Varicocele-induced infertility （VCI） is a common andrological disease in clinical practice. Oxidative stress represents the primary mechanism through which varicocele causes male infertility. Traditional Chinese medicine （TCM） treatment， characterized by its multi-target， multi-component， multi-system， and multi-pathway actions， has achieved favorable outcomes in the field of VCI treatment. This paper summarizes the underlying oxidative stress mechanism of VCI and the relevant signaling pathways involved. By reviewing the current research status on how monomers， active fractions， compound formulas， and related preparations of TCM can intervene in oxidative stress through the regulation of these signaling pathways to improve VCI， it is found that the nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathway， the mitogen-activated protein kinase （MAPK） signaling pathway， and the hypoxia-inducible factor-1α （HIF-1α） signaling pathway are closely related to the development of VCI. TCM monomers and active fractions （flavonoids from Cuscutae Semen， polysaccharides from Astragali Radix， curcumin， ginsenoside Rg1， hyperin and echinacoside）， as well as compound formulas and related preparations of TCM （modified Dahuang zhechong granules， Shengjing huoxue formula， modified Tianxiong san， Tongjingling， Bushen huoxue formula， Mailuoshutong pill， Zishen yutai pill， Danhong tongjing formula） can alleviate oxidative stress， reduce lipid peroxidation damage， improve mitochondrial dysfunction， decrease sperm DNA fragmentation， and inhibit apoptosis by activating the Nrf2 signaling pathways and inhibiting the MAPK and HIF-1α signaling pathways， thereby improving reproductive function.

Objective: To analyze the correlation between serum homocysteine (Hcy) and both folic acid (FA) and sperm DNA fragmentation index (DFI), so as to provide the evidence for male fertility assessment. Methods: Males who visited and measured the serum Hcy in the Reproductive Medicine Center of Huzhou Maternal and Child Health Care Hospital from September 2022 to September 2023 were selected as the study subjects. Sperm quality parameters and sperm DFI were analyzed by collecting sperm. Hcy and FA were measured by collecting venous blood. Participants were stratified into a high Hcy group (Hcy≥15.0 μmol/L) and a normal group (Hcy<15.0 μmol/L). The correlations between serum Hcy and FA and sperm DFI were evaluated using linear regression models. Results: A total of 173 participants were enrolled, including 39 in the high Hcy group and 134 in the normal group. The sperm concentration in the high Hcy group was significantly lower than that in the normal group [(91.77±61.11)×106/mL vs. (144.21±106.82)×106/mL, P<0.05]. No statistically significant differences were observed in semen volume, sperm motility, curvilinear velocity, straight-line velocity, average path velocity, or sperm morphology normal rate (all P>0.05). The FA level in the high Hcy group was lower than that in the normal group [(4.44±1.79) nmol/L vs. (7.64±3.68) nmol/L, P<0.05]. The sperm DFI in the high Hcy group was higher than that in the normal group [(19.21±8.85)% vs. (13.07±6.43)%, P<0.05]. Serum Hcy level showed a negative correlation with FA level (r=-0.369, P<0.05) and a positive correlation with sperm DFI (r=0.351, P<0.05). Conclusion Serum Hcy level is associated with sperm concentration, FA and sperm DFI, suggesting that serum Hcy may affect sperm quality.

Gliomas are the most common primary neuroepithelial tumors of the central nervous system in adults, of which glioblastoma is the deadliest subtype. Apart from the intrinsically indestructible characteristics of glioma (stem) cells, accumulating evidence suggests that the tumor microenvironment also plays a vital role in the refractoriness of glioblastoma. The primary functions of platelets are to stop bleeding and regulate thrombosis under physiological conditions. Furthermore, platelets are also active elements that participate in a variety of processes of tumor development, including tumor growth, invasion, and chemoresistance. Glioma cells recruit and activate resting platelets to become tumor-educated platelets (TEPs), which in turn can promote the proliferation, invasion, stemness, and chemoresistance of glioma cells. TEPs can be used to obtain genetic information about gliomas, which is helpful for early diagnosis and monitoring of therapeutic effects. Platelet membranes are intriguing biomimetic materials for developing efficacious drug carriers to enhance antiglioma activity. Herein, we review the recent research referring to the contribution of platelets to the malignant characteristics of gliomas and focusing on the molecular mechanisms mediating the interaction between TEPs and glioma (stem) cells, as well as present the challenges and opportunities in targeting platelets for glioma therapy.
Humans ; Glioma/metabolism* ; Blood Platelets/physiology* ; Brain Neoplasms/pathology* ; Tumor Microenvironment

