Chinese Medical Journal最新文献

Abstract: The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future.

Background: Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.

Methods: This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed.

Results: The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.

Conclusions: The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.

Methods: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9.

Results: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A , AQP5 , and MUC5AC . CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment.

Conclusions: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Abstract: Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

Background: Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2 , a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression.

Methods: Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2 -associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC.

Results: NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro . NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models.

Conclusions: Collectively, NUF2 -mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.