Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Clinical study of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma.

Herein, we aimed to evaluate the efficacy and safety of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (OSCC). Fifty-one patients with OSCC, treated from July 2020 to October 2022, were analyzed. Of them, 41 patients underwent surgery 4-8 weeks after undergoing two cycles of camrelizumab (200 mg IV Q3W) combined with docetaxel (75 mg/m2 IV Q3W) and carboplatin (area under the curve = 5-6 IV Q3W). The primary endpoint was the pathological complete response rate. All 51 patients (100%) experienced treatment-related grades 1-2 adverse events, and 2 patients (3.9%) experienced grade 4 events (including elevated alanine transaminase/aspartate transferase levels and Guillain-Barre syndrome). Fifty patients were evaluated for the treatment efficacy. Of them, 13 achieved complete response, and the objective response rate was 74%. Only 41 patients underwent surgical treatment. The pathological complete response rate was 17.1%, the major pathological response rate was 63.4%, and the R0 resection rate was 100%. Approximately 22% of the patients had tumor regression grades 0. Eight patients (19.5%) developed surgery-related complications. The median follow-up time was 18 months (range: 3-29 months). Four patients experienced disease progression, while four died. The median disease-free survival and overall survival were not reached. Camrelizumab combined with docetaxel and carboplatin is an effective and safe neoadjuvant treatment for locally advanced OSCC. This regimen may afford a potential strategy to treat patients with locally advanced OSCC.

Long-term exposure to arsenic in drinking water leads to myocardial damage by oxidative stress and reduction in NO.

Chronic arsenic exposure causes myocardial damage. The aim of this study is to investigate if oxidative stress and reduction in NO is involved in the myocardial damage induced by arsenic in drinking water. Rats were divided into a control group and different doses of sodium arsenite. With increasing sodium arsenite concentrations in drinking water, localised inflammatory foci and necrotic myocardial tissues were gradually observed. Compared to the control group, the activities and gene expression of antioxidant enzymes in arsenic-exposed rats decreased. NO content and the NOS activity as well as the expression of NOS mRNA in the myocardial tissue of exposed rats, decreased, and the extracellular NO content of cardiomyocytes treated with sodium arsenite also decreased. The rate of cell apoptosis induced by sodium arsenite decreased after treatment with sodium nitroprusside (an NO donor). In conclusion, arsenic exposure in drinking water can lead to myocardial injury and cardiomyocyte apoptosis through oxidative stress and a reduction in NO content.

Nanoparticle-based polyacrylonitrile monolithic column for highly efficient micro solid-phase extraction of carotenoids and vitamins in human serum.

In this work, a biocompatible monolithic column based micro-solid-phase extraction (µ-SPE) method was developed for biological fluid analysis. A novel nanoparticle-based polyacrylonitrile monolithic column (C30 NP-PMC) was fabricated by incorporating triacontyl (C30) modified silica nanoparticles (NPs) into the polyacrylonitrile monolithic matrix through thermally induced phase separation. With efficient mass transfer and sorption capacity, C30 NP-PMC exhibited outstanding performance for the extraction of carotenoids and fat-soluble vitamins (FSVs) from human serum samples, superior to commercial C18 cartridges as well as liquid-liquid extraction (LLE) method. Under optimal conditions, the proposed µ-SPE method coupled with high-performance liquid chromatography-diode array detection (HPLC-DAD) achieved satisfactory limits of detection (LODs) (1.5-75.0 ng/mL) and good recoveries (85.0-106.5 %) with relative standard deviations (RSDs) of less than 12.1% by consuming lower sorbent (35.0 mg) and organic solvent (0.8 mL). Successful application of the developed method demonstrated the great potential of such monolithic sorbents for efficient isolation and preconcentration of trace analytes from blood samples.

Detection of human papillomavirus type 16 DNA in formalin-fixed, paraffin-embedded tissue specimens of gastric carcinoma.

OBJECTIVES: Human papillomavirus type 16 (HPV16) is regarded as one of the important tumor-related viruses, which are known to have a role in cervical carcinoma; however, there are few reports on HPV16 in gastric carcinoma (GC). Our study aimed to investigate the relationship between HPV16 and the occurrence of GC. METHODS: Liquid PCR (LPCR) and in-situ PCR (ISPCR) methods were carried out to detect the HPV16 oncogene E6 cell-type-specific enhancer in the long control region of HPV16 in 40 GCs and corresponding gastric adjacent normal mucosa (GANM). The patients were from Shaanxi Province in China; Helicobacter pylori (Hp) was detected by immunohistochemistry and by hematoxylin and eosin staining in their gastric tissues. RESULTS: The HPV16 E6 gene was detected in 37.5% (15/40) of the GCs and 5% (2/40) of the GANMs with LPCR, as was the cell-type-specific enhancer; however, the positive rate of E6 was 27.5% (11/40) in GCs and 0% (0/40) in GANMs, respectively, with ISPCR. HPV16 DNA was mainly located in the nucleus of gastric glandular epithelium cells. The infection rate of HPV16 DNA in GCs was higher than that in GANMs (P=0.0004), and the HPV16 had no statistical correlations with sex, age, invasion, grading or lymph node metastasis (P>0.05). The infection rate of HPV16 in cardiac GCs was significantly higher than that in noncardiac ones (P=0.0136), and HPV16 had no correlation with Hp in GCs (P=0.0829). Receiver operator characteristic curve analysis indicated that there was no statistical difference between the LPCR and ISPCR methods in our study through optimizing parameters in ISPCR procedures (P=0.768). CONCLUSIONS: These findings suggested that HPV16 can infect gastric glandular epithelium cells and that viral infection might play a role in the occurrence of GCs independent of or without the cooperation of an Hp infection.