Lymph node metastasis (LNM) plays a key role in the treatment of patients with early gastric cancer (EGC), especially elderly patients (over 65 years old). The accurate preoperative prediction of LNM is still a challenge, and studies of elderly patients are lacking. The purpose of this study was to develop and validate an effective model based on machine learning to predict the risk of preoperative LNM in elderly patients with EGC. The data of 1578 patients from 2010 to 2020 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Five different machine learning algorithms were applied to construct the models. The external validation data were obtained from 127 elderly patients in our hospital. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity of the models were compared and evaluated. A Cox regression model was used to determine the prognostic factors for overall survival (OS) in elderly patients with EGC. Of the 1578 patients included in this study, 165 (10.46

Ganglioside GM3 (NeuAcα3Galβ4Glcβ1Cer) is the simplest sialic acid-containing glycosphingolipid and can inhibit tumor growth via multiple pathways. Based on the multivalent effect, we screened mannose-containing GM3 analogues from previously synthesized GM3 analogues with improved antitumor activity, and it was mutivalently assembled as di-, tri-, and tetramers (M2, M3, M4). In vitro assays demonstrated that oligomers exhibited stronger cytotoxicity than the monomer (M1), particularly against B16F10 and HCT116 cells. Wound healing and transwell assays revealed that M2 and M4 significantly suppressed migration and invasion in B16F10 and BxPC-3 cells. Western blot analysis suggested that these compounds inhibit tumor cell movement by targeting the EGFR/VEGFR-β-catenin signaling pathway and EMT. These findings highlight the potential of GM3-based oligomers as anticancer agents.

Breast cancer is the most common malignancy in women, with KIF2C acting as an oncogene. However, its role in ferroptosis and posttranslational regulation in BC cells is unclear. Our study analyzed KIF2C expression in BC tissues using bioinformatics and found it overexpressed, correlating with poorer survival. RNA-seq of KIF2C-deficient BC cells showed upregulation of ferroptosis genes. Functional assays revealed KIF2C enhances cell viability, promotes cell cycle progression, and increases migration/invasion while suppressing ferroptosis in erastin-treated BC cells. We identified Ubiquitin-Specific Peptidase 36 as a regulator of KIF2C stability through K48-linked deubiquitination. Overexpressed in BC and linked to poor prognosis, USP36 recapitulates KIF2C's role in protecting cells from erastin-induced ferroptosis. Manipulating KIF2C expression counteracts USP36's effects. In vivo studies showed USP36-deficient tumors exhibited reduced proliferation and increased ferroptosis. These findings underscore the critical role of the USP36-KIF2C axis in suppressing ferroptosis, suggesting targeting this pathway may improve BC outcomes.

AIMS:TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1. METHODS:Breast cancer cells were induced to quiescence by hypoxia and low glucose. The relationship of cell metabolism with HSP90 and TRAP1 was investigated by Western blotting, ECAR, OCR, mitochondrial complex activity, and proteomic analysis. The targets of C210 and their functions were analyzed by SPR and immunoprecipitation. The antitumor effect in vivo was investigated with mouse tumor model. RESULTS:In hypoxia and glucose deprivation, breast cancer cells exhibited elevated TRAP1 and an OXPHOS-enhanced quiescent phenotype. These cells were highly resistant to DOX but more sensitive to C210. C210 disrupted TRAP1's interaction with OXPHOS-associated client proteins, prompting proteasome-dependent degradation of these proteins, thereby reducing OCR, mitochondrial ATP production and resulting in selective elimination of the quiescent cancer cells by inducing mitochondrial apoptosis which could be reversed by exogenous ATP. Moreover, C210 targeted glycolytic, amino acid, and β-oxidation-associated proteome. C210 demonstrated promising in vivo anticancer efficacy which was particularly related to OXPHOS inhibition. CONCLUSIONS:C210 eliminates DOX-resistant quiescent breast cancer cells by targeting TRAP1-dependent bioenergetics.

