The incidence of breast cancer(BC)is on the rise.The effective and precise management of BC continues to be topical.Tumor in-filtrating lymphocytes(TILs),significant biomarkers indicative of the biological behavior of BC,have not been well recognized in clinical prac-tice.There are some impediments,including the lack of a standard protocol for the quantification of TILs,an optimized threshold for TILs,and a repeatable noninvasive method for the assessment of TILs.These issues are the major controversies preventing the use of TILs as bio-markers in the clinical management of BC.Nevertheless,the value of TILs as biomarkers in the assessment of the prognosis and prediction of the response to treatment cannot be neglected,as they show promise in promoting precise and individualized management of BC.We aimed to offer a comprehensive outline of the current controversies and consensus regarding TILs as biomarkers in the management of BC,with the aim of providing a basis for the rational application of TILs as biomarkers.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective To investigate the effects of Duzhi Pills combined with MOTOmed training on limb function and activities of daily living in patients with cerebral infarction of qi deficiency and blood stasis type.Methods A prospective randomized controlled trial enrolled 98 cerebral infarction patients with qi deficiency and blood stasis treated at Qinhuangdao Hospital,Oriental Hospital of Beijing University of Chinese Medicine(Qinhuangdao Hospital of Traditional Chinese Medicine)from June 2022 to December 2024.Participants were randomized into control group(n=49,receiving conventional rehabilitation)and observation group(n=49,receiving additional Duzhi Pills+MOTOmed training)for 8 weeks.All patients received standard medication.Limb motor function and activities of daily living,and quality of life were assessed before and after treatment.Results(1)After treatment,both groups showed significant increases in Carroll Hand Function Test for Upper Extremity(CHFT-UE)scores,Fugl-Meyer Assessment Scale for Upper Extremity(FMA-UE)scores,and Simple Test for Evaluating Hand Function(STEF)scores compared to baseline(P＜0.05),with significantly greater improvements observed in the observation group(P＜0.01).(2)After treatment,both groups exhibited significant increases in Barthel Index scores for daily activity(P＜0.05),with the observation group demonstrating significantly greater improvement(P＜0.01).(3)After treatment,all subscale scores of the 36-Item Short-Form Health Survey(SF-36),including physical function,bodily pain,mental health,vitality,social functioning,emotional role,and general health,were significantly increased in both groups(P＜0.05),with significantly greater improvements in the observation group,the difference being statistically significant(P＜0.01).Conclusion The combined regimen of Duzhi Pills and MOTOmed training significantly enhances limb function,daily activity,and quality of life in cerebral infarction patients with qi deficiency and blood stasis syndrome,demonstrating clinical value for rehabilitation.

Objective To assess the clinical value of prognostic nutritional index(PNI)in predicting the prognosis of patients with advanced liver cancer treated with transarterial chemoembolization(TACE)combined with ablation therapy.Methods A total of 112 patients with advanced liver cancer,who received TACE combined with ablation at the Lishui Municipal Central Hospital of China from January 2020 to January 2024,were enrolled in this study.The general data,survival status,and survival time were collected.The Youden index of PNI was calculated using the receiver operating characteristic(ROC)curve model,and the optimal cutoff value was determined.Based on the optimal cutoff value,the patients were divided into low-PNI group and high-PNI group.The progression-free survival(PFS)and overall survival(OS)time were compared between the two groups,and the independent risk factors affecting PFS and OS were analyzed.Results The Youden index for PNI was 0.43,and the optimal cutoff value of PNI was 43.95.The low-PNI group included 65 patients,and the high-PNI group included 47 patients.There were no statistically significant differences in the baseline data between the two groups.The median PFS and the median OS in the high-PNI group were 13.21 months(95％CI=4.37-22.03)and 40.80 months(95％CI=31.55-50.05)respectively,which were longer than 9.20 months(95％CI=6.58-11.82)and 21.37 months(95％CI=16.56-26.17)respectively in the low-PNI group,the differences were statistically significant(both P＜0.05).The 6-month,one-year and 2-year PFS in the high-PNI group was 56.95％,47.25％and 33.87％respectively,which were higher than 43.95％,32.56％and 16.31％respectively in the low-PNI group.The one-year,2-year and 3-year cumulative survival rates in the high-PNI group were 80.77％,66.66％and 39.40％respectively,which were higher than 63.79％,34.31％and 27.75％respectively in the low-PNI group.Multivariate regression analysis indicated that the number of nodules,metastasis and PNI significantly affected OS,and metastasis and PNI strikingly affected PFS.High PNI was a protective factor for both PFS and OS.Conclusion For patients with advanced liver cancer treated with TACE combined with ablation therapy,PNI is an effective indicator for predicting the prognosis.

