Objective:To investigate the types and number of symptom clusters in patients undergoing sphincter-preserving surgery for rectal cancer and explore the influencing factors of these symptom clusters.Methods:Totally 192 patients who underwent sphincter-preserving surgery for rectal cancer in the Department of General Surgery at Peking University Third Hospital between January 2021 and January 2023 were selected by convenience sampling. A general information questionnaire, Post-sphincter-preserving Surgery Symptom Questionnaire, and the International Physical Activity Questionnaire-Short Form (IPAQ-SF) were used for data collection.Results:A total of 192 questionnaires were distributed, with 159 valid questionnaires returned. Exploratory factor analysis on 18 symptoms with an incidence rate of over 10.0% identified five primary symptom clusters: the psychological symptom cluster, increased defecation cluster, fatigue-pain cluster, sleep disturbance cluster, and constipation-related cluster. Logistic regression analysis showed that postoperative duration was an influencing factor for the psychological symptom cluster ( P<0.05) ; preoperative radiotherapy and postoperative duration were influencing factors for the increased defecation cluster ( P<0.05) ; postoperative chemotherapy was an influencing factor for the fatigue-pain cluster ( P<0.05) ; and weekly sedentary time was an influencing factor for the sleep disturbance cluster ( P<0.05) . Conclusions:Patients undergoing sphincter-preserving surgery for rectal cancer experience multiple symptom clusters. Preoperative radiotherapy and prolonged sedentary behavior increase the risk of symptom clusters, and different postoperative periods are associated with varying risks for different symptom clusters. However, physical activity levels do not appear to influence the occurrence of symptom clusters. Healthcare providers should implement targeted interventions based on the symptom clusters and their influencing factors to reduce the incidence of symptoms in patients.

The aim of this study is to investigate the effect of Dahuang Fuzi decoction(DHFZT)on the killing effect of natural killer(NK)cells and the growth of lung cancer xenografts in mice.Lewis lung cancer xenograft model was constructed,and the mice were randomly divided to the normal saline group,low and high concentrations of DHFZT groups.The growth of lung cancer xenografts in mice in the control group,low and high concentration of DHFZT treatment groups was detected.The levels of IFN-y,IL-2 and IL-10 were detected by ELISA.The killing effect of NK cells was detected by calcein release assay.The release of CD107α was detected by flow cytometry.The expression of activated receptors and the tumor cell surface ligands were detected in the con-trol group and DHFZT treatment groups.The results showed that the xenografts of Lewis mice in the DHFZT treatment groups were grown slower than that in the control group in a dose depend-ent manner(P＜0.05).Compared with the control groups,the levels of IL-2 and IFN-y in tumor tissues were increased in DHFZT treatment groups(P＜0.05),but no significant changes in IL-10.Calcein release assay showed that the killing efficiency of NK cells in the DHFZT treatment groups was increased(P＜0.05).The secretion level of IFN-y in the culture supernatant was increased by DHFZT treatment(P＜0.05).DHFZT treatment increased the expression level of CD107α of NK cells.The expression of MIC A/B on the surface of A549 and H1299 cells was up-regulated by DHFZT treatment,but not the expression of inhibitory ligand HLA-ABC.The results showed that DHFZT enhanced the killing effect of NK cells on mouse lung cancer cells by up-reg-ulating the expression of MIC A/B,increasing the secretion of IFN-y and CD107α.Hence,these re-sults indicated that DHFZT suppresses the lung cancer growth potential through regulating the killing effect of NK cells.

Objective:To explore the overall efficacy of pediatric liver transplantation (LT) and the risk factors affecting the long-term outcomes.Methods:From October 2006 to December 2022, clinical profiles, intraoperative findings, perioperative managements and long-term follow-ups were retrospectively reviewed for 3004 cases (including 40 cases of retransplantation) of children with end-stage liver disease undergoing LT. Overall patient and graft survival rates after transplantation were explored by Kaplan-Meier survival curve. The survival rates of recipients receiving living donor liver transplantation and deceased donor liver transplantation, recipients with body weight ≤5 kg and >5 kg at the time of transplantation, recipients with age ≤5 months and >5 months, graft recipient weight ratio (GRWR) ≤5% and >5 %, and recipients with compatible and incompatible blood types were compared, as well as the survival rates of recipients from 2006 to 2011, 2012 to 2017, and 2018 to 2022. The occurrence of complications was analyzed. Cox regression was used to analyze the risk factors of long-term mortality, and those with <0.05 were included in the LASSO regression model to identify the independent risk factors.Results:As of December 2022, overall survivals at 1/5/10-year were 95.1 %(2 819/2 964), 93.1 % (2 759/2 964) and 91.8% (2 721/2 964) and 1/5/10-year graft survival rate 94.5 % (2 839/3 004), 92.0 % (2 764/3 004) and 86.2 % (2 589/3 004 ). The 5-year survival rate improved : Five-year survival rate at pediatric LT centers were 71.6 % (63/88, from 2006 to 2011), 91.6 % (1 009/1 101 ,from 2012 to 2017) and 95.5 % (1 695/1 775, from 2018 to 2022 ). Survival rates were lower in recipients with body weight ≤5 kg [83.7 % (41 /49) vs 94.4 % (2 746/2 915), P=0.001) ] and GRWR >5 % [90.0 % (378/420) vs 94.6 % (2 046/2 544), P=0.007 ] compared to those >5 kg and ≤5 %. Difference in surgical age and blood type compatibility were not statistically ( P=0.26 and 0.4 ). Infection [35.3 % (70/198) ]and surgical complications [24.2 % (48/198) ]were the main causes of mortality after transplantation. While infection [35.7% (25/70) ] ,portal vein complications [18.6%(13/70) ]and lung injury [15.7 % (11/70) ]were the main reasons of death within 1 month after transplantation. The incidence of postoperative infection and acute rejection decreased from 86.5 %(76/88) and 38.2% (34/88) in 2006-2011 to 75.5% (1 340/1 775) and 22.2% (394/1 775). Post-transplantation surgery-related complications included portal veinous complications (3.1 %, 92/3 004), hemorrhage (2.3 %, 68/3 004) ,hepatic arterial complications (1.7 %, 50/3 004) and hepatic venous complications (1.1 %, 33/3 004). Univariate analysis revealed that risk factors related to postoperative mortality included preoperative anemia ( P=0.012), high preoperative leucocyte count ( P=0.026), preoperative renal insufficiency ( P=0.008), hypoproteinemia ( P=0.001), coagulation dysfunction ( P= 0.005), low body weight ( P=0.007), GRWR>5% ( P=0.001), intraoperative volume of blood loss and transfusion ( P<0.001) ,postoperative intensive care unit (ICU) time ( P<0.001), hospital length post-LT ( P=0.045) ,postoperative lung infection ( P<0.001), abdominal infection ( P=0.029), postoperative hemorrhage ( P<0.001), intestinal perforation ( P<0.001), acute rejection ( P<0.001) Epstein-Barr virus (EBV) infection ( P<0.001) and post-transplant lymphoproliferative disorder (PTLD) ( P=0.018). Multivariable analysis revealed that preoperative creatinine ( HR=1.015, 95% CI: 1.002-1.028, P=0.024), GRWR ( HR=2.082, 95% CI: 0.473-9.157, P=0.031) ,pulmonary infection ( HR=4.389, 95% CI: 2.248-8.569, P<0.001) ,postoperative abdominal hemorrhage ( HR= 6.922, 95% CI:1.871-25.610, P=0.004), intestinal perforation ( HR=9.154, 95% CI: 2.307-36.323, P=0.002) and acute rejection ( HR=0.452, 95% CI: 0.210-0.971, P=0.042) were important influencing factors of long-term survival post-LT. Conclusions:LT is currently the most effective treatment for end-stage liver disease in children. Improving preoperative organ function, optimizing surgical techniques, minimizing intraoperative hemorrhage and preventing postoperative complications can effectively enhance the long-term outcomes of LT recipients.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To investigate the impact of air pollution on dynamic changes in lung function and further explore the association between genetic factors and lung function and its changes.Methods:Research data were from 14 506 participants in the United Kingdom Biobank with two complete baseline and follow-up lung function tests. Particulate matter [including particulate matter with aerodynamic diameter ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10)], nitrogen dioxide (NO 2), and nitrogen oxides (NO x) concentrations were estimated using land-use regression models. Annual changes in lung function were calculated based on baseline and follow-up lung function tests. Polygenic risk scores (PRS) of lung function [forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), and the ratio of FEV 1 to FVC (FEV 1/FVC)] were constructed by genetic variations. The association between air pollution concentrations and lung function changes was analyzed by multiple linear regression models, and the impact of genetic factors on lung function and its changes was also assessed. Results:PM 2.5, PM 10, NO 2, and NO x showed a negative correlation with FVC changes [PM 2.5: -6.66 (95% CI: -9.92- -3.40) ml/year; PM 10: -0.40 (95% CI: -0.77- -0.03) ml/year; NO 2: -1.84 (95% CI: -2.60- -1.07) ml/year; NO x: -1.37 (95% CI: -2.27- -0.46) ml/year]. Additionally, PM 2.5, PM 10and NO 2 were also negatively correlated with changes in FEV 1 [PM 2.5: -3.19 (95% CI: -5.79- -0.59) ml/year; PM 10: -3.00 (95% CI: -5.92- -0.08) ml/year; NO 2: -0.95 (95% CI: -1.56- -0.34) ml/year]. PRS of lung function were positively correlated with baseline lung function (FVC, FEV 1, and FEV 1/FVC) and lung function changes (all β>0, all P<0.001). In different PRS stratification analyses, the effect of air pollution on lung function changes remained significant, and there was no apparent heterogeneity. Conclusions:PRS of lung function are significantly associated with baseline and lung function changes. Long-term exposure to air pollution accelerates the decline of lung function indicators such as FVC and FEV 1. The effects of air pollution are consistent in individuals with different genetic risk scores.

In recent years, an increasing number of emerging environmental pollutants have been identified, garnering widespread attention. Many of these pollutants are characterized by their environmental persistence and bioaccumulation, which pose significant threats to both the ecological environment and human health. However, the molecular mechanisms underlying their effects remain unclear, limiting our ability to assess their adverse impacts and develop effective protective measures. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor traditionally known to be activated by dioxins and polycyclic aromatic hydrocarbons (PAHs) and is involved in the metabolism of exogenous chemicals. Recent research has shown that the AHR can be activated by a diverse range of exogenous and endogenous chemicals and participates in various biological processes. Studies have demonstrated that AHR mediates the toxic effects of emerging environmental pollutants such as perfluorooctane sulfonamide (PFOSA) and N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone (6PPDQ). This paper provided an overview of the AHR activation and the toxic effects induced by emerging environmental pollutants, with a focus on how the AHR activation interacts with multiple signaling pathways. The significance of these interactions in environmental risk assessment and toxicological research was also discussed. We aim to provide a scientific basis for environmental protection and risk assessment.