Colorectal cancer (CRC) is the second most prevalent cause of oncological mortality, and its diagnostic and therapeutic decision-making processes is complex. Alteration in molecular characteristic expression is closely related to tumor invasiveness and can serve a novel biomarker for predicting cancer prognosis. In this study, we aimed to construct radiomic models through machine learning to predict the progression of CRC. We collected the clinical, pathological, and magnetic resonance imaging (MRI) data of 136 CRC patients who underwent direct surgical resection. Immunohistochemistry analysis was performed to detect the expression levels of p53, synaptophysin (Syn), human epidermal growth factor receptor 2 (HER2), perineural invasion (PNI), and vascular invasion (VI) expression levels in CRC tissues. After the manual lesion segmentation, 1781 radiomics features were extracted from the transverse T2-weighted image of MRI (T2W-MRI). We employed Spearman's rank correlation coefficient, greedy recursive deletion strategy, minimum redundancy, maximum relevance, least absolute shrinkage, and selection operator regression were utilized to screen for radiological features. Radiomics and clinical models were constructed using the K-nearest neighbor (KNN). The diagnostic efficiencies of the prediction models were evaluated using receiver operating characteristic curves and quantified employing the area under the curve (AUC). Our research results indicate that compared with the single radioactive model, the clinical radiomics model in the validation cohort showed better diagnostic performance, as indicated by the AUC values (p53 = 0.758, Syn = 0.739, HER2 = 0.786, PNI = 0.835, VI = 0.797). Furthermore, the calibration curve and decision curve analyses showed the clinical benefits. In summary, we developed and validated a clinical radiomics model to preoperative prediction of the biological characteristic expression levels of CRC. The findings of this research may offer a promising noninvasive method for evaluating CRC risk stratification and may lay the groundwork for treatment of this disease.

Long non-coding RNAs (lncRNAs) and autophagy play pivotal roles in the pathogenesis of nasopharyngeal carcinoma (NPC), yet the mechanisms underlying lncRNA-mediated autophagy regulation in NPC remain largely unknown. This study aimed to identify critical autophagy-related lncRNAs in NPC and to elucidate the functional role and molecular mechanisms of ZNF295-AS1 in modulating autophagy and tumor progression. We systematically screened for autophagy-associated lncRNAs by analyzing the NPC gene expression dataset GSE12452 from the GEO database, employing integrated differential expression analysis coupled with machine learning techniques. Subsequently, we constructed a co-expression network of lncRNAs and autophagy-related genes using bioinformatics tools. The expression and clinical implications of ZNF295-AS1 and its target HDAC6 were validated through a combination of RNA in situ hybridization, quantitative RT-PCR, immunohistochemistry, and functional assays conducted in NPC cell lines and xenograft models. We assessed autophagic flux using fluorescence dual-reporter assays, Western blotting, and transmission electron microscopy, while investigating the role of miR-762 in regulatory mechanisms via molecular interaction assays. Our results highlight that ZNF295-AS1 is a novel autophagy-associated lncRNA that is positively correlated with HDAC6 and is downregulated in NPC tissues, with low expression levels being associated with poor prognosis. Overexpression of ZNF295-AS1 was found to inhibit NPC cell proliferation, migration, and invasion, while disrupting autophagic flux and leading to an accumulation of p62 and LC3B-II; these effects were reversed by HDAC6 knockdown and miR-762 overexpression. Mechanistically, ZNF295-AS1 functions as a competing endogenous RNA, sponging miR-762 and thus relieving the repression of HDAC6, ultimately influencing autophagy and tumor progression. In conclusion, ZNF295-AS1 is implicated in the regulation of autophagy and malignancy in NPC through the miR-762/HDAC6 axis, suggesting its potential as a novel diagnostic and therapeutic target in NPC management.

