Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective To investigate the protective effect of Gynostemma pentaphyllum on memory of individuals rapidly ascending to high altitudes.Methods Twenty-one healthy subjects were randomly divided into a G.pentaphyllum food group(n=12)and a control group(n=9).The first group consumed G.pentaphyllum food for seven consecutive days while the control group received placebos.Both groups ascended from the plains to an altitude of 3600 m.Memory function was assessed using the matching memory and sequential memory tests of a cognitive evaluation system on day 1 and day 7 on the plains,and at 24 and 48 h after ascending to the high altitude.Scores of acute mountain sickness symptoms were also recorded.Results After 24 h of stay at the high altitude,the score of headache of the G.pentaphyllum food group was significantly lower than that of the control group(P＜0.05).Cognitive test results showed that the matching memory accuracy and sequential memory accuracy of the control group at 24 and 48 h were significantly lower than those on the plains(P＜0.05).In contrast,the G.pentaphyllum food group performed significantly better than the control group in these metrics(P＜0.05).Conclusion Regular consumption of G.pentaphyllum food can effectively alleviate headache symptoms in individuals rapidly ascending to high altitudes and mitigate the decline in working memory,short-term memory,and memory spans caused by acute hypoxic exposure.

Objective To investigate the expression levels of microRNA-34a(miR-34a),β-catenin and pro-grammed death receptor-1(PD-L1)in cancer tissues of patients with cervical cancer(CC)and their correla-tion with patients' prognosis.Methods A total of 83 patients with CC admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University from June 2021 to January 2024 were selected as the research objects.General data,CC tissue and adjacent normal tissue samples of all patients were collected.The mRNA expres-sion levels of miR-34a,β-catenin and PD-L1 in CC tissues and adjacent normal tissues were detected by fluo-rescence quantitative PCR and compared.The expression levels of β-catenin and PD-L1 in CC tissues and adja-cent normal tissues were detected by immunohistochemistry.Multivariate Logistic regression analysis was used to analyze the influencing factors of prognosis in CC patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of miR-34a,β-catenin and PD-L1 expression levels in CC pa-tients with poor prognosis.Results Compared with adjacent normal tissues,the expression level of miR-34a of the CC tissues was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).The positive expression rates of β-catenin and PD-L1 protein in CC tissues were higher than those of adjacent nor-mal tissues(89.16％vs.10.84％,78.31％vs.20.48％,x2=101.807,55.526,P＜0.05).There were no sig-nificant differences in age and body mass index(BMI)between the good prognosis group and the poor progno-sis group(t=1.508,1.820,both P＞0.05),while there were significant differences in International Federa-tion of Gynecology and Obstetrics(FIGO)stage and differentiation degree between the two groups(x2=8.451,9.115,both P＜0.05).Compared with the good prognosis group,the expression level of miR-34a of the poor prognosis group was lower,while the expression levels of β-catenin and PD-L1 were higher(P＜0.05).Multivariate Logistic regression analysis showed that increased expression of miR-34a was an protective factor for poor prognosis in CC patients,while the increased expression levels of β-catenin and PD-L1,Ⅱ a and Ⅱ b FIGO staging and low differentiation were independent risk factors for poor prognosis in CC patients(P＜0.05).ROC curve analysis showed that miR-34a,β-catenin and PD-L1 all had certain predictive value for the poor prognosis of CC patient,and the area under the curve(AUC)of the single detection was 0.765,0.836 and 0.797,respectively.The AUC of the combined detection was 0.914(Z=2.631,2.331,2.571,P=0.009,0.020,0.010).Conclusion The expression levels of miR-34a,β-catenin and PD-L1 mRNA affect the prognosis of CC patients.Increased expression of miR-34a is an protective factor for poor prognosis in CC patients,in-creased β-catenin and PD-L1 expressions are independent risk factors for poor prognosis in CC patients,and all three factors can be used as biomarkers to predict poor prognosis in CC patients,and the combined detection of the three has the highest prognostic value.

Objective:To explore the efficacy of letrozole combined with palbociclib in the treatment of hormone receptor +/human epidermal growth factor receptor-2 - (HR +/HER2 -) advanced breast cancer and its influence on serum thymidine kinase 1 (TK1) and proliferating cell nuclear antigen (Ki67) levels. Methods:A total of 82 patients with HR +/HER2 - advanced breast cancer, all admitted from Jan. 2022 to Jan. 2024 from Department of Oncology, Affiliated Hospital of Jining Medical University, were assigned to the control group ( n=41, letrozole) and the study group ( n=41, letrozole + palbociclib) according to the random number table. The therapeutic effect, tumor markers, immune function and serum TK1 and Ki67 levels were compared between the two groups. Results:The study group higher objective response rate and disease control rate than the other group [14.63% (6/41) and 85.37% (35/41) vs. 0.00% (0/41) and 58.54% (24/41) ] (Continuity correction χ2/χ2=4.50, 7.31, P<0.05). After treatment, carbohydrate antigen 153 (CA153), CA125 and carcinoembryonic antigen (CEA) in the study group were lower than the control group [ (12.17±3.19) U/mL, (23.57±3.35) U/mL and (19.51±4.13) ng/mL vs (24.37±5.25) U/mL, (35.16±5.08) U/mL, (34.28±5.72) ng/mL] ( t=12.72, 12.20, 13.41, P<0.05), serum TK1 and Ki67 levels were also lower [ (3.61±0.75) pmol/L and (7.89±1.16) ng/mL vs. (4.76±0.88) pmol/L and (10.85±1.94) ng/mL] ( t=6.37, 8.39, P<0.05). After treatment, CD3 +, CD4 +, CD4 +/CD8 + higher than the control group [ (48.64±5.88) %, (31.34±4.06) %, (1.22±0.27) vs. (43.16±6.09) %, (27.04±3.35) %, (0.87±0.35) ] ( t=4.15, 5.23, 5.07, P<0.05), while CD8 + was lower [ (25.73±4.11) % vs. (30.94±4.47) %] ( t = 5.49, P<0.05) . Conclusions:Letrozole combined with palbociclib is effective in the treatment of HR +/HER2 - advanced breast cancer and can reduce tumor markers and serum TK1 and Ki67 levels in patients.

Ethanol (EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin (CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4 (CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65 (NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.
Ethanol/toxicity* ; Animals ; Gastric Mucosa/metabolism* ; Signal Transduction/drug effects* ; Oxidative Stress/drug effects* ; Capsaicin/pharmacology* ; Male ; NADPH Oxidases/genetics* ; Mice ; Humans ; src-Family Kinases/genetics*

In the past decade, real-world data (RWD) research has undergone significant transformations due to data aggregation and processing technologies. However, there is still a lack of consensus regarding the scope of RWD applications and the value of real-world evidence (RWE). This study briefly outlined the origins of the concept of RWD study and its early research scope to promote further development in this area. We also reviewed the understanding of RWD applications and research models from the five perspectives of healthcare professionals, medical institutions, decision-making departments, cross-regional cooperation model, and the practice of the One-Health model. Finally, we systematically summarized the renewed understanding of the value of RWE while looking ahead to the challenges and future developments in this field.

Objective:To develop and validate a combined model integrating radiomics, dosiomics, and clinical parameters based on CT simulation and dosimetric images in order to predict the occurrence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC).Methods:A retrospective study was conducted on the clinic data of 143 NSCLC patients who received radiotherapy at the Affiliated Hospital of Jining Medical University from January 2016 to December 2022. Patients were randomly stratified into a training group ( n = 100) and an internal validation group ( n = 43) at a 7∶3 ratio. Moreover, clinic data were collected from 34 NSCLC patients who received radiotherapy at the Jining Cancer Hospital between January 2019 and December 2022 as an external validation group. All three groups (the training group, internal validation, and external validation groups) were further categorized into two groups based on the RP severity (i.e., RP ≥ grade 2 and RP < grade 2). Their radiotherapy dose, CT simulation, and 3D dose distribution images were collected. Then, the total lung minus planning target volume (TL-PTV) was defined as the region of interest (ROI) for radiomics and dosiomic feature extraction, followed by feature dimensionality reduction. Consequently, key features associated with RP were determined. Four predictive models were developed using machine learning approaches (especially multilayer perceptron, MLP): a clinical model (CM), a radiomics model (RM), a dosiomics model (DM), and a radiomics and dosiomics nomogram (RDN), with a nomogram subsequently constructed. Ultimately, the performance and clinical feasibility of these models were assessed using receiver operating characteristic (ROC), area under the curve (AUC), and decision curve analysis (DCA). Results:A total of 1 834 radiomic features and 1 834 dosiomic features were extracted. Using the occurrence of RP ≥ grade 2 as the marker variable, 14 radiomic features, 15 dosiomic features, and three clinical features were selected from the training group to construct the prediction models (CM, RM, DM, and RDN). The performance and generalizability of these models were subsequently validated in both the internal validation and external validation groups. Specifically, the RDN exhibited AUCs of 0.915 (95% CI: 0.852-0.978), 0.879 (95% CI: 0.777-0.982), and 0.838 (95% CI: 0.701-0.975) in the three groups, respectively. A nomogram was established for RDN by integrating the radiomics score (R-score), dosiomics score (D-score), mean lung dose (MLD), V20, and V30. This nomogram allowed for individualized risk estimation of RP and facilitated personalized radiotherapy planning. Conclusions:The RDN model that is developed based on CT simulation and 3D dose distribution images and integrates radiomics, dosiomics, and clinical features can effectively predict the RP risk of NSCLC patients. The integration of multidimensional data contributes to the formation of the optimal predictive model, offering guidance for clinicians.