OBJECTIVE: To quantitatively evaluate the accuracy of data obtained from liquid-interference surfaces using an intraoral 3D scanner (IOS) integrated with a compressed airflow system, so as to provide clinical proof of accuracy for the application of the compressed airflow system-based scanning head in improving data quality on liquid-interference surfaces. METHODS: The study selected a standard model as the scanning object, adhering to the "YY/T 1818-2022 Dental Science Intraoral Digital Impression Scanner" guidelines, a standard that defined parameters for intraoral scanning. To establish a baseline for accuracy, the ATOS Q 12M scanner, known for its high precision, was used to generate true reference values. These true values served as the benchmark for evaluating the IOS performance. Building on the design of an existing scanner, a new scanning head was developed to integrate with a compressed airflow system. This new design aimed to help the IOS capture high-precision data on surfaces where liquid-interference, such as saliva, might otherwise degrade scanning accuracy. The traditional scanning method, without airflow assistance, was employed as a control group for comparison. The study included five groups in total, one control group and four experimental groups, to investigate the effects of scanning lens obstruction, airflow presence, liquid media, and the use of the new scanning head on scanning process and accuracy. Each group underwent 15 scans, generating ample data for a robust statistical comparison. By evaluating trueness and precision in each group, the study assessed the impact of the compressed airflow system on the accuracy of IOS data collected from liquid-interference surfaces. Additionally, we selected Elite and Primescan scanners as references for numerical accuracy values. RESULTS: The scanning accuracy on liquid-interference surfaces was significantly reduced in terms of both trueness and precision [Trueness: 18.5 (6.5) vs. 38.0 (6.7), P < 0.05; Precision: 19.1 (8.5) vs. 31.7 (15.0), P < 0.05]. The use of the new scanning head assisted by the compressed airflow system significantly improved the scanning accuracy [Trueness: 22.3(7.6) vs. 38.0 (6.7), P < 0.05; Precision: 25.8 (9.6) vs. 31.7 (15.0), P < 0.05]. CONCLUSION The scanning head based on the compressed airflow system can assist in improving the accuracy of data obtained from liquid-interference surfaces by the IOS.
Imaging, Three-Dimensional/methods* ; Humans ; Dental Impression Technique/instrumentation*

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

To monitor and analyze the molecular variation of the H3N2 influenza virus in Guangzhou during the COVID-19 pandemic, respiratory samples of influenza-like cases from influenza monitoring sentinel hospitals were collected from influenza monitoring sentinel hospitals for virus isolation and whole genome sequencing. The results showed that during COVID-19, there was only one peak of H3N2 influenza in the second quarter of 2022 in Guangzhou (the positive rate was 52.23%), and the epidemic intensity and duration were both higher than those in 2019. The HA gene and NA gene of the epidemic strain in Guangzhou in 2022 belonged to the 3C.2a1b. 2a. 1a. 1 branch, which had a good antigenic site matching with the vaccine strain (A/Cambodia/e0826360/2020) from 2021 to 2022 and had no antigen drift. In 2022 strains, the variation of antigen determinant mainly occurred in the I48T of C region, while no variation occurred in the A, B, D, and E regions. The binding site of the HA protein receptor was consistent with the vaccine strain (A/Cambodia/e0826360/2020). Most of the strains in 2022 carried 13 glycosylation sites on the HA protein, but an outbreak of strains caused a loss of glycosylation sites at 24-NST. In conclusion, the strains that caused the epidemic of H3N2 influenza in Guangzhou in 2022 were not evolved or transmitted from the local strains in 2019 during the COVID-19 pandemic.

To monitor and analyze the molecular variation of the H3N2 influenza virus in Guangzhou during the COVID-19 pandemic, respiratory samples of influenza-like cases from influenza monitoring sentinel hospitals were collected from influenza monitoring sentinel hospitals for virus isolation and whole genome sequencing. The results showed that during COVID-19, there was only one peak of H3N2 influenza in the second quarter of 2022 in Guangzhou (the positive rate was 52.23%), and the epidemic intensity and duration were both higher than those in 2019. The HA gene and NA gene of the epidemic strain in Guangzhou in 2022 belonged to the 3C.2a1b. 2a. 1a. 1 branch, which had a good antigenic site matching with the vaccine strain (A/Cambodia/e0826360/2020) from 2021 to 2022 and had no antigen drift. In 2022 strains, the variation of antigen determinant mainly occurred in the I48T of C region, while no variation occurred in the A, B, D, and E regions. The binding site of the HA protein receptor was consistent with the vaccine strain (A/Cambodia/e0826360/2020). Most of the strains in 2022 carried 13 glycosylation sites on the HA protein, but an outbreak of strains caused a loss of glycosylation sites at 24-NST. In conclusion, the strains that caused the epidemic of H3N2 influenza in Guangzhou in 2022 were not evolved or transmitted from the local strains in 2019 during the COVID-19 pandemic.

