[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.

In 2040, neurodegenerative diseases (NDD) will overtake cancer as the second leading cause of death after cardiovascular and cerebrovascular diseases. Therefore, the search for effective intervention measures has become the top priority to deal with this difficult burden. Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years to treat conditions such as decompression sickness, carbon monoxide poisoning and radiation damage. In recent years, studies have confirmed that HBOT has good effects in improving cognitive impairment after brain injury and stroke, and alleviating neurodegeneration and dysfunction related to NDD. Here we reviewed the pathogenesis and treatment state of NDD, introduced the application of HBOT in animal models and clinical studies of NDD, and expounded the application potential of HBOT in the treatment of NDD from the perspective of mitochondrial function, neuroinflammation, neurogenesis and angiogenesis, oxidative stress, apoptosis, microcirculation and epigenetics.
Hyperbaric Oxygenation ; Humans ; Neurodegenerative Diseases/physiopathology* ; Animals ; Oxidative Stress ; Apoptosis ; Mitochondria/physiology* ; Neurogenesis ; Epigenesis, Genetic

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

To explore the immunomodulatory effects of a new vegetable oil adjuvant(named E515)containing vitamin E(VE)and ginsenosides(GS)on rabbit peripheral blood lymphocytes and Bordetella of rabbit inactivated vaccine.E515,Bordetella bronchiseptica(Bb)and LPS were co-cultured with rabbit peripheral blood lymphocytes in vitro,and the lymphocyte conversion rate was detected by CCK8 method,and the content of lymphocyte supernatant cytokines was detected by ELISA method.After rabbits were immunized with E515-Bb vaccine,the antibody level was detec-ted by indirect ELISA,the serum cytokine content was detected by ELISA,and the protective effect of E515-Bb vaccine on rabbits was observed by challenge test.In vitro cell experiments showed that E515 could significantly increase lymphocyte proliferation and TH1/TH2 cytokine se-cretion in rabbit peripheral blood.In vivo animal experiments showed that E515 adjuvant could sig-nificantly enhance the level of Bb specific antibody induced by Bordetella vaccine in rabbits.In-crease the secretion level of TH1/TH2 cytokines and decrease the secretion level of TNF-α;It can effectively protect rabbits against Bordetella infection with a protection rate of 91.67％.Therefore,E515 as a new vegetable oil adjuvant deserves further study.

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures