Uncover the anticancer potential of lycorine.

BACKGROUND: Natural products have a long history in drug discovery. Lycorine is an alkaloid derived from Amaryllidaceae plants, demonstrating significant pharmacological potential. Lycorine and its hydrochloride salt, lycorine hydrochloride, have shown outstanding anticancer effects both in vitro and in vivo. PURPOSE: This review aims to comprehensively summarize recent research advancements regarding the anticancer potential of lycorine and lycorine hydrochloride. It intends to elucidate current research limitations, optimization strategies, and future research directions to guide clinical translation. METHODS: Various databases, e.g., Web of Science, PubMed, and Chinese National Knowledge Infrastructure, are systematically searched for relevant articles using keywords such as lycorine, cancer, pharmacokinetics, and toxicity. The retrieved literature is then categorized and summarized to provide an overview of the research advancements in the anticancer potential of lycorine and lycorine hydrochloride. RESULTS: Lycorine and lycorine hydrochloride demonstrate significant anticancer activities against various types of cancer both in vitro and in vivo, employing diverse mechanisms such as inducing cell cycle arrest, triggering cellular senescence, regulating programmed cell death, inhibiting angiogenesis, suppressing metastasis, and modulating immune system. Furthermore, pharmacokinetic profiles and toxicity data are summarized. Additionally, this review discusses the druggability, limitations, optimization strategies, and target identification of lycorine, offering insights for future preclinical studies. CONCLUSION: The anticancer effects and safety profile of lycorine and lycorine hydrochloride suggest promising potential for clinical applications. Further research on their in-depth mechanisms and optimization strategies targeting their limitations will enhance the understanding and druggability of lycorine and lycorine hydrochloride.

Clinical value of thromboelastography in predicting the risk of recurrence of acute ischemic stroke.

Background: Thromboelastography (TEG) can objectively reflect the formation, development and rupture process of thrombosis in patients, but there are limited data on whether TEG can be used as a predictive tool for recurrence in patients with acute ischemic stroke. Objective: To explore the TEG risk of recurrence in patients with acute ischemic stroke predictive value. Methods: A total of 441 patients with acute ischemic stroke who met the research criteria in the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2020 to December 2021 were selected as the research objects. TEG was measured in all patients, and the main parameters of TEG (R value, indicating coagulation reaction time; K value and Angle, the rate of blood clot formation; MA value, indicating the maximum amplitude). The primary outcome of this study was ischemic stroke recurrence. Recurrent events included cerebral infarction, cerebral hemorrhage, TIA, and were determined by combining imaging events and clinical events. Logistic regression analysis was used to explore the influencing factors of recurrence in patients with acute ischemic stroke. Results: Fifty-six patients (12.7%) had recurrence. Multivariate Logistic regression analysis showed that: Age [OR = 1.078, 95%CI(1.024, 1.135)], triglyceride [OR = 1.541, 95%CI(1.033, 2.298)], glycosylated hemoglobin [OR = 1.401, 95%CI(1.097, 1.790)], history of hypertension [OR = 16.046, p < 0.05], 95%CI(4.726, 54.489), R value [OR = 0.533, 95%CI(0.351, 0.809)], MA value [OR = 1.399, 95%CI(1.004, 1.949)] were independent influencing factors for hemorrhagic transformation in patients with acute ischemic stroke. Conclusion: TEG has some value in predicting recurrence in patients with acute ischemic stroke, and the MA value in TEG [AUC = 0.806 (95%CI:0.747-0.867), with a sensitivity of 78.6% and a specificity of 70.4%], predicted the most significant efficiency of AIS recurrence.

Depressive disorders in Chinese left-behind children and adolescents from Yunnan province: prevalence and association with self-harm behaviors.

BACKGROUND: The prevalence of clinically diagnosed depressive disorders (DD) in Chinese left-behind children (LBC) remains unknown. We aim to estimate the prevalence of DD, discuss the associations between DD and self-harm (SH) behaviors in a large representative sample of Chinese LBCs chosen from Yunnan province. METHODS: A total of 5462 LBCs were selected from the most recent datasets of the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a mega population-based two-phase cross-sectional survey. Weighted prevalence rates and designed Logistic regression were adopted to estimate the prevalence of DD and the association between DD and SH. RESULTS: The weighted prevalence of lifetime and current DD were 4.22% (95% CI: 3.13-6.00%) and 3.84% (95% CI: 2.85-5.00%) in Chinese LBCs. Higher lifetime and current DD prevalence rates were observed in girls and those reported adverse parental marital status and SH behaviors. The absence of DD was associated with significantly decreased odds of SH behavior (OR = 0.06), repetitive SH (OR = 0.09), using multiple SH methods (OR = 0.09), and severe SH (OR = 0.15). Subsequently performed stratified analyses identified prominent effect modification by sex and age, as a stronger association between DD and SH was found in girls (OR = 0.02 versus OR = 0.07 in boys) and younger adolescents (OR = 0.08 versus OR = 0.22 in older adolescents). CONCLUSION: The prevalence of DD was high in Chinese LBCs. DD was associated with prominently increased risk of SH behaviors in LBCs. Attention and intervention are needed in this vulnerable population.

Preparation, pharmacokinetics and anti-obesity effects on dogs of nuciferine liposomes.

BACKGROUND: Nuciferine (NUC), a natural compound extracted from lotus leaves, has been proven to have anti-obesity effects. However, the development and application of NUC as an anti-obesity drug in dogs are hindered due to its poor water solubility and low bioavailability. OBJECTIVE: To promote the development of NUC-related products for anti-obesity in dogs, this study prepared NUC into a liposome formulation and evaluated its characteristics, pharmacokinetics in dogs, and anti-obesity effects on high-fat diet dogs. METHODS: NUC liposomes were prepared by the ethanol injection method, using NUC, egg lecithin, and ß-sitosterol as raw materials. The characteristics and release rate in vitro of liposomes were evaluated by particle size analyser and dialysis method, respectively. The pharmacokinetics in dogs after oral administration of NUC-liposomes was carried out by the high-performance liquid chromatography (HPLC) method. Moreover, we investigated the anti-obesity effect of NUC-liposomes on obese dogs fed with a high-fat diet. RESULTS: NUC-liposome was successfully prepared, with an EE of (79.31 ± 1.06)%, a particle size of (81.25 ± 3.14) nm, a zeta potential of (-18.75 ± 0.23) mV, and a PDI of 0.175 ± 0.031. The cumulative release rate in vitro of NUC from NUC-liposomes was slower than that of NUC. The T1/2 and relative bioavailability of NUC-liposomes in dogs increased, and CL reduced compared with NUC. In addition, the preventive effect of NUC-liposomes on obesity in high-fat diet dogs is stronger than that of NUC. CONCLUSIONS: The liposome formulation of NUC was conducive to improve its relative bioavailability and anti-obesity effect in dogs.

NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway.

Background: The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs. Methods: Neuro-oncological ventral antigen 2 (NOVA2) expression in liver CSCs was examined by real-time polymerase chain reaction (PCR). In vitro experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance. Results: In our study, the expression of the RBP NOVA2 was higher in CSCs. NOVA2 also increased the capacity for self-renewal and carcinogenesis of the liver CSCs via the Wnt pathway. Further, suppressing the Wnt pathway leads to desensitization of the hepatocellular carcinoma (HCC) cells that overexpress NOVA2 to apoptosis caused by lenvatinib. Analyzing patient data confirmed reduced levels of NOVA2 and therefore we speculate that NOVA2 may serve as a potential indicator for response to lenvatinib in patients with HCC. Methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1)-dependent N6-methyladenosine (m6A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM). Conclusions: NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC.

The association between female age and pregnancy outcomes in patients receiving first elective single embryo transfer cycle: a retrospective cohort study.

This study aimed to explore the relationship between female age and pregnancy outcomes in patients undergoing their first elective single embryo transfer (eSET) of in vitro fertilization (IVF) cycles. The retrospective cohort study encompassed 7089 IVF/intracytoplasmic sperm injection (ICSI) patients of the Reproductive Medicine Center, Henan Provincial Peoples' Hospital of China, from September 1, 2016, to May 31, 2022. Patients all received the first eSET in their IVF/ICSI cycles. A generalized additive model (GAM) was employed to examine the the dose-response correlation between age and pregnancy outcomes, namely the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). Logistic regression model was employed to ascertain the correlation between the CPR/OPR and age. The study cohort has an average age of 30.74; 3843 patients got clinical pregnancy rate of 61.40% and ongoing pregnancy rate of 54.21%. The multiple pregnancy rate of is 1.24%. For patients aged 34 and above, the CPR decreased by 10% for every 1-year increase in age (adjusted OR 0.90, 95% CI 0.84-0.96, p < 0.0001). Similarly, the OPR decreased by 16% for every 1-year increase in age (adjusted OR 0.84, 95% CI 0.81-0.88, p < 0.0001). Patients aged 35-37 years had an acceptable OPR of 52.4% after eSET, with a low multiple pregnancy rate (1.1%). Pregnancy outcomes were significantly better in blastocyst cycles compared to cleavage embryo cycles, and this trend was more pronounced in older patients. There was a non-linear relationship between female age and pregnancy outcomes in patients undergoing their first eSET cycles. The clinical pregnancy rate and ongoing pregnancy rate decreased significantly with age, especially in women older than 34 years. For patients under 37 years old, single embryo transfer should be prioritized. For patients over 38 years old with available blastocysts, eSET is also recommended.

Prognosis poor, immune infiltration of colon adenocarcinoma associated with low expression levels of calcium-activated chloride channel.

The calcium-activated chloride channel (CLCA4) in colon adenocarcinoma (COAD) and immunological infiltration have not been extensively studied. This work thoroughly employed several datasets to assess the expression, prognosis, and association between immune infiltration and clinicopathological characteristics of CLCA4 in cancer, as well as look into potential signalling pathways. The human protein atlas (HPA), TIMER, UALCAN, TISIDB, GSCA, SangerBox, GeneMANIA, and LinkedOmics were among the datasets that were used. The findings demonstrated that, in comparison to normal tissues, COAD tissues had lower levels of CLCA4 expression. The prognosis was worse for those whose levels of CLCA4 expression were lower. For validation, immunohistochemistry (HPA) was used. Positive correlations between CLCA4 mRNA expression and its copy number variation (CNV) were observed, and CLCA4 CNV was linked to immunological infiltration. Subsequent investigation demonstrated the association between immune cell markers, immune checkpoint genes, and immunological infiltration with CLCA4. The overall survival and disease-free survival of M0 patients were considerably better than those of M1 patients, and the groups with tumour stages M0 and M1 had notably different levels of CLCA4 expression. Its substantial enrichment in ion channel activity, transmembrane transporter activity, digestion, and other biological processes was revealed by gene ontology analysis. Oxidative phosphorylation, pancreatic secretion, Parkinson's and Alzheimer's diseases, renin secretion, and other signalling pathways were the primary associations found for CLCA4. It is evident that the immunological microenvironment and functions like ion transport, metabolism, and intestinal digestion are all impacted by CLCA4 expression.

Maresin2 negatively regulates DC's maturation via the MAPK/NF-κB pathway in DCs.

OBJECTIVE: To observe the effects and mechanisms of Maresin2 on the function of DCs(Dendritic cells). METHOD: The levels of IL-6, IL-12, TNF-α and IL-1ß secreted by BMDCs (Bone marrow-derived Dendritic cells) after Maresin2 treatment were detected by ELISA. At the same time, the expressions of costimulatory molecules CD40 and CD86 on the surface, the ability of phagocytosis of ovalbumin(OVA) antigen, and antigen presentation function in BMDCs were analyzed by flow cytometry. Finally, MAPK and NF-κB pathway signaling phosphorylation in Maresin2-treated BMDCs were detected by western blot. RESULTS: The secretion levels of IL-6, IL-12, TNF-α and IL-1ß were significantly decreased in the Maresin2 treatment group after LPS treatment (P < 0.05). The expression levels of CD86 and CD40 were significantly decreased after Maresin2 treatment (P < 0.05). Maresin2 enhanced the phagocytosis ability of ovalbumin(OVA) (P < 0.05), but the ability of antigen presentation of BMDCs with the treatment of Maresin2 changed slightly (P > 0.05). Phosphorylation of p38, JNK, p65, ikka/ß and ERK peaked at 15 min in the LPS group, while phosphorylation of p-p38 and p-ERK weakened 30 min and 60 min after treatment with Maresin2. CONCLUSIONS: Maresin2 inhibits inflammatory cytokine secretion but enhances phagocytosis via the MAPK/NF-κB pathway in BMDCs, which may contribute to negatively regulating inflammation.

Polycyclic polyprenylated acylphloroglucinols from the pericarps of Garcinia multiflora champ. ex Benth. with cytotoxic property.

The phytochemical investigation on the pericarps of Garcinia multiflora resulted in the isolation of 12 previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-12) with a variety of skeletons. Their structures were determined by comprehensive spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Compounds 6-9 possess a rare bicyclo[4.3.1]decane skeleton. Additionally, the anti-tumor activity of the 12 isolates was evaluated. The results indicated that compounds 5, 9, and 12 exhibited significant cytotoxicity in a wide range of cancer cell lines, including the human breast cancer MDA-MB-231 cells, human lung cancer A549 cells, human colon cancer SW480 cells and human ovarian cancer HEY cells. Further studies indicated that compound 5 induced cell cycle arrest and apoptosis, to inhibit the growth of MDA-MB-231 cells. Taken together, these findings expand the chemical diversity of PPAPs and further demonstrate the potential of PPAPs as candidates for cancer treatment.

microRNA maintains nutrient homeostasis in the symbiont-host interaction.

Endosymbionts provide essential nutrients for hosts, promoting growth, development, and reproduction. However, the molecular regulation of nutrient transport from endosymbiont to host is not well understood. Here, we used bioinformatic analysis, RNA-Sequencing, luciferase assays, RNA immunoprecipitation, and in situ hybridization to show that a bacteriocyte-distributed MRP4 gene (multidrug resistance-associated protein 4) is negatively regulated by a host (aphid)-specific microRNA (miR-3024). Targeted metabolomics, microbiome analysis, vitamin B6 (VB6) supplements, 3D modeling/molecular docking, in vitro binding assays (voltage clamp recording and microscale thermophoresis), and functional complementation of Escherichia coli were jointly used to show that the miR-3024/MRP4 axis controls endosymbiont (Serratia)-produced VB6 transport to the host. The supplementation of miR-3024 increased the mortality of aphids, but partial rescue was achieved by providing an external source of VB6. The use of miR-3024 as part of a sustainable aphid pest-control strategy was evaluated by safety assessments in nontarget organisms (pollinators, predators, and entomopathogenic fungi) using virus-induced gene silencing assays and the expression of miR-3024 in transgenic tobacco. The supplementation of miR-3024 suppresses MRP4 expression, restricting the number of membrane channels, inhibiting VB6 transport, and ultimately killing the host. Under aphids facing stress conditions, the endosymbiont titer is decreased, and the VB6 production is also down-regulated, while the aphid's autonomous inhibition of miR-3024 enhances the expression of MRP4 and then increases the VB6 transport which finally ensures the VB6 homeostasis. The results confirm that miR-3024 regulates nutrient transport in the endosymbiont-host system and is a suitable target for sustainable pest control.

Childhood maltreatment associated suicidal risk in Chinese children and adolescents: a mediation of resilience.

BACKGROUND: Existing evidence suggests that children and adolescents who had experienced childhood maltreatment (CM) are at higher suicidal risk. However, the mediation role of resilience in this association remains unclear. We aim to investigate the mediation via resilience in the associations between CM and three suicidal risk indicators (suicidal ideation, SI; suicidal plan, SP; suicidal attempt, SA) among a large sample of Chinese children and adolescents. METHODS: A population-based cross-sectional survey was conducted in southwestern China Yunnan province. A total of 9723 children and adolescents were included and analyzed by using a multi-stage stratified cluster sampling design. Univariate and multivariate logistic regression models were fitted to explore the associations between CM, resilience, and the three suicidal risk indicators, dose-response trends further elucidated by using the restricted cubic splines. Path models were adopted to estimate the mediation of resilience. RESULTS: The estimated prevalence rates for one-year SI, SP and SA were 32.86% (95% CI: 31.93-33.80%), 19.36% (95% CI: 18.57-20.16%) and 9.07% (95% CI: 8.51-9.66%). After adjustment, CM significantly associated with all 3 suicidal risk indicators, and the odds ratios (ORs) were 2.13 (95% CI: 1.91-2.37), 2.45 (95% CI: 2.13-2.81), and 3.61 (95% CI: 2.90-4.52) for one-year SI, SP, and SA, respectively. Path models revealed that resilience significantly mediated the associations between CM and the three suicidal risk indicators, and among all dimensions of resilience, family support presented the strongest mediation consistently. CONCLUSIONS: Our study results suggest that intervention measures which focusing on improving psychological resilience might be effective in reducing suicidal risk for children and adolescents who had experienced maltreatment. Prospective studies should be done to corroborate our findings.

Safety and efficacy of baricitinib in steroid-resistant or relapsed immune thrombocytopenia: An open-label pilot study.

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.

BACKGROUND: This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). METHODS: A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). RESULTS: A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270). CONCLUSION: Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.

Efficacy and safety of acupuncture for cognitive impairment in Alzheimer's disease: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy of acupuncture in the treatment of cognitive impairment in Alzheimer's disease (AD) by meta-analysis, in order to provide evidence-based evidence for the application of acupuncture therapy in the clinical process of AD. Methods: From the establishment of the database to December 31, 2022, China Biomedical Literature Database (CBM), China National Knowledge Network (CNKI), VIP database, WanFang Database, Pubmed, Embase and Cochrane Library Database were systematically searched. To collect published randomized controlled clinical trials (RCTS) of acupuncture in the treatment of cognitive impairment in AD. The subjects in the intervention group were given acupuncture alone or combined with other treatments the same as the control group; the control group received conventional Western medicine treatment. The main outcome indicators of the study were cognitive function assessment of subjects, including: Simple Mental State Examination Scale (MMSE), Assessment of daily Living Ability Scale (ADL), Alzheimer's Disease Cognitive Function Assessment Scale (ADAS-Cog), TCM syndrome score (SDSD), Montreal Cognitive Test (MoCA), Secondary outcome indicators were the occurrence of adverse reactions. Literature screening, data extraction, and quality evaluation of the included literature were performed independently by two researchers, according to bias risk assessment tools recommended in the Cochrane manual. Data were analyzed by RevMan5.3 software. Dichotomous variables were represented by risk ratio (OR) and 95% CI, and continuity variables were represented by mean difference (MD) and 95% CI. For heterogeneity analysis, when P > 0.1 and I 2 ≤ 50%, fixed effect model was applied. When P ≤ 0.1 and I 2 > 50%, the random effects model is applied. Results: A total of 1,172 eligible subjects were included in 18 RCTS, including 595 in the intervention group and 577 in the control group. The results of meta-analysis are as follows: acupuncture intervention group improved MMSE [MD = 1.67, 95% CI (0.94, 2.41), P < 0.00001], ADL [MD = -1.18, 95% CI (-3.09, 0.72), P = 0.22], ADAS-Cog [MD = 3.31, 95% CI (5.84, 0.78), P = 0.01], SDSD [MD = 2.40, 95% CI (3.53, 1.26), P < 0.0001], MoCA [MD = 4.80, 95% CI (3.74, 5.86), P = 0.04] were better than the control group. No serious adverse reactions related to acupuncture were observed in the intervention group, and the incidence and severity of adverse reactions were lower than those in the control group, with statistical significance [OR = 0.17, 95% CI (0.04, 0.67), P = 0.01]. Conclusion: Existing data show that acupuncture therapy has certain advantages in improving cognitive dysfunction and improving self-care ability of patients with Alzheimer's disease. However, due to the small number of RCTS and cases evaluating the efficacy of acupuncture, and the possibility of measurement bias and selectivity bias in included studies, it is still unable to conduct high-intensity demonstration on its effectiveness. Further large-scale, high-quality randomized, double-blind controlled trials are needed to evaluate its efficacy. Systematic Review Registration: https://inplasy.com/inplasy-2021-12-0125/, identifier: INPLASY2021120125.

Analysis of 12 kinds of cytokines in seminal plasma by flow cytometry and their correlations with routine semen parameters.

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

[Analysis of correlation between high expression of nucleoporin 85 (NUP85) and immune cell infiltration in hepatocellular carcinoma].

Objective To investigate the significance of nucleoporin 85 (NUP85) ex-pression in hepatocellular carcinoma (HCC) and analyze its relevance to immune response. Methods A comprehensive analysis was conducted using various online databases to assess the mRNA and protein expression of NUP85 in HCC, as well as its mutation status and prognostic diagnostic value. The immune relevance of NUP85 was evaluated using single-cell sequencing data and resources from the Tumor Immune Estimation Resource (TIMER) and the Gene Expression Profiling Interactive Analysis 2021 (GEPIA2021) databases. The drug sensitivity of NUP85 was analyzed through the Genomic Landscape of Cancer (GSCA) and the Clinical Bioinformatics Home. Co-expressed genes of NUP85 in HCC were filtered using the Hepatocellular Carcinoma Comprehensive Molecular Database (HCCDB), and the correlation between NUP85 and its related genes was analyzed using the R language "limma" package. The gene ontology (GO) functions, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) of NUP85 and its related genes were performed using the R language "clusterProfiler" package. The Clinical Bioinformatics Home was utilized to construct heatmaps and prognostic risk scoring models for NUP85 and its related genes. Results NUP85 mRNA and protein expression were upregulated in HCC, showing high levels across dif-ferent stages and grades, which indicates a poor prognosis for patients. The mutation rate of NUP85 in HCC samples was 19%, significantly affecting the overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) of patients. NUP85 was highly expressed in various immune cells, including macrophages, B cells, and T cells, and was positively correlated with the infiltration levels of multiple immune cells. The expression of NUP85 was significantly correlated with multiple drugs, such as Milademetan (PD0325901), a structural analog of Vemurafenib (PLX4720), and Regorafenib (PD0325901). The GO functions of NUP85 and its co-expressed genes were mainly enriched in organelle fission, nuclear division, and chromosome segregation, while the KEGG pathways were primarily enriched in the cell cycle and kinesin proteins. These factors significantly and unfavorably affected the OS of HCC patients, and the areas under the ROC curve (AUC) for the 1-year, 3-year, and 5-year OS prognostic diagnosis of HCC patients were all greater than 0.7. Conclusion The high expression of NUP85 in HCC is correlated with a poor prognosis and is related to various immune cells and drugs, making it a potential biomarker for di-agnosis, treatment, and prognosis in HCC.

Protein S-acylation, a new panacea for plant fitness.

Protein S-acylation or palmitoylation is a reversible post-translational modification that influences many proteins encoded in plant genomes. Exciting progress in the past 3 years demonstrates that S-acylation modulates subcellular localization, interacting profiles, activity, or turnover of substrate proteins in plants, participating in developmental processes and responses to abiotic or biotic stresses. In this review, we summarize and discuss the role of S-acylation in the targeting of substrate proteins. We highlight complex roles of S-acylation in receptor signaling. We also point out that feedbacks of protein S-acyl transferase by signaling initiated from their substrate proteins may be a recurring theme. Finally, the reversibility of S-acylation makes it a rapid and efficient way to respond to environmental cues. Future efforts on exploring these important aspects of S-acylation will give a better understanding of how plants enhance their fitness under ever changing and often harsh environments.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Dixon MRI-based quantitative parameters of extraocular muscles, intraorbital fat, and lacrimal glands for staging thyroid-associated ophthalmopathy.

OBJECTIVE: To investigate the value of Dixon magnetic resonance imaging (MRI)-based quantitative parameters of extraocular muscles (EOMs), intraorbital fat (IF), and lacrimal glands (LGs) in staging patients with thyroid-associated ophthalmopathy (TAO). METHODS: Two hundred patients with TAO (211 active and 189 inactive eyes) who underwent Dixon MRI for pretreatment evaluation were retrospectively enrolled and divided into training (169 active and 151 inactive eyes) and validation (42 active and 38 inactive eyes) cohorts. The maximum, mean, and minimum values of the signal intensity ratio (SIR), fat fraction (FF), and water fraction (WF) of EOMs, IF, and LGs were measured and compared between the active and inactive groups in the training cohort. Binary logistic regression analysis, receiver operating characteristic curve analysis, and the Delong test were used for further statistical analyses, as appropriate. RESULTS: Compared with inactive TAOs, active TAOs demonstrated significantly greater EOM-SIRmax, EOM-SIRmean, EOM-SIRmin, IF-SIRmax, IF-SIRmean, LG-SIRmax, LG-SIRmean, EOM-WFmean, EOM-WFmin, IF-WFmax, IF-WFmean, and LG-WFmean and lower EOM-FFmax, EOM-FFmean, IF-FFmean, IF-FFmin, and LG-FFmean values (all p < 0.05). The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were independently associated with active TAO (all p < 0.05). The combination of the EOM-SIRmean, LG-SIRmean, and LG-FFmean values showed better performance than the EOM-SIRmean value alone in staging TAO in both the training (AUC, 0.820 vs 0.793; p = 0.016) and validation (AUC, 0.751 vs 0.733, p = 0.341) cohorts. CONCLUSION: Dixon MRI-based parameters of EOMs, LGs, and IF are useful for differentiating active from inactive TAO. The integration of multiple parameters can further improve staging performance. CRITICAL RELEVANCE STATEMENT: In this study, the authors explored the combined value of quantitative parameters of EOMs, IF, and LGs derived from Dixon MRI in staging TAO patients, which can support the establishment of a proper therapeutic plan. KEY POINTS: The quantitative parameters of EOMs, LGs, and IF are useful for staging TAO. The EOM-SIRmean, LG-SIRmean, and LG-FFmean values were found to independently correlate with active TAO. Joint evaluation of orbital tissue improved the ability to assess TAO activity.