Objective: To quantitatively assess the health risk of preservatives from beverages around primary schools in Anshun City, and to provide scientific basis for precise food safety supervision. Methods: From December 2023 to July 2024, 602 beverage samples were randomly collected from within 100 meters of 19 primary schools in Anshun City. The content of benzoic acid, sorbic acid, and dehydroacetic acid was detected according to GB 5009 series standards. Combined with children s physiological parameters (body weight 30 kg, daily intake 0.15 L), the Hazard Quotient (HQ) and Hazard Index (HI) models were used to evaluate health risks. Results: The total detection rate of preservatives from beverages around primary schools was 63.0%, and the total over limit rate was 9.0%. The detection rate of preservatives in flavored beverages was the highest (72.6%), and the highest over limit rate of preservatives in special purpose beverages was the highest (17.2%). The single preservative HQ (benzoic acid up to 0.47 ) and mixed HI (up to 0.55) of all samples were below 1(safety threshold). However, the HQ value of benzoic acid in flavored beverages (0.47) was 2.9 times that of sorbic acid (0.16), contributing significantly to health risk. Sensitivity analysis showed that if the daily consumption increased to 0.3 L, the HI value of flavored beverages would rise to 1.11, exceeding the safety threshold. Enterprise scale analysis showed that the exceedance rate of special purpose beverages in large enterprises reached 30.0%, while micro enterprises, accounting for a dominant market share (52.2%), constituted the main source of children s daily exposure to their products. Conclusions The overall health risk of perservatives in beverages sold near primary schools in Anshun City is controllable, but there is a noticeable risk of gradient. The risk of children’s exposure to preservatives through beverage consumption should not be ignored.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective To explore the value of diffusion tensor imaging analysis index along the perivascular space(DTI-ALPS)for assessing age-related functional changes in glymphatic system(GS).Methods Totally 27 healthy subjects from Meizhou People's Hospital and 100 healthy subjects from neuroimaging informatics tools and resources collaborator database who underwent T1-weighted magnetization-prepared rapid gradient echo(T1-MPRAGE)and DTI scanning were retrospectively enrolled and divided into youth group(n=38),middle-aged group(n=57)and elderly group(n=32).Automated DTI-ALPS index analysis procedure was used to minimize manual errors and derive DTI-ALPS index.The general data,neuropsychological assessment results and DTI-ALPS indices were compared among groups.Spearman correlation analysis was performed to observe the relationships of DTI-ALPS index and age,gender,as well as neuropsychological scores.Results The average age in youth group,middle-aged group and elderly group was(28.5±5.8),(53.7±6.8)and(73.8±2.3)years,respectively.No significant difference of DTI-ALPS index was found between middle-aged group and elderly group(P＞0.05),which were both lower than that in youth group(both P＜0.05).DTI-ALPS index was weakly negatively correlated with age(rs=-0.340,P＜0.001),but not significantly correlated with gender nor neuropsychological assessment results(both P＞0.05).Conclusion DTI-ALPS index was negatively correlated with age in healthy individuals,hence having potential utility for assessing age-related functional changes in GS.

The intestine and liver are closely connected both physiologically and pathologically, forming a so-called gut-liver axis, with the gut microbiota serving as a pivotal link in their bidirectional communication. Gut microbiota dysbiosis and gut-liver axis disruption play a key role in the development and progression of colorectal cancer liver metastasis (CRLM), though the underlying mechanisms have not been clearly elucidated. Certain gut microbiota, such as Escherichia coli and Enterococcus spp., can breach the intestinal barrier and translocate to the liver, promoting the formation of pre-metastatic niche. Fusobacterium nucleatum and Enterococcus faecalis enhance tumor cell invasion/migration, while Parabacteroides spp. suppress anti-tumor immunity in the liver TME. Interventions like fecal microbiota transplantation, dietary modifications, and traditional Chinese medicine have shown potential in clinical and preclinical studies to improve patient outcomes by targeting the gut microbiota, but their long-term efficacy and safety require further investigation. Future research should focus on elucidating the effects of specific bacterial species, metabolites, viruses, and fungi on tumorigenesis. Exploring the potential of gut microbiota-based precision medicine and personalized therapies will improve risk stratification and enable more targeted interventions for CRLM patients.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation and joint destruction. Iguratimod (IGU) is a novel conventional synthetic disease-modifying antirheumatic drugs (csDMARD) with good efficacy and safety for the treatment of active RA in China and Japan. However, the long-term effects of IGU on the progression of bone destruction or radiographic progression in patients with active RA remain unknown. We aimed to investigate the efficacy and safety of iguratimod (IGU), a combination of methotrexate (MTX) and IGU, and IGU in patients with active rheumatoid arthritis (RA) who were naïve to MTX. METHODS: This multicenter, double-blind, randomized, non-inferiority clinical trial was conducted at 28 centers for over 52 weeks in China. In total, 911 patients were randomized (1:1:1) to receive MTX monotherapy (10-15 mg weekly, n = 293), IGU monotherapy (25 mg twice daily, n = 297), or IGU + MTX (10-15 mg weekly for MTX and 25 mg twice daily for IGU, n = 305) for 52 weeks. The patients' clinical characteristics, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), disease activity score in 28 joints-C-reactive protein (DAS28-CRP) level, and disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) were assessed at baseline. The primary endpoints were the proportion of patients with ≥20% improvement according to the American College of Rheumatology (ACR20) response and changes in the van der Heijde-modified total Sharp score (vdH-mTSS) at week 52. RESULTS: The proportions of patients achieving an ACR20 response at week 52 were 77.44%, 77.05 %, and 65.87% for IGU monotherapy, IGU + MTX, and MTX monotherapy, respectively. The non-inferiority of IGU monotherapy to MTX monotherapy was established with the ACR20 (11.57%; 95% confidence interval [CI], 4.35-18.79%; P <0.001) and vdH-mTSS (-0.37; 95% CI, -1.22-0.47; P = 0.022). IGU monotherapy was also superior to MTX monotherapy in terms of ACR20 ( P = 0.002) but not the vdH-mTSS. The superiority of IGU + MTX over MTX monotherapy was confirmed in terms of the ACR20 (11.18%; 95% CI, 3.99-18.37%; P = 0.003), but not in the vdH-mTSS (-0.68; 95% CI, -1.46-0.11; P = 0.091). However, the difference in the incidence rates of adverse events was not statistically significant. CONCLUSIONS: IGU monotherapy/IGU + MTX showed a more favorable clinical response than did MTX monotherapy. IGU may have some clinical benefits over MTX in terms of radiographic progression, implying that IGU may be considered as an initial therapeutic option for patients with active RA. TRIAL REGISTRATION https://classic.clinicaltrials.gov/ , NCT01548001.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Chromones/adverse effects* ; Double-Blind Method ; Drug Therapy, Combination ; Methotrexate/adverse effects* ; Treatment Outcome ; Sulfonamides

Objective:To understand the expectations of Hong Kong residents to seek for medical treatment in Shenzhen and the influencing factors,so as to provide a reference for promoting the medical cooperation between Shenzhen and Hong Kong and the integration of medical services in Guangdong-Hong Kong-Macao Greater Bay Area.Methods:Based on the Anderson model,a questionnaire survey on medical expectations was conducted among 1 592 Hong Kong residents who sought medical treatment at the University of Hong Kong-Shenzhen Hospital.Binary logistic regression was used to analyze the influencing factors of medical ex-pectations in different dimensions.Results:The overall expectation score of Hong Kong residents for medical treatment in Shenzhen was 3.01,and the most important concern was the professionalism and accessibility of medical services.The results of binary logis-tic regression analysis showed that gender,education level,birth and growth area,long-term living area,frequency of visiting Shenzhen,opinions of relatives and friends and monthly income were the influencing factors of medical treatment expectation of Hong Kong residents(P＜0.05).Conclusion:It is suggested that Hong Kong residents'sense of identity and trust in Shenzhen's healthcare should be enhanced,and that Shenzhen and Hong Kong should make innovations in the convergence of medical security systems,the supply of Hong Kong's medicines and devices in Shenzhen,so as to promote the integrated development of medical and health services in Shenzhen and Hong Kong,and jointly build a"health community"in the GBA.

Objective:To understand the expectations of Hong Kong residents to seek for medical treatment in Shenzhen and the influencing factors,so as to provide a reference for promoting the medical cooperation between Shenzhen and Hong Kong and the integration of medical services in Guangdong-Hong Kong-Macao Greater Bay Area.Methods:Based on the Anderson model,a questionnaire survey on medical expectations was conducted among 1 592 Hong Kong residents who sought medical treatment at the University of Hong Kong-Shenzhen Hospital.Binary logistic regression was used to analyze the influencing factors of medical ex-pectations in different dimensions.Results:The overall expectation score of Hong Kong residents for medical treatment in Shenzhen was 3.01,and the most important concern was the professionalism and accessibility of medical services.The results of binary logis-tic regression analysis showed that gender,education level,birth and growth area,long-term living area,frequency of visiting Shenzhen,opinions of relatives and friends and monthly income were the influencing factors of medical treatment expectation of Hong Kong residents(P＜0.05).Conclusion:It is suggested that Hong Kong residents'sense of identity and trust in Shenzhen's healthcare should be enhanced,and that Shenzhen and Hong Kong should make innovations in the convergence of medical security systems,the supply of Hong Kong's medicines and devices in Shenzhen,so as to promote the integrated development of medical and health services in Shenzhen and Hong Kong,and jointly build a"health community"in the GBA.

