Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

This article explores the construction and practice of the"Party Building+Health Science Popularization"model,using the"Yixian Health Science Popularization Guangdong Tour"campaign conducted by Sun Yat-sen Memorial Hospital as a case study.The initiative has achieved remarkable results.Additionally,it summarizes innovative measures,as well as uni-versal and exemplary experiences,providing new insights and pathway recommendations for public hospitals to develop the"Party Building+Health Science Popularization"model.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

This article explores the construction and practice of the"Party Building+Health Science Popularization"model,using the"Yixian Health Science Popularization Guangdong Tour"campaign conducted by Sun Yat-sen Memorial Hospital as a case study.The initiative has achieved remarkable results.Additionally,it summarizes innovative measures,as well as uni-versal and exemplary experiences,providing new insights and pathway recommendations for public hospitals to develop the"Party Building+Health Science Popularization"model.

Objective To summarize the clinical and genetic characteristics of children with sodium taurocholate co-transporting polypeptide(NTCP)deficiency.Methods Clinical data of children with NTCP deficiency diagnosed and treated at the First People's Hospital of Yunnan Province from July 2022 to March 2025 were retrospectively analyzed.Results A total of 14 children were included(6 males,8 females),all with normal growth and development.Reasons for initial consultation included elevated serum bile acids in 7 cases,jaundice in 4 cases,cholestatic hepatitis in 1 case,and one case each of pneumonia and cow's milk protein allergy.At the first visit,all patients had elevated serum total bile acids beyond the normal range,with a mean of 152.5 μmol/L.Elevated alanine aminotransferase was observed in 1 case,elevated aspartate aminotransferase in 2 cases,and elevated total bilirubin in 10 cases.Genetic sequencing revealed that all children carried the homozygous SLC10A1 variant c.800C>T(p.Ser267Phe),classified as likely pathogenic.Conclusions NTCP deficiency often lacks obvious clinical symptoms and signs.Some children present with transient hyperbilirubinemia,cholestasis,or other liver function abnormalities.Persistent isolated elevation of serum bile acids warrants suspicion for this disease.Biallelic pathogenic variants in SLC10A1 constitute the basis for definitive diagnosis.There is no specific treatment for this disease,and management is mainly symptomatic.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

AIM To evaluate the quality of Changmaile Capsules(Ⅰ).METHODS The analysis was performed on a 35℃ thermostatic Thermo Scientific AccucoreTM XL C18 column(4.6 mm×250 mm,4 μm),with the mobile phase comprising of methanol-acetonitrile-0.5% phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 230,280 nm.The contents of gastrodin,danshensu,quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside,3′-hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin,rosmarinic acid,lithospermic acid,ononin,daidzein,salvianolic acid B,calycosin,paeoniflorin and isoquercitrin were determined,after which HPLC fingerprints were established,along with the calculation of similarities.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 87.4%-103.9% with the RSDs of 0.54%-3.10% .At 230 nm,the fingerprints of ten batches of samples demonstrated similarities of 0.954-0.999,which displayed obvious differences at 280 nm.3′-Hydroxypuerarin,puerarin,3′-methoxypuerarin,puerarin apioside,daidzin and daidzein were main differential constituents,paeoniflorin and isoquercitrin exhibited stable contents in various batches of samples.CONCLUSION This simple,accurate and reliable method can be used for the quality control of Changmaile Capsules(Ⅰ).

Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.