With the advancement of world population aging, dysphagia has become a pressing health challenge. Providing texture-improved foods is an effective strategy to reduce risk during eating for patients with dysphagia. In this study, the gel quality of pea protein isolate was effectively improved by curdlan gum combined with ultrasonic treatment, and it could be swallowed safely. Curdlan and/or ultrasound could improve the strength and waterholding capacity of pea protein isolate gel and increase the proportion of immobilized water. It was observed that ultrasound reduced the particle size of pea protein isolate in the sol, which might be beneficial for the interaction between protein and water, as well as the unfolding and cross-linking of the protein. In addition, ultrasound and/ or curdlan promoted the formation of the uniform and dense gel structure by affecting the sol-gel transition process and modifying the protein conformation. In this regard, molecular dynamics simulation revealed that curdlan and pea protein molecules could be crosslinked through non-covalent interactions such as hydrogen bonding, van der Waals forces, and electrostatic forces, thus forming a stable three-dimensional network. The modified gels had good swallowing properties and were assessed as levels 5-6 according to the International Dysphagia Diet Standardization Initiative framework. Overall, ultrasound and curdlan are promising approaches for improving the quality of pea protein isolate gel. This study provides a new perspective on the precise regulation of gel food texture, which is valuable for the design of texture-improved food for elderly patients with dysphagia.

Although overproliferation and high migration of keratinocytes are the key pathological features of middle ear cholesteatoma (MEC), the underlying mechanism remains unclear. We found low CD9 and high ADAM17 expression in MEC specimens, alone with their colocalization, and elevated EGF levels. To investigate the role of CD9 in MEC, we created stable CD9-knockdown keratinocyte cell lines. Results showed enhanced proliferation and migration in CD9-knockdown cells, which were inhibited upon restoring CD9. Exogenous EGF reversed the inhibition. Increased ADAM17 sheddase activity in CD9-knockdown cells promoted the release of EGF, activating the EGFR/ERK/WAVE2 pathway. The colocalization of p-ERK and WAVE2 activated the Arp2/3 complex, promoting F-actin polymerization and pseudopodia formation. Similar findings were observed in MEC specimens. Overall, we confirmed that the reduction of CD9 promotes the proliferation and migration of MEC keratinocytes through F-actin remodeling. Therefore, EGFR or Arp2/3 inhibitors could have therapeutic potential in MEC.

Nuclear transcription factor-κB (NF-κB) activation is a pivotal event in the pathogenesis of osteoarthritis (OA). OA patients frequently exhibit vitamin D (VD) deficiency, which is commonly associated with NF-κB activation. Our study aimed to investigate whether VD could protect against OA by modulating NF-κB pathway and to explore the underlying mechanisms. Proteins levels were assessed by western blot analysis, gene expression was quantified by quantitative real-time polymerase chain reaction (qRT‒PCR) in vivo and in vitro. The expression of phosphorylated-p65 (p-p65) in knee OA rats was detected by immunohistochemistry, and an NF-κB nuclear translocation assay was validated in chondrocytes. Immunoprecipitation was employed to detect the interaction between NF-κB and vitamin D receptor (VDR) in vivo and in vitro. Small interfering RNA (Si-NF-κB and Si-VDR) transfection was used to investigate the role of NF-κB and VDR signaling pathway in knee OA rats under VD influence. Cartilage changes were visualized of knee OA rats using hematoxylin and eosin as well as safranin-O/fast green of staining. Our findings indicated that VD alleviates OA by inhibiting NF-κB pathway, which in turn reduces chondrocyte apoptosis and extracellular matrix (ECM) degradation. Further analysis revealed that VD primarily stabilizes NF-κB through the interaction of VDR and NF-κB, modulating the AMPK/mTOR signaling pathway to enhance autophagy and delay the progression of OA. This study highlights the protective role of VD in OA by stabilization of NF-κB, mainly through the interaction between VDR and NF-κB. This interaction regulates the AMPK/mTOR signaling pathway, promoting autophagy and suggesting a potential therapeutic strategy for OA management.

Background: The risk of liver metastasis (LM) may be estimated using predictive nomograms. While the nomogram has recently been applied in oncology, there are relatively few studies concentrating on predicting LM in patients with early-onset colon cancer. We aimed to identify independent risk factors for LM in patients with early-onset colon cancer and develop a nomogram for predicting the probability of LM in these patients. Methods: Our study encompassed 4,890 early-onset colon cancer patients with LM who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. These patients were randomly allocated into training and validation cohorts at a ratio of 7:3. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors for LM, and a nomogram was developed using these factors. The model's discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristics (ROC), calibration, and decision curve analyses. Results: Overall, 4,890 patients with early-onset colon cancer and LM were selected from the SEER database. LM incidence in these patients was 18.4%. Univariate and multivariate analyses revealed histological type, T stage, N stage, and carcinoembryonic antigen (CEA) level as independent risk factors. ROC curve analysis revealed that the predictive nomogram for LM risk had an area under the curve of 0.812 [95% confidence interval (CI): 0.795-0.829] and 0.809 (95% CI: 0.784-0.834) in the training and validation sets, respectively, demonstrating good discriminatory ability of the model. Calibration curve analysis showed good agreement between predicted values from the nomogram and actual observations, and the decision curve analysis (DCA) demonstrated the high clinical utility of the nomogram. Conclusions: LM incidence was higher in patients with early-onset colon cancer. Our nomogram demonstrates a high level of efficacy in predicting the risk of LM in patients with early-onset colon cancer, thereby assisting clinicians in making well-informed treatment decisions prior to further intervention.

BACKGROUND The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

BackgroundGanoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.MethodsIn this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.ResultsWe found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR.ConclusionA triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.

A postoperative surgical site infection (SSI) is a prevalent complication after loop ileostomy closure. There are few studies on the risk factors and the development of predictive models for postoperative SSIs. The aim of this study was to develop and validate a nomogram model capable of accurately predicting the occurrence of postoperative SSIs. This retrospective analysis examined the clinical data of 369 patients who underwent loop ileostomy closure at a local hospital from January 2015 to March 2022. A logistic regression model was used to identify the potential risk factors for a postoperative SSI after loop ileostomy closure. A nomogram was established using independent risk factors, and the prediction performance of the model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Forty-eight (13.0

According to past and current literature, metastasis of the lymph nodes at the inferior mesenteric artery (IMA-LN), also known as 253LN of colorectal cancer has been seldom investigated. To date, there are still controversies on whether the 253LN need to be routinely cleaned. Using specific criteria, 347 patients who underwent radical resection for rectal cancer between April 2019 and July 2022 were selected for the study. Logistic regression was used to determine the likelihood that a patient may suffer 253LN metastasis, and a nomogram for 253LN metastasis subsequently developed. The c-index and calibration curve were used to evaluate precision and discrimination in the nomogram, and the appropriateness of the final nomogram for the clinical setting determined using decision curve analysis (DCA). 253LN metastases appeared in the pathological specimens of 29 (8.4%) of the selected patients. Logistic regression showed that preoperative parameters including serum carcinoembryonic antigen (CEA) value ( > 5 ng / ml, OR = 2.894, P = 0.023), distance from anal margin (> 9 cm, OR = 2.406, P = 0.045) and degree of differentiation (poor, OR = 9.712, P < 0.001) were significantly associated with 253LN metastasis. A nomogram to predict 253LN metastasis in rectal cancer was developed and showed considerable discrimination and good precision (c-index = 0.750). Furthermore, DCA confirmed that the nomogram has some feasibility for the clinical environment. Clinicopathological and radiological patient data can be pivotal for making surgical decisions relating to 253LN metastasis. A nomogram was developed using this data, providing an objective method that can significantly improve prognoses in colorectal cancer.

ObjectiveVarious stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models.MethodsThe PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots.ResultsThirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = −2.50, 95% CI: –3.07 to –1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation.ConclusionThe evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

Background: The functions of GOLPH3, STIP1, and the STAT3 signaling pathway in the invasion and migration of CC cells were examined in this study. Method: High-speed centrifugation was used to collect the exosomes. The expression of GOLPH3, STIP1, and epithelial-mesenchymal transition (EMT)-related proteins in CC tissues, cells, and exosomes were analyzed using Western blotting (WB) experiments. The abilities of CC cell invasion and migration were evaluated by the Transwell assay. The binding relationship between GOLPH3 and STIP1 was validated through Co-immunoprecipitation (Co-IP), and their sublocalization in CC cells was determined by immunofluorescence detection under laser confocal microscopy. Immunohistochemistry (IHC) experiments detected the expression levels of each protein in the transplanted tumor mass. Animal experiments confirmed the impact of the GOLPH3/STIP1/STAT3 regulatory axis on the CC growth. Results: In CC tissues and cells, GOLPH3 was highly expressed, and silencing GOLPH3 not only greatly reduced CC cell invasion and migration but also prevented EMT. Furthermore, GOLPH3 and STIP1 interacted in CC cells, and the GOLPH3-STIP1 complex affected the capacity for cell invasion and migration by triggering the STAT3 signaling pathway. Noteworthily, GOLPH3, and STIP1 could also be detected in CC cell exosomes, and the exosomes carried the GOLPH3-ST1P1 complex to act on CC cells to activate intracellular STAT3 signaling, ultimately affecting the cancer cell migration and invasion. The above molecular regulatory mechanisms have also been validated in mice. Conclusion: The GOLPH3-STIP1 complex acted on surrounding CC cells through exosomes and activated the STAT3 signaling pathway to stimulate CC cell invasion and migration

Lytic induction therapy was devised to selectively combat malignancies associated with Epstein-Barr virus (EBV) by triggering viral reactivation from latency. At present, the major challenges of lytic induction therapy are to maximize reactivating efficiencies and meanwhile minimize infectious virion production. C210, a novel curcumin derivative with potent Hsp90 inhibitory activity, was explored for EBV-reactivating and virion-producing effects in EBV-positive nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) cell lines. And the molecular mechanisms underlying these effects were determined. Follow C210 treatment, EBV lytic RNAs and proteins were upregulated, but infectious virions were not produced. Knockdown of heat shock protein 90 (Hsp90) induced expression of lytic RNAs and proteins, and diminished C210-driven EBV lytic induction. Pretreatment with an X box binding protein 1 (XBP1) inhibitor reduced C210-induced EBV lytic RNA. Furthermore, we demonstrated that C210 inhibited the binding of Hsp90 with its clients, signal transducer and activator of transcription 3 (STAT3) and xeroderma pigmentosum group B-complementing protein (XPB), which subsequently promoted their proteasomal degradation. Degradation of STAT3 by C210 enhanced the EBV-reactivating and anticancer capacity of suberoylanilide hydroxamic acid (SAHA). Depletion of XPB blocked SAHA-induced expression of late viral genes and production of infectious virions. These results elucidate a novel Hsp90 inhibitor targeting EBV lytic phase and extend the research on lytic induction strategy, which may offer reference value in the treatment of EBV-positive malignancies.

To determine the protective effects of FM0807 against diabetes-induced renal inflammation and fibrosis and the underlying mechanisms in vivo and in vitro. FM0807 was administered to db/db mice. Glomerular mesangial cells (HBZY-1) were cultured under high glucose conditions with or without FM0807. Gene and protein expression was assessed by quantitative real-time PCR, western blotting, and immunofluorescence. Mitochondrial reactive oxygen species were detected with MitoSOX Red. FM0807 markedly reduced blood glucose, glycosylated hemoglobin, triglycerides, and low-density lipoprotein-cholesterol levels and improved the liver organ index, the high-density lipoprotein-cholesterol level, and renal function, as evidenced by decreased 24-h urinary protein excretion and the creatinine and blood urea nitrogen levels. FM0807 ameliorated pathologic renal changes in diabetic mice (reduced glomerulosclerosis, diminished interstitial cellular inflammation, and less tubular luminal narrowing). Treatment with FM0807 also led to a significant reduction in the expression of inflammatory markers, including JAK2, STAT3, TNF-α, IL-1β, IL-6, TGF-β1, and Smad2/3, in addition to alterations in the expression of proteins associated with kidney injury. These data suggest that FM0807 alleviates diabetes-induced renal inflammation and fibrosis by modulating the JAK2/STAT3 and TGF-β1/SMAD2/3 signaling pathways.

