Objective To explore the relationship between uric acid, visceral fat thickness and insulin resistance in elderly patients with hypertriglyceridemia (HTG). Methods A total of 347 elderly patients with HTG admitted to the hospital from January 2021 to January 2025 were retrospectively selected, and the related factors of insulin resistance in elderly HTG were analyzed. Results Among the 347 elderly patients with HTG, 218 cases had insulin resistance and 129 cases did not develop insulin resistance, and were included in the insulin resistance group (n=218) and the non-insulin resistance group (n=129) respectively. Compared with the non-insulin resistance group, patients in the insulin resistance group had higher proportions of severe HTG and concurrent fatty liver, higher levels of IL-6, TNF- α, FFA and uric acid, and thicker visceral fat thickness (P<0.05). After logistic regression analysis, it was found that the related factors for insulin resistance in elderly patients with HTG included the severity of HTG, IL-6, FFA, uric acid, and visceral fat thickness (P<0.05). Conclusion The severity of HTG, IL-6, FFA, uric acid, and visceral fat thickness are related to insulin resistance in elderly HTG patients. Clinically, it is necessary to pay attention to targeted interventions for uric acid control and visceral fat reduction in elderly patients with HTG so as to improve the insulin resistance status.

To develop an multimodal interpretable model that integrates whole slide images(WSI) and clinical features, and to validate its efficacy in predicting pathological complete response(pCR) in lung cancer patients following neoadjuvant therapy.

Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Objective:To investigate expression changes of tumor infiltrating lymphocytes(TILs)and their subtypes CD4+TILs,CD8+TILs,CD20+TILs and Foxp3+TILs in paired tumor samples pre-and post-neoadjuvant chemotherapy(NACT)in high-grade serous ovarian cancer(HGSOC)patients and their association with chemotherapy sensitivity and prognosis.Methods:A total of 40 patients with HGSOC who underwent NACT and interval debulking surgery(IDS)at Fourth Hospital of Hebei Medical University from August 2017 to February 2023 were retrospectively analyzed.CD4+TILs,CD8+TILs,CD20+TILs and Foxp3+TILs expressions in paired tumor samples pre-and post-NACT were detected by immunohistochemical staining.Divided patients into two groups based on KELIM score and platinum sensitivity,expressions of TILs,CD4+TILs,CD8+TILs,CD20+TILs and Foxp3+TILs were compared be-tween two groups,and their correlation with prognosis was analyzed.Results:Density of TILs(P=0.003,P=0.01),CD8+TILs(P<0.001,P=0.014)and CD20+TILs(P<0.001,P=0.003)post-NACT in patients with KELIM scores≥1 and platinum sensitivity were in-creased compared with pre-NACT.In contrast,there was no significant change in density of TILs pre-and post-NACT in patients with KELIM scores<1 and platinum resistance.Patients with high expression of CD8+TILs pre-NACT had longer progression free survival(PFS)and overall survival(OS)than patients with lower expression(P<0.001,P=0.011);patients with high expression of TILs post-NACT showed prolonged median PFS and OS(P<0.001,P=0.009);patients with high expression of CD20+TILs post-NACT showed prolonged median PFS(P=0.005).In multivariate analysis,density of CD8+TILs pre-NACT(HR=0.309,P=0.032),density of TILs post-NACT(HR=0.192,P=0.014),age(HR=2.962,P=0.036)were independent prognostic factors for PFS.Conclusion:Patients with HGSOC who have increased TILs density after NACT are more likely to be platinum sensitive.Expression of TILs,CD8+TILs and CD20+TILs in tumor site can serve as effective prognostic factors in HGSOC patients.

Trophoblast cell surface antigen 2 (Trop2) is a glycoprotein that is barely expressed in normal tissues but highly expressed in malignant tumors; it is remarkably associated with poor prognosis. Various targeted therapeutics against Trop2, such as anti-Trop2 antibodies and antibody-drug conjugate drugs targeting Trop2, have been developed, and some therapeutics have been approved or are in clinical trials for cancer treatment. In this review, we comprehensively discuss the gene structure, mechanism of action, clinical research, drug development, and other aspects of Trop2 to provide references for the clinical development of effective and safe Trop2-targeting drugs.

Objective:To investigate the mutation spectrum of the PIK3CA gene in breast cancer, providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.Methods:A retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University. Next-generation sequencing (NGS) was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies. The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene. The clinical and pathological characteristics, including age of onset, molecular subtypes, and Ki-67, were also analyzed. The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test. Logistic regression was employed to analyze factors influencing PIK3CA mutations. Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.Results:Among the 144 breast cancer samples, 61 (42.3%, 61/144) exhibited PIK3CA gene mutations, of which 23 cases (53.5%, 23/43) were HER2-positive breast cancer, 28 cases (44.4%, 28/63) were luminal breast cancer, and 10 cases (27.8%, 10/36) were triple-negative breast cancer. Of the detected mutations, three hotspot mutations (H1047R, E545K, and E542K) accounted for 72.1% of the total PIK3CA mutations, with H1047R (52.4%), E545K (16.4%), and E542K (3.3%) most commonly detected. The remaining rare mutations accounted for 26.3%. Co-mutations involving PIK3CA and other genes were also observed in the cohort, occurring with TOP2A and FOXA1, while being mutually exclusive with GATA3 and BRCA2. PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age, menopausal status, HR status, Ki-67 index, molecular typing, TNM stage or pCR status. Likewise, no significant correlation was found between different PIK3CA mutation status and overall survival.Conclusions:This cohort study shows the overall mutation rate of PIK3CA in breast cancer and the mutation frequencies across different molecular subtypes. The findings reveal a significant correlation between PIK3CA mutations and HER2 status, which provides a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.

Objective:To investigate the mutation spectrum of the PIK3CA gene in breast cancer, providing a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.Methods:A retrospective analysis was conducted on 144 breast cancer patients who underwent biopsy before neoadjuvant therapy archived from 2015 to 2020 at the Fourth Hospital of Hebei Medical University. Next-generation sequencing (NGS) was utilized to detect the mutations of 520 genes closely related to the development of solid tumors and targeted therapies. The study compared the differences between reported mutation types and focused on analyzing the mutation status of the PIK3CA gene. The clinical and pathological characteristics, including age of onset, molecular subtypes, and Ki-67, were also analyzed. The correlation between PIK3CA mutations and clinicopathological characteristics was examined using Pearson×s chi-square test and Mann Whitney test. Logistic regression was employed to analyze factors influencing PIK3CA mutations. Kaplan-Meier survival analysis and Cox regression models were constructed using R programming.Results:Among the 144 breast cancer samples, 61 (42.3%, 61/144) exhibited PIK3CA gene mutations, of which 23 cases (53.5%, 23/43) were HER2-positive breast cancer, 28 cases (44.4%, 28/63) were luminal breast cancer, and 10 cases (27.8%, 10/36) were triple-negative breast cancer. Of the detected mutations, three hotspot mutations (H1047R, E545K, and E542K) accounted for 72.1% of the total PIK3CA mutations, with H1047R (52.4%), E545K (16.4%), and E542K (3.3%) most commonly detected. The remaining rare mutations accounted for 26.3%. Co-mutations involving PIK3CA and other genes were also observed in the cohort, occurring with TOP2A and FOXA1, while being mutually exclusive with GATA3 and BRCA2. PIK3CA mutations were significantly associated with HER2 status and were not significantly correlated with the patient′s age, menopausal status, HR status, Ki-67 index, molecular typing, TNM stage or pCR status. Likewise, no significant correlation was found between different PIK3CA mutation status and overall survival.Conclusions:This cohort study shows the overall mutation rate of PIK3CA in breast cancer and the mutation frequencies across different molecular subtypes. The findings reveal a significant correlation between PIK3CA mutations and HER2 status, which provides a new basis for the precise treatment of breast cancer with PIK3CA inhibitors.

