ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.

Functional disorders of the Golgi apparatus are harmful to the health of organisms, leading to various diseases. Removing damaged Golgi apparatus is crucial for maintaining cellular homeostasis, therefore, autophagy of Golgi apparatus has gradually attracted attention. This article summarizes Golgi autophagy, briefly describes its structure and functions, Golgi autophagy receptors, and the role of Golgi autophagy in disease treatment. It also proposes the new concept of Golgimedicine, which looks forward to the role of Golgi in disease diagnosis, treatment, prognosis, genetic diseases, and rare diseases. This article aims to explore the scientific connotations of Golgi autophagy, Golgi structure and function from the perspective of Golgimedicine, providing theoretical references for drug target research, new drug development, and the healthy development of humanity.

Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

BackgroundCurrently， the problem of depressed mood in college students is becoming more prominent. The experience of childhood maltreatment is a significant contributor to depression among college students. Although the association between the two has been confirmed， the specific psychosocial mechanisms underlying how childhood maltreatment affects college students' mental health remain insufficiently evidenced. ObjectiveTo explore the mediating role of emotion regulation difficulties in the relationship between childhood maltreatment and depression among college students， and to investigate the moderated effects of psychological resilience and family socioeconomic status， aiming to provide references for improving depressive symptoms in college students. MethodsOn 14 March 2024， a cluster sampling method was employed to recruit 751 college students from a university in Heilongjiang Province. Participants were assessed with Childhood Trauma Questionnaire （CTQ）， Difficulties in Emotion Regulation Scale （DERS）， Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， 10-item Connor-Davidson Resilience Scale （CD-RISC-10） and Family Socioeconomic Status Questionnaire. Pearson correlation analysis was adopted to examine the correlation between the scores of scales. Model 4 and model 7 in Process 4.2 were used to test the mediating effects of emotional regulation difficulties and the moderated effects of psychological resilience and family socioeconomic status. Results① A total of 712 （94.81%） valid questionnaires were collected. ② College students' CTQ score was positively correlated with DERS score and PHQ-9 score （r=0.296， 0.507， P<0.01）， and negatively correlated with CD-RISC-10 score and Family Socioeconomic Status Questionnaire score （r=-0.148， -0.229， P<0.01）. ③ The indirect effect value of difficulties in emotion regulation on the relationship between childhood maltreatment and depression was 0.091 （95% CI： 0.018~0.046）， accounting for 17.95% of the total effect. ④ The first half of the mediation model "childhood maltreatment → difficulties in emotion regulation → depression" （childhood maltreatment → difficulties in emotion regulation） was moderated by psychological resilience （β=-0.030， t=-6.147， 95% CI： -0.040~-0.020） and family socioeconomic status （β=-0.051， t=-3.929， 95% CI： -0.077~-0.026）. ConclusionChildhood maltreatment exerts both a direct effect on college students' depression and an indirect effect through emotion regulation difficulties. The childhood maltreatment → emotion regulation difficulties pathway in this mediation model is moderated by psychological resilience and family socioeconomic status. ［Funded by Qiqihar Medical University Graduate Student Innovation Fund Project （number， QYYCX2023-48）； Special Research Fund Project for Young Doctors of Qiqihar Academy of Medical Sciences （number， QMSI2021B-08）］

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.

ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*