Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Purpose To investigate the role of tumor-associated neutrophils(TANs)in the sternness characteris-tics of breast cancer cells.Methods Flow cytometry was used to identify and validate the successful generation of TANs.Breast cancer cell lines were co-cultured with TANs-conditioned supernatant,and their sphere-forming capacity was assessed.Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the expression of stem cell-associated markers.In breast cancer clinical specimens,immunohistochemistry(IHC)was performed to quantify TANs infiltration and the expression of sternness-related markers.Correlations be-tween TANs infiltration and sternness marker expression,as well as their associations with clinicopathological features of breast cancer patients,were analyzed.Results Flow cytometry results demonstrated a significantly higher survival rate of TANs compared to normal neutrophils(NEUs)(P＜0.05).In vitro,TANs-derived supernatant significantly en-hanced the sphere-forming capacity of breast cancer cells compared to NEU-derived supernatant(P＜0.05).RT-qPCR analysis revealed that the mRNA expression levels of sternness-related markers such as CD133 and SOX9 in tumor cells was significantly increased after TANs supernatant co-cultured with breast cancer cells(P＜0.05).The results of western blot further confirmed that the protein expression levels of CD133 and SOX9 were markedly increased in the TANs supernatant group relative to the NEU supernatant group(P＜0.01).Immunophenotypic analysis showed that the infiltration density of CD66b+TANs in breast cancer tissues was positively correlated with the expression of CD133(r=0.429,P＜0.001)and SOX9(r=0.561,P＜0.001)in tumor cells.Prognostic and clinicopathological analy-ses indicated that patients in the high CD66b+TANs infiltration group,high CD133 expression group,and high SOX9 expression group had significantly shorter progression-free survival(PFS)than those in the corresponding low-expres-sion/infiltration groups(P＜0.05).Furthermore,the infiltration density of CD66b+TANs was significantly associated with patient age,histological grade,and lymph node metastasis status(all with P＜0.05).CD133 expression was cor-related with patient age,lymph node metastasis,and progesterone receptor(PR)status(all with P＜0.05),while SOX9 expression was associated with patient age and lymph node metastasis status(all with P＜0.05).Conclusion TANs can promote the acquisition and maintenance of sternness characteristics in breast cancer cells.These findings may provide novel insights into the development of neutrophil-targeted immunotherapeutic strategies for breast cancer.

BACKGROUND:Currently,numerous observational studies have frequently associated dietary antioxidant intake and circulating antioxidant levels with osteoarthritis.Nevertheless,the underlying causal mechanisms remain unclear.Therefore,this study employs publicly available genome-wide association data to investigate the causal associations between antioxidant intake,circulating levels,and osteoarthritis,offering evidence for the prevention and treatment of osteoarthritis.OBJECTIVE:To assess the potential causal associations between dietary antioxidants(including vitamins A,C,E,and carotenoids)and circulating antioxidants(such as Glutathione S-transferase,glutathione peroxidase,catalase,superoxide dismutase,ascorbic acid,α-tocopherol,γ-tocopherol,albumin,uric acid,bilirubin,zinc,and selenium)with osteoarthritis through Mendelian randomization.METHODS:Data from genome-wide association studies on four dietary antioxidants and twelve circulating antioxidants were employed as exposure variables.The outcome variable was the osteoarthritis consortium dataset,which comprised 77 052 osteoarthritis cases and 378 169 healthy controls.Causal effects were evaluated using the inverse variance-weighted method,MR-Egger regression,and the weighted median approach.Stability and reliability of the findings were assessed through horizontal pleiotropy tests and sensitivity analyses.RESULTS AND CONCLUSION:(1)These results demonstrated that dietary vitamin C intake was inversely associated with knee osteoarthritis risk(OR=0.83,95%CI:0.71-0.96,P=0.015).Conversely,vitamin E intake was positively associated with knee osteoarthritis(OR=1.20,95%CI:1.05-1.34,P=0.004)and both knee and hip osteoarthritis(OR=1.15,95%CI:1.03-1.27,P=0.008).(2)Circulating antioxidant albumin levels were negatively associated with knee(OR=0.94,95%CI:0.91-0.97,P=0.001),hip(OR=0.95,95%CI:0.91-0.99,P=0.03),and knee or hip osteoarthritis(OR=0.95,95%CI:0.92-0.98,P=0.01).Uric acid levels were positively associated with knee osteoarthritis(OR=1.10,95%CI:1.03-1.17,P=0.003).(3)Sensitivity analyses yielded consistent results without evidence of horizontal pleiotropy.(4)European genome-wide data indicated that vitamin C intake was associated with a decreased risk of knee osteoarthritis,and lower serum albumin levels were associated with reduced risks of knee and hip osteoarthritis.In contrast,vitamin E intake and higher serum uric acid were associated with an increased risk of knee osteoarthritis.These findings support public health education and osteoarthritis interventions,indicating that serum albumin could be a potential biomarker for risk assessment.(5)The study underscores the role of certain antioxidants in osteoarthritis prevention and provides evidence to inform nutritional guidelines and public health strategies for the Chinese population.Furthermore,it contributes to biomarker research in arthritis,facilitating the development of early diagnostic tools and risk assessment strategies for the Chinese population.

