Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

This article explores the technological innovations and clinical prospects of robot-assisted hiatal hernia repair (RAHHR). RAHHR demonstrates outstanding performance in hiatal hernia repair, particularly for complex hernias, owing to its advantages such as 3D visualization and 7-degree-of-freedom robotic arms, which contribute to reduced recurrence rates and accelerated recovery. However, challenges remain, including high costs and limited operative space. Future directions include the development of single-port robotic systems, force feedback technology, and AI-powered surgical navigation. Standardized training and technological innovations are expected to promote its widespread application.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Phages, as obligate bacterial and archaeal parasites, constitute a virus group of paramount ecological significance due to their exceptional abundance and genetic diversity. These biological entities serve as critical regulators in Earth's ecosystems, driving biogeochemical cycles, energy fluxes, and ecosystem services across terrestrial and marine environments. Within soil microbiomes, phages function as microbial "dark matter," maintaining the soil-plant system balance through precise modulation of the microbial community structure and functional dynamics. Despite the growing research interests in soil phages in recent years, the proportion of such studies in environmental virology remains disproportionately low, which is primarily attributed to researchers' limited familiarity with the research methodologies for phage microecology, incomplete technical frameworks, and inherent challenges posed by soil environmental complexity. To address these challenges, this review synthesizes cutting-edge methodologies for soil phage investigation from four aspects: (1) tangential flow filtration (TFF)-based phage enrichment strategies; (2) integrated quantification approaches combining double-layer agar plating, epifluorescence microscopy, and flow cytometry; (3) multi-omics analytical pipelines leveraging metagenomics and viromics datasets; and (4) computational frameworks merging machine learning algorithms with eco-evolutionary theory for deciphering phage-host interaction networks. Through comparative analysis of methodological principles, technical merits, and application scopes, we establish a comprehensive workflow for soil phage research. Future research in this field should prioritize: (1) construction of soil phage resource libraries, (2) exploration of RNA phages based on transcriptomes, (3) functional characterization of unknown genes, and (4) deep integration and interaction validation of multi-omics data. This systematic methodological synthesis provides critical technical references for addressing fundamental challenges in characterizing soil phages regarding the community structure, functional potential, and interaction mechanisms with hosts.
Bacteriophages/physiology* ; Soil Microbiology ; Ecosystem ; Microbiota ; Metagenomics/methods*

Objective To establish a rapid analysis method for cyanide based on a ratiometric fluores-cent probe,providing a quantitative strategy for on-site visual and rapid detection of cyanide.Methods A dual-emission ratiometric fluorescent probe(AuNCs-FL)was constructed by using bovine serum al-bumin(BSA)-stabilized gold nanoclusters(AuNCs,fluorescence emission at 660 nm)as the responsive signal unit and fluorescein(FL,emission at 515 nm)as the internal reference.Results The etching effect of cyanide on AuNCs resulted in fluorescence quenching at 660 nm,while the fluorescence inten-sity of FL at 515 nm remained unchanged,enabling a rapid response analysis of cyanide shift from red to green fluorescence.The developed probe enabled rapid analysis of cyanide within 3 min,with a limit of detection(LOD)of 3.4 mg/L and a visual detection range of 10-100 mg/L.Conclusion The AuNCs-FL fluorescent probe is structurally simple,low-cost,and easy to operate,delivering rapid and accurate results.It also avoids the interference from sulfides encountered in commercial cyanide test kits,making it suitable for the on-site rapid detection of suspected powder samples in cyanide poisoning cases.