Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

Depression is closely associated with a neuro-endocrine-immune(NEI)system imbalance.The"excessive vitality leading to restraint and counter-regulation(Kang Hai Cheng Zhi)"theory elucidates the self-regulating mechanism for maintaining dynamic equilibrium in the body,and serves as an importance principle guiding treatment formulation and medication selection.Based on the correlation between NEI system imbalance and the traditional Chinese medicine pathogenesis of depression,and integrating the"Kang Hai Cheng Zhi"theory,the author posits that the pathogenesis of depression lies in overactive liver invading spleen,earth dampness impeding wood′s ascendancy,and disharmony between body and mind,as well as imbalance in storage and discharge functions of liver and kidney,disharmony between Yin and Yang,and disrupted counter-regulation.This dosely aligns with two key pathological methanisms at the micro level:microglial-limbic system homeostatic imbalance and hypothalamic-pituitary-adrenal axis-inflammatory circuit dysregulation.Clinically,the treatment principle for depression adheres to supporting the counter-regulation to restrain excess,with herbal interventions using strategies such as restraining wood to support earth,dredging earth to unblock wood,and harmonizing pivotal functions,as well as nourishing water to nurture wood,warming kidney to tonify liver,and relieving depression to calm the spirit.These approaches aim to regulate the liver,spleen,and kidney,embodying the core therapeutic tenet of"striving for equilibrium,"thereby restoring the body′s self-regulating capability.

Sepsis-associated delirium(SAD)is a common and severe central nervous system(CNS)complication in patients with sepsis,whose occurrence mechanism is unclear and there is no effective treatment at present.Neuroendocrine immune regulation disorder is closely related to occurrence and development of SAD.Immune mediators can deliver peripheral immune information to CNS by humoral transport or through afferent nerves.Immune mediators invading center can not only directly damage neurons,but also activate innate immune cells of brain,further aggravate neuroinflammation,and cause neurotransmitter imbalance,neurotoxic effects,resulting in neuronal dysfunction,even apoptosis and subsequent behavioral and cognitive symptoms.This paper aims to review mechanisms of neuro-endocrine-immune regulation in occurrence and development of SAD,and to find effective targets for prevention and treatment of sepsis and SAD.

Chronic limb-threatening ischemia(CLTI)is a serious peripheral arterial disease(PAD)characterized by reduced blood flow in the limbs,resulting in tissue damage and dysfunction.Mesenchymal stem cells(MSCs)have become a research hotspot in the field of CLTI treatment in recent years due to their unique regenerative ability and immunomodulatory properties.In the environment of hypoxia and tissue injury,MSCs can promote angiogenesis,reduce inflammation and promote tissue repair by secreting cytokines,cell differentiation and inter-cellular signal transduction,so as to improve the symptoms and prognosis of patients with CLTI,showing a broad clinical application prospect.

Depression is closely associated with a neuro-endocrine-immune(NEI)system imbalance.The"excessive vitality leading to restraint and counter-regulation(Kang Hai Cheng Zhi)"theory elucidates the self-regulating mechanism for maintaining dynamic equilibrium in the body,and serves as an importance principle guiding treatment formulation and medication selection.Based on the correlation between NEI system imbalance and the traditional Chinese medicine pathogenesis of depression,and integrating the"Kang Hai Cheng Zhi"theory,the author posits that the pathogenesis of depression lies in overactive liver invading spleen,earth dampness impeding wood′s ascendancy,and disharmony between body and mind,as well as imbalance in storage and discharge functions of liver and kidney,disharmony between Yin and Yang,and disrupted counter-regulation.This dosely aligns with two key pathological methanisms at the micro level:microglial-limbic system homeostatic imbalance and hypothalamic-pituitary-adrenal axis-inflammatory circuit dysregulation.Clinically,the treatment principle for depression adheres to supporting the counter-regulation to restrain excess,with herbal interventions using strategies such as restraining wood to support earth,dredging earth to unblock wood,and harmonizing pivotal functions,as well as nourishing water to nurture wood,warming kidney to tonify liver,and relieving depression to calm the spirit.These approaches aim to regulate the liver,spleen,and kidney,embodying the core therapeutic tenet of"striving for equilibrium,"thereby restoring the body′s self-regulating capability.

Sepsis-associated delirium(SAD)is a common and severe central nervous system(CNS)complication in patients with sepsis,whose occurrence mechanism is unclear and there is no effective treatment at present.Neuroendocrine immune regulation disorder is closely related to occurrence and development of SAD.Immune mediators can deliver peripheral immune information to CNS by humoral transport or through afferent nerves.Immune mediators invading center can not only directly damage neurons,but also activate innate immune cells of brain,further aggravate neuroinflammation,and cause neurotransmitter imbalance,neurotoxic effects,resulting in neuronal dysfunction,even apoptosis and subsequent behavioral and cognitive symptoms.This paper aims to review mechanisms of neuro-endocrine-immune regulation in occurrence and development of SAD,and to find effective targets for prevention and treatment of sepsis and SAD.

Objective:To investigate the efficacy, feasibility, and safety of task-oriented exercise training for hospitalized elderly diabetic patients.Methods:This study is a parallel randomized controlled trial with a positive control and a single-blinded assessor.From July 2020 to July 2021, we included 84 elderly patients with type 2 diabetes who were hospitalized in the Department of Endocrinology at Beijing Hospital.These patients were randomly divided into two groups: the task-oriented exercise training group(TOE group)and the regular exercise training group(regular group). The TOE group participants were trained using a task-oriented exercise program that was specifically developed by our research team.On the other hand, the regular group participants were trained using a classical program that comprised of all exercise modes.Each subject received individualized exercise training for 10 consecutive days while staying in the hospital.We evaluated the efficacy, feasibility, and safety of the training programs by measuring the physical fitness of the participants, assessing the feasibility of the program, and monitoring any exercise-related adverse events that occurred.Results:A total of 79 subjects completed the entire intervention and follow-up period, with 40 subjects in the TOE group and 39 subjects in the regular group.In terms of efficacy, both groups showed improvement in their physical fitness indexes after the intervention, with no significant differences in the degree of improvement between the two groups(all P>0.05). When considering feasibility, the TOE group had a higher proportion of prospective feasibility at 87.5%(35 out of 40)compared to the regular group at 71.8%(28 out of 39). Similarly, the TOE group had a higher proportion of practical feasibility at 75.0%(30 out of 40)compared to the regular group at 53.8%(21 out of 39). The TOE group showed a significant advantage in practical feasibility between the two groups( χ2=3.862, P=0.049). As for safety, there were no exercise-related adverse events during the intervention in either group. Conclusions:The efficacy and safety of the task-oriented exercise program for hospitalized elderly diabetic patients is comparable to that of the regular program.Additionally, the task-oriented program is more feasible than the regular program.

Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

BACKGROUND:Combining seed cells with 3D bioprinting technology enables the specific construction of various tissues and organs to meet the demands of tissue repair.However,further research is needed on the promotion of angiogenesis in damaged tissues. OBJECTIVE:By cultivating a 3D scaffold structure of methacrylated gelatin loaded with fibroblasts,obtaining the supernatant,and mixing it in different proportions with a complete culture medium to simulate the cellular microenvironment during tissue repair,this study aimed to explore the role of various cellular microenvironments in promoting angiogenesis in endothelial cells. METHODS:A methacrylated gelatin scaffold structure loaded with fibroblasts was prepared using an extrusion-based 3D bioprinting process.Hydrogel scaffold extract was prepared and mixed with a complete culture medium in ratios of 1:1,1:2,and 1:4 to obtain conditioned medium.Mouse embryonic fibroblasts BALB3T3 and human umbilical vein endothelial cells were co-cultured with complete medium(control group)and hydrogel scaffold extract,respectively.Cell proliferation was assessed using the CCK-8 assay and cell viability was analyzed using live/dead staining.Three kinds of conditioned medium and complete medium(control group)were used to co-culture with human umbilical vein endothelial cells for tube formulation assay,vascular genetic testing,and immunofluorescence staining of CD31. RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the methacrylated gelatin scaffold exhibited a porous structure,and rheological results demonstrated excellent mechanical properties of the hydrogel.CCK-8 assay and live/dead cell staining showed that the hydrogel scaffold extract had no obvious cytotoxicity.(2)Tube formulation assay indicated that the hydrogel showed the total length of cell tubules in 1:1 conditioned medium group was smaller than that in the control group(P<0.05).There were no statistical differences among the four groups in the number of vascular branches formed by endothelial cells(P>0.05).(3)qRT-PCR results showed that for vascular endothelial growth factor mRNA expression,the 1:2 conditioned medium group was lower than the 1:1 conditioned medium group on day 1(P<0.01).On day 3,the expression level of vascular endothelial growth factor in the 1:2 conditioned medium group was higher than that in the control group(P<0.01).On day 5,the cytokine expression level in the 1:2 conditioned medium group was significantly higher than that in the other three groups(P<0.01 or P<0.000 1).The expression in the 1:1 conditioned medium group was significantly lower than that in the other three groups(P<0.05 or P<0.01).On day 1,the expression level of basic fibroblast growth factor in the 1:1 conditioned medium group was significantly higher than that in the control group and 1:4 conditioned medium group(P<0.01,P<0.05).The expression was higher in the 1:2 conditioned medium group than that in the control group(P<0.05).On day 3,the expression levels of cytokines in the 1:4 conditioned medium group was higher than that in the control group(P<0.05).(4)On day 3,the expression of CD31 in the 1:2 conditioned medium group was higher than that in the control group and the 1:4 conditioned medium group(P<0.05).(5)The results indicate that the resulting conditioned media can simulate the microenvironment of vascular regeneration after tissue damage,promoting the vascularization process of endothelial cells.The best promotion of vascularization in endothelial cells was observed when the ratio of supernatant to complete culture medium was 1:2.

