Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Objective:To explore the causal relationship between asthma, allergic rhinitis (AR), and chronic sinusitis (CRS), using two sample Mendelian randomization (MR) analysis, thereby providing foundational evidences for the pathogenesis and treatment of CRS.Methods:The genetic variations in AR and asthma were used as instrumental variables, with genetic data from the Integrated Epidemiology Unit (IEU) Open database. A total of 14 283 asthma and 18 934 AR cases were included, with 98 300 and 64 595 corresponding normal control cases, respectively. For CRS, there were 3 236 CRSwNP and 8 524 CRSsNP, respectively, with 167 849 and 167 849 corresponding normal control cases, respectively. The genetic data were analyzed using the inverse variance weighting method (IVW), MR Egger method, weighted median method, and Cochran′s Q-test.Results:The IVW analysis showed that asthma increased the risk of both CRSwNP ( OR=482.8, 95% CI: 57.18-4 077.78, P<0.001) and CRSsNP ( OR=25.73, 95% CI: 9.79-67.56, P<0.001); AR significantly increased the risk of CRSsNP ( OR=5.40, 95% CI: 1.68-17.26, P=0.004), but not CRSwNP ( OR=7.38, 95% CI: 0.80-67.73, P=0.077). Conversely, neither CRSwNP nor CRSsNP increased the risk of asthma or AR. Conclusion:According to Mendelian genetic laws, asthma is a risk factor for CRSwNP and CRSsNP, while AR is a risk factor for CRSsNP.

Objective:Previous studies have revealed a correlation between eosinophils and allergic rhinitis,but the causal relationship has not been fully confirmed.This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization(MR)method. Methods:Summary data from the Genome-Wide Association Study Catalog(GWAS)for eosinophil count(exposure variable)and allergic rhinitis(outcome variable)were collected.GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol,while data for the outcome variable were sourced from the FinnGen Biobank(Finland)database.The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted(IVW)analysis.Sensitivity analyses were conducted using the weighted median method,MR-Egger regression,leave-one-out analysis,and funnel plots. Results:An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis(OR=1.187,95%CI 1.051 to 1.341,P=0.006).This finding was consistent across the weighted median method and MR-Egger regression.Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference. Conclusion:There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.

Objective:To explore the role of c-Jun N-terminal kinase (JNK) /c-Jun signaling pathway mediated by endoplasmic reticulum stress in triptolide-induced apoptosis of melanoma A375 cells.Methods:Nude mice were subcutaneously inoculated with melanoma A375 cells on the back to establish the animal model of melanoma. Tumor formation could be observed at approximately 3 weeks after inoculation, and then the mice were divided into 4 groups (4 mice in each group) : control group (injected with sodium chloride physiological solution via the tail vein), 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (injected with 0.1, 0.2, and 0.4 mg/kg triptolide via the tail vein, respectively). Injections were performed twice a week. After 3 weeks of injections, tumors were resected, and their size and weight were measured. The apoptosis levels of tumor xenografts were detected by the terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. qPCR was conducted to determine the mRNA expression of inositol-requiring enzyme 1 (IRE1), JNK, and c-Jun, and Western blot analysis to determine the protein expression of IRE1, JNK, c-Jun, phosphorylated-JNK (p-JNK), and phosphorylated-c-Jun (p-c-Jun). Comparisons among multiple groups were performed using one-way analysis of variance, and multiple comparisons were performed using Dunnett's test.Results:Significant differences were observed in the tumor mass, volume and tumor suppression rate among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (all P < 0.05) ; all the triptolide groups showed significantly decreased tumor masses and volumes (all P < 0.05), but significantly increased tumor suppression rates compared with the control group (all P < 0.05). The tumor apoptosis index significantly differed among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups (7.67% ± 1.15%, 9.67% ± 3.21%, 62.00% ± 6.08%, and 85.67% ± 5.51%, respectively; F = 305.91, P < 0.001), and the 0.2- and 0.4-mg/kg triptolide groups showed significantly increased tumor apoptosis indices compared with the control group ( t = 17.56, 27.72, respectively, both P < 0.05). qPCR and Western blot analysis revealed significant differences in the mRNA expression of IRE1, JNK, and c-Jun among the control group, 0.1-, 0.2-, and 0.4-mg/kg triptolide groups ( F = 112.23, 27.51, 112.37, respectively, all P < 0.05), as well as in the relative protein expression levels of IRE1, JNK, c-Jun, p-JNK, and p-c-Jun among the above 4 groups (all P < 0.05). Additionally, the 0.4-mg/kg triptolide group showed significantly increased mRNA and protein expression of IRE1, JNK and c-Jun (including p-JNK, p-c-Jun) compared with the control group (all P < 0.05). The mRNA and protein expression levels of IRE1, JNK, and c-Jun in the tumor tissues tended to increase with the rise in drug concentrations, and the protein expression levels of p-JNK and p-c-Jun showed the same trend. Conclusion:Triptolide could activate the JNK/c-Jun signaling pathway mediated by the endoplasmic reticulum stress, and then induce apoptosis of melanoma A375 cells in mice.