Background: Endoscopic surgery for malignant breast tumors is becoming more and more popular and has been applied in the clinical setting. Single-port endoscopic-assisted radical mastectomy in retrograde way and immediate reconstruction using prosthesis implantation are rare. Therefore, this study described a new endoscopic technique for breast surgery. Methods: This is a cross-sectional study. A total of 12 patients with breast cancer diagnosed in the Department of Thyroid Breast Surgery of The Second Affiliated Hospital of Fujian Medical University from January 2019 to June 2022 were retrospectively selected and underwent axillary single-port endoscopicassisted radical mastectomy in retrograde way and immediate reconstruction using prosthesis implantation. Results: The average operation time was 190.25 +/- 25.40 min, the average blood loss was 86.25 +/- 33.11 mL, the average drainage volume was 207.92 +/- 65.90 mL 3 days after surgery, and the average hospital stay was 9.67 +/- 2.57 days. The follow-up period ranged from 11 to 21 months, with an average of 16.75 months. Medial paresthesia was present in only one patient, which decreased or disappeared after 3 months. No complications such as wound infection or limb dysfunction occurred in the remaining patients. Postoperative follow-up showed that 10 patients were very satisfied, one patient was relatively satisfied, and one patient was not satisfied. Conclusions: Preliminary data attested the feasibility and the safety of this approach. It can improve patient satisfaction compared with traditional modified radical mastectomy for suitable candidates. However, long-term data are needed to confirm the oncological safety and the esthetic stability of the result.

BACKGROUND:Whole brain radiotherapy (WBRT) is the mainstay of treatment for patients with non-small cell lung cancer (NSCLC) with multiple brain metastases (BMs); however, the BRAIN study showed that the efficacy of WBRT is unsatisfactory. This prospective phase II study aimed to evaluate the efficacy and safety of WBRT combined with anlotinib, a novel anti-angiogenic multi-target tyrosine kinase inhibitor (TKI), in patients with multiple BMs (>3) from advanced NSCLC. METHODS:Patients with advanced NSCLC with multiple BMs who had received two or more lines of treatment were eligible for enrolment into this study. All patients were treated with anlotinib (8-12 mg, QD, on days 1-14 of a 21-day cycle) combined with WBRT (DT 30 Gy/12 F), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint of this study was the intracranial progression-free survival (iPFS). The secondary endpoints were intracranial objective response rate (iORR), intracranial disease control rate (iDCR), overall survival (OS) and treatment safety. RESULTS:Between May 2019 and January 2021, 28 patients were enrolled, all of whom were evaluable for efficacy and safety. The median age was 57.7 years, and 46.4% were male. Twenty-five patients had adenocarcinoma (89.3%), six had EGFR mutations (21.4%) and two had ALK mutations (7.1%). The median iPFS was 11.1 months (95% confidence interval (CI): 5.4-16.8 months) and the median OS was 13.4 months (95% CI: 5.2-21.6 months). The iORR was 71.4% (six complete responses + 14 partial responses). The most frequently observed adverse events (AEs) were hypertension (71.4%), fatigue (64.3%), anorexia (46.4%), and foot and hand skin reactions (25.0%). No patients developed ≥ grade 4 AEs. No intracranial haemorrhages occurred during treatment. Dose adjustment due to AEs occurred in 17.9% of patients. CONCLUSIONS:Anlotinib combined with WBRT is effective and well-tolerated in patients with NSCLC with multiple BMs.