【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).
Recombinational DNA Repair ; DNA-Binding Proteins/metabolism* ; DNA Repair ; DNA Damage ; DNA

Based on the national policies, regulations and documents on residency training, this paper sorts out the historical evolution of the standardized residency training system in China, and divides its development into four stages: preliminary exploration, local pilot, national trials, and implementation. It also puts forward some practical thoughts on its development law and future trend, such aspects as that the system reform follows the top-down administrative order and indicative plan, the system pays attention to the gradual implementation on the basis of summing up practical experience, and the system needs continuous implementation and improvement from the overall perspective.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Maili moxibustion can alleviate cancer pain, reduce bone marrow suppression, alleviate gastrointestinal reaction of chemotherapeutic drugs, alleviate cancer-related fatigue, inhibit neurotoxic reaction, improve quality of life and prolong patients' survival. It plays therapeutic effects by regulating immunity, inhibiting tumor cell proliferation and regulating tumor microenvironment. The researches of Maili moxibustion for tumor focus on reducing the toxic or side effects of radiotherapy or chemotherapy. In the future, we should continue to study the combination of Maili moxibustion and other therapies on the treatment of tumor.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective:To explore the associations of stress, coping strategies and quality of life in globus patients.Methods:A total of 180 patients diagnosed with globus were retrospectively analyzed between September 2018 to July 2020 in the First Affiliated Hospital of Zhengzhou University.The questionnaire included baseline characteristics and assessment scales. Quality of life was measured by short-form health survey-36 (SF-36), which included physical composite score (PCS) and mental composite score (MCS). Perceived stress was measured by perceived stress scale 10 (PSS-10). The coping strategy was evaluated by medical coping modes questionnaire (MCMQ). We analyzed the relationship between baseline characteristics, stress, coping strategies, and quality of life, and the influential factors of quality of life.Results:PCS was affected by the number of previous chronic illness, age, stress, confrontation, and avoidance ( F=3.647, r=-0.263, -0.634, 0.249, -0.329, all P<0.05). MCS was related to monthly income, marital status, stress, confrontation, and resignation ( F=1.963, 5.764, r=-0.312, 0.384, -0.360, all P<0.05). Based on the data of multiple linear regression analysis, stress was negatively correlated with both PCS and MCS ( t=-3.883, -9.708, all P<0.01), confrontation was positively correlated with both PCS and MCS ( t=2.030, 2.798, P=0.044, 0.006), and resignation was negatively correlated with MCS ( t=-1.585, P=0.025). Besides, age was negatively correlated with PCS ( t=-2.736, P=0.007), and monthly income was positively correlated with MCS ( t=2.497, P=0.013). Conclusion:Aging, low income, over stress, resignation rather than confrontation as a coping style impair the quality of life in globus patients.

Objective:To evaluate the effect of pomegranate peel polyphenols on sebum secretion in golden hamsters, and to explore its possible mechanisms.Methods:Thirty golden hamsters were randomly and equally divided into 5 groups: (ointment) vehicle group, 0.48%-, 0.96%-, 1.92%-pomegranate peel polyphenol ointment groups, and retinoic acid cream group. Corresponding cream or ointments were applied to bilateral sebaceous gland spots of the golden hamsters at a dose of 1 gram twice a day for 4 consecutive weeks. The area of bilateral sebaceous gland spots was measured on days 0, 7, 14, 21 and 28 after the start of treatment, which was calculated by the maximum longitudinal diameter multiplied by the maximum transverse diameter. Twenty-four hours after the last treatment, immunohistochemical study was conducted to determine the expression of AKT/Sox9 signaling pathway in sebaceous gland spots resected from the golden hamsters. The area of sebaceous gland spots in these groups at different time points was compared by repeated measures analysis of variance, and other data were analyzed by one-way analysis of variance or Kruskal-Wallis H test. Results:The area of sebaceous gland spots was significantly smaller in the 0.96%-, 1.92%-pomegranate peel polyphenol ointment groups (50.48±2.41 mm 2, 48.24±2.56 mm 2, respectively) and retinoic acid cream group (48.31±2.76 mm 2) than in the vehicle group (57.99±3.29 mm 2; t=2.69, 3.98, 3.65, P=0.012, 0.001, 0.001, respectively) . Sox9 expression was significantly lower in the 1.92%-pomegranate peel polyphenol ointment group (0.39±0.04) and retinoic acid cream group (0.38±0.03) than in the vehicle group (0.44±0.02, P=0.040) . However, there was no significant difference in AKT expression among the 5 groups ( F=1.645, P=0.199) . Conclusion:Pomegranate peel polyphenols can reduce the sebaceous gland spot area and inhibit sebum secretion in golden hamsters, which may be related to the inhibition of Sox9 expression.

Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.
Coronary Artery Disease ; Gastrointestinal Microbiome ; Humans ; Methylamines ; Oxides

Selenylation modification of polysaccharides from the extract residue of Sarcandra glabra(Thunb.) Nakai was operated with sodium selenite as modification agent and barium chloride as the catalyst.The synthesis conditions were optimized by orthogonal experiment with the yields and contents of selenium as indicators.Then, the purity,molecular weight,infrared spectroscopy,thermophysical properties and antitumor activity of the seleny-lated polysaccharides were determined.Results showed that the optimum conditions for preparing selenylated polysaccharides from the extract residue of S.glabra(Thunb.)Nakai were at 70 ℃ for 7 h with 1.0％ nitric acid using 1.5 g barium chloride as catalyst.Under the optimum condition,the physicochemical properties of the derivatives were measured and the results showed that the total carbohydrate content was(94.89 ± 0.83)％,the yield was(21.93 ± 0.85)％,the content of selenium was(944.54 ± 13.91)μg/g,the molecular weight was 1 339 kD. In vitro antitumor activity indicated that exposure of HepG2 cells to the increasing concentrations of the crude polysaccharide from the residue of S.glabra(Thunb.)Nakai and its selenylated products decreased cell viability in dose-dependent and time-dependent manner.The selenium polysaccharide demonstrated a better antitumor activity compared with the raw polysaccharide,which could be explored as a potential antitumor drug from abandoned extracted residue for the functional foods and pharmaceutical industries.