ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer （CRC） and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit， followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group， low-dose Xianlian Jiedu prescription （XLJDP-L） group （6.45 g·kg^-1·d^-1）， medium-dose Xianlian Jiedu prescription （XLJDP-M） group （12.9 g·kg^-1·d^-1）， high-dose Xianlian Jiedu prescription （XLJDP-H） group （25.8 g·kg^-1·d^-1）， and 5-fluorouracil （5-FU） group （1×10^-3 g·kg^-1·d^-1）. The mice were euthanized after 14 days of continuous intervention， and recurrent tumor tissue was harvested. Hematoxylin and eosin （HE） staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry （IHC） was employed to assess the expression of proliferating cell nuclear antigen （Ki67）， vascular endothelial growth factor （VEGF）， and platelet-endothelial cell adhesion molecule （CD31） in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 （ANG-2）， VEGF， phosphorylated-protein kinase B （p-Akt）， protein kinase B （Akt）， phosphorylated-phosphatidylinositol 3-kinase （p-PI3K）， and phosphatidylinositol 3-kinase （PI3K） in recurrent tumor tissue. ResultsBefore treatment， there were no statistical differences in tumor volume， tumor weight， and body mass among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group， indicating model stability. After treatment， compared with those in the model group， the tumor volume and tumor weight in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01）， showing dose dependency. Meanwhile， there were no significant differences in body weight among the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group， tumor tissue in the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group had loosely arranged cells， increased intercellular spaces， small and shriveled nuclei， light staining， fewer mitotic figures and atypical nuclei， and increased necrotic areas. IHC showed that compared with those of the model group， the positive rates of Ki67， VEGF， and CD31 in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly reduced （P<0.01） in a dose-dependent manner. Western blot results showed that compared with those of the model group， the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L， XLJDP-M， and XLJDP-H groups and the 5-FU group were significantly downregulated （P<0.05， P<0.01）， and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner （P<0.05， P<0.01）. ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2， VEGF， and CD31.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.

AIM To study the chemical constituents from the stems and barks of Maytenus variabilis(Hemsl.)C.Y.Cheng.METHODS The 95％ethanol extract from the stems and barks of M.variabilis was isolated and purified by silica gel,Sephadex LH-20 and semi preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as β-amyrin(1),3β-acetoxyolean-12-en-11-one(2),ursa-12-ene-11-one-3-ol octocosate(3),friedelin(4),canophyllol(5),pinoresinol(6),medioresinol(7),isolariciresinol(8),dihydrodehydrodiconiferyl alcohol(9),vanillic acid(10),7R,8S-5-methoxydihydrodehydroconiferyl alcohol(11),β-hydroxypropiovanillone(12),triptregeline B(13),triptregeline E(14),(+)-evofolin B(15),2,5-dimethoxybenzoquinone(16),olean-12-ene-3,11-dione(17),β-sitosterol(18),(-)-(7R,7'R,7"S,8S,8'S,8"S)-4',4"-dihydroxy-3,3',3",5-tetramethoxy-7,9',7',9-diepoxy-4,8"-oxy-8,8'-sesquineolignan-7",9"-diol(19),phyllostadimer B(20),rayalinol(21),lyoniresinol(22),dihydrobuddlenol B(23).CONCLUSION Compounds 3,9-11,13-14,16,19-21,23 are isolated from genus Maytenus for the first time,and compounds 2,4-5,7-8,12,15,17,22 are first found from this plant.

AIM To study the chemical constituents of Anaphalis margaritacea(L.)Benth.& Hook.f.and their antioxidant activities.METHODS Separation and purification were performed using silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH method and ABTS method.RESULTS Twenty-three compounds were isolated and identified as trans-tilidroside(1),4'-hydroxydehydrokawain(2),apigenin(3),3-O-kaempferol-3-O-acetyl-6-O-(p-coumamoyl)-α-D-glucopyranoside(4),kaempferol(5),quercetin-3-O-β-D-(6-O-Z-p-coumamoyl)-glucopyranoside(6),tiliroside(7),kaempferol-3-O-β-D-glucoside(8),3,5-dihydroxy-7,8-dimethoxyflavone(9),bis(2-ethylhexyl)adipate(10),3,5-dihydroxy-6,7,8-trimethoxyflavone(11),stigmasterol(12),myriophylloside B(13),1-hexadecanol(14),chlorogenic acid(15),4-hydroxy-N-{ 4-[3-(4-hydroxyphenyl)-E-acryloylamino]-butyl}-benzamide(16),3,6-dimethylpiperazine-2,5-dione(17),β-adenosine(18),5,6-dehydrokawain(19),kaempferol-3-O-(2",6"-di-O-E-p-coumaroyl)-β-D-glucopyranoside(20),kaempferol-3-O-(3"-O-E-p-coumaroyl)-(6"-O-E-feruloyl)-β-D-glucopyranoside(21),4,5-di-caffeoylquinic acid butyl ester(22),3,4-di-caffeoylquinic acid butyl ester(23).The IC50 values of compounds 1,7,22-23 against DPPH free radicals were(24.67±1.63)-(53.41±1.61)μmol/L,and the IC50 values of compounds 8,21-23 against ABTS+free radicals were(15.22±0.89)-(41.66±6.29)μmol/L.CONCLUSION Compounds 9,19-23 are isolated from genus Anaphalis for the first time,and 2,10,13,14,16,17,19-23 are first isolated from this plant.Compounds 1,7-8,21-23 have strong antioxidant activity.

