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.

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.

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 of different doses of bortezomib combined with chemotherapy for multiple myeloma (MM).Methods:A prospective case series study was performed. A total of 81 MM patients at Leshan People's Hospital from February 2022 to May 2023 were collected as study subjects. According to the random number table method, patients were divided into high-dose bortezomib group (39 cases treated with 1.6 mg/m 2 bortezomib combined with dexamethasone and thalidomide) and low-dose bortezomib group (42 cases treated with 1.3 mg/m 2 bortezomib combined with dexamethasone and thalidomide). The clinical efficacy after 4 courses of treatment, adverse reactions, C-reactive protein (CRP), β 2 microglobulin (β 2-MG) and serum creatinine levels before and after treatment, survival and prognosis of patients in both groups were compared. Results:There were 29 males and 10 females in the high-dose bortezomib group and the age was (59±5) years; there were 31 males and 11 females in the low-dose bortezomib group and the age was (59±6) years. The differences in the general data of both groups were statistically significant (all P > 0.05). The overall effectiveness rate was 87.2% (34/39) and 80.9% (34/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 0.58, P = 0.446). The incidence rate of adverse reactions was 30.8% (12/39), 19.0% (8/39), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 1.49, P = 0.222). Before treatment, there were no statistically significant differences in the levels of CRP, β 2-MG and serum creatinine between the 2 groups (all P > 0.05); after treatment, there were statistically significant differences in the levels of CRP [(23.6±2.2) g/L vs. (31.5±3.6) g/L)], β 2-MG [(2 317±63) μg/L vs. (4 212±114) μg/L] and serum creatinine [(70±5) μmol/L vs. (79±7) μmol/L] in the high-dose bortezomib group and the low-dose bortezomib group ( t value was 4.28, 18.29, 4.00, all P<0.05); and the levels of above 3 indicators after treatment were lower than those before treatment of both groups (all P < 0.05). The mortality rate was 10.3% (4/39) and 14.3% (6/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group 1-year follow-up after treatment, and the difference was not statistically significant ( χ2 = 0.30, P = 0.582). Conclusions:The efficacy and safety of high-dose bortezomib combined with chemotherapy are comparable to those of low-dose bortezomib combined with chemotherapy in treatment of MM, while the former could improve renal function and inflammatory status of MM patients.

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.

Objective To explore the risk factors for retinopathy in patients with metabolic syndrome.Methods A total of 120 patients with metabolic syndrome admitted to Nanyang Central Hospital from July 2021 to July 2023 were selected as the research subjects,and the patients were categorized into the retinopathy group(n=58)and the non-retinopathy group(n=62)according to the results of fundus examination.The clinical data of patients with metabolic syndrome in both groups were collected and compared.10 mL of blood was collected from the elbow vein of patients in both groups,and the hemoglobin level was measured using a fully automatic blood cell analyzer.The levels of total cholesterol(TC),triacylglycerol(TG),high density lipoprotein-cholesterol(HDL-C),and low density lipoprotein-cholesterol(LDL-C)in the two groups were measured using an automatic biochemical analyzer.The glycosylated hemoglobin(HbA1c)level was determined by high-performance liquid chromatography.The estimated glomerular filtration rate(eGFR)was calculated using the chronic kidney disease epidemiology collaboration equation.Multivariate logistic regression analysis was used to determine the risk factors for retinopathy in patients with metabolic syndrome.Results There were no statistically significant differences in smoking history,drinking history,usage rates of hypoglycemic drugs,lipid-lowering drugs and antihypertensive drugs,systolic blood pressure,cataract,TC,TG,HDL-C,LDL-C,and eGFR between the two groups(P＞0.05).The age,disease duration,insulin usage rate,diastolic blood pressure,HbA1c level,and anemia incidence of patients in the retinopathy group were significantly higher than those in the non-retinopathy group(P＜0.05).Multivariate logistic regression analysis showed that older age,longer disease duration,insulin injection,higher diastolic blood pressure,higher HbA1c level,and lower hemoglobin level were independent risk factors for retinopathy in patients with metabolic syndrome(P＜0.05).Conclusion Old age,long disease duration,insulin injection,high systolic blood pressure,high HbA1c level,and low hemoglobin level are independent risk factors for retinopathy in patients with metabolic syndrome.

Objective To investigate the risk factors and risk prediction model of retinal detachment in patients with myopia.Methods The clinical data of myopic patients treated in our hospital from January 2021 to December 2023 were retrospectively analyzed.A total of 128 patients(128 eyes)with myopic retinal detachment who met the requirements were selected as the retinal detachment group,and 128 myopic patients(128 eyes)without retinal detachment were selected as the control group.The clinical data of patients in the two groups were collected and compared,including age,gender,di-opter,education level,affected side,whether to bear load or not,whether to vibrate or not,whether to have cataract or not,whether to have asthenopia or not,blood pressure,history of diabetes,history of ocular trauma,history of ophthal-mic surgery,and retinal thickness.Risk factors related to retinal detachment in myopia were determined through the multi-variate logistic regression analysis,and based on these factors,the risk prediction model was established.The receiver op-erating characteristic(ROC)curve was used to evaluate the predictive value of the model.Results The age,diopter,systolic blood pressure,cataract incidence,asthenopia incidence,ocular trauma and ophthalmic surgery rates of myopic patients in the retinal detachment group were significantly higher than those in the control group(all P＜0.05).The retinal thickness and choroidal thickness of myopic patients in the retinal detachment group were significantly smaller than those in the control group(both P＜0.05).The risk factors for retinal detachment in myopic patients were older age,higher diopter(absolute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner choroid,and thinner retina(all OR＞1,P＜0.05).The areas under the ROC curve(0.95CI)for predication of retinal de-tachment based on age,ocular disease or discomfort,diopter,choroidal thickness,and retinal thickness alone and their combination were 0.668(0.382-0.936),0.645,0.676(0.407-0.942),0.731(0.503-0.933),0.745(0.499-0.983),and 0.844(0.692-0.983),respectively.The area under the curve(0.844),sensitivity,specificity,and accuracy of the prediction model based on the combination of the five indicators were higher,indicating that this model had a better predic-tion effect.Conclusion The risk factors for retinal detachment in myopic patients are older age,higher diopter(abso-lute value),accompanied by ocular diseases or discomfort such as cataract,asthenopia and ocular trauma,thinner cho-roid,and thinner retina.The risk prediction model constructed based on these factors has a high evaluation effect.