Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

"Tendency of disease" is an important concept in the theory of traditional Chinese medicine （TCM）. It was born out of and rooted in the thinking of "conducting by tendency" of ancient Chinese philosophy， meaning that the development and change of humans and nature have their own inevitable laws and dynamic tendencies. Based on the concept of holism and constant motion， the basic definition of "tendency"， the origin of the idea， the influence factors and related concepts were analysed， to grasp the overall connection in the dynamic changes in space and time， and to find a scientific and comprehensive objective law of development. The "tendency" was regarded as dynamic forces in the complex system， when yin and yang harmonized， called normal tendency； when fail to keep normal， called disease tendency； the season have sequential tendency， the earth has geographical tendency， people have body tendency， medications have medical tendency， and pulse has pulse tendency. Then the "eight methods of treating tendency" were summed up as observing tendency， evaluating tendency， waiting for tendency， accumulating tendency， favoring tendency， counteracting tendency， preventing tendency， and borrowing tendency， and condenses the methodo-logical thinking of "treatment according to disease tendency"， with a view to re-understanding the internal logic of TCM diagnosis and treatment， and providing metaphysical contemplation and exploration for the construction of a new paradigm of TCM syndrome differentiation and treatment.

Objective To create a mouse model of colorectal polyps with Apc-Kras-Cre gene mutations using the tamoxifen induction method.Methods Mice with Apc-Kras-Cre mutations were divided into four groups and injected intraperitoneally with different concentrations and dosages of tamoxifen for different durations,with group 1 injected with low dosage tamoxifen(5 mg/kg)for 1 day,group 2 injected with low dosage tamoxifen(5 mg/kg)for 3 days,group 3 injected with high dosage tamoxifen(50 mg/kg)for 1 day,group 4 injected with high dosage tamoxifen(50 mg/kg)for 3 days.C57BL/6J mice were used as a healthy control group and survival and changes in body weight were observed.All mice were euthanized 4 weeks post-tamoxifen induction and the colon length and number and size of intestinal polyps were observed.Histological changes in the intestinal tissue and polyps were detected by hematoxylin and eosin staining.Results The survival rate of male mice was higher(P＜0.001)and the morbidity rate of male mice was lower compared with female mice(P＜0.05).The survival rate differed significantly among the four groups(P＜0.01).All groups showed significant changes in body weight compared with the healthy control group(P＜0.001).There were also significant differences in weight changes between tamoxifen-induced groups 1 and 2,between groups 2 and 3,and between groups 1 and 4(P＜0.001,P＜0.01,P＜0.05,respectively).There were no significant differences in colon length between any treated group and the healthy control group(P＞0.05),but colon length did differ between tamoxifen-induced groups 1 and 3(P＜0.05).Polyp size varied in each group of tamoxifen-treated mice,with most polyps occuring at the distal end of the colon,while mice in groups 3 and 4 had more and larger polyps.Histopathological examination showed intestinal polyps with uneven and misaligned glandular and epithelial arrangements,a loosely-packed intestinal mucosal barrier,and irregularly-distributed crypts in tamoxifen-induced mice compared with the healthy control group,while mice in tamoxifen-induced groups 3 and 4 showed signs of inflammation and mice in group 4 showed necrosis of cells in some regions.Conclusions Tamoxifen-induced Apc-Kras-Cre model mice were successfully established,with the group 3 induction method being the most suitable.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

ObjectiveTo study effect of brusatol （BR） on proliferation of human gastric cancer HGC-27 cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the survival rate of HGC-27 cells at different concentrations of BR. HGC-27 cells were treated with BR （7.5， 15， 30 μmol·L^-1） for 24 h， and then the cell clone formation was analyzed. 2，7-Dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescent probe and lipid peroxidation sensor （C11-BODIPY） were employed to detect the levels of intracellular reactive oxygen species （ROS） and lipid peroxidation， respectively. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the messenger ribonucleic acid （mRNA） and protein expressions of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， solute carrier family 40 member 1 （SLC40A1）， transferrin， nuclear factor E₂-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1）， respectively. ResultThe survival rate of HGC-27 cells was decreased with the increase of BR concentration， and the IC₅₀ was 15.34 μmol·L^-1. Compared with the conditions in blank group， the cell clone formation of BR （7.5， 15， 30 μmol·L^-1） groups was inhibited in a dose-dependent manner （P<0.05，P<0.01）， while the levels of intracellular ROS and lipid peroxidation， iron concentration， and lactic dehydrogenase （LDH） leakage were increased in a dose-dependent manner （P<0.05，P<0.01）. Compared with the blank group， the BR （15， 30 μmol·L^-1） groups lowered the mRNA and protein expressions of SLC7A11， GPX4， SLC40A1， Nrf2 and HO-1， while elevated the mRNA and protein expression of TRF in a dose-dependent manner （P<0.05，P<0.01）. ConclusionBR suppressed the proliferation of HGC-27 cells through inducing ferroptosis via inhibiting Nrf2/HO-1 pathway.

To summarize the nursing experience of a post-operational patient with valvular heart disease and prolonged weaning due to tracheomalacia.Key points of nursing include real-time monitoring of bleeding and coagulation,dynamic implementation of anticoagulation programs;strengthening airway management,early warning and treatment of airway collapse;multi-dimensional joint diagnosis and treatment to speed up the rehabilitation process;real-time assessment,sequential management of sedation,analgesia and nutrition programs.After 27 days of careful treatment and nursing,the patient was weaned from a ventilator successfully and transferred to another department,and was discharged after 5 days.