[摘 要] 目的：探究银杏内酯B（GKB）调控蛋白激酶R样内质网激酶（PERK）/转录激活子4（ATF4）/C/EBP同源蛋白（CHOP）信号通路对肝癌细胞增殖、迁移、凋亡和上皮间质转化（EMT）的影响。方法：将人肝癌细胞MHCC-97H随机分为对照组、GKB组、GSK2656157（PERK抑制剂）组和GKB + GSK2656157组，以GKB和GSK2656157分别干预后，采用MTT法和EdU染色检测各组细胞的增殖活性及增殖率，划痕愈合实验、流式细胞术分别检测各组细胞的迁移及凋亡水平，WB法检测各组细胞中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。构建MHCC-97H细胞裸鼠移植瘤模型，以同法分组及药物干预后测定各组移植瘤体积，采用免疫组化、TUNEL染色分别检测各组肿瘤细胞增殖、凋亡水平，WB法检测各组移植瘤组织中EMT和PERK/ATF4/CHOP信号通路相关蛋白的表达水平。结果：与对照组比较，GKB组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著降低（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著升高（均P < 0.05）；GSK2656157组各指标变化与GKB组相反（均P < 0.05）。与GKB组比较，GKB + GSK2656157组细胞活性、增殖率、迁移率、移植瘤体积、Ki-67阳性细胞率、MMP2、N-cadherin与MMP9蛋白表达均显著升高（均P < 0.05），细胞凋亡率、TUNEL阳性细胞率、p-PERK/PERK与E-cadherin、ATF4、CHOP蛋白表达均显著降低（均P < 0.05）。结论：GKB可通过激活PERK/ATF4/CHOP信号通路抑制肝癌MHCC-97H细胞增殖、迁移和EMT并促进其凋亡。

Objective: To systematically evaluate the clinical efficacy of topical preparations of Mongolian medicine Manggari hot compress therapy (hereafter referred to as Manggari hot compress therapy) in treating cervical spondylotic radiculopathy (CSR) and explore the possible pharmacological material basis in the formula, providing evidence for the clinical application of Mongolian medicine in the treatment of CSR. Methods: The clinical trial employed a randomized, controlled, open-label, and outcome-assessor-blinded design. The CSR patients who were treated at the Department of Traditional Therapeutics Outpatient Clinic, Xilinguole Meng Mongolian General Hospital between July 1, 2024 and August 31, 2025, were enrolled. They were randomly assigned to three groups: an oral control group (administration of oral administration of mecobalamin tablets combined with cervical electric traction), an experimental group (Manggari external hot compress), and a patch control group (flurbiprofen gel plaster). The intervention lasted two weeks. Before and after treatment, the following subjective indicators were recorded: Mongolian Medicine Syndrome (MMS) score, Visual Analog Scale (VAS) score, Northwick Park Neck Pain Questionnaire (NPQ) score, and tongue morphology. Serum levels of inflammatory markers [tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β)] and oxidative stress markers [malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity] were measured using enzyme-linked immunosorbent assay (ELISA). Overall therapeutic efficacy was evaluated. One month after treatment completion, a follow-up assessment was conducted, and the MMS, VAS, and NPQ scores were recorded again for all patients. For the pharmacological substance exploration, ultra-high-performance liquid chromatography-Q-exactive orbitrap-mass (UHPLC-QE-MS) was employed to analyze blood-absorbed prototype components of Manggari, under both positive and negative ion modes. The targeting relationship between the core active compounds and the target protein was validated using molecular docking. Results: This study ultimately included 90 patients with CSR for analysis. Baseline characteristics showed no statistically significant differences among the three groups (P > 0.05). (i) Symptom scores. After treatment, the MMS, VAS, and NPQ scores decreased significantly from baseline in all three groups (P < 0.001). At follow-up, there was no significant difference in MMS, VAS, and NPQ scores of the experimental group compared with those at the end of the treatment (P > 0.05). After treatment, the experimental group showed significantly greater reductions in MMS, VAS, and NPQ scores than oral control and patch control groups (P < 0.001). At follow-up, these differences remained significant (P < 0.001). (ii) Inflammatory and oxidative stress markers. After treatment, serum levels of TNF-α, IL-6, and IL-1β, and MDA activity decreased significantly from baseline in all three groups (P < 0.001), and SOD content and GSH-Px activity increased significantly from baseline (P < 0.05). After treatment, the experimental group had significantly lower serum levels of TNF-α, IL-6, and IL-1β than oral and patch control groups. Additionally, it exhibited lower MDA activity and higher SOD content and GSH-Px activity compared with the two control groups. (P < 0.05). (iii) Overall efficacy. The total effective rate was 93.33% in the experimental group, 86.66% in the oral control group, and 83.33% in the patch control group. (iv) Pharmacological substance analysis. A total of 152 compounds were identified in the blood-absorbed components of Manggari. Among them, the core compounds—4-hydroxycoumarin, N-methylanthranilic acid, genistein, and ginsenoside-Rk1—showed binding energies to the key target proteins TNF-α and IL-1β range from − 4.7 to − 7.1 kcal/mol, with the majority of the binding energies being below − 5.0 kcal/mol, suggesting that it generally has a good binding affinity. Conclusion Mongolian medicine hot compress therapy effectively modulates inflammatory and oxidative stress responses through the combined action of its thermal effects and active pharmaceutical ingredients Manggari. It inhibits cervical nerve root inflammation and alleviates radicular pain, improving clinical symptoms, reducing pain severity, and alleviating neck functional disability.