Objective:To establish and validate a lipid parameter-based prognostic model for predicting recurrence free survival (RFS) in pancreatic cancer patients receiving postoperative adjuvant chemotherapy.Methods:A retrospective analysis was conducted on the clinical and pathological data of 155 patients who underwent pancreatic cancer resection followed by adjuvant chemotherapy at Affiliated Hospital of Qingdao University between January 2019 and December 2022. The patients were randomly divided into a training set ( n=108) and a validation set ( n=47) in a 7∶3 ratio. X-tile software was used to determine cutoff values for lipid parameters. Univariate and multivariate Cox regression analyses were performed to construct a model predicting RFS, which was then visualized using a nomogram. The model's predictive performance, accuracy and stability, and clinical application value were evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), respectively. Individual risk scores for recurrence were calculated based on the nomogram model, and X-tile software was employed to identify optimal cutoff values for risk stratification, which was used to divide patients into low-risk and high-risk groups. Survival differences between two groups were analyzed using survival curves. Results:Among lipid parameters, patients with higher apolipoprotein A1 level had obviously longer RFS than those with low apolipoprotein A1 level (10.17 months vs 8.92 months, HR=0.397, 95% CI 0.237~0.664); patients with high total cholesterol level had obviously shorter RFS than those with low total cholesterol level (8.33 months vs 16.27months, HR=3.382, 95% CI 1.901~5.824) ; patients with high low-density lipoprotein level had obviously shorter RFS than those with low low-density lipoprotein level (8.53 months vs 11.43 months, HR=1.617, 95% CI 1.013~2.582) ; patients with high lipoprotein(a) had shorter RFS than those with low lipoprotein(a) (8.53 months vs 14.43 months, HR=2.640, 95% CI 1.514-4.604) ; and all the differences were statistical significant (all P value <0.05). Univariate Cox regression analysis identified advanced T stage, advanced N stage, high total cholesterol level, high low-density lipoprotein level, low apolipoprotein A1 level, high apolipoprotein B level, and high lipoprotein(a) level as risk factors for RFS. Multivariate Cox regression analysis revealed that tumors located in the pancreatic body or tail ( HR=0.63, 95% CI 0.36-0.86, P=0.042), advanced T stage ( HR=4.85, 95% CI 1.47-16.04, P=0.010), advanced N stage ( HR=0.48, 95% CI 0.26-0.87, P=0.015), elevated total cholesterol levels ( HR=3.61, 95% CI 1.46-8.91, P=0.005), high density lipoprotein levels ( HR=0.48, 95% CI 0.26-0.87, P=0.015), and elevated lipoprotein(a) levels ( HR=3.17, 95% CI 1.61-6.24, P<0.001) were independent risk factors for RFS. The nomogram model incorporating these six factors above demonstrated an AUC of 0.78 (95% CI 0.70-0.87) in the training set and 0.75 (95% CI 0.59-0.91) in the validation set. Calibration curves indicated a high degree of agreement between predicted and observed outcomes. DCA suggested that the model provides substantial clinical benefit. Kaplan-Meier survival curve analysis showed that patients in the high-recurrence risk group from training set and validation set both had significantly shorter RFS compared to those in the low-recurrence risk group (6.93 months vs 12.13 months, HR=4.024, 95% CI 2.594-6.243; 6.85 months vs 11.93 months, HR=2.314, 95% CI 1.227-4.362); and all the differences were statistical significant (all P value <0.05). Conclusions:The nomogram model based on lipid parameters can effectively predict recurrence free survival in patients undergoing adjuvant chemotherapy after pancreatic cancer surgery.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Prostate cancer (PC) is one of the common malignant tumors among men, and its incidence has been increased in China across these years. Radiotherapy is the mainstay therapy for PC. Due to the special biological characteristics of PC and the development of precision radiotherapy technology, hypofractionated regimens of radiotherapy are progressing rapidly, which has been increasingly applied in clinical practice and extensively studied by more and more researchers. In this review, the biological mechanisms of hypofractionated regimens, related clinical research, and practical applications of hypofractionated radiotherapy (such as definitive radiotherapy, postoperative adjuvant / salvage radiotherapy, oligometastasis radiotherapy, and pelvic lymph node radiotherapy) were summarized and its efficacy and toxicity profiles were analyzed, aiming to provide reference for scientific promotion of short‐course, hypofractionated precision radiotherapy for PC in China.