Objective:To investigate the influence of nutritional therapy on short-term efficacy of gastric cancer patients with malnutrition after radical gastrectomy.Methods:The prospec-tive randomized control study was conducted. The clinicopathological data of patients with malnutri-tion after radical resection of gastric cancer who were admitted to the Zhongshan Hospital of Fudan University from December 2020 to December 2022 were selected. Based on random number table, all patients were allocated into the nutritional therapy group and the control group. Patients in the nutritional therapy group were given dietary guidance and daily oral nutrition supplements for 90 days after discharge, while patients in the control group were only given the same dietary guidance. Observation indicators: (1) grouping situations of the enrolled patients; (2) follow-up; (3) comparison of nutritional indicators at 90 days after discharge; (4) comparison of inflammation and physical function indicators at 90 days after discharge; (5) comparison of clinical outcome indicators at 90 days after discharge. Measurement data with normal distribution were expressed as Mean± SD, and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(IQR), and non-parameter rank sum test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and chi-square test was used for comparison between groups. Comparison of ordinal data was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 187 patients were selected for eligibility. There were 131 males and 56 females, aged (65±12)years. Of the 187 patients, there were 95 patients in the nutritional therapy group and 92 patients in the control group, respectively. The gender (male, female), age, cases with cardiovascular complications, cases with respiratory complications, cases with diabetes, surgical methods (partial gastrectomy, total gastrectomy), tumor staging (Ⅰ stage, Ⅱ stage, Ⅲ stage), body mass, body mass index (BMI), skeletal muscle index, albumin (Alb), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), 6-minutes walking distance, grip strength were 68, 27, (64±12)years, 21, 4, 7, 59, 36, 17, 27, 51, (59±11)kg, (21.5±3.1)kg/m 2, (42±7)cm 2/m 2, (39±5)g/L, (112±25)g/L, 2.3(8.0), (456±97)m, (29±8)kg in patients of the nutritional therapy group, versus 63, 29, (66±13)years, 22, 3, 9, 56, 36, 14, 24, 54, (58±11)kg, (21.1±2.9)kg/m 2, (42±7)cm 2/m 2, (39±4)g/L, (111±26)g/L, 2.2(8.4), (459±98)m, (29±8)kg in patients of the control group, showing no significant difference in the above indicators between the two groups ( χ2=0.21, t=-1.29, χ2=0.09, 0, 0.35, 0.03, 0.51, t=0.80, 0.85, 0.19, 0.14, 0.16, Z=-0.28, t=-0.17, 0.43, P>0.05). (2) Follow-up. All 187 patients were followed up for 90 days after surgery. During the follow-up period, all patients had good compliance and were able to follow the dietary guidance. Five patients in the nutrition therapy group experienced diarrhea and nausea adverse reactions, which were relieved after symptomatic treatment. No adverse reactions were found in the control group. (3) Comparison of nutritional indicators at 90 days after discharge. The body mass, body mass loss, BMI, skeletal muscle index, Alb, Hb were (58±10)kg, 2(6)kg, (21.0±2.9)kg/m 2, (41±7)cm 2/m 2, (41±4)g/L, (125±18)g/L in patients of the nutritional therapy group, versus (56±10)kg, 3(6)kg, (20.4±2.7)kg/m 2, (39±7)cm 2/m 2, (41±4)g/L, (121±21)g/L in patients of the control group. There were significant differences in body mass loss and skeletal muscle index between the two groups ( Z=-4.70, t=2.39, P<0.05), and there was no significant difference in body mass, BMI, Alb, and Hb ( t=1.30, 1.51, 0.80, 1.32, P>0.05). (4) Comparison of inflammation and body function indicators at 90 days after discharge. The NLR, 6-minutes walking distance, grip strength were 2.1(5.1), (478±99)m, and (33±9)kg in patients of the nutritional therapy group, versus 2.2(5.7), (465±96)m, (30±8)kg in patients of the control group. There was a significant difference in grip strength between the two groups ( t=2.08, P<0.05), and there were no significant difference in NLR and 6-minutes walking distance ( Z=-1.28, t=0.91, P>0.05). (5) Comparison of clinical outcome indicators at 90 days after discharge. The quality of life score and readmission rate were (79±14)points, 4.2%(4/95) in patients of the nutritional therapy group, versus (78±16)points, 6.5%(6/92) in patients of the control group, showing no significant difference in the above indicators between the two groups ( t=0.58, χ2=0.14, P>0.05). Conclusion:Nutritional therapy with daily oral nutrition supplements can improve the short-term nutritional status and body function of patients with malnutrition after radical gastrectomy for gastric cancer.

