ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

Objective To explore the risk factors associated with the occurrence of dampness syndrome based on peripheral blood multiple laboratory indicators,construct predictive model and validate it.Methods A retrospective analysis was conducted on 180 patients who visited the Preventive Treatment Center of Guangdong Provincial Hospital of Chinese Medicine from May 2022 to December 2023.They were divided into two groups according to the diagnostic criteria:the damp syndrome of TCM group(n=118)and the balanced yin-yang constitution group(n=62),with the latter serving as the"non-syndrome"control group for dampness syndrome.Serum biochemical indicators were detected by electrochemiluminescence(ECL),immune cell subsets were analyzed through flow cytometer,and routine blood parameters were assessed using an automatic hematology analyzed.Logistic regression analysis was employed to screen risk factors and develop a predictive model.The Bootstrap method was used for data resampling to draw the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA)to evaluate the predictive value,consistency,and clinical efficacy of the model.Results Compared with the balanced yin-yang constitution group,the damp syndrome of TCM group showed increased levels of insulin(INS),non-high-density lipoprotein cholesterol(non HDL-C),red blood cells(RBC)and the proportion of CD4+T cells,the proportion of triglyceride(TG)>1.70 mmol/L,total cholesterol(TC)>5.20 mmol/L,low-density lipoprotein cholesterol(LDL-C)>3.37 mmol/L,and high-density lipoprotein cholesterol(HDL-C)≤1.15 mmol/L were also significantly higher,with statistical significance(U/t/χ2=-2.900～4 626,all P＜0.05).Logistic regression analysis showed that INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and the proportion of CD4+T cells were independent risk factors for the occurrence of damp syndrome of TCM(all P＜0.05).Based on the screened risk factors,a forecasting model was established and a nomogram was plotted.The model had an area under the ROC curve area under curve(AUC)of 0.747(95%CI=0.672～0.822),a Brier score of 0.184 for the calibration curve,and demonstrated clinical net benefit at threshold probabilities ranging from 0.30 to 1.00.Conclusion The forecasting model constructed based on INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and CD4+T cells ratio has a high predictive value for damp syndrome of TCM.

Breast cancer is the most prevalent malignant tumor that poses a threat to women's health in China,with incidence and mortality rates persistently increasing.Given this critical situation,there is an urgent need to optimize therapeutic options through basic translational research to address current treatment challenges.This article provided a comprehensive overview of the significant advancements in fundamental translational breast cancer research in China over the past five years,aiming to provide a scientific basis and new directions for precision treatment of breast cancer.This research encompasses a range of subjects,including molecular typing,biomarker identification,exploration of drug resistance mechanisms,optimization of precision treatment strategies,and identification of new targets in breast cancer.In the domain of molecular typing,researchers have revealed substantial disparities in treatment responses among distinct subtypes of breast cancer through in-depth analysis.This has led to the proposal of specific therapeutic strategies for each subtype,thereby establishing a robust theoretical foundation for individualized treatment approaches.The identification of biomarkers plays a pivotal role in selecting appropriate treatment options for patients.Recent research advancements have demonstrated the potential of liquid biopsy and proteomics technologies in uncovering promising biomarkers,offering novel prospects for the early diagnosis and prognostic assessment of breast cancer.In the investigation of resistance mechanisms,researchers have elucidated the molecular underpinnings of resistance to endocrine therapy and human epidermal growth factor receptor 2(HER2)-targeted therapy and proposed potential strategies to overcome resistance.This has paved the way for novel approaches to enhance therapeutic efficacy.In the context of immunotherapy and targeted therapies,the discernment of novel targets and biomarkers has facilitated novel perspectives on breast cancer treatment.Based on advanced comprehension of tumor heterogeneity,researchers constantly optimize precision treatment strategies through multiomics analysis,thus offering patients with breast cancer enhanced personalized treatment options.Concurrently,the implementation of novel technologies has been instrumental in facilitating the advancement of precision treatment for breast cancer.For instance,the application of artificial intelligence technology has demonstrated considerable potential in the early screening,diagnosis,efficacy assessment and prognosis prediction of breast cancer.Conversely,the advent of innovative drug delivery systems facilitated by nanotechnology has led to enhanced targeting and efficacy of pharmaceutical agents.Furthermore,research into hydrogel patch technology and tumor vaccines has yielded novel strategies for the treatment of breast cancer.Overall,China has accomplished remarkable achievements in the field of basic translational research on breast cancer.These findings not only enhance our understanding of the molecular mechanisms of breast cancer,but also provide new directions and hope for the development of future therapeutic strategies.With the advancement of multidisciplinary integration and the application of new emerging technologies,precision therapy is expected to provide more benefits to breast cancer patients.

