Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

OBJECTIVE To compare the efficacy and safety of different classes of antibacterial agents in hospitalized adult patients with community-acquired pneumonia （CAP）.METHODS PubMed， Embase，the Cochrane Library，Web of Science，CNKI，and Wanfang data were searched from inception to January 1，2026，to identify randomized controlled trials that evaluated different classes of antibacterial agents in hospitalized adults with CAP.After screening the literature， extracting the data， and evaluating the quality of the literature， a network meta-analysis was performed using Stata 18.0.RESULTS A total of 25 studies were included，involving 7 863 patients. In terms of efficacy，compared with carbapenems，penicillins，cephalosporins，macrolides，and pleuromutilins were associated with significantly higher treatment failure rates （ P ＜0.05），carbapenems and traditional tetracyclines were ranked as the top two by the surface under the cumulative ranking curve area （SUCRA）. No statistically significant differences were observed in mortality among the interventions （ P ＞0.05），carbapenems and other quinolones were ranked as the top two by SUCRA. In terms of safety，no statistically significant differences were observed among the interventions in the incidence of adverse events or discontinuation rates （ P ＞0.05）；traditional tetracyclines and novel tetracyclines were ranked as the top two by SUCRA for the incidence of adverse events，while novel tetracyclines and pleuromutilins were ranked as the top two by SUCRA for discontinuation rates.CONCLUSIONS Carbapenems significantly reduced the treatment failure rate in hospitalized adults with CAP. The safety profiles of all antibacterial agents were comparable， with novel tetracyclines showing a more favorable safety profile.

Objective:To investigate the therapeutic effect and potential mechanism of Nepetoidin B on rheumatoid arthritis (RA).Methods:DBA/1 mice were divided into four groups using the random number method, namely the control group, model group, methotrexate group, and Nepetoidin B group. The collagen-induced arthritis (CIA) model was prepared. Mice were treated from day 21th to day 60th. Arthritis symptoms were evaluated every three days during treatment. At the end of treatment, pathological changes of joint tissue were observed through HE staining. Serum IL-17, IL-6, MDA, and NO levels were measured using ELISA and biochemical colorimetric assays. The Nrf2/HO1 pathway in joint tissues was detected using western blot. A group of CIA mice was treated with Nepetoidin B, followed by an Nrf2 inhibitor to validate the mechanism. One-way analysis of variance was used to compare between multiple groups with homogeneity of variance, pairwise comparison using LSD- t test. Results:The study found that mice treated with methotrexate and Nepetoidin B exhibited a significant reduction in arthritis scores(CIA+Meth group 5.2±1.3, CIA+NepB group 6.8±1.2 vs. CIA group 11.0±1.7, t=6.69, P=0.004; t=5.00, P=0.009), and joint histopathology compared to the CIA mice(CIA+Meth group 1.5±1.0, CIA+NepB group 2.2±0.8 vs. CIA group 4.0±0.9, t=4.44, P<0.001; t=3.84, P=0.005). Additionally, there was a significant decrease in serum IL-17[CIA+Meth group(257±69)ng/ml, CIA+NepB group (279±103)ng/ml vs. CIA group(414±71)ng/ml, t=3.86, P=0.006; t=2.63, P=0.020], IL-6[CIA+Meth group(32±6)ng/ml, CIA+NepB group (44±5)ng/ml vs. CIA group(56±11)ng/ml, t=4.69, P<0.001; t=2.48, P=0.040) ,MDA [CIA+Meth group(22±4)μmol/L, CIA+NepB group(22±8)μmol/L vs. CIA group(34±11)μmol/L, t=2.77, P=0.038; t=2.29, P=0.049]and NO[ CIA+Meth group(37±12)μmol/L, CIA+NepB group(37±11)μmol/L vs. CIA group(56±12)μmol/L, t=2.71, P=0.040; t=2.90, P=0.035] levels, and a significant elevation in the Nrf2( 0.263±0.021, 0.273±0.022 vs. 0.221±0.034, t=3.18, P=0.044; t=2.70, P=0.049)/HO1 (0.524±0.021, 0.501±0.014 vs. 0.453±0.033, t=3.95, P=0.006; t=3.41, P=0.032) pathway in methotrexate and Nepetoidin B treated group. It was also observed that Nrf2 inhibitors could counteract the treatment effects of Nepetoidin B on arthritis (1.8±0.8 vs. 3.2±0.8, t=3.07, P=0.024). Conclusion:Nepetoidin B has the ability to inhibit oxidative stress by activating the Nrf2/HO1 pathway, which alleviates collagen-induced arthritis in mice.

Objective:To explore the effect and mechanism of Chlorfortunone A(ChlA) in the treatment of diabetic nephropathy(DN) in mice.Methods:The DN model mice were assigned to DN, low-dose ChlA(ChlAL) and high-dose ChlA(ChlAH), and the normal control groups(Ctrl). Kidney tissue was analyzed via HE and Masson staining, and urine albumin, fasting blood glucose and kidney weight were measured. Collagen1 and α-SMA proteins were detected in renal tissues. The level of GSH-px, SOD, CAT, and TGF-β were detected. The TGF-β/Smad2 pathway in kidney tissue was detected. The mechanism was verified by setting the high glucose+ ChlA+ TGF-β group in MPC-5 cells. The proliferation of the cells and DCFDA staining were detected.Results:Compared to the Ctrl group, the DN group had significantly higher UACR and kidney weight( P<0.001). High-dose ChlA reduced UACR and kidney weight( P<0.05), with no effect on blood glucose( P>0.05). Masson staining showed reduced fibrosis with ChlA treatment. Collagen I and α-SMA expressions were significantly higher in DN( P<0.001) and decreased with ChlA treatment( P<0.05). GSH-px, SOD, and CAT levels were lower in DN( P<0.001), while TGF-β was elevated( P<0.001); ChlA increased antioxidant enzymes and decreased TGF-β( P<0.05). The TGF-β/Smad2 pathway was upregulated in DN( P<0.001) and inhibited by ChlA( P<0.001). In vitro, ChlA reduced cell proliferation( P<0.05) and increased ROS levels( P<0.001). Conclusions:ChlA alleviates kidney injury and fibrosis in DN mice, reduces oxidative stress, which may be related to the inhibition of the TGF-β/Smad2 pathway.

Objective To investigate the clinical efficacy of the traditional Chinese medicine(TCM)throat opening and brightening method in treating unilateral vocal cord paralysis(UVCP).Methods Sixty patients with UVCP were prospectively collected and randomly assigned to two groups:the Chinese herbal medicine group(trea-ted with Buyang Huanwu Decoction,n=30)and the throat opening and brightening method group(treated with TCM throat opening and brightening method,n=30).The clinical studies that had utilized injection laryngoplasty for the treatment of UVCP(historical control group).Evaluation indicators included the voice handicap index-10(VHI-10),GRBAS-G,objective acoustic measurements of voice(vocal intensity,F0,shimmer,jitter,HNR),and aerodynamic measurements(maximum phonation time,MPT).Results Before treatment,no significant differences were observed between the two groups in all the evaluation indicators(P＞0.05).Post-treatment,the throat open-ing and brightening method group demonstrated significant improvements in VHI-10,GRBAS-G,shimmer,jitter,HNR,and MPT compared to pre-treatment values(P＜0.01),and these improvements were superior to those in the Chinese herbal medicine group.Pre-treatment VHI-10,GRBAS-G,and shimmer scores in the throat opening and brightening method group were significantly higher than those in the historical literature group(P＜0.01).Af-ter treatment,no significant differences were noted in any assessed parameters between the two groups(P＞0.05).Conclusion The TCM throat opening and brightening method significantly enhances phonatory function and quality of life in patients with UVCP,showing comparable efficacy to injection laryngoplasty.

ObjectiveStarting from the etiology， pathogenesis， and treatment strategies of endometriosis and adenomyosis， to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology. MethodsAccording to the systematic review of text and opinion （SrTO） process developed by the Joanna Briggs Institute （JBI） in Australia， this paper determined literature screening criteria by searching China National Knowledge Infrastructure （CNKI）， VIP， Wanfang， and China Biomedical Literature Database. Information was extracted after literature screening， and quality evaluation was conducted using the JBI Narrative， Text， and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative， Opinion， Text Evaluation， and Review Tool Summary Table was used for information synthesis， and data analysis and display were conducted in the form of text and charts. ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics， meridian circulation location， pathological product evolution， disease duration， emotional psychology， lifestyle habits， preference for food and drink， innate endowment， and acquired injury. In terms of treatment， it was advocated to divide the stage， treat according to different types， adapt to the times， integrate nature and humans， and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects， make good use of classic formulas and small prescriptions， pay attention to protecting the spleen and stomach and regulating emotions， and make good use of self-formulated empirical formulas for internal or external use. Besides， individualized long-term management of patients was also advocated. ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes， mechanisms， diagnosis， and treatments of endometriosis， providing a scientific and standardized reference for future theoretical exploration.

Objective: To investigate the effects of usnic acid(UA) on proliferation, cell cycle, apoptosis and autophagy of lung cancer cells A549 and NCI-H358. Methods: The CCK-8 method was used to detect the inhibitory effect of UA on two kinds of lung cancer cells proliferation. Flow cytometry was used to detect the cell cycle arrest effect of UA on two types of lung cancer cells. The fluorescence amount of UA-induced reactive oxygen species(ROS) in two kinds of lung cancer cells were detected by DCFH-DA probe assay and flow cytometry. Western blot was used to detect the expression of apoptosis related proteins Bax, Caspase-3, Cleaved-Caspase-3, and autophagy related proteins LC3-Ⅰ and LC3-Ⅱ in two types of lung cancer cells after treatment with UA and UA+ROS inhibition. Results: (1) Usnic acid reduced the survival rates of two types of cells and had a stronger ability to inhibit the proliferation of A549 cells than NCI-H358 cells.(2) Usnic acid blocked A549 cells in the G0/G1phase, while NCI-H358 cells in the G2/M and S phases.(3) Usnic acid induced an increase in ROS content in two types of cells. Compared to A549, NCI-H358 cells showed a greater increase in ROS, and the ROS inhibitor reduced the intracellular ROS increase induced by UA.(4) Usnic acid induced high expression of apoptosis-related proteins Bax and Cleaved Caspase-3 and increased the ratio of autophagy-related proteins LC3-Ⅱ/LC3-Ⅰ in both lung adenocarcinoma cells, and its pro-apoptotic and autophagic effects were stronger in A549 than in NCI-H358. After ROS inhibition, the expression levels of Bax and Cleaved Caspase-3 and the LC3-Ⅱ/LC3-Ⅰ ratio of both lung adenocarcinoma cells decreased, and the decrease was greater in NCI-H358 cells. Conclusion Usnic acid inhibits the proliferation of lung cancer A549 and NCI-H358 cells, induces cell cycle arrest, and induces apoptosis and autophagy in cancer cells. The inhibitory and killing effect of UA on A549 cells is stronger than that on NCI-H358 cells. In this case, the induced cell ROS are involved in the action of UA in two types of lung cancer cells. In contrast to A549 cells,ROS might play a more significant role in mediating the apoptosis and autophagy induced by usnic acid in NCI-H358 cells.

Reactive astrocytes, which exhibit a correlation with the degeneration of dopaminergic neurons, are present in a considerable number during the progression of Parkinson's disease (PD). However, the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated. Here, we demonstrate that fibroblast growth factor 7 (FGF7)/FGF receptor 2 (FGFR2) autocrine signaling intensifies astrocyte reactivity and inflammation. Genetic deletion of Arrb2, β-Arrestin2 encoding gene, led to escalated astrocyte reactivity in MPTP-treated mice, which was further substantiated in astrocyte-specific Arrb2 knockdown mice. RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity. Subsequently, conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes. Furthermore, deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice. Mechanistically, STAT1 was distinguished as the transcription factor suppressing Fgf7 expression, while β-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220, an E3 ubiquitin ligase for STAT1. More importantly, selectively engaging dopamine D2 receptor (Drd2)/β-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production, thereby restoring balance in astrocyte reactivity. Collectively, our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system, particularly within the context of PD. The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective:To investigate the effect of short-term intensive insulin pump therapy on blood glucose control and renal function in type 2 diabetes mellitus (T2DM) patients with diabetic kidney disease (DKD).Methods:The clinical data of 360 T2DM patients with DKD in Shanxi Bethune Hospital from January 2022 to October 2024 were retrospectively analyzed. These patients were divided into an observation group ( n=192; treated with continuous subcutaneous insulin infusion) and a control group ( n=168; treated with conventional hypoglycemic therapy) according to the different treatment modalities; subsequently, 103 pairs of patients entered final analysis by using the propensity score matching method. The differences in glycemic control and improvement of renal function were compared between these two groups. Results:Before the treatment, the blood glucose-, blood glucose fluctuation-, and kidney function-related indicators showed no significant differences between these two groups (all P>0.05). After the treatment, fasting blood glucose, two-hour postprandial blood glucose, and average blood glucose significantly decreased in both groups and were significantly lower in the observation group than in the control group (all P<0.05). In addition, the amplitude of postprandial blood glucose fluctuation, standard deviation of intraday multi-point blood glucose, and difference between the maximum and minimum intraday blood glucose values significantly declined after treatment and were also significantly lower in the observation group than in the control group (all P<0.05). The observation group had a significantly higher total glycemic control rate and a significantly lowr incidence of hypoglycemia (both P<0.05). Finally, the 24-hour urine protein level, serum creatinine level, and urine albumin/creatinine ratio of the observation group significantly dropped after the treatment, and these results were significantly lower than those in the observation group (all P<0.05). Conclusions:Intensive insulin pump therapy benefits T2DM patients with DKD by improving glycemic control and enhancing renal function.