Autoimmune hepatitis （AIH） is an immune-mediated chronic liver inflammatory disease with unknown pathogenesis， and intestinal barrier dysfunction is considered an important factor. Meanwhile， there are sex and age differences in the incidence rate of AIH， suggesting that hormone may be involved in regulation. On this basis， this article focuses on the association between estrogen， intestinal barrier， and immune homeostasis， systematically reviews the evidence that estrogen deficiency disrupts intestinal barrier homeostasis， and further summarizes the potential mechanism of estrogen in regulating the development and progression of AIH via intestinal barrier.

Ten-eleven translocation 2 （TET2）， as a core enzyme in epigenetic regulation， dynamically regulates the differentiation and function of CD4⁺ T cells by mediating DNA demethylation. Recent studies have shown that TET2 deficiency can promote the progression of autoimmune hepatitis （AIH） by disrupting the Th17/Treg balance and activating inflammatory signals along the gut-liver axis. This article systematically reviews the bridging role of TET2 between CD4⁺ T cells and gut microbiota， explores the molecular mechanisms by which it drives AIH through the gut microbiota-epigenetics-immunity network， and discusses the potential intervention strategies targeting the TET2-microbiota axis.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

Chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS） is a prevalent and complex condition in urology and one of the leading causes of chronic pelvic pain. Due to its prolonged duration and recurrent episodes，CP/CPPS significantly impacts patients' quality of life. Abnormal activation of the nuclear transcription factor-κB （NF-κB） pathway influences pathological processes such as the inflammatory response，oxidative stress，apoptosis，and tissue fibrosis in the body，thereby promoting the progression of CP/CPPS. Currently，Western medical therapies include antibiotics，pain relievers，α-blockers，and physiotherapy，yet they still fail to halt the pathological process of CP/CPPS. Research indicates that traditional Chinese medicine （TCM） can modulate the NF-κB pathway through a multi-target and multi-pathway approach，effectively reducing prostate tissue damage and prostate index and alleviating pain and lower urinary tract symptoms. On the basis of existing studies，this paper systematically examines the intrinsic connection between CP/CPPS and the NF-κB pathway and summarizes the effects of TCM active ingredients （e.g.，emodin，quercetin，and gentiopicroside），extracts （e.g.，Oldenlandia diffusa extract），classical medidcinal pairs （e.g.，Phellodendri Chinensis Cortex-Smilacis Glabrae Rhizoma），and compound prescriptions and Chinese patent medicines （e.g.，Qianliexiao decoction，Jiedu Huoxue decoction，Qianlie Shutong capsules） in treating CP/CPPS by regulating the NF-κB signaling pathway. The review of the research findings on treating CP/CPPS through this pathway aims to offer insights for clinical practice of TCM in the prevention and treatment of CP/CPPS，as well as to provide references for basic research and new drug development in this domain.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress（CUMS）， to evaluate the quality marker（Q-Marker） and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography（HPLC） was used to establish the characteristic profiles of Baihe Dihuangtang， and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group， model group， fluoxetine group（3 mg·kg^-1）， low and high dose groups of ancient process（6.5， 26 g·kg^-1）， and low and high dose groups of modern process（6.5， 26 g·kg^-1）， with 10 mice in each group. Except for the normal group， CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling， administration groups were given the corresponding drugs by gavage every day， and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded， tail suspension test and open field test were used to evaluate the depressive behavior of mice， and enzyme-linked immunosorbent assay（ELISA） was employed to determine the contents of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established， the similarity between the two was 0.951， and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that， compared with the normal group， the model group showed increased immobility time in the tail suspension test， reduced total movement distance in the open field test， and elevated IL-1β， IL-6 and TNF-α levels in the serum（P<0.01）. Compared with the model group， the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise， and the levels of IL-1β， IL-6 and TNF-α in serum were significantly reduced（P<0.05， P<0.01）. Baihe Dihuangtang prepared by the two processes both had antidepressant effects， and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content， and the pharmacological effects are consistent， indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.

Objective:To explore and analyze the feasibility and efficacy of the 22G needle-guided suture for orbital septum fat flap fixation on the periosteum.Methods:The retrospective study was conducted. From January 2022 to November 2023, patients with tear trough deformity and eyelid bags underwent surgery of releasing the orbicularis retaining ligament (ORL) complex, orbital septum fat pad combined with 22G needle-guided suture in Department of Burn and Plastic Surgery, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology. Postoperative follow-up was conducted to observe the occurrence of complications. The lacrimal depression deformity was classified according to the Hirmand standard and the degree of lower eyelid bags was graded to evaluate the surgical outcome. Patients were evaluated their satisfaction using the visual analogue scale (very dissatisfied, dissatisfied, average, satisfied, very satisfied).Results:A total of 32 patients (30 females and 2 males) were included in this study. The age range was 31-62 years old with an average of 50.2 years. All patients were followed up for 6 months postoperatively. None of the patients had any severe complications, such as inferior eyelid ectropion, inferior eyelid retraction, scar hyperplasia, and diplopia. Four patients showed mild eyelid-eyeball separation, two patients had conjunctival edema, and all recovered in 1 month. The orbital fat protrusion, tear trough depression deformity, and lower eyelid skin laxity were significantly improved compared to before the operation. Postoperative satisfaction was 22 cases, very satisfied 10 cases, and patient satisfaction rate was 100% (32/32) after surgery.Conclusion:The method of 22G needle-guided suture to fix orbital septum fat pad represents a technically feasible, easy, and suitable for promotion.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.