Breast cancer is the most prevalent malignant tumor that poses a threat to women's health in China,with incidence and mortality rates persistently increasing.Given this critical situation,there is an urgent need to optimize therapeutic options through basic translational research to address current treatment challenges.This article provided a comprehensive overview of the significant advancements in fundamental translational breast cancer research in China over the past five years,aiming to provide a scientific basis and new directions for precision treatment of breast cancer.This research encompasses a range of subjects,including molecular typing,biomarker identification,exploration of drug resistance mechanisms,optimization of precision treatment strategies,and identification of new targets in breast cancer.In the domain of molecular typing,researchers have revealed substantial disparities in treatment responses among distinct subtypes of breast cancer through in-depth analysis.This has led to the proposal of specific therapeutic strategies for each subtype,thereby establishing a robust theoretical foundation for individualized treatment approaches.The identification of biomarkers plays a pivotal role in selecting appropriate treatment options for patients.Recent research advancements have demonstrated the potential of liquid biopsy and proteomics technologies in uncovering promising biomarkers,offering novel prospects for the early diagnosis and prognostic assessment of breast cancer.In the investigation of resistance mechanisms,researchers have elucidated the molecular underpinnings of resistance to endocrine therapy and human epidermal growth factor receptor 2(HER2)-targeted therapy and proposed potential strategies to overcome resistance.This has paved the way for novel approaches to enhance therapeutic efficacy.In the context of immunotherapy and targeted therapies,the discernment of novel targets and biomarkers has facilitated novel perspectives on breast cancer treatment.Based on advanced comprehension of tumor heterogeneity,researchers constantly optimize precision treatment strategies through multiomics analysis,thus offering patients with breast cancer enhanced personalized treatment options.Concurrently,the implementation of novel technologies has been instrumental in facilitating the advancement of precision treatment for breast cancer.For instance,the application of artificial intelligence technology has demonstrated considerable potential in the early screening,diagnosis,efficacy assessment and prognosis prediction of breast cancer.Conversely,the advent of innovative drug delivery systems facilitated by nanotechnology has led to enhanced targeting and efficacy of pharmaceutical agents.Furthermore,research into hydrogel patch technology and tumor vaccines has yielded novel strategies for the treatment of breast cancer.Overall,China has accomplished remarkable achievements in the field of basic translational research on breast cancer.These findings not only enhance our understanding of the molecular mechanisms of breast cancer,but also provide new directions and hope for the development of future therapeutic strategies.With the advancement of multidisciplinary integration and the application of new emerging technologies,precision therapy is expected to provide more benefits to breast cancer patients.

OBJECTIVES: To examine the changes in serum levels of endoplasmic reticulum stress (ERS) proteins GRP78/CHOP in patients with lupus nephritis (LN) and analyze their diagnostic value and association with renal pathological features. METHODS: From a sample bank established based on a multicenter cohort study of systemic lupus erythematosus (SLE), 60 LN patients and 35 SLE patients without renal involvement were randomly selected. ELISA was used to detect serum levels of GRP78 and CHOP in the patients to analyze their correlation with clinical features and their diagnostic ability for LN and active LN. MRL/lpr mice were used as an animal model of LN to examine their serum levels of GRP78 and CHOP expression and renal expressions of endoplasmic reticulum apoptosis-related proteins. RESULTS: Serum GRP78 and CHOP levels were significantly higher in LN patients than in SLE patients without renal involvement (P<0.05), and were also higher in active LN patients than in patients in the stable phase (P<0.05). Correlation analysis indicated that serum GRP78 and CHOP levels were positively correlated with SLEDAI scores and 24-h urinary protein. ROC analysis showed that CHOP had a high diagnostic ability for LN (AUC=0.762) and active LN (AUC=0.933). Consistent with the clinical findings, serum GRP78 and CHOP levels were elevated in LN mice, and the expressions of PERK and IRE1α pathway proteins were also increased in the kidneys of the mice. TUNEL staining showed increased renal cell apoptosis and elevated renal expressions of apoptosis-related proteins in LN mice. CONCLUSIONS Serum levels of GRP78/CHOP are increased in LN patients possibly in association with ERS-induced apoptosis mediated by the PERK/IRE1α dual pathway.
Endoplasmic Reticulum Chaperone BiP ; Lupus Nephritis/blood* ; Transcription Factor CHOP/blood* ; Heat-Shock Proteins/blood* ; Animals ; Apoptosis ; Humans ; Mice ; Mice, Inbred MRL lpr ; Female ; Adult ; Endoribonucleases/metabolism* ; Male ; eIF-2 Kinase/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Young Adult ; Endoplasmic Reticulum Stress ; Kidney/metabolism* ; Middle Aged ; Signal Transduction

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To explore the risk factors associated with the occurrence of dampness syndrome based on peripheral blood multiple laboratory indicators,construct predictive model and validate it.Methods A retrospective analysis was conducted on 180 patients who visited the Preventive Treatment Center of Guangdong Provincial Hospital of Chinese Medicine from May 2022 to December 2023.They were divided into two groups according to the diagnostic criteria:the damp syndrome of TCM group(n=118)and the balanced yin-yang constitution group(n=62),with the latter serving as the"non-syndrome"control group for dampness syndrome.Serum biochemical indicators were detected by electrochemiluminescence(ECL),immune cell subsets were analyzed through flow cytometer,and routine blood parameters were assessed using an automatic hematology analyzed.Logistic regression analysis was employed to screen risk factors and develop a predictive model.The Bootstrap method was used for data resampling to draw the receiver operating characteristic(ROC)curve,calibration curve,and clinical decision curve analysis(DCA)to evaluate the predictive value,consistency,and clinical efficacy of the model.Results Compared with the balanced yin-yang constitution group,the damp syndrome of TCM group showed increased levels of insulin(INS),non-high-density lipoprotein cholesterol(non HDL-C),red blood cells(RBC)and the proportion of CD4+T cells,the proportion of triglyceride(TG)>1.70 mmol/L,total cholesterol(TC)>5.20 mmol/L,low-density lipoprotein cholesterol(LDL-C)>3.37 mmol/L,and high-density lipoprotein cholesterol(HDL-C)≤1.15 mmol/L were also significantly higher,with statistical significance(U/t/χ2=-2.900～4 626,all P＜0.05).Logistic regression analysis showed that INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and the proportion of CD4+T cells were independent risk factors for the occurrence of damp syndrome of TCM(all P＜0.05).Based on the screened risk factors,a forecasting model was established and a nomogram was plotted.The model had an area under the ROC curve area under curve(AUC)of 0.747(95%CI=0.672～0.822),a Brier score of 0.184 for the calibration curve,and demonstrated clinical net benefit at threshold probabilities ranging from 0.30 to 1.00.Conclusion The forecasting model constructed based on INS,TC>5.20 mmol/L,HDL-C≤1.15 mmol/L,and CD4+T cells ratio has a high predictive value for damp syndrome of TCM.

Objective:To investigate molecular mechanisms underlying the inflammatory response induced by Cutibacterium acnes ( C. acnes) biofilms in human primary keratinocytes. Methods:A C. acnes biofilm model was established in vitro, and confocal fluorescence microscopy was performed to examine its three-dimensional structure. The cultured human primary keratinocytes were divided into 3 groups: a dimethyl sulfoxide (DMSO) control group (treated with 0.01% DMSO alone), a C. acnes suspension group (co-incubated with C. acnes suspensions), and a C. acnes biofilm group (co-incubated with C. acnes biofilms). Real-time fluorescence-based quantitative PCR (RT-qPCR) was performed to determine the relative mRNA expression of interleukin (IL) -6, IL-8, and tumor necrosis factor (TNF) -α in the groups after 6-hour culture, enzyme-linked immunosorbent assay to detect the free protein levels of IL-6, IL-8, and TNF-α in the groups after 24-hour culture, and Western blot analysis to determine the protein expression of Toll-like receptor 2 (TLR2) in keratinocytes. In addition, some human primary keratinocytes were pretreated with key molecular blockers targeting the TLR2/mitogen-activated protein kinase (MAPK) /nuclear factor (NF) -κB signaling pathway (C29, ST2825, BAY11-7082, SB203580, U0126-EtOH), and then co-incubated with C. acnes biofilms; the DMSO control group and the C. acnes biofilm group receiving no pretreatment were simultaneously set as negative and positive controls, respectively. The mRNA and free protein expression levels of IL-6, IL-8, and TNF-α were then detected in the above groups. One-way analysis of variance was used for comparisons among multiple groups, and the Bonferroni method was used for multiple comparisons. Results:Confocal fluorescence microscopy demonstrated a three-dimensional C. acnes biofilm structure resembling a lawn, and the biofilm grew well. RT-qPCR and ELISA showed significant differences in the mRNA and free protein expression levels of IL-6, IL-8, and TNF-α among the C. acnes biofilm group, C. acnes suspension group and DMSO control group (mRNA: F = 89.70, 312.17, 46.09, respectively, all P < 0.001; free protein: F = 886.12, 634.25, 307.01, respectively, all P < 0.001) ; in detail, the mRNA and free protein expression levels of IL-6, IL-8, and TNF-α were significantly higher in the C. acnes biofilm group than in the C. acnes suspension group and DMSO control group (all P < 0.001) ; the C. acnes suspension group showed significantly increased expression levels of IL-6 mRNA and TNF-α free protein compared with the DMSO control group ( P < 0.001, = 0.003, respectively), while there were no significant differences in the expression of IL-6 free protein, TNF-α mRNA, or IL-8 mRNA and free protein between the 2 groups (all P > 0.05). Western blot analysis showed that the TLR2 protein expression was significantly higher in the C. acnes suspension group and C. acnes biofilm group than in the DMSO control group. After the pretreatment with molecular blockers targeting the MAPK/NF-κB signaling pathway and co-incubation with C. acnes biofilms, the mRNA and free protein expression levels of IL-6, IL-8 and TNF-α were all significantly lower in the C29 group, ST2825 group, BAY11-7082 group, SB203580 group, U0126-EtOH group, as well as in the DMSO control group compared with the C. acnes biofilm group (all P < 0.05) . Conclusion:The C. acnes biofilms exhibited a strong ability to induce inflammatory responses in human keratinocytes, possibly through the activation of the TLR2/MAPK/NF-κB signaling pathway.

Objective:This study aimed to explore and put forward adaptive methods for implementing S&T (Science and Technology) evaluation reform in health science, according to the development requirements of achieving high level scientific and technological self-reliance and self-improvement.Methods:This article used theoretical research and policy analysis to summarize the reform requirements of S&T evaluation and proposed the methodology of S&T evaluation in health science by comparative analysis with the main S&T evaluations of typical countries.Results:A five-step evaluation framework for health science was proposed, including classifying achievements, determining evaluation methods, clarifying value judgment, selecting evaluation contents, and applying evaluation results.Conclusions:Besides the evaluation method framework, implementing the S&T evaluation reforms in health science needed to promote the consensus evaluation ecology in some aspects comprehensively, i. e., evaluating subject, pathway and method, value orientation and purpose, etc.