Background A large amount of iron deposition in the brain can cause neuronal damage by inducing oxidative stress, neuroinflammation, and abnormal mitochondrial function. In addition, iron deposition is also reported to be closely related to the pathogenesis of Alzheimer's disease (AD). The neurofibrillary tangles aggregated by tau hyperphosphorylation are one of the important pathological features of AD. Objective To investigate potential effect of exogenous trivalent iron ions on neuronal activity in human neuroblastoma (SH-SY5Y) cells and tau hyperphosphorylation and aggregation. Methods SH-SY5Y cells were treated with ferric chloride (FeCl₃) at four concentrations (10, 100, 200, and 400 mg·L⁻¹). Cell survival rate was then detected by CCK8 assay. Intracellular iron content was determined prussian blue (Perl's) by iron staining after 24 h exposure to FeCl₃ at 10 or 200 mg·L⁻¹. Transfection of tau-P301L plasmid was conducted to construct an AD-like cell model for tau overexpression. The differences in the expression of the phosphorylated tau (p-tau) protein in SH-SY5Y cells and SH-SY5Y cells with tau overexpression were detected by Western blotting after 24 h exposure to FeCl₃ at 10 and 200 mg·L⁻¹. After dilution with phosphate buffered saline (PBS), FeCl₃, human tauR3, and FeCl₃ + tauR3 were incubated at 37℃, and the fluorescence intensity reflecting tau aggregation level was measured by thioflavin T(ThT) method at 12, 24, 36, 48, 60, 72, 84, and 96 h, respectively. Meanwhile, after 96 h coincubation of FeCl₃ and tauR3, the fibers formed by tau aggregation were observed under a transmission electron microscope (TEM). Results After 24 h of FeCl₃ exposure, the cell survival rate of SH-SY5Y cells among all groups was statistically different (F=8.63, P<0.01). The cell survival rates in the 200 and 400 mg·L⁻¹ groups were 80.1% and 68.7% of the control group, respectively (P<0.05). Compared with the control group, the nuclei of the 200 mg·L⁻¹ FeCl₃ group were mainly yellowish-brown after iron staining and the positive cell rate was up-regulated by 12.9% (P<0.01). After 24 h of FeCl₃ exposure , the p-tau (Ser396) protein expression was statistically different among all groups (F=11.6, P<0.01). Compared with the control group, the p-tau protein expression level of SH-SY5Y cells in the 200 mg·L⁻¹ group was up-regulated by 72.7% (P<0.01). After FeCl₃-treated SH-SY5Y cells with tau overexpression for 24 h, the p-tau (Ser396) protein expression was statistically different among all groups (F=27.8, P<0.01). Compared with the tau group, the p-tau (Ser396) protein expression level of SH-SY5Y cells in the tau + 200 mg·L⁻¹ group was up-regulated by 44.6% (P<0.05). Compared with the tauR3 group, the fluorescence intensities in the 84 and 96 h tauR3 + FeCl₃ groups were up-regulated by 49.9% and 53.7% (P<0.01) respectively. After 96 h of coincubation, compared with the tauR3 group, FeCl₃ + tauR3 aggravated tau aggregation and formed fiber deposition under TEM. Conclusion Exogenous trivalent iron ions may inhibit SH-SY5Y cell viability, promote the phosphorylation of tau in SH-SY5Y cells transfected with tau-P301L plasmid, and aggravate tauR3 aggregation and fiber production.

Pulpitis, periodontitis, jaw bone defect, and temporomandibular joint damage are common oral and maxillofacial diseases in clinic, but traditional treatments are unable to restore the structure and function of the injured tissues. Due to their good biocompatibility, biodegradability, antioxidant effect, anti-inflammatory activity, and broad-spectrum antimicrobial property, chitosan-based hydrogels have shown broad applicable prospects in the field of oral tissue engineering. Quaternization, carboxymethylation, and sulfonation are common chemical modification strategies to improve the physicochemical properties and biological functions of chitosan-based hydrogels, while the construction of hydrogel composite systems via carrying porous microspheres or nanoparticles can achieve local sequential delivery of diverse drugs or bioactive factors, laying a solid foundation for the well-organized regeneration of defective tissues. Chemical cross-linking is commonly employed to fabricate irreversible permanent chitosan gels, and physical cross-linking enables the formation of reversible gel networks. Representing suitable scaffold biomaterials, several chitosan-based hydrogels transplanted with stem cells, growth factors or exosomes have been used in an attempt to regenerate oral soft and hard tissues. Currently, remarkable advances have been made in promoting the regeneration of pulp-dentin complex, cementum-periodontium-alveolar bone complex, jaw bone, and cartilage. However, the clinical translation of chitosan-based hydrogels still encounters multiple challenges. In future, more in vivo clinical exploration under the conditions of oral complex microenvironments should be performed, and the combined application of chitosan-based hydrogels and a variety of bioactive factors, biomaterials, and state-of-the-art biotechnologies can be pursued in order to realize multifaceted complete regeneration of oral tissue.