Background:The incidence and mortality rates of severe acute pancreatitis(SAP)have been increasing year by year.Therefore,early and rapid identification,along with timely intervention in the progression of acute pancreatitis(AP),is of particular importance.Aims:To explore the value of red blood cell distribution width(RDW)combined with BISAP score in the early prediction of SAP.Methods:A total of 561 AP patients admitted from January 2019 to December 2021 at the General Hospital of the Central Theater Command of the PLA were enrolled and divided into SAP group and non-SAP group according to the disease severity.Venous blood samples were collected within 24 hours of admission.The relevant clinical data,laboratory indices,BISAP score,and MCTSI score were compared between the two groups.Logistic regression analysis was used to identify the risk factors for SAP.Spearman correlation coefficient was employed to assess the correlation of these risk factors with the severity of AP,as well as the correlation of RDW with BISAP score and MCTSI score.The predictive values of these risk factors for SAP were evaluated by ROC curve analysis.Results:Compared with the non-SAP group,the prevalence of hypertension,length and cost of hospital stay,neutrophil count(NEUT),neutrophil-to-lymphocyte ratio(NLR),RDW,serum potassium,aspartate transaminase(AST),blood urea nitrogen(BUN),serum creatinine(SCr),BISAP score and MCTSI score were significantly increased in the SAP group(all P<0.05),while the lymphocyte count(LYM),serum calcium and albumin(ALB)were significantly decreased(all P<0.05).RDW(OR=1.582,95%CI:1.066-2.348,P=0.023),SCr(OR=1.018,95%CI:1.001-1.035,P=0.040),BISAP score(OR=6.210,95%CI:3.121-12.356,P<0.001),and MCTSI score(OR=2.917,95%CI:2.160-3.939,P<0.001)were the independent risk factors for SAP.RDW(rs=0.320,P<0.001),SCr(rs=0.103,P=0.015),BISAP score(rs=0.516,P<0.001),and MCTSI score(rs=0.512,P<0.001)were positively correlated with the severity of AP.Moreover,RDW was positively correlated with BISAP score(rs=0.428,P<0.001)and MCTSI score(rs=0.408,P<0.001).ROC curve analysis revealed that the areas under the ROC curve of RDW,SCr,BISAP score,MCTSI score,and combination of RDW and BISAP score for predicting SAP were 0.753,0.581,0.889,0.888,and 0.905,respectively.Conclusions:RDW,SCr,BISAP score,and MCTSI score are the independent risk factors for SAP.RDW combined with BISAP score can enhance the predictive value for SAP.

To investigate the mechanism of action of Syngnathus extract in treating knee osteoarthritis of rats, forty-eight male SD rats were randomly divided into the blank group, model group, positive drug group, as well as low-dose, medium-dose, and high-dose groups of Syngnathus extract. The rat model of knee osteoarthritis was constructed by intra-articular injection of sodium iodoacetate. After successful modeling, celecoxib(18 mg·kg~(-1)·d~(-1)) and Syngnathus extract(0.4, 0.8, and 1.6 g·kg~(-1)·d~(-1)) were given in different groups by gavage intervention for two weeks. Hematoxylin-eosin(HE) staining was used to observe the histopathological changes of cartilage in knee joints, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression level of inflammatory factors in serum. Real-time fluorescence quantitative PCR, Western blot, and immunohistochemistry were used to detect the levels of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target protein of rapamycin(mTOR) pathway-related mRNA and protein expression. The results showed that, comparied with the blank group, the cartilage surface of the knee joints of rats in the model group was uneven, with disorganized levels and defective cartilage tissue. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) and the mRNA levels of PI3K, Akt, and mTOR in cartilage tissue, as well as the protein expression levels of phosphorylated PI3K(p-PI3K)/PI3K, phosphorylated Akt(p-Akt)/Akt, phosphorylated mTOR(p-mTOR)/mTOR, and P62 were significantly increased. Beclin1 protein expression was decreased. Comparied with the model group, the number of chondrocytes in the knee joint of rats in each group of Syngnathus extract increased, and the arrangement of chondrocytes was relatively neat. The cartilage layer was restored, and the serum levels of IL-1β, IL-6, and TNF-α, as well as the mRNA expression levels of PI3K, Akt, and mTOR in cartilage tissue were significantly reduced. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, and P62 were significantly reduced in the rats in the middle-dose and high-dose groups of Syngnathus extract, and the Beclin1 protein expression was significantly increased. The protein expression levels of p-PI3K/PI3K, p-Akt/Akt, and P62 in rats in the low-dose group of Syngnathus extract were significantly reduced. In summary, Syngnathus extract may be used to treat knee osteoarthritis by inhibiting the expression of PI3K/Akt/mTOR signaling pathway, so as to alleviate the inflammatory response in the organism, enhance the autophagy activity of chondrocytes, and reduce the apoptosis of chondrocytes.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Male ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans

This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

This study predicts the potential mechanism of Hippocampus in the treatment of knee osteoarthritis(KOA) through network pharmacology, with preliminary verification using molecular docking and animal experiments. The database was used to screen the active chemical components of Hippocampus and the targets of KOA, and Gene Ontology(GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and molecular docking were performed on the relevant core targets to preliminarily explore the potential targets and mechanisms of Hippocampus in the treatment of KOA. A rat KOA model was constructed by intra-articular injection of sodium iodoacetate, and the rats were intervened with different doses of Hippocampus decoction and celecoxib. The expression of relevant targets was detected through hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), RT-qPCR, and Western blot to further validate the network pharmacology results. A total of 23 drug-like components of the Hippocampus were screened, and 128 common targets with KOA were identified, involving interleukin-17(IL-17) signaling pathway, transcription factor(FoxO) signaling pathway, tumor necrosis factor(TNF) signaling pathway. Molecular docking results showed that the screened core chemical components exhibited good affinity with key targets. HE staining demonstrated that Hippocampus improved the morphology of the cartilage layer. ELISA confirmed that Hippocampus significantly reduced the levels of IL-6 and TNF-α in the serum of KOA rats. Western blot and RT-qPCR analysis showed that Hippocampus significantly reduced the expression of IL-6, TNF-α, matrix metalloproteinase(MMP) 13, IL-17A, nuclear factor κB activator 1(ACT1), tumor necrosis factor receptor-associated factor 6(TRAF6) and nuclear factor κB(NF-κB) in cartilage tissue. The results suggest that Hippocampus can alleviate the degree of joint damage in the KOA rat model induced by sodium iodoacetate. The mechanism of action is related to the inhibition of the IL-17 signaling pathway, reduction of inflammation, and inhibition of extracellular matrix(ECM) degradation.
Animals ; Molecular Docking Simulation ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Male ; Osteoarthritis, Knee/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Humans ; Interleukin-17/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Hippocampus/chemistry*

Dendrobium officinale(DO) is a traditional Chinese medicinal and edible plant, while it is critically endangered worldwide. This article, primarily based on the original research findings of the author's team and available articles, provides a comprehensive overview of the factors contributing to the endangerment of DO and the key technologies for the conservation, efficient cultivation, and value-added utilization of this plant. The scarcity of wild populations, low seed-setting rates, lack of endosperm in seeds, and the need for symbiosis with endophytic fungi for seed germination under natural conditions are identified as the primary causes for the rarity and endangerment of DO. Artificial seed production and tissue culture are highlighted as key technologies for alleviating the endangered status. The physiological and ecological mechanisms underlying the adaptation of DO to epiphytic growth are explored, and it is proposed that breaking the coupling of high temperature and high humidity is essential for preventing southern blight, a devastating affliction of DO. The roles of endophytic fungi in promoting the growth, improving the quality, and enhancing the stress resistance of DO are discussed. Furthermore, the integration of variety breeding, environment selection, and co-culture with endophytic fungi is emphasized as a crucial approach for efficient cultivation. The value-added applications of DO in pharmaceuticals, health foods, food products, and daily chemicals-particularly in the food and daily chemical industries-are presented as key drivers for a 10-billion-RMB-level industry. This systematic review offers valuable insights for the further development, utilization, and industrialization of DO resources, as well as for the broader application of conservation strategies for other rare and endangered plant species.
Dendrobium/microbiology* ; Endangered Species ; Seeds/microbiology* ; Fungi/physiology*

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors