AIM: To investigate the relationship between serum levels of sirtuins(Sirts)1-6 and oxidative stress markers, and to evaluate their diagnostic value for age-related cataract(ARC).METHODS:A prospective cohort of ARC patients admitted to the hospital between June 2019 and July 2021 was enrolled as the study subjects. Concurrently, age-matched healthy individuals undergoing routine physical examinations at the hospital during the same period were recruited as the control group. Baseline demographic and clinical characteristics were compared between the two groups. Serum levels of Sirt1-6 and oxidative stress markers including malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and total antioxidant capacity(TAC)were compared. Pearson correlation analysis was performed to assess the associations between serum Sirt1-6 levels and oxidative stress parameters. Multivariate Logistic regression analysis was conducted to analysis risk factors associated with ARC occurrence. Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of serum Sirt1-6 levels and oxidative stress indicators for ARC.RESULTS: The study included 127 ARC patients, comprising 68 men and 59 women, with a mean age of 66.05±2.58 y; the concurrent control group consisted of 121 patients, comprising 63 men and 58 women, with a mean age of 65.54±2.86 y. Serum levels of Sirt1, 3 and 6, SOD, GSH-Px, and TAC were significantly lower in the ARC group compared to the control group(all P<0.001), whereas MDA levels were markedly elevated(P<0.001). Pearson correlation analysis revealed that serum levels of Sirt1, Sirt3, Sirt6 in the ARC group were positively correlated with SOD, GSH-Px, and TAC, and negatively correlated with MDA. Multivariate Logistic regression analysis demonstrated that serum Sirt1, Sirt6, MDA, SOD, and GSH-Px were significantly associated with the occurrence of ARC(all P<0.001). ROC curve analysis showed that the combination of Sirt1, Sirt6, MDA, SOD, and GSH-Px yielded an area under the curve(AUC)of 0.995 for diagnosing ARC, which was significantly higher than that of Sirt1 alone(Z=4.978,P<0.001), Sirt6 alone(Z=7.487,P<0.001), MDA alone(Z=6.449,P<0.001), SOD alone(Z=5.773,P<0.001), or GSH-Px alone(Z=5.056,P<0.001), indicating superior diagnostic accuracy of the multimarker panel(P<0.05). CONCLUSION: Serum levels of Sirt1, 3, and 6 are generally reduced in ARC patients and are closely associated with oxidative stress imbalance. Specifically, decreased serum levels of Sirt1 and Sirt6, along with oxidative stress markers(elevated MDA and reduced SOD and GSH-Px)are identified as risk factors for ARC. Moreover, the combined detection of these indicators presents high diagnostic value for ARC.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Amino acid metabolism plays a critical role in the progression and development of breast cancer. Cancer cells, including those in breast cancer, reprogram amino acid metabolism to meet the demands of rapid proliferation, survival, and immune evasion. This includes alterations in the uptake and utilization of amino acids, such as glutamine, serine, glycine, and arginine, which provide essential building blocks for biosynthesis, energy production, and redox homeostasis. Notably, the metabolic phenotypes of breast cancer cells vary across molecular subtypes and disease stages, emphasizing the need for patient stratification and personalized therapeutic strategies. Advances in multi-level diagnostics, including phenotyping and predictive tools, such as AI-based analysis and body fluid profiling, have highlighted the potential for tailoring treatments to individual metabolic profiles. Enzymes, such as glutaminase and serine hydroxymethyltransferase, often upregulated in breast cancer, represent promising therapeutic targets. Understanding the interplay between amino acid metabolism and breast cancer biology, alongside the integration of personalized medicine approaches, can uncover novel insights into tumor progression and guide the development of precision therapies. This review explores the metabolic pathways of amino acids in breast cancer, with a focus on their implications for personalized treatment strategies.
Humans ; Breast Neoplasms/therapy* ; Female ; Amino Acids/metabolism*

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

The global outbreak of monkeypox in 2022 has aroused widespread concern in public health. To date, the prevention and treatment of monkeypox has mainly relied on smallpox vaccines and drugs. This study aims to screen and obtain therapeutic antibodies with high affinity, neutralizing activity, and protective effects, and provide candidate molecules for the development of specific therapeutic antibodies against monkeypox. Therefore, humanized mice were immunized to screen for antibodies against the envelope protein of the mpox virus. Two M1R-specific antibodies, 12G5 and 12H6, were obtained, with the affinity of 0.095 nmol/L and 0.089 nmol/L, respectively. The 50% reduction of the plaque counts (PRNT₅₀) of 12G5 and 12H6 was (1.821±1.766) μg/mL and (17.605±2.383) μg/mL, respectively. The two antibodies targeted two binding epitopes of M1R. Moreover, 12H6 could protect 60% of mice from death following the vaccinia virus challenge. This study provides research materials for subsequent in-depth studies on the immunoprotection of mpox virus and potential therapeutic strategies.
Animals ; Mice ; Antibodies, Viral/immunology* ; Monkeypox virus/immunology* ; Mpox, Monkeypox/immunology* ; Antibodies, Neutralizing/immunology* ; Viral Envelope Proteins/immunology* ; Humans ; Antibodies, Monoclonal/biosynthesis* ; Female

Inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, is associated with a significantly increased risk of both venous and arterial thromboembolism. Common risk factors for thrombosis include disease activity, surgery, older age, central venous catheterization, etc. However, thrombotic events related to pharmacological treatment are often under-recognized, despite their potential for severe consequences. With the rapid expansion of therapeutic options for IBD in recent years, it has become increasingly important to acknowledge that different agents carry varying levels of thrombotic risk. This review summarizes current evidence on the thrombotic risks associated with IBD therapies and outlines preventive strategies, aiming to optimize the thrombosis risk management and reduce treatment-related thrombotic events in IBD patients.

OBJECTIVE: To explore the effect mechanism of electroacupuncture (EA) for ameliorating diabetic peripheral neuropathy (DPN) based on the analysis of gut microbiota and metabolomics. METHODS: Thirty SPF-grade male SD rats were randomly divided into a normal group, a model group, and an EA group, with 10 rats in each one. Except in the normal group, the intraperitoneally injection with streptozotocin was used to induce diabetes mellitus model in the rest groups. In the EA group, acupuncture was delivered at bilateral "Zusanli" (ST36), "Sanyinjiao" (SP6), "Pishu" (BL20) and "Shenshu" (BL23), and electric stimulation was attached to "Zusanli" (ST36)-"Sanyinjiao" (SP6) and "Pishu" (BL20)-"Shenshu" (BL23), on the same side, with continuous wave and a frequency of 2 Hz, for 10 min in each intervention. The intervention measure of each group was delivered once every 2 days, 3 times a week, for 8 consecutive weeks. Body weight, random blood glucose (RBG), thermal withdrawal latency (TWL), and mechanical withdrawal threshold (MWT) before intervention, and in 4 and 8 weeks of intervention, separately, as well as sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV) of the sciatic nerve after intervention were measured. Metagenomic sequencing (MS) was used to analyze gut microbiota and screen for differential species. Liquid chromatography-mass spectrometry (LC-MS) was employed to detect the differential metabolites in plasma, and the metabolic pathway enrichment analysis was performed on the differential metabolites. Spearman correlation analysis was adopted to assess the relationship between gut microbiota and metabolomics. RESULTS: After 4 and 8 weeks of intervention, when compared with the model group, the EA group showed the increase in body weight, TWL, MWT (P<0.01), and the decrease in RBG (P<0.01). Compared with the normal group, SCV and MCV, as well as Chao1 index were dropped in the model group (P<0.01), and those were elevated in the EA group when compared with those in the model group (P<0.01). The dominant bacterial phyla of each group were Firmicutes (F) and Bacteroidota (B), the ratio of them (F/B) in the model group was lower than that of the normal group (P<0.05), and F/B in the EA group was higher when compared with that in the model group (P<0.05). In comparison with the normal group, the relative abundance increased in Prevotella, Segatella, Prevotella-hominis and Segatella-copri (P<0.05); and it decreased in Ligilactobacillus, Eubacterium, Pseudoflavonifractor, Ligilactobacillus-murinus (P<0.05) in the model group. Compared with the model group, the relevant abundance of the above mentioned gut bacteria was all ameliorated in the EA group (P<0.05, P<0.01). Among the three groups, 120 differential metabolites were identified and enriched in 28 key metabolic pathways, such as glycerophospholipid and linoleic acid, of which, glycerophospholipid was the most significantly affected pathway in EA intervention. Spearman correlation analysis showed that 6 phosphatidylcholine metabolites were significantly positively correlated with Pseudoflavonifractor and were negatively with Prevotella, Segatella, Prevotella-hominis, Segatella-copri; 5 phosphatidylethanolamine metabolites were significantly negatively correlated with Pseudoflavonifractor and positively correlated with Prevotella, Segatella, Prevotella-hominis, Segatella-copri. CONCLUSION EA may regulate metabolic pathways such as glycerophospholipid, modulate specific gut microbiota such as Pseudoflavonifractor, Prevotella, and Segatella, and the co-expressed differential metabolites like phosphatidylcholine and phosphatidylethanolamine, thereby reducing blood glucose and protecting nerve function, so as to relieve the symptoms of DPN of rats.
Animals ; Electroacupuncture ; Male ; Gastrointestinal Microbiome ; Diabetic Neuropathies/microbiology* ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Humans ; Acupuncture Points

Objective To analyze the trends in the disease burden of schistosomiasis in China from 1992 to 2021, and to project the disease burden of schistosomiasis in China from 2022 to 2030, so as to provide insights into the elimination of schistosomiasis in China. Methods The prevalence, age-standardized prevalence, disability-adjusted life year (DALYs) rate and age-standardized DALYs rate of schistosomiasis, as well as the years lost due to disability (YLDs) rate and age-standardized YLDs rate of anemia attributable to Schistosoma infections in China, the world and different socio-demographic index (SDI) regions were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources, and the trends in the disease burden due to schistosomiasis were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI). In addition, the age, period and cohort effects on the prevalence of schistosomiasis were examined in China using an age-period-cohort (APC) model, and the disease burden of schistosomiasis was predicted in China from 2022 to 2030 using a Bayesian age-period-cohort (BAPC) model. Results The age-standardized prevalence and DALYs rate of schistosomiasis, and the age-standardized YLDs rate of anemia attributable to Schistosoma infections were 761.32/10⁵, 5.55/10⁵ and 0.38/10⁵ in China in 2021. These rates were all lower than the global levels (1 914.30/10⁵, 21.90/10⁵ and 3.36/10⁵, respectively), as well as those in the medium SDI regions (1 413.61/10⁵, 12.10/10⁵ and 1.93/10⁵, respectively), low-medium SDI regions (2 461.03/10⁵, 26.81/10⁵ and 4.48/10⁵, respectively), and low SDI regions (5 832.77/10⁵, 94.48/10⁵ and 10.65/10⁵, respectively), but higher than those in the high SDI regions (59.47/10⁵, 0.49/10⁵ and 0.05/10⁵, respectively) and high-medium SDI regions (123.11/10⁵, 1.20/10⁵ and 0.12/10⁵, respectively). The prevalence and DALYs rate of schistosomiasis were higher among men (820.79/10⁵ and 5.86/10⁵, respectively) than among women (697.96/10⁵ and 5.23/10⁵, respectively) in China in 2021, while the YLDs rate of anemia attributable to Schistosoma infections was higher among women (0.66/10⁵) than among men (0.12/10⁵). The prevalence of schistosomiasis peaked at ages of 30 to 34 years among both men and women, while the DALYs rate of schistosomiasis peaked among men at ages of 15 to 19 years and among women at ages of 20 to 24 years. The age-standardized prevalence of schistosomiasis showed a moderate decline in China from 1992 to 2021 relative to different SDI regions [EAPC = -1.51%, 95% CI: (-1.65%, -1.38%)], while the age-standardized DALYs rate [EAPC = -3.61%, 95% CI: (-3.90%, -3.33%)] and age-standardized YLDs rate of anemia attributable to Schistosoma infections [EAPC = -4.16%, 95% CI: (-4.38%, -3.94%)] appeared the fastest decline in China from1992 to 2021 relative to different SDI regions. APC modeling showed age, period, and cohort effects on the trends in the prevalence of schistosomiasis in China from 1992 to 2021, and the prevalence of schistosomiasis appeared a rise followed by decline with age, and reduced with period and cohort. BAPC modeling revealed that the age-standardized prevalence and age-standardized DALYs rate of schistosomiasis, and age-standardized YLDs rate of anemia attributable to Schistosoma infections all appeared a tendency towards a decline in China from 2022 to 2030, which reduced to 722.72/10⁵ [95% CI: (538.74/10⁵, 906.68/10⁵)], 5.19/10⁵ [95% CI: (3.54/10⁵, 6.84/10⁵)] and 0.30/10⁵ [95% CI: (0.21/10⁵, 0.39/10⁵)] in 2030, respectively. Conclusions The disease burden of schistosomiasis appeared a tendency towards a decline in China from 1992 to 2021, and is projected to appear a tendency towards a decline from 2022 to 2030. There are age, period and cohort effects on the prevalence of schistosomiasis in China. Precision schistosomiasis control is required with adaptations to current prevalence and elimination needs.

AIM: To investigate the effect of corneal topography-guided phacoemulsification with transparent corneal incision on cataract patients.METHODS:A total of 92 cataract patients(92 eyes)admitted to our hospital from February 2021 to February 2023 were prospectively selected and randomly divided into two groups: the control group(46 eyes)received the conventional 11:00 clear corneal incision scheme, and the study group(46 eyes)received the steepest meridian clear corneal incision scheme. The uncorrected visual acuity, corneal surface morphology indicators, including surface regularity index(SRI), surface asymmetry index(SAI), and cylinder(CYL), subjective dry eye symptoms questionnaire scoring scale(SDES), tear film break-up time(BUT), and complications were compared between the two groups.RESULTS:All patients completed the follow-up. The uncorrected visual acuity of the study group was significantly better than that of the control group at 1 wk, 1 and 3 mo after surgery(all P<0.05); there were statistical significance in the SAI and CYL of both groups of patients at 3 mo after surgery(all P<0.05); the fluctuation levels of SDES and BUT in the study group were significantly lower than those in the control group at different time points after surgery(all P<0.05); and there was no statistical difference in complications between the two groups(P>0.05).CONCLUSION:Under the guidance of corneal topography, phacoemulsification through the transparent corneal incision of the steepest meridian of the cornea can improve the uncorrected visual acuity of cataract patients, restore the corneal surface morphology, and have few complications.