Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

CD8⁺ T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8⁺ T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8⁺ T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective To evaluate the short-term clinical effect of arthroscopic repair of rotator cuff injury with all-suture anchor using a prospective and single-cohort clinical trial.Methods Twenty-five patients with rotator cuff injuries(1.5 cm0.05).Conclusion Arthroscopic rotator cuff repair with all-suture anchor is feasible and safe,and has good short-term clinical effect.

A growing body of evidence has linked the gut microbiota to liver metabolism. The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health. However, the effects of Lactobacillus gasseri LA39, a potential probiotic, on liver metabolism remain unclear. Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes, and used the germ-free (GF) mouse model to evaluate host-microbe interaction. Here, we explored the effects of L. gasseri LA39 gavage on the protein expression profiles of the liver of GF mice. Our results showed that a total of 128 proteins were upregulated, whereas a total of 123 proteins were downregulated by treatment with L. gasseri LA39. Further bioinformatics analyses suggested that the primary bile acid (BA) biosynthesis pathway in the liver was activated by L. gasseri LA39. Three differentially expressed proteins (cytochrome P450 family 27 subfamily A member 1 (CYP27A1), cytochrome P450 family 7 subfamily B member 1 (CYP7B1), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1)) involved in the primary BA biosynthesis pathway were further validated by western blot assay. In addition, targeted metabolomic analyses demonstrated that serum and fecal β‍-muricholic acid (a primary BA), dehydrolithocholic acid (a secondary BA), and glycolithocholic acid-3-sulfate (a secondary BA) were significantly increased by L. gasseri LA39. Thus, our data revealed that L. gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation. Based on these findings, we suggest that L. gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.
Mice ; Animals ; Bile Acids and Salts/metabolism* ; Lactobacillus gasseri ; Proteomics ; Liver/metabolism* ; Biotransformation

Objective:To compare the clinical efficacy between reservation and sacrifice of remnants in the footprint area in arthroscopic repair of rotator cuff tear.Methods:A retrospective study was conducted to analyze the clinical data of 32 patients with rotator cuff tear plus remnants in the footprint area (2 cm < tear size <5 cm) who had been admitted to Department of Sports Medicine, The People's Hospital of Northern Jiangsu from May 2020 to July 2021. The patients were divided into 2 groups according to reservation or sacrifice of remnants in the footprint area in arthroscopic repair of rotator cuff tear. In the remnant-reservation group (16 cases): 5 males and 11 females with an age of (61.8±9.9) years, 9 left and 7 right shoulders affected, and (3.7±1.1) cm in size of rotator cuff tear; in the remnant-sacrifice group (16 cases): 4 males and 12 females with an age of (61.3±8.8) years, 8 left and 8 right shoulders affected, and (3.9±0.9) cm in size of rotator cuff tear. The 2 groups were compared in terms of visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley shoulder function score (Constant score), and range of motion of the affected shoulder before surgery, 3 months after surgery and at the last follow-up. The ratio of bilateral abductor muscle strengths (affected side/healthy side) was analyzed and compared between the 2 groups, and the healing of the rotator cuff was evaluated by MRI at the last follow-up.Results:The 2 groups were comparable because there were no significant differences in all their preoperative demographic data ( P>0.05). The 32 patients were followed up for (14.3±3.5) months after surgery. At 3 months after surgery, the VAS score in the remnant-reservation group [1.0 (0.0,1.0) point] was significantly lower than that in the remnant-sacrifice group [1.0 (1.0,1.0) point] ( P<0.05), but there was no significant difference between the 2 groups in ASES score, Constant score or range of motion of the affected shoulder ( P>0.05). At the last follow-up, the ASES score, forward flexion, abduction and ratio of bilateral abductor muscle strengths (affected side/healthy side) in the remnant-reservation group [(96.1±4.8) points, 170.0 (170.0,170.0)°, 160.0 (160.0,170.0)°, and 85.5%±13.8%]were significantly better than those in the remnant-sacrifice group [(91.4±5.9) points, 160.0 (160.0,170.0)°, 150.0 (140.0,155.0)°, and 72.6%±16.9%] ( P < 0.05), but there were no statistically significant differences between the 2 groups in VAS score, Constant score, neutral external rotation angle, or body-side internal rotation ( P>0.05). The Sugaya grading for MRI rotator cuff healing was significantly different between the 2 groups at the last follow-up ( P<0.05). Conclusion:In arthroscopic repair of rotator cuff tear, reservation of remnants in the footprint area can significantly relieve postoperative shoulder pain, and has obvious advantages in restoration of shoulder forward flexion, abduction and abductor muscle strength, leading to better healing of the rotator cuff and the large nodule than the remnant-sacrifice technique.

【Objective】 To evaluate the performance of electrochemiluminescence immunoassay (ECLIA) in detecting HIV antigen/antibody in blood screening. 【Methods】 A total of 128 donors, reactive to anti-HIV(ELISA)testing, from September 2016 to September 2020 were enrolled, and seven samples were reactive to double anti-HIV reagents, among which 6 were confirmed by WB, 1 confirmed by NAT as negative.Two group of donors, reactive to solo anti-HIV reagent but being confirmed negative by WB(n=121) vs.randomly selected donors non-reactive to ELISA + NAT(June to September 2020, n=1360), were subjected to HIV antigen/antibody testing using ECLIA to compare the testing results, including concordance rate, sensitivity and specificity. 【Results】 The ECLIA results remained non-reactive for 1360 samples initially non-reactive to both ELISA and NAT.The concordance rate of anti-HIV reactivity by ECLIA and ELISA+ WB were 100%(6/6). For 122 samples, reactive to ELISA anti-HIV testing but nonreactive to confirmatory testing, 4(3.28%)of them were reactive to HIV antigen/antibody testing and 118(96.72%) nonreactive, with the concordance rate of ECLIA and ELISA at 96.88%(124/128). The sensitivity, specificity and false positive rate of ECLIA and ELISA were 100% vs 100%, 99.73% vs 91.77%, and 0.27% vs 8.23%, respectively. 【Conclusion】 ECLIA for HIV antigen/antibody detection has good sensitivity and specificity, which can meet the requirements of blood screening, and the false positive rate is lower than that of ELISA, adopted commonly in blood bank at present.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the changes of regulatory B cells (Bregs) and lymphocyte subsets in children with primary immune thrombocytopenia (ITP), and to analyze their relationship with ITP duration and remission time.Methods:Proportion of different immune cell subsets were detected in the peripheral blood of 88 ITP children before treatmen, 84 ITP children after treatmen and 45 normal controls by flow cytometry. The treatments included glucocorticoids, intravenous IgG as first-line treatment. The changes of lymphocyte subsets in ITP children with different remission time after treatment were compared.Results:The Th, natural killer (NK), Breg cell counts and Th/Tc ratio in all children with ITP were significantly lower than those in the control group ( P<0.05), while the Tc and CD19 + B cells were significantly higher than those in the control group ( P<0.05). The Breg cell count in the persistent and chronic ITP groups was significantly lower than that in the newly diagnosed ITP ( P<0.05). A total of 84 children with ITP were relieved after treatment: 58 cases (69.1%) achieved long-term remission, and 26 cases (30.9%) had short-term remission. The Breg and lymphocyte subsets in the short-term remission ITP group after treatment were not significantly different from those before treatment, but there were still significant differences from the control group ( P<0.05); The Breg and lymphocyte subpopulations in the long-term remission ITP group after treatment were not significantly different from those in the control group, but compared with those before treatment, other cell subpopulations except Tc were significantly increased ( P<0.05); The NK cells and Breg cells in the long-term remission ITP group were significantly higher than those in the short-term remission ITP group ( P<0.05). Conclusions:The Bregs in peripheral blood of long-duration ITP children significantly decrease. After treatment, the Bregs in ITP children with long-term remission increase significantly, indicating that the restoration of the immune mechanism of Bregs may be related to the long-term remission of children with ITP.