Objective:To discuss the effect of D-limonene on the proliferation and apoptosis of the glioblastoma(GBM)cells,and to clarify its possible mechanism.Methods:The GBM cells were divided into control group(0 mmol·L-1 D-limonene)and 0.2,0.4,0.6,0.8,and 1.0 mmol·L-1 D-limonene groups.CCK-8 method was used to detect the inhibitory rates of proliferation of the cells in various groups;clone formation assay was used to detect the clone formation rates of the cells in various groups;Annexin Ⅴ-FITC/PI method was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and poly adenosine diphosphate(ADP)-ribose polymerase(PARP)proteins in the cells in various groups;imunofluorescence method was used to detect the expression levels of cleaved Caspase-3 protein in the cells in various groups.Fifteen model mice with subcutaneous tumor xenografts were randomly divided into blank group(0 mg·kg-1·d-1 D-limonene),low dose of D-limonene group(200 mg·kg-1·d-1 D-limonene),and high dose of D-limonene group(400 mg·kg-1·d-1 D-limonene),and there were 5 mice in each group.The inhibitory rates of the tumor in vitro in various groups were calculated;HE staining and immunohistochemical staining were used to observe the morphology of subcutaneous tumor tissue of the mice in various groups and the growth curves of the tumor were drawn;immunohistochemical assay was used to detect the positive expression rates of Ki67 protein in subcutaneous tumor tissue of the mice in various groups;TUNEL staining was used to detect the apoptosis of the tumor cells in various groups.Results:In control group,the cells were spindle-shaped,in good condition,growing closely and adherently,with normal organelles and cytoplasm.After treated for 48 h,the cells in 0.6 mmol·L-1 D-limonene group showed reduced volume,intact but more permeable cell membranes,shrunken cytoplasm,internal vacuole structures,and some fragments floating in the solution.The cells in 0.8 and 1.0 mmol·L-1 D-limonene groups exhibited significant apoptotic bodies and were in an apoptotic state.The CCK-8 results showed that compared with control group,the inhibitory rates of proliferation of the U87,LN229,and GL261 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01),the inhibitory rates of proliferation of the U87 and GL261 cells were significantly increased(P<0.01).The clone formation assay results showed that compared with control group,the clone formation rates of the U87,LN229,and GL261 cells in 0.4,0.6,and 0.8 mmol·L-1 D-limonene groups were significantly decreased(P<0.05 or P<0.01).The AnnexinⅤ-FITC/PI results showed that compared with control group,after treated with D-limonene for 48 h,the apoptotic rates of the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Bax proteins in the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01),while the expression levels of AKT and Bcl-2 proteins were significantly decreased(P<0.01),the expression level of PARP protein in the LN229 cells in 0.8 and 1.0 mmol·L-1 D-limonene group was significanthy increased(P<0.01).The immunofluorescence results showed that compared with control group,the expression levels of cleaved Caspase-3 protein in the LN229 cells in 0.6,0.8,and 1.0 mmol·L-1 D-limonene groups were significantly increased(P<0.01).Compared with blank group,the tumor volumes of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.01).Compared with blank group,the tumor weights of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.05),and the inhitory rates of tumor were significantly increased(P<0.05).The tumor cells in blank group were diffusely distributed,with deepened nuclear staining and increased nucleocytoplasmic ratio;a large number of degenerated and necrotic tumor cells were observed in tumor tissue of the mice in low and high doses of D-limonene groups.Compared with blank group,the positive expression rates of Ki67 protein in tumor tissue of the mice in low and high doses of D-limonene groups were significantly decreased(P<0.01).Compared with blank group,the apoptotic rates of tumor cells of the mice in low and high doses of D-limonene groups were significantly increased(P<0.01).Conclusion:D-limonene has the inhibitory effect on the proliferation of the GBM cells;its mechanism may be related to the regulation of AKT protein expression and the activation of the Caspase-3 pathway to induce the apoptosis.