Objective To explore the value of diffusion tensor imaging analysis index along the perivascular space(DTI-ALPS)for assessing age-related functional changes in glymphatic system(GS).Methods Totally 27 healthy subjects from Meizhou People's Hospital and 100 healthy subjects from neuroimaging informatics tools and resources collaborator database who underwent T1-weighted magnetization-prepared rapid gradient echo(T1-MPRAGE)and DTI scanning were retrospectively enrolled and divided into youth group(n=38),middle-aged group(n=57)and elderly group(n=32).Automated DTI-ALPS index analysis procedure was used to minimize manual errors and derive DTI-ALPS index.The general data,neuropsychological assessment results and DTI-ALPS indices were compared among groups.Spearman correlation analysis was performed to observe the relationships of DTI-ALPS index and age,gender,as well as neuropsychological scores.Results The average age in youth group,middle-aged group and elderly group was(28.5±5.8),(53.7±6.8)and(73.8±2.3)years,respectively.No significant difference of DTI-ALPS index was found between middle-aged group and elderly group(P＞0.05),which were both lower than that in youth group(both P＜0.05).DTI-ALPS index was weakly negatively correlated with age(rs=-0.340,P＜0.001),but not significantly correlated with gender nor neuropsychological assessment results(both P＞0.05).Conclusion DTI-ALPS index was negatively correlated with age in healthy individuals,hence having potential utility for assessing age-related functional changes in GS.

Antibody-drug conjugates(ADCs)represent a breakthrough in precision therapy for breast cancer,offering a unique targeted drug delivery mechanism that enhances tumor selectivity while reducing the nonspecific toxicity associated with conventional chemotherapy.In recent years,the clinical applications of ADCs in breast cancer have expanded significantly,particularly in human epidermal growth factor receptor 2(HER2)-positive and HER2-low breast cancer,reshaping the therapeutic landscape.Trastuzumab emtanserin(T-DM1)was the first ADC drug to replace lapatinib plus capecitabine as a second-line treatment for HER2-positive breast cancer,while trastuzumab deruxtecan(T-DXd)demonstrated remarkable efficacy in HER2-low breast cancer in the DESTINY-Breast04 trial,becoming the first approved ADC for this patient subgroup.Furthermore,trophoblast cell surface antigen 2(Trop-2)-targeting ADCs,such as sacituzumab govitecan(SG),have shown promising clinical benefits in patients with triple-negative breast cancer(TNBC)and hormone receptor-positive/HER2-negative breast cancer.Advances in next-generation ADC technologies,including improvements in linker stability,drug-to-antibody ratio(DAR)optimization,and enhanced bystander effects,have further improved the therapeutic efficacy and safety profile of these agents,reinforcing their role in the precision treatment of breast cancer.Although ADCs have demonstrated substantial clinical benefits,they are associated with target-and payload-related toxicities.However,with ongoing advancements in management strategies,their safety profile has been significantly improved.HER2-targeting ADCs present specific adverse events,including interstitial lung disease(ILD)associated with T-DXd,thrombocytopenia,and liver function abnormalities observed with T-DM1,while Trop-2-targeting ADCs such as SG are linked to hematologic toxicity and gastrointestinal side effects.Notably,structural optimizations in next-generation ADCs have led to significant improvements in their safety profile.Early monitoring,individualized dose modifications,and supportive care measures have been shown to effectively reduce the incidence of severe adverse events.Clinical studies indicate that toxicity management strategies for ADCs have matured,with most adverse effects being effectively controlled through optimized treatment regimens and adjunctive supportive care.Thus,in clinical practice,it is essential to consider patient-specific factors,prior treatment history,and comorbidities to devise an optimal ADC treatment strategy that maximizes both efficacy and safety.As ADC technology continues to evolve,breast cancer treatment is expected to become increasingly precise.The development of novel HER2-Trop-2 bispecific ADCs offers new therapeutic options for patients with HER2-low and HER2-negative breast cancer.Additionally,studies investigating the combination of T-DXd with immune checkpoint inhibitors(ICIs),CDK4/6 inhibitors,and poly(ADP-ribose)polymerase(PARP)inhibitors have demonstrated synergistic antitumor effects,further expanding the prospects for precision medicine in breast cancer.This review systematically summarized the latest advancements in ADCs for breast cancer,with a focus on the clinical applications,safety management strategies,and future development of HER2-and Trop-2-targeting ADCs,aiming to provide valuable insights for the future of precision breast cancer treatment.

The intestine and liver are closely connected both physiologically and pathologically, forming a so-called gut-liver axis, with the gut microbiota serving as a pivotal link in their bidirectional communication. Gut microbiota dysbiosis and gut-liver axis disruption play a key role in the development and progression of colorectal cancer liver metastasis (CRLM), though the underlying mechanisms have not been clearly elucidated. Certain gut microbiota, such as Escherichia coli and Enterococcus spp., can breach the intestinal barrier and translocate to the liver, promoting the formation of pre-metastatic niche. Fusobacterium nucleatum and Enterococcus faecalis enhance tumor cell invasion/migration, while Parabacteroides spp. suppress anti-tumor immunity in the liver TME. Interventions like fecal microbiota transplantation, dietary modifications, and traditional Chinese medicine have shown potential in clinical and preclinical studies to improve patient outcomes by targeting the gut microbiota, but their long-term efficacy and safety require further investigation. Future research should focus on elucidating the effects of specific bacterial species, metabolites, viruses, and fungi on tumorigenesis. Exploring the potential of gut microbiota-based precision medicine and personalized therapies will improve risk stratification and enable more targeted interventions for CRLM patients.