BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

In recent years, the prevalence of obstructive coronary artery disease has continued to rise. Despite the widespread application of strategies such as intensive pharmacotherapy, coronary artery bypass grafting, or percutaneous coronary intervention, a subset of patients still experience recurrent angina symptoms, which severely impacts their quality of life. For such cases of refractory angina (RA), researchers domestically and internationally have explored therapeutic approaches such as spinal cord stimulation, transmyocardial laser revascularization, and sympathectomy. However, existing studies are largely limited to small-scale clinical trials, and their clinical translation still faces challenges due to insufficient validation of safety and efficacy. Injectable hydrogels, as functional materials with hydrophilic three-dimensional network structures, demonstrate unique advantages in the treatment of RA. They can not only provide mechanical support but also serve as controlled-release carriers for drugs and proteins, and synergize with gene therapy and stem cell therapy to promotemyocardial tissue repair. This article systematically reviews the application prospects of injectable hydrogels in the treatment of RA, aiming to provide insights for future therapeutic strategies.

The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Objective:To analyze the genetic evolution characteristics of hemagglutinin (HA) and neuraminidase (NA) of influenza B virus in Tongling during 2019-2022 surveillance years.Methods:Twenty-two strains of Victoria influenza B virus isolated from our laboratory during 2019-2022 were selected for whole genome sequencing. The sequence comparison and phylogenetic analysis were conducted by using bioinformatic analysis software.Results:During 2019-2022, seasonal influenza in Tongling City was predominantly caused by influenza B Victoria lineage viruses, which fell within the V1A.3 branch. Among these, 14 strains isolated in the 2021-2022 season were further classified into the V1A.3a.2 sub-branch. Compared with vaccine strains, multiple amino acid mutation sites were detected in both HA and NA proteins of the 22 influenza B Victoria lineage viruses. Notably, all four major antigenic sites (120-loop, 150-loop, 160-helix, and 190-helix regions) in the HA protein exhibited variations. Although no mutations were detected at resistance sites on the NA protein, a change occurred in the glycosylation site at position 197 NETQ in the HA protein.Conclusions:The main amino acid sites of the HA protein of the influenza B Victoria lineage viruses in Tongling City from 2019 to 2022 have undergone significant variation, which may lead to antigenic drift. Therefore, it is essential to strengthen the monitoring of influenza virus mutations.

ObjectiveTo evaluate the effect of women's body mass index （BMI） on pregnancy outcomes of ovulation induction intrauterine insemination （OI-IUI） in patients with unexplained primary infertility. MethodsThe study included 764 OI-IUI cycles from January 2016 to December 2022 in reproductive center of Sun Yat-sen Memorial Hospital. According to BMI，patients were divided into three groups：low BMI （BMI<18.5 kg/m²）， normal BMI （18.5 kg/m² ≤BMI＜23.0 kg/m²）， and high BMI （BMI≥23.0 kg/m²）. Comparison of clinical data and pregnancy outcomes was performed between the groups. Logistic regression was used to analyze the association between BMI and live birth rate. ResultsFrom the low BMI group to the high BMI group， the HCG positive rate （7.08%，9.74%， 13.19%）， clinical pregnancy rate（5.51%， 7.91%， 13.19%）， and live birth rate （4.72%， 6.90%， 12.50%） increased. Among them， the live birth rate of the high BMI group was significantly higher than that of the low BMI group and the normal BMI group， with a statistically significant difference （P=0.034）. While the early miscarriage rate （14.28%， 10.26%， 5.26%） decreased from the low BMI group to the high BMI group. The binary logistic regression analysis revealed that BMI was an independent factor in live birth， and high BMI resulted in a better live birth rate than low BMI （OR=3.15，95%CI=1.191-8.329，P=0.021）. ConclusionLow BMI is associated with poor OI-IUI outcomes in patients with unexplained primary infertility. These patients are encouraged to gain weight in a healthy manner.

Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P＜0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P＜0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.