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.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

It is considered that although meibomian gland dysfunction （MGD）-associated dry eye is mainly manifested by signs of dryness such as ocular dryness and burning sensation， it may also be accompanied by signs of dampness， including thick meibomian secretions， epigastric and abdominal fullness， and a greasy tongue coating， thus presenting a pattern characterized by the coexistence of dryness and dampness. Based on LIU Wansu's theory of "promoting the flow of dampness to moisten dryness"， this disease is understood from the perspectives of an imbalance between dryness and dampness in the middle jiao （焦） and abnormal distribution of body fluids. For dampness and turbidity constraint and stagnation， treatment should focus on diffusing the lung， fortifying the spleen， promoting the flow of dampness， and resolving turbidity， with modified Sanren Decoction （三仁汤） combined with Shenling Baizhu Powder （参苓白术散） commonly used. For steaming of dampness-heat， treatment should focus on clearing heat， draining dampness， and moistening dryness with sweet and cool medicinals， with modified Jinzhi Qingmu Formula （金栀清目方） combined with Shashen Maidong Decoction （沙参麦冬汤） commonly used. For dryness-toxin damaging the physical form， treatment should focus on nourishing yin and blood， unblocking the collaterals， and resolving toxins， with modified Qiju Dihuang Pill （杞菊地黄丸） combined with Taohong Siwu Decoction （桃红四物汤） commonly used.

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 investigate the effect of Atractylenolide Ⅰ(AtraⅠ)on chronic colitis rats by regulation of cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response binding protein(CREB)pathway.Methods Rats were randomly divided into control group,chronic colitis model group[model,free feeding with 2%dextran sulfate sodium(DSS)followed by 7 days of conventional drinking water alternatively for 42 days],AtraⅠ low(AtraⅠ-L,8.33 mg/kg AtraⅠ)and high(AtraⅠ-H,33.32 mg/kg AtraⅠ)intervention model group,positive drug(mesalazine)group(150 mg/kg mesalazine)and high concentration of AtraⅠ+cAMP inhibitor(SQ22536)group(33.32 mg/kg AtraⅠ+2.13 mg/kg SQ22536),18 rats in each group.Disease activi-ty index(DAI)and colon length were measured.HE staining was applied to detect pathological changes in colon tissue.Immunohistochemical staining was applied to detect the expression of zonula occluden-1(ZO-1)and mucin 2(MUC2)in colon tissue.ELISA was applied to detect level of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10 and cAMP in colon tissue.Western blot was applied to detect p-PKA and p-CREB proteins in colon tissue.Results Compared with the control group,the colon wall of the model group was edema and thickened,the number of inflammatory cell infiltration was increased,the colon length was shortened.DAI score and TNF-α and IL-6 level in the colon tissue were increased.The positive expression of MUC2 and ZO-1,the level of IL-10 and the protein of cAMP,p-PKA and p-CREB in colon tissues were decreased(P＜0.05).Compared with model group,the pathological damage of colon tissue in AtraⅠ-L group,AtraⅠ-H group,and mesalazine group was alleviated,the colon length increased,the DAI score reduced,level of TNF-α and IL-6 in colon tissue reduced and the posi-tive expression of MUC2 and ZO-1,level of IL-10,and cAMP,p-PKA,and p-CREB proteins in colon tissue were all elevated(P＜0.05).SQ22536 attenuated the improvement effect of AtraⅠ-H on intestinal mucosal barrier func-tion and the inhibitory effect on inflammatory response in rats with chronic colitis.Conclusions AtraⅠ improves intestinal mucosal barrier function and inhibits inflammation in rats with chronic colitis,and its mechanism may be related to the upregulation of the cAMP/PKA/CREB pathway.

Flowering and bolting are important agronomic traits in cruciferous crops such as Brassica juncea. Timely flowering can ensure the crop organ yield and quality, as well as seed propagation. The WRKY family plays an important role in regulating plant bolting and flowering, while the function and mechanism of WRKY12 in B. juncea remain unknown. To explore its function and mechanism in bolting and flowering of B. juncea, we cloned and characterized the BjuWRKY12 gene in B. juncea and found that its expression levels were significantly higher in flowers and inflorescences than in leaves. BjuWRKY12 belonged to the Ⅱc subfamily of the WRKY family, and subcellular localization indicated that the protein was located in the nucleus. Ectopic overexpression of BjuWRKY12 in transgenic lines promoted bolting and flowering, leading to significant increases in the expression levels of flowering integrators SOC1 and FUL. Furthermore, yeast one-hybrid and dual luciferase reporter system assays confirmed that BjuWRKY12 directly bound to the promoters of BjuSOC1 and BjuFUL, undergoing protein-DNA interactions. This discovery gives new insights into the regulation network and molecular mechanisms of BjuWRKY12, laying a theoretical foundation for the breeding of high-yield and high-quality varieties of B. juncea.
Mustard Plant/metabolism* ; Flowers/growth & development* ; Plant Proteins/physiology* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/genetics* ; Transcription Factors/metabolism* ; MADS Domain Proteins/metabolism*

Objective:To analyze the gallbladder morphology in ultrasound examinations of children with biliary atresia, classify them accordingly, and compare the gallbladder size of different types of patients and healthy infants.Methods:Clinical data of 711 cases with biliary atresia treated at the Department of General Surgery at the Capital Center for Children's Health, Capital Medical University from January 2017 to July 2022 were retrospectively analyzed, including 407 males and 304 females, aged (46.5±26.9) days. Additionally, 106 healthy infants recruited from the same hospital between January 2024 and March 2024 were included in the control group, including 60 males and 46 females, aged (48.5±23.9) days. The gallbladder morphology was classified into four types (A, B, C and D) based on its size and shape on ultrasonography. The long diameter of the gallbladder gradually increased, with its shape gradually approaching normal. The proportions of gender, time of jaundice onset (calculated from birth), total bilirubin, direct bilirubin, γ-glutamyl transferase (γ-GT), gallbladder contraction rate, hepatic portal cyst, and cholangiography were compared among different types. The gallbladder length and width of type D were also compared with those of the healthy control group.Resluts:Among the 711 patients, 123(17.3%) were of type A, 330 (46.4%) were of type B, 112 (15.8%) were of type C, and 146 (20.5%) were of type D. There were no statistically significant differences in the male ratio, the timing of jaundice onset, total bilirubin levels, direct bilirubin levels, or γ-GT levels among the four types of patients (all P>0.05). However, the incidences of combined hepatic portal cysts in type C and D were higher than those in type A and B (all P<0.01). Notably, 68.5% (100/146) of type D patients had a gallbladder contraction rate of ≤25%, lower than the 91.8% (303/330) of type B and 95.5% (107/112) of type C ( χ2=42.41, 29.22, both P<0.001). The success rates of cholangiography for type C and D patients were 75.0% (84/112) and 76.7% (112/146), respectively, both higher than the 11.4% (14/123) for type A and 45.2% (149/330) for type B (all P<0.001). In the healthy control group, the length and width of gallbladder were larger than those in type D patients ( t=10.64, 11.62, both P<0.001). Conclusion:The ultrasonic gallbladder morphology in biliary atresia patients is diverse, and there are no significant clinical differences among the four types. However, there are differences in gallbladder contraction rates and the success rates of gallbladder imaging. The gallbladder length and width of type D patients, with a nearly normal gallbladder morphology, are smaller than those of healthy infants at the same age.

Laparoscopic pancreaticoduodenectomy(LPD) poses a high risk of intraoperative bleeding due to the complex anatomy and rich blood supply in the pancreatic head region. This paper innovatively proposes a blood flow control technique system for LPD, adopting a strategy of “priority devascularization and pre-blocking”.By first addressing the peripheral collateral blood supply and the gastroduodenal artery, and then performing dual-system pre-blocking, the dorsal pancreatic artery and the inferior pancreaticoduodenal artery are treated in situ through a combined middle and left posterior approach. This progressive blood flow control method enhances surgical safety and oncological radicality, offering a new paradigm for the development of minimally invasive pancreatic surgery.

Objective To investigate the histological and cellular bases for the improvement of portal hypertension(PH)by observing liver histopathological changes after treatment in patients with cirrhotic portal hypertension,and to provide a basis for clinical drug development.Methods A total of 322 patients with hepatitis B cirrhosis who completed 48 weeks of antiviral therapy or combined anti-fibrotic treatment in 20 hospitals across 12 provinces in China from September 2014 to October 2018 were enrolled,and the noninvasive diagnostic criteria for clinically significant portal hypertension(CSPH)from Baveno Ⅶ were used to assess the severity of PH;43 patients with a confirmed diagnosis of CSPH were identified based on liver stiffness measurement(LSM)≥25 kPa before treatment,and according to whether the severity of PH was reduced by≥2 grades after treatment,the patients were divided into PH improvement(n=19)group and PH non-improvement group(n=24).Related data were collected,including demographic data,laboratory tests.Liver fibrosis were assessed,including HE staining and reticular fiber staining;liver microvascular lesions were assessed,including obliterative portal venopathy(OPV),nodular regenerative hyperplasia(NRH),and incomplete septal fibrosis(ISF).Single immunohistochemical staining was performed for von Willebrand factor(vWF),and fibronectin;multiplex immunohistochemical staining was performed for fibrinogen,CD32b,CD31,alpha-smooth muscle actin(α-SMA).The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results After 48 weeks of treatment,43 patients had significant improvements in red blood cell count,alanine aminotransferase,aspartate aminotransferase,aspartate aminotransferase-to-platelet ratio index score,liver fibrosis grade,and PH grade(all P<0.05),among whom 19 patients showed a reduction in PH severity by≥2 grades(PH improvement group),while the remaining patients were enrolled as the PH non-improvement group.There was no significant difference in the outcome of liver fibrosis between the two groups(χ2=3.380,P=0.066).Microvascular lesion assessment showed that compared with the PH non-improvement group,the PH improvement group had significantly lower OPV severity,microvascular density(the expression level of vWF),and expression of fibronectin(all P<0.05),while there were no significant differences in NRH severity,ISF severity,and the expression level of fibrinogen between the two groups(all P>0.05).Cytological evaluation showed no significant differences in the expression levels of CD32b,CD31,and α-SMA between the two groups before and after treatment(all P>0.05),and comparison of the expression levels before and after treatment showed that the PH improvement group had a significant increase in the expression level of CD32b(t=-2.007,P=0.045)and a significant reduction in the expression level of α-SMA(t=2.628,P=0.013).Conclusion The pathological features of PH improvement are associated with liver fibrosis regression and the improvement in liver microvascular lesions,and at the cellular level,PH improvement is associated with the dedifferentiation of liver sinusoidal endothelial cells and the activated phenotype of hepatic stellate cells.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.