Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

Amblyopia is a common visual development disorder and is the main cause of monocular vision impairment in children and adults. Photobiomodulation(PBM), a non-invasive treatment method, has gradually gained attention in the field of ophthalmology. This paper begins with the macroscopic manifestation of light on the animal model of amblyopia. Additionally, it discusses the pathological changes of the amblyopic retina and the human eye's central nervous system, as well as the influence and mechanism of PBM on the visual perception and processing system and its chemical effect on the visual system through dopamine and melatonin. It examines its mechanism of action, current clinical application status, and future development direction in order to provide new ideas and theoretical foundation for amblyopia treatment.

ObjectiveTo investigate the association between Eya3 expression and CD8⁺ T cell infiltration levels in the tumor microenvironment， as well as their prognosis in esophageal carcinoma （EC） patients following neoadjuvant chemoradiation （neo-CRT）. MethodsThe pathological specimens before treatment and after surgery and clinical data were collected from 50 patients with EC who received neo-CRT combined with surgery. The correlation between the Eya3 expression and postoperative pathological features， CD8⁺ T cell infiltration levels， disease-free survival（DFS） and overall survival （OS） were analyzed using immunohistochemistry（IHC） and multicolor immunofluorescence staining. ResultsThe rate of pathological complete response （pCR） was higher in patients with low baseline Eya3 expression in the EC before treatment（P=0.001 8）. Both median DFS （37.2 months vs. 15.3 months， HR：2.731，95% CI：1.167-6.394，P=0.021） and median OS （not reached vs. 26.7 months， HR：3.959，95%CI：1.539-10.18，P=0.004 3） are significantly longer for patients with low Eya3 than those with high Eya3. The expression of Eya3 significant negatively correlated with tumor-infiltrating CD8⁺T lymphocytes （ P＜0.001）， GZMB⁺CD8⁺T lymphocytes P=0.002） in surgical pathological specimens . The patients with high CD8⁺T lymphocytes and GZMB⁺CD8⁺T lymphocytes had significantly longer DFS than those with low level. ConclusionPatients with EC who have high expression of Eya3 have a poorer prognosis， and the infiltration levels of CD8⁺T lymphocytes and GZMB⁺CD8⁺T lymphocytes in the tumor microenvironment are lower. This suggests that the expression of Eya3 may affect the tumor immune microenvironment and thereby influence the prognosis of EC patients， and it may become a molecular marker for predicting the prognosis of EC patients..

Objective To analyze the occurrence status and risk factors of frailty in elderly patients with heart failure (HF), and improve the prognosis of elderly patients with HF. Methods Totally 306 elderly patients with HF who received treatment in the hospital were selected from April 2021 to April 2024 as the study subjects. The occurrence of frailty was counted, and the patients were divided into frailty group and non-frailty group according to occurrence status of frailty. Univariate and logistic multivariate regression analyses were adopted to analyze the risk factors of frailty in elderly HF patients. Results Among the 306 patients, there were 92 cases of frailty, with an incidence rate of 30.07%. There were obvious differences in age, HF grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine between groups (P<0.05). After logistic multivariate analysis, it was found that age≥70 years old, HF grading, malnutrition, negative emotions and creatinine were the high risk factors for frailty in elderly patients with HF, and left ventricular ejection fraction and hemoglobin level were the protective factors (OR: 1.662, 95%CI: 0.845-3.268; OR: 4.586, 95%CI: 2.318-9.071; OR: 3.971, 95%CI: 1.806-8.731; OR: 3.307, 95%CI: 1.457-7.503; OR: 0.456, 95%CI: 0.255-0.816; OR: 0.525, 95%CI: 1.156-0.967, P<0.05). Conclusion The risk of frailty is high in elderly patients with HF, and is affected by age, heart failure grading, nutritional status, negative emotions, left ventricular ejection fraction, hemoglobin and creatinine. Clinically, it is necessary to take prevention and intervention measures for such patients to reduce the occurrence of frailty.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective:To analyze the correlation between homocysteine (Hcy), ferritin and gestational anemia in advanced age pregnant women, and the effect on adverse pregnancy outcomes.Methods:The clinical data of 344 advanced age pregnant women in Handan City Maternal and Child Health Hospital from March 2021 to June 2022 were retrospectively analyzed. The adverse pregnancy outcomes were followed up and recorded. The pregnant women were divided into anemia group (114 cases) and control group (230 cases) according to the diagnostic criteria for anemia. The levels of Hcy and ferritin, etc. were compared between two groups, different degrees of anemia and different pregnancy outcomes. Pearson method was used to analyze the correlation between Hcy, ferritin and hemoglobin. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcomes in advanced age pregnant women with gestational anemia.Results:The Hcy in anemia group was significantly higher than that in control group: (31.39 ± 3.34) mol/L vs. (9.28 ± 1.44) mol/L, the ferritin was significantly lower than that in control group: (69.81 ± 5.08) μg/L vs. (96.43 ± 7.52) μg/L, and there were statistical differences ( P<0.01). Among 114 advanced age pregnant women with gestational anemia, 64 cases were mild anemia (mild anemia group), 35 cases were moderate anemia (moderate anemia group), and 15 cases were severe anemia (severe anemia group). The levels of Hcy in the control group, mild anemia group, moderate anemia group and severe anemia group were gradually increased: (9.28 ± 1.44), (24.79 ± 3.25), (37.63 ± 5.51) and (45.01 ± 7.23) mol/L, the levels of ferritin were gradually decreased: (96.43 ± 7.52), (81.19 ± 5.14), (64.82 ± 4.47) and (32.96 ± 2.01) μg/L, and the difference between pairwise comparisons were statistically significant ( P<0.05). Pearson correlation analysis result showed that Hcy was negatively correlated with hemoglobin ( r = - 0.596, P<0.01), and ferritin was positively correlated with hemoglobin ( r = 0.685, P<0.01). Among 114 advanced age pregnant women with gestational anemia, 35 cases had adverse pregnancy outcomes, and 79 cases had normal pregnancy outcomes. The age, gestational reproductive tract infection rate and Hcy in advanced age pregnant women with adverse pregnancy outcomes were significantly higher than those in advanced age pregnant women with normal pregnancy outcomes: (41.17 ± 3.74) years old vs. (38.25 ± 4.28) years old, 28.57% (10/35) vs. 10.13% (8/79) and (49.56 ± 4.12) mol/L vs. (23.34 ± 2.63) mol/L, the ferritin was significantly lower than that in advanced age pregnant women with normal pregnancy outcomes: (38.36 ± 3.08) μg/L vs. (83.74 ± 6.25) μg/L, and the degree of gestational anemia was more serious than that in advanced age pregnant women with normal pregnancy outcomes, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that age, gestational reproductive tract infection, Hcy, ferritin and the degree of gestational anemia were the independent risk factors of adverse pregnancy outcomes in advanced age pregnant women with gestational anemia ( OR = 1.570, 1.758, 1.865, 1.556 and 1.652; 95% CI 1.154 to 2.136, 1.181 to 2.617, 1.223 to 2.842, 1.100 to 2.201 and 1.175 to 2.323; P<0.01). Conclusions:The level of Hcy in advanced age pregnant women with gestational anemia is relatively higher, and the level of ferritin is relatively lower. The ferritin and Hcy levels are risk factors for adverse pregnancy outcomes in advanced age pregnant women with gestational anemia, and may be involved in the occurrence and development of gestational anemia in advanced age pregnant women.

Objective:To investigate the relationship of multi-slice CT (MSCT) findings and epidermal growth factor receptor (EGFR), kirsten rat sarcoma viral oncogene (KRAS) and survival outcome in patients with isolated lung adenocarcinoma.Methods:The clinical data of 120 patients with solitary lung adenocarcinoma treated in the First Hospital of Qinhuangdao from January 2019 to September 2021 were collected retrospectively, the MSCT findings were analyzed, the correlationship of MSCT findings and EGFR, KRAS were analyzed by Spearman correlation, the MSCT findings of patients with different prognosis were compared, the prognostic risk factors were analyzed by Cox proportional risk model. A decision curve was drawn to analyze the net return of MSCT findings and biological factors combined to predict the prognosis of patients with isolated lung adenocarcinoma.Results:The MSCT findings results of 120 patients of isolated lung adenocarcinoma showed that the tumor diameter was (16.22 ± 3.31) mm, 88 patients with lobed signs, 74 patients with burr signs, 16 patients with vascular cluster signs, 76 patients with pleural indentation signs, 12 patients with cystic cavity changes, 75 patients with pure ground glass density shadows, 45 patients with mixed ground glass density shadows, 67 patients with round or almost round, and 53 patients with irregular shapes. There were positive correlation between MSCT findings (lobed signs, burr signs, pleural indentation signs, and cystic cavity changes) and EGFR and KRAS status in patients with isolated lung adenocarcinoma ( P<0.05). After 12 months of follow-up, 4 patients were lost, 96 patients survived and 20 patients died. The results of Cox proportional risk model analysis showed that lobed signs, pleural indentation signs, EGFR and KRAS mutants were high risk factors for death in patients with isolated lung adenocarcinoma ( P<0.05). The results of decision curve analysis showed that when the threshold value was 0.1 - 0.5, the model combined with lobed signs, pleural indentation signs, EGFR and KRAS status predicted the net death rate was better than the prediction value of simple indicators. Conclusions:MSCT findings in patients with isolated lung adenocarcinoma is closely related to EGFR and KRAS status, and the combination of these three factors has a higher net return in predicting prognosis, which is conductive to guiding clinical treatment and prognosis evaluation.