Chitosan/chemistry* ; Tissue Engineering ; Hydrogels/chemistry* ; Biocompatible Materials/chemistry* ; Cartilage ; Tissue Scaffolds/chemistry*

Background Occupational and environmental particulate matter may cause fibrosis, accompanied by RNA m⁶A modification changes. Neodymium oxide (Nd₂O₃) can cause mouse lung fibrosis, which contains a large number of fibroblasts. Objective To investigate m⁶A modification of tumor necrosis factor receptor-associated protein 6/nuclear factor-κB (TRAF6/NF-κB) signaling pathway in fibrosis of human embryonic lung fibroblasts induced by Nd₂O₃, and identify the key m⁶A modification sites of TRAF6. Methods Designed concentrations of Nd₂O₃ (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100, and 200 mg∙L⁻¹) were infected with HELF cells for 24 and 48 h, and cell viability was detected to determine exposure time and dose. Measurements included indicators of fibrosis [hydroxyproline (HYP) and transforming growth factor-β1 (TGF-β1)], m⁶A methylation level, methyltransferases (METTL3 and METTL14), demethylases (FTO and ALKBH5), reading proteins (YTHDC2 and YTHDF2), fibrosis-associated genes (collagen-І, vimentin, and α-SMA), and proteins related to signaling pathway (TRAF6, NFKB1, P65, and P-P65). The enrichment of m⁶A in TRAF6 mRNA was measured by methylated RNA immunoprecipitation-quantitative real-time PCR (MeRIP-qPCR). Results The results of cell viability indicated that 6.25, 12.5, 25 mg∙L⁻¹ Nd₂O₃ and 48 h exposure time were used for subsequent experiments. After 48 h exposure, compared with the control group, the HYP level in the 25 mg∙L⁻¹ Nd₂O₃ group was increased, and the levels of TGF-β1 in the 6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05); the overall m⁶A methylation levels of HELF cells in the 12.5 and 25 mg∙L⁻¹ Nd₂O₃ groups were increased (P<0.05). At mRNA level, compared with the control group, the mRNA expression levels of methyltransferases METTL3 and METTL14 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression level of reading protein YTHDF2 (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) was increased (P<0.05), while the mRNA expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the mRNA expression levels of demethylases FTO (12.5 and 25 mg∙L⁻¹ Nd₂O₃) and ALKBH5 (25 mg∙L⁻¹ Nd₂O₃) were decreased (P<0.05); the mRNA expression levels of fibrosis-related genes vimentin, α-SMA, and collagen-Ⅰ (6.25, 12.5, and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the mRNA expression levels of pathway-related genes TRAF6 (25 mg∙L⁻¹ Nd₂O₃) and NFKB1 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05). At protein level, compared with the control group, the expression levels of methyltransferases METTL3 (25 mg∙L⁻¹ Nd₂O₃) and METTL14 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) were increased (P<0.05); the expression level of reading protein YTHDF2 (12.5 and 25 mg∙L⁻¹ Nd₂O₃) was increased, while the expression level of YTHDC2 (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of demethylase FTO (25 mg∙L⁻¹ Nd₂O₃) was decreased (P<0.05); the expression level of fibrosis-associated protein vimentin was increased at 25 mg∙L⁻¹ Nd₂O₃, and the expression levels of α-SMA and collagen-Ⅰ were increased at 12.5 and 25 mg∙L⁻¹ Nd₂O₃ (P<0.05); the expression levels of TRAF6 and P-P65 were increased at 25 mg∙L⁻¹ Nd₂O₃ (P<0.05). The MeRIP-qPCR results showed that compared with the control group, the concentrations of m⁶A in all Nd₂O₃ groups were significantly increased (P<0.05). Conclusions Upon exposure of HELF cells to Nd₂O₃, the alterations in fibrosis-related indexes increase the expression of some m⁶A methylases and decrease the expression of demethylases, thereby increasing the m⁶A methylase level, and may promote the progression of fibrosis by activating the TRAF6/NF-κB signaling pathway.

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms ; Biomarkers ; Immunotherapy/methods* ; Biomarkers, Tumor/genetics* ; Prognosis ; Tumor Microenvironment