Objective To investigate the effect and molecular mechanism of safflower yellow(SY)on wound healing of diabetic foot ulcer(DFU)in mice.Methods Forty-five C57BL/6 mice were injected intraperitoneally with streptozotocin to establish diabetic models.The diabetic mice were randomly divided into the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with insulin-like growth factor-1(IGF-1)group,with 9 mice in each group.Before modelling,mice in the model group were not given any intervention,mice in the low-dose SY intervention group and high-dose SY intervention group were injected intraperitoneally with 5 and 20 mg·kg-1 SY,respectively,and mice in the high-dose SY combined with IGF-1 group were injected intraperitoneally with 20 mg·kg-1 SY and 0.03 mg·kg-1 IGF-1.Except for the sham operation group,the DFU model was established by incising the dorsal skin of the foot in the remaining four groups of mice.No wound on the dorsal skin of the foot was made in the sham operation group,and the remaining surgical steps were the same as those in the model group.The body mass of mice in each group was measured on day 14 after modelling using an electronic scale,tail vein blood was collected for fasting blood glucose measurement,and the wound width was measured using a small vernier caliper.Then,the mice were executed to collect the wound tissues.Hematoxylin-eosin staining was used to detect the histopathological changes in the wound tissues of mice in each group.Reverse transcription-quantitative real-time polymerase chain reaction was used to measure the relative expression levels of platelet-derived growth factor(PDGF),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),type Ⅰ collagen(collagen Ⅰ),protein tyrosine phosphatase 1B(PTP1B)and advanced glycation end products(AGEs)mRNA in the wound tissues of mice in each group.Western blot was used to detect the relative expression levels of proliferation marker Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-associated proteins(caspase-3,caspase-6,and caspase-7),p85 phosphatidylinositol-3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT)protein in the wound tissues of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the wound tissues of mice in each group.Results The differences in blood glucose and body mass of mice among the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with IGF-1 group were not statistically significant(P＞0.05).The healing rate of wound tissues in the high-dose SY intervention group was significantly greater than that in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the healing rate of wound tissues among the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＞0.05).In the high-dose SY intervention group,a large number of collagen fibers were densely and orderly arranged in the wound tissues,accompanied by a large number of neovessels;in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group,the wound tissues were sparsely populated with collagen fibers,accompanied by a small number of neovessels.The relative expression levels of PDGF,VEGF,α-SMA and collagen Ⅰ mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expression levels of PTP1B and AGEs mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).The relative expression levels of PDGF,VEGF,α-SMA,collagen Ⅰ,PTP1B and AGEs mRNA showed no statistically significant difference among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The relative expression levels of Ki-67 and PCNA protein in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expre-ssion levels of caspase-3,caspase-6,caspase-7,p85 PI3K,and p-AKT protein were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the relative expression levels of Ki-67,PCNA,caspase-3,caspase-6,caspase-7,p85 PI3K and p-AKT protein among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＜0.01).There was no statistically significant difference in the levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the model,low-dose SY intervention and high-dose SY combined with IGF-1 groups(P＞0.05).Conclusion High-dose SY intervention promotes DFU wound healing in mice by increasing angiogenesis,collagen formation and cell proliferation and reducing insulin resistance,inflammatory response and cell apoptosis,which may be related to the inhibition of the PI3K/AKT pathway.