Objective To investigate the relationship between daily intake of monounsaturated fatty acids(MUFAs)and polyunsaturated fatty acids(PUFAs)and non-alcoholic fatty liver disease(NAFLD),and to determine the threshold values of daily MUFAs and PUFAs intake for NAFLD risk.Methods Date were collected from the Dryad database.We enrolled a total of 1 068 healthy subjects aged 18 years and older(534 in the control group and 534 with NAFLD group)who had physical check-up in the Affiliated Nanping First Hospital of Fujian Medical University from April 2015 to August 2017.Comprehensive medical histories were obtained through questionnaires;information on dietary intake was collected using a semi-quantitative food frequency questionnaire and daily MUFAs and PUFAs intake were calculated.Baseline characteristics were compared between the two groups,and Logistic regression and restricted cubic spline(RCS)analyses were used to explore the relationship between daily MUFAs or PUFAs intake and NAFLD.Results Compared with the control group,the prevalence of hypertension,tea drinking,body mass index(BMI),daily energy intake,and daily MUFAs and PUFAs intakes were significant higher in patients with NAFLD(all P＜0.05),but the proportion of physical activities was significantly lower(P＜0.05).Logistic regression analysis revealed that after adjusting other confounding factors such as age,gender and BMI,for every 10 g increase in daily MUFAs or PUFAs intake,the risk of NAFLD increased by 53％(95％ CI:1.25-1.87,P＜0.001)and 3.30 times(95％ CI:2.98-6.20,P＜0.001),respectively.RCS indicated an approximately linear relationship between daily MUFAs intake and NAFLD(P for nonlinearity=0.064)and a nonlinear relationship between daily PUFAs intake and NAFLD(P for nonlinearity＜0.05).Subgroup analysis results were generally consistent,and there was statistical evidence of interactions between MUFAs and factors such as gender,hypertension and education level,with interaction between PUFAs and BMI observed(P＜0.05).Conclusion Increased daily intake of MUFAs or PUFAs is significantly associated with an increased risk of NAFLD,and further research is needed to clarify their specific roles in hepatic lipid accumulation.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.

Objective To investigate the effect of quercetin on paraptosis induced by low-concentration hydrogen peroxide(H2O2)in human lens epithelial cells(LECs).Methods The human lens epithelial cell line SRA01/04 was cul-tured in vitro and randomly divided into the following groups:control group,H2O2 group(50 μmol·L-1 H2O2),and H2O2+Quercetin group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quercetin).The area and number of endoplasmic reticulum vacuoles in the cells were observed using transmission electron microscopy and super-resolution laser confocal microscopy.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Western blot was performed to detect the expression levels of the following proteins:insulin-like growth factor 1 receptor(IGF1R),phos-phorylated IGF1R(p-IGF1R),ALG-2-interacting protein X(ALIX),glucose-regulated protein 78(GRP78),extracellular signal-regulated kinase(ERK),phosphorylated ERK(p-ERK),P38,and phosphorylated P38(p-P38).Additionally,len-ses from 8-week-old Sprague-Dawley rats were subjected to ex vivo culture and divided into the normal group,the H2O2 treatment group(50 μmol·L-1 H2O2),and the combination treatment group(50 μmol·L-1 H2O2 and 20 μmol·L-1 quer-cetin).The degree of lens opacity was observed under a stereomicroscope,and the area of lens opacity was quantified.The ultrastructure of the endoplasmic reticulum in the rat LECs was observed by transmission electron microscopy.Western blot was used to detect the expression levels of the aforementioned proteins in the rat LECs.Results Compared with the control group,the H2O2 group exhibited significant increases in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative protein expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was decreased(all P＜0.001).Compared with the H2 O2 group,the H2O2+quercetin group showed signifi-cant reductions in the area and number of endoplasmic reticulum vacuoles,ROS levels,and the relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78,while the relative expression of ALIX protein was increased(all P＜0.01).In the ex vivo cultured rat lens model,compared with the normal group,the H2O2 group displayed a significant increase in lens opac-ity area,expanded endoplasmic reticulum area in LECs,elevated relative expression levels of p-IGF1R,p-ERK,p-P38,and GRP78 proteins,and decreased ALIX expression(all P＜0.000 1).In contrast,the combination treatment group showed significantly reduced lens opacity area,decreased endoplasmic reticulum area in LECs,lower relative expression of p-IGF1R,p-ERK,p-P38,and GRP78,and increased ALIX expression compared to the H2O2 group(all P＜0.01).Conclu-sion Quercetin inhibits activation of the IGF1R/MAPK signaling pathway and alleviates endoplasmic reticulum stress,thereby effectively attenuating paraptosis in lens epithelial cells.These findings provide a novel strategy for the prevention and treatment of early age-related cataract.

Objective To investigate the relationship between daily intake of monounsaturated fatty acids(MUFAs)and polyunsaturated fatty acids(PUFAs)and non-alcoholic fatty liver disease(NAFLD),and to determine the threshold values of daily MUFAs and PUFAs intake for NAFLD risk.Methods Date were collected from the Dryad database.We enrolled a total of 1 068 healthy subjects aged 18 years and older(534 in the control group and 534 with NAFLD group)who had physical check-up in the Affiliated Nanping First Hospital of Fujian Medical University from April 2015 to August 2017.Comprehensive medical histories were obtained through questionnaires;information on dietary intake was collected using a semi-quantitative food frequency questionnaire and daily MUFAs and PUFAs intake were calculated.Baseline characteristics were compared between the two groups,and Logistic regression and restricted cubic spline(RCS)analyses were used to explore the relationship between daily MUFAs or PUFAs intake and NAFLD.Results Compared with the control group,the prevalence of hypertension,tea drinking,body mass index(BMI),daily energy intake,and daily MUFAs and PUFAs intakes were significant higher in patients with NAFLD(all P＜0.05),but the proportion of physical activities was significantly lower(P＜0.05).Logistic regression analysis revealed that after adjusting other confounding factors such as age,gender and BMI,for every 10 g increase in daily MUFAs or PUFAs intake,the risk of NAFLD increased by 53％(95％ CI:1.25-1.87,P＜0.001)and 3.30 times(95％ CI:2.98-6.20,P＜0.001),respectively.RCS indicated an approximately linear relationship between daily MUFAs intake and NAFLD(P for nonlinearity=0.064)and a nonlinear relationship between daily PUFAs intake and NAFLD(P for nonlinearity＜0.05).Subgroup analysis results were generally consistent,and there was statistical evidence of interactions between MUFAs and factors such as gender,hypertension and education level,with interaction between PUFAs and BMI observed(P＜0.05).Conclusion Increased daily intake of MUFAs or PUFAs is significantly associated with an increased risk of NAFLD,and further research is needed to clarify their specific roles in hepatic lipid accumulation.

The incidence of breast cancer(BC)is on the rise.The effective and precise management of BC continues to be topical.Tumor in-filtrating lymphocytes(TILs),significant biomarkers indicative of the biological behavior of BC,have not been well recognized in clinical prac-tice.There are some impediments,including the lack of a standard protocol for the quantification of TILs,an optimized threshold for TILs,and a repeatable noninvasive method for the assessment of TILs.These issues are the major controversies preventing the use of TILs as bio-markers in the clinical management of BC.Nevertheless,the value of TILs as biomarkers in the assessment of the prognosis and prediction of the response to treatment cannot be neglected,as they show promise in promoting precise and individualized management of BC.We aimed to offer a comprehensive outline of the current controversies and consensus regarding TILs as biomarkers in the management of BC,with the aim of providing a basis for the rational application of TILs as biomarkers.

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.