Objective:To explore the influence of chronic rhinitis on depressive symptoms of college freshmen and the mediating effect of avoidant personality.Methods:A cluster sampling method was used to survey 8 079 college freshmen from April 2018 to October 2018 using the Beck depression inventory and the avoidant personality diagnosis questionnaire based on DSM-Ⅳ.SPSS 25.0 software was used for descriptive statistics and Spearman correlation analysis, and the macro program PROCESS version 3.3 was used for the mediating effect.Results:(1) The detection rates of chronic rhinitis, avoidant personality and depressive symptoms were 22.90% (1 850/8 079), 19.22% (1 553/8 079) and 6.28% (507/8 079). The scores for avoidant personality disorder and depressive symptoms were 1.00 (0, 3.00) and 1.00 (0, 4.00), respectively. (2) The chronic rhinitis, avoidant personality and depressive symptoms were positively correlated ( rchronic rhinitis-avoidant personality=0.094, rchronic rhinitis-depressive symptoms=0.095, ravoidant personality-depressive symptoms=0.416, all P<0.001). (3) Chronic rhinitis could positively predict depressive symptoms ( β=1.113, P<0.001). (4) Avoidant personality played a mediating role between chronic rhinitis and depressive symptoms ( β=1.094, P<0.001), and accounted for 44.92%(0.500/1.113) of the total effect. Conclusion:Chronic rhinitis directly affect the depressive symptoms of college freshmen, and indirectly affect the depressive symptoms of college freshmen through the mediating role of avoidant personality.

Objective:To investigate the effect of triptolide on the apoptosis of human melanoma A375 cells through the inositol-requiring enzyme 1 (IRE1) /c-Jun N-terminal kinase (JNK) signaling pathway, and to explore its possible mechanisms.Methods:Cultured A375 cells were treated with triptolide at different concentrations of 0, 50, 100, 200 nmol/L (experimental control group, 50, 100, 200 nmol/L triptolide groups, respectively), and a blank control group (DMEM high-glucose medium without cells) was set up. Methyl thiazol tetrazolium (MTT) assay was performed to evaluate the cell viability at 24, 48, and 72 hours after the start of treatment, flow cytometry to detect cell apoptosis at 24 hours after the start of treatment, and real-time fluorescence-based quantitative PCR (RT-qPCR) and Western blot analysis were conducted to determine mRNA and protein expression of IRE1, JNK, and c-Jun, respectively. After pretreatment with the JNK inhibitor SP600125 for 72 hours, some A375 cells were then treated with 100 nmol/L triptolide for 24 hours (SP600125 + 100 nmol/L triptolide group), and the A375 cells only treated with 100 nmol/L triptolide served as control group (100 nmol/L triptolide group). Effects of triptolide on the mRNA expression of IRE1, JNK, and c-Jun in A375 cells, as well as on cell apoptosis, were investigated. Statistical analysis was performed using two-way analysis of variance, one-way analysis of variance, and Dunnett′s test.Results:After the treatment with different concentrations of triptolide for different durations, the cell viability was significantly lower in all triptolide groups than in the experimental control group ( Ftriptolide concentration = 18.36, P = 0.002), and gradually decreased over time ( F time = 8.54, P = 0.018). After 24-hour treatment, the apoptosis rate of A375 cells significantly differed among the 4 groups treated with different concentrations of triptolide ( F = 5 234.97, P < 0.001) ; additionally, the apoptosis rate was significantly higher in the 50, 100, and 200 nmol/L triptolide groups (16.99% ± 0.33%, 30.78% ± 0.40%, 38.91% ± 0.51%, respectively) than in the experimental control group (4.33% ± 0.02%, all P < 0.05), and gradually increased with the rising concentrations of triptolide. The mRNA expression levels of IRE1, JNK, and c-Jun were all significantly higher in the 50, 100, and 200 nmol/L triptolide groups than in the experimental control group (all P < 0.05), and gradually increased with the increase of triptolide concentration. Moreover, the protein expression levels of IRE1, JNK, c-Jun, p-JNK, and p-c-Jun in A375 cells in the triptolide groups also showed the same trend. After pretreatment with the JNK inhibitor SP600125 for 72 hours, the apoptosis rate was significantly lower in the SP600125 + 100 nmol/L triptolide group (21.88% ± 0.55%) than in the 100 nmol/L triptolide group without SP600125 pretreatment (30.78% ± 0.40%, t = -22.51, P < 0.001), and the mRNA expression levels of IRE1, JNK, and c-Jun were also significantly decreased in the SP600125 + 100 nmol/L triptolide group compared with the 100 nmol/L triptolide group (all P < 0.05) . Conclusion:Triptolide may induce apoptosis of human melanoma A375 cells by activating the IRE1/JNK signaling pathway.

Objective:To evaluate the relationship between early postoperative recovery and frailty after digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in the elderly.Methods:This study retrospectively selected hospitalized patients, aged ≥65 yr, scheduled for elective gastrointestinal endoscopic treatment.Early postoperative recovery time was defined as the period from the end of propofol administration to the achievement of a modified Aldrete score of 9.All the patients were divided into 2 groups according to whether the early recovery time after operation was less than 75%: normal early postoperative recovery time group and delayed early postoperative recovery time group.Frailty was assessed using the frailty phenotype (FP score 0-5), and the patient was diagnosed as frail (FP ≥3) or non-frail (FP 0-2). The age, sex, height, weight, smoking history, American Society of Anesthesiologists (ASA) Physical Status classification, type of operation, and baseline mean arterial pressure and heart rate were recorded.Logistic regression analysis was used to identify the risk factors for delayed early postoperative recovery time after minimally invasive digestive endoscopy under intravenous anesthesia in elderly patients.Results:A total of 214 patients were enrolled and divided into normal early postoperative recovery time group ( n=169) and delayed early postoperative recovery time group ( n=45). There were significant differences in frailty, age, drinking history of more than 10 yr, preoperative ASA Physical Status classification and propofol administration time between delayed early postoperative recovery time group and normal early postoperative recovery time group ( P<0.05). The results of logistic regression analysis indicated that frailty, age, ASA Physical Status classification Ⅲ, and propofol administration time were independent risk factors for the occurrence of delayed early postoperative recovery ( P<0.05). Conclusions:Frailty, age, ASA Physical Status classification Ⅲ and propofol administration time are independent risk factors for delayed early postoperative recovery time following digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in elderly patients.

Malnutrition and dehydration are prevalent in the elderly poplulation, and obesity is also a growing problem, which pose a serious challenge to the nutritional management in geriatrics. In order to better guide clinical practice, the European Society for Clinical Nutrition and Metabolism (ESPEN) published the practical guideline on clinical nutrition and hydration in geria-trics on March 5, 2022. This guideline provides 82 recommendations on clinical nutrition and hydration in geriatrics based on clinical practicability, covering basic problems and general prin-ciples, prevention and treatment of malnutrition/nutri-tional risk, prevention and treatment of specific diseases, as well as prevention and treatment of obesity, along with flow-charts, hoping to be convenient for doctors, nutritionists and nurses to use in clinical practice.

Objective:To study the genetic profile of neonatal hyperbilirubinemia with unknown etiology in Guangdong Province and the clinical significance of jaundice-related genetic screening.Methods:From July to September, 2021, neonates with hyperbilirubinemia of unknown etiology born in different hospitals in Guangdong Province were studied. 24 neonatal jaundice-related exons were sequenced using targeted capture and high-throughput sequencing technology. The pathogenic variants were analyzed.Results:A total of 331 cases, 139 (42.0%) cases showed positive screening results with five diseases, including 65 (19.6%) cases of Gilbert syndrome, 48 (14.5%) cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency,18 (5.4%) cases of sodium taurocholate cotransporting polypeptide deficiency, 4 (1.2%) cases of Citrin deficiency and 4 (1.2%) cases of Dubin-Johnson syndrome. 149 (45.0%) cases carried one or more genetic variants and 43 (13.0%) cases showed no clinically significant variants. The 8 high-frequency mutation loci (carrier rate >1%) are UGT1A1 gene c.211G>A and c.1091C>T, G6PD gene c.1466G>T and c.1478G>A, SLC10A1 gene c.800C>T, SLC25A13 gene c.852_855del TATG, HBB gene c.126_129delCTTT and c.316-197C>T.Conclusions:Genetic factors are important for neonatal hyperbilirubinemia with unknown etiology in Guangdong. The common pathogenic genes are UGT1A1, G6PD, SLC10A1, and SLC25A13 and the population carries high-frequency mutation loci. Therefore, genetic screening in neonates with hyperbilirubinemia of unknown etiology has important clinical significance.