalence of colorectal polyps and its subtypes in a high-risk population in China. METHODS: We included 6783 Chinese participants aged 40-80 years who were at high risk of colorectal cancer (CRC) in the Lanxi Pre-colorectal Cancer Cohort (LP3C). Dietary information was obtained through a validated food-frequency questionnaire (FFQ), and colonoscopy screening was used to detect colorectal polyps. Dose-response associations of fruit and vegetable intake with the prevalence of polyps were calculated using multivariate-adjusted regression models, which was reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 2064 cases of colorectal polyps were ascertained in the LP3C during 2018-2019. Upon multivariable adjustments, including the diet quality, fruit consumption was inversely associated with the prevalence of polyps (P trend = 0.02). Participants in the highest tertile of fruit intake had a 25% lower risk (OR: 0.75; 95% CI 0.62‒0.92) compared to non-consumers, while vegetable consumption had no significant association with polyp prevalence (P trend = 0.86). In terms of colorectal histopathology and multiplicity, higher fruit intake was correlated with 24, 23, and 33% lower prevalence of small polyps (OR: 0.76; 95% CI 0.62‒0.94; P trend = 0.05), single polyp (OR: 0.77; 95% CI 0.62‒0.96; P trend = 0.04), and distal colon polyps (OR: 0.67; 95% CI 0.51‒0.87; P trend = 0.003), respectively. CONCLUSIONS: Fresh fruit is suggested as a protective factor to prevent colorectal polyps in individuals at high risk of CRC, and should be underscored in dietary recommendations, particularly for high-risk populations.

Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

[Retracted] Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis.

[This retracts the article DOI: 10.3892/etm.2016.3992.].

In era of immunotherapy: the value of trastuzumab beyond progression in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer.

Background: For patients with human epidermal growth factor receptor-2 (HER2)-positive advanced or metastatic gastric cancer who have progressed on first-line trastuzumab therapy, the clinical value of the continuous use of trastuzumab beyond progression (TBP) is controversial. Objectives: The present study was conducted to evaluate the efficacy and explore new treatment strategies of TBP for patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer in the era of cancer immunotherapy. Design: Retrospective analysis. Methods: Patients with HER2-positive advanced or metastatic gastric cancer who have failed first-line treatment based on trastuzumab-targeted therapy from June 2019 to December 2020 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival curves of patients were estimated by the Kaplan-Meier method and compared using the log-rank test. Results: In all, 30 patients received TBP with chemotherapy, immunotherapy, or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0 [95% confidence interval (CI) = 3.8-8.2] and 3.5 (95% CI = 2.2-4.8) months, respectively (p = 0.038), and the median OS was 12.3 (95% CI = 10.4-14.2) and 9.0 (95% CI = 6.6-11.4) months (p = 0.008). The patients who received TBP treatment had more favorable PFS and OS than the non-TBP population. In the TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR (40.0% versus 16.7%), DCR (90.0% versus 50.0%), and showed a significant improvement in PFS (7.0 versus 1.9 m) compared to TBP with chemotherapy alone. Subgroup analysis suggested that patients with male, HER2 positive with immunohistochemistry score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The incidence of Grade 3-4 adverse events in the TBP and non-TBP groups was 43.3% and 38.5%. Conclusion: The continuous use of TBP improves PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well-tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy may further enhance the clinical benefit and provide a new treatment strategy. Trial registration: This study is a retrospective study, which does not require clinical registration.

The value of TBP in trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer Patients with human epidermal growth factor receptor-2 (HER2) positive advanced or metastatic gastric cancer who have failed from first-line treatment based on trastuzumab targeted therapy from June 2019 to December 2020 were retrospectively analyzed. 30 patients received TBP with chemotherapy, immunotherapy or anti-angiogenic therapy, and the other 26 patients received treatment of physician's choice without trastuzumab. The median PFS in the TBP and non-TBP population was 6.0(95% CI = 3.8-8.2) and 3.5 (95% CI = 2.2-4.8) months, respectively (P = 0.038), and the median OS was 12.3 (95% CI = 10.4-14.2) and 9.0 (95% CI = 6.6-11.4) months (P = 0.008). In TBP group, patients who received trastuzumab plus chemotherapy and immunotherapy had higher ORR, DCR and showed a significant improvement in PFS compared to TBP with chemotherapy-alone (p = 0.024). Subgroup analysis suggested that patients with male, HER2-positive with IHC score 3+ and PFS of first-line treatment less than 6 months had a greater benefit from TBP. The continuous use of TBP does not increase the incidence of adverse events (AEs). The continuous use of TBP improve PFS and OS in patients with trastuzumab-resistant HER2-positive advanced or metastatic gastric cancer with well tolerated toxicity. In the era of immunotherapy, TBP combined with chemotherapy and immunotherapy further enhanced the clinical benefit and provide new treatment strategy.

Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial.

Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.