Objective To investigate the risk factors for postoperative recurrence and metastasis in patients with T1 stageⅢ/Ⅳ clear cell renal cell carcinoma(ccRCC), and to analyze the influence of surgical methods on prognosis, so as to provide prognostic evaluation and treatment guidance for clinical practice. Methods A retrospective analysis was conducted on 398 patients diagnosed with T1 stage Ⅲ/Ⅳ ccRCC who underwent either partial nephrectomy(PN)or radical nephrectomy(RN)at Jiangsu Province Hospital during Jan. 2008 and Sep. 2022. The patients were divided into recurrence group(n=49)and non-recurrence group(n=349)according to whether the tumor recurred during the follow-up period. The general, clinical data and prognosis were compared between the two groups. Univariate and multivariate Cox regression analyses were used to explore the factors influencing disease-free survival(DFS)and overall survival(OS)after surgery. Subgroup analysis using Kaplan-Meier curves was performed for T1a and T1b patients. Results During the median follow-up of 67(42, 98)months, the recurrence group was characterized by older age, larger tumor diameter, higher proportion of T1b stage, and more complex tumor anatomy. Univariate and multivariate Cox regression analyses showed that age ≥55 years and R.E.N.A.L. score ≥7 were independent risk factors for poorer DFS and OS(P＜0.05). Subgroup analysis revealed that PN or RN did not significantly affect DFS or OS in T1a patients and OS in T1b patients, while RN significantly improved DFS in T1b patients(P＜0.05). Conclusion Age ≥55 years and R.E.N.A.L. score ≥7 are independent risk factors for poor DFS and OS in highgrade T1 ccRCC patients. For T1b patients, RN may improve DFS.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

Objective:To establish a quantitative analysis of multi-components by single marker(QAMS)for the determination of 6 alkaloid components,which is benzoylmesaconine,benzoyl-hypaconine,benzoylaconine,mesaconitine,hypaconitine,and aconitine in Zhachong Shisanwei Pills,and prove the scientificity and feasibility of the method in the quality analysis.Methods:The chromatographic separation was performed on an Agilent Eclipse Plus C18(250 mm×4.6 mm,5 μm)with gradient elution using 0.1 mol·L-1 ammonium acetate(0.5 mL of gla-cial acetic acid per 1 000 mL)(A)-acetonitrile:tetrahydrofuran(25∶15)(B),as the mobile phase(0-50 min,18%B-28%B),the detection wavelength was switched from 235 nm,the column temperature was kept at 40℃and the flow rate was 1.0 mL·min-1.The relative correction factors(fs/i)were established with the other 5 compo-nents to be measured using benzoylaconine as the internal reference,which were used to calculate the mass fraction of each component.At the same time,the mass fractions of the 6 effective constituents in Zhachong Shisanwei Pills were calculated by the external standard method(ESM).By comparing the content results of ESMand QAMS,the accura-cy of QAMS method were evaluated.Results:The relative correction factors(fs/i)of benzoylmesaconine,benzoylhyp-aconine,mesaconitine,hypaconitine,and aconitine in Mongolian medicine Zhachong Shisanwei Pills were reproduci-ble with good reproducibility,which were 0.680 4,0.450 6,0.850 8,0.676 1 and 0.757 0,the result obtained by QAMS approximated those obtained by external standard method(ESM).Conclusion:The method is simple,stable and reproducible,and can be used for the quality control of 6 alkaloid components in Zhachong Shisanwei Pills.

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Objective:To introduce the research and innovations around the application of aquatic rehabilitation techniques in the treatment of lumbago, and to summarize specific methods and applications in aeromedicine. Literature resource and selection Literature on the prevention and treatment of lumbago using aquatic rehabilitation techniques as well as on the rehabilitation of lumbago in pilots was retrieved and selected. Literature quotation Sixty-one references were cited. Literature synthesis Aquatic rehabilitation techniques can be classified into shower therapy, immersion therapy, and aquatic exercise therapy according to treatment regimens. Among them, immersion therapy and aquatic exercise therapy are commonly used in the treatment of lumbago. Aquatic rehabilitation techniques can effectively alleviate patients′ lumbago, improve their functional disorders, and enhance their quality of life. Prior to aquatic therapy, patients with lumbago need to have their motor function assessed to tailor the treatment protocol based on diagnostic findings and specific therapeutic objectives. Aquatic rehabilitation techniques, when used to prevent and treat lumbago in pilots under convalescence, are not only more effective than land-based training, but also more accessible to pilots due to their comfort and compliance. Many of our military rehabilitation and convalescent centers in China have integrated modern aquatic rehabilitation techniques into rehabilitation treatment by drawing on their rich water resources so as to improve the physical and mental health, social adaptability and military adaptability of pilots. Conclusions:When used for the prevention and treatment of lumbago, aquatic rehabilitation techniques are highly effective, safe and enjoyable, so they should be made more accessible to pilots during convalescence.