Objective To analyze the impact of sarcopenia on the efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer.Methods Patients with locally advanced or metastatic gastric cancer confirmed by pathology who were not eligible for radical surgery were selected as study subjects.A body composition analyzer was used to measure the appendicular muscle mass of the patients and calculate the skeletal muscle mass index(SMI).Based on the SMI,the patients were divided into sarcopenia group and non-sarcopenia group.On the basis of nutritional intervention and comprehensive exercise therapy,the patients were administered immu-notherapy combined with chemotherapy.The efficacy and adverse reactions were evaluated.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were the objec-tive response rate(ORR)and treatment-related adverse reactions.Results A total of 52 gastric cancer patients were included,with 23 in the sarcopenia group and 29 in the non-sarcopenia group.The median PFS in the non-sarcopenia group was 9.8 months(95％CI,8.9 to 12.4),and was 5.4 months in the sarcopenia group(95％CI,4.9 to 8.1).The median PFS in the non-sarcopenia group was longer than that in the sarcopenia group,and the difference was statistically significant[HR(95％CI)=0.41(0.23 to 0.73),P=0.003].The results of the multivariate Cox propor-tional hazards regression model showed that comorbidities,treatment cycles,and sarcopenia were all independent prognostic factors affecting the PFS of gastric cancer patients(P＜0.05).The ORR in the non-sarcopenia group was 48.28％(14/29),and was 17.39％(4/23)in the sarcopenia group(x2=5.276,P＜0.05).Treatment-related adverse reactions with grading ≥3 in both groups were mainly hematological toxicities.In the non-sarcopenia group,the incidence of grading ≥ 3 treat-ment-related adverse reactions was 27.59％(8/29),and the incidence of grading＜3 treatment-re-lated adverse reactions(including those with no adverse reactions)was 72.41％(21/29).In the sarcopenia group,the incidence of grading ≥3 treatment-related adverse reactions was 56.52％(13/23),and the incidence of grading＜3 treatment-related adverse reactions(including those without adverse reactions)was 43.48％(10/23).The incidence of grading ≥3 treatment-related adverse reactions in the non-sarcopenia group was lower than that in the sarcopenia group(P=0.035).Conclusion For patients with locally advanced or metastatic gastric cancer complicated with sarcopenia,the median PFS of immunotherapy combined with chemotherapy is shorter,the ORR is lower,and the incidence of treatment-related adverse reactions is increased.Therefore,ear-ly intervention for sarcopenia should be implemented to improve the quality of life of patients with advanced gastric cancer.

Objective:To compare the efficacy of in situ repair and conversion to full-thickness repair in patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears. Methods:A retrospective analysis was performed on 81 patients who underwent shoulder arthroscopic surgery due to Ellman grade III partial tears on the rotator cuff bursa side in Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022, according to the different intraoperative supraspinatus tendon repair methods, the patients were divided into the in situ repair group ( n=44) and the partial-to-full-thickness repair group ( n=37). Patients in the in situ repair group were treated with in situ repair for supraspinatus tendon repair, while those in the partial-to-full-thickness repair group were treated with partial-to-full-thickness repair for supraspinatus tendon repair. The general information, pain visual analogue scale (VAS) score, University of California, Los Angeles (UCLA) shoulder joint score and Constant score of the patients were compared and analyzed; the operation time, number of anchors used, and rotator cuff re-tear rate 1 year after surgery were compared and analyzed. The measurement data were expressed as mean ± standard deviation ( ± s), and comparisons between groups were performed using the independent samples t-test. The count data were expressed as the number of cases and percentages, and comparisons between groups were performed using the Chi-square test. Results:All 81 patients completed the follow-up. One year after surgery, the pain VAS scores of the in situ repair group and the partial-to-full-thickness repair group were 1.48±1.07 and 1.38±0.83, respectively, with no significant statistical difference ( P=0.647). The UCLA shoulder joint score and Constant score in the in situ repair group were 30.09±1.46 and 83.05±10.94, respectively, and those in the partial-to-full-thickness repair group were 30.46±1.04 and 84.95±9.20, respectively, there were no significant statistical difference ( P=0.203, 0.405). There was no significant statistical difference in the operation time between the in situ repair group and the partial-to-full-thickness repair group ( P=0.276), but the partial-to-full-thickness repair group was about 11.5 min slower on average. The number of anchors used in the in situ repair group (1.86±0.88) was significantly less than that in the partial-to-full-thickness repair group (2.51±0.65), and the difference was statistically significant ( P<0.001). There was no significant statistical difference in the re-tear rate between the two groups 1 year after surgery ( P=0.625). Conclusions:For patients with partial tears of the supraspinatus tendon bursa side in rotator cuff tears, both in situ repair and partial-to-full-thickness repair can achieve good clinical results, but conversion to full-thickness repair requires longer operation time and more anchors. The choice of specific surgical method needs to be determined based on the patient′s condition and the doctor′s technical proficiency.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.