Objective:To investigate the plasma level of interleukin(IL)-37 and assess its regulatory effects on monocyte activity in type 1 diabetes mellitus(T1DM) patients.Methods:This prospective study included 57 T1DM patients and 21 healthy controls who were continuously enrolled from December 2022 to January 2024 at Xinxiang Central Hospital. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble interleukin 1 receptor 8(IL-1R8) levels were measured by enzyme-linked immunosorbent assay(ELISA). Levels of IL-37 receptor subunits in monocytes were analyzed via flow cytometry. Purified monocytes were stimulated with recombinant IL-37 and co-cultured with a human pancreatic β-cell line to assess cytotoxicity, measured by target cell death and cytokine levels. Additionally, monocytes were co-cultured with autologous CD4 + T cells to evaluate antigen presentation by measuring interferon-γ(IFN-γ) and IL-17A secretion. Results:Plasma IL-37 level and IL-37 receptor subunit expression in monocytes were significantly lower in T1DM patients compared to controls(both P<0.001). However, there was no significant difference in soluble IL-1R8 levels between the groups( P=0.457). Monocytes from T1DM patients exhibited increased cytotoxicity, as indicated by higher target cell death and elevated levels of granzyme A, granzyme B, granzyme H, IL-1β, IL-6, and tumor necrosis factor-α( P<0.05). Additionally, monocyte-induced secretion of IFN-γ and IL-17A by CD4 + T cells was elevated in T1DM patients(all P<0.05). Stimulation of T1DM monocytes with recombinant IL-37 reduced target cell death and decreased granzyme B secretion compared to unstimulated monocytes(both P<0.05). However, IL-37 stimulation had no significant effect on other cytokine levels or monocyte-induced IFN-γ and IL-17A secretion( P>0.05). Conclusions:Monocytes exhibit enhanced cytotoxicity and antigen-presenting capacity in T1DM patients. IL-37 reduces monocyte cytotoxicity by inhibiting granzyme B secretion, but does not affect antigen presenting function in T1DM.

Objective To investigate the mechanism of action of the Astragalus-Chinese yam combination in treating cancer-related fatigue(CRF)in mice.Methods The active components and related targets of Astragalus-Chinese yam were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform.CRF-associated targets were identified using the GeneCards database.Intersecting targets were analyzed using the DAVID database for gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses.A network diagram depicting"drug-active component-intersecting targets-disease"was constructed using Cytoscape software,and a protein-protein interaction network was created to identify the top five core target proteins based on degree values.Molecular docking simulations were performed using Autodock Vina software.Twenty-five mice were divided randomly into a blank group and a modeling group in a 1∶4 ratio.After successfully establishing the CRF model using Lewis lung cancer cells,mice in the modeling group were further divided into model,Chinese yam(0.2 g/kg),Astragalus(0.6 g/kg),and Astragalus-Chinese yam combination groups(0.3+0.1 g/kg)(n=5 mice per group).The treatments were administered by gavage twice daily for 14 consecutive days.Grip-strength and forced-swimming tests were conducted.The mice were then euthanized and tissues were collected.The gastrocnemius muscles were weighed and stained with hematoxylin and eosin to reveal the muscle fiber morphology.Results A total of 23 effective active components of Astragalus-Chinese yam were identified through network pharmacology analysis,with 199 intersecting drug-disease targets.These targets mainly participated in biological processes such as protein phosphorylation through cellular components(cytoplasm,membrane,nucleus)and performed molecular functions such as protein binding.A total of 155 signaling pathways,including pathway in cancer and the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,were involved in CRF.The critical targets of Astragalus-Chinese yam for CRF included serine/threonine kinase,tumor necrosis factor,epidermal growth factor receptor,B-cell lymphoma 2,and caspase 3.The active components quercetin and diosgenin interacted with the highest number of targets and demonstrated binding energies＜-5.0 kJ/mol with the five core targets,indicating strong ligand-receptor binding affinity.Mice in the Chinese yam and Astragalus groups exhibited increased grip strength and prolonged swimming times compared with the model group.Gastrocnemius muscle volume and mass were increased,with well-organized muscle fibers and clear boundaries,and the effects were even more pronounced in the Astragalus-Chinese yam combination group.Conclusions Astragalus-Chinese yam treats CRF via a multi-target,multi-pathway approach,enhancing muscle strength and endurance in mice,improving gastrocnemius muscle volume and mass,and alleviating muscle atrophy,thereby mitigating the associated symptoms of CRF in mice.

The development of malignant tumors is influenced by multiple factors,including genetics,environment,lifestyle,and pathogen infection.Viral infection plays a significant role in tumor development and progression.This article integrates the common pathways of seven oncogenic viruses(HPV,EBV,HBV,HCV,KSHV,HTLV-1,and HIV)based on the theory of cancer toxin pathomechanism.The findings reveal that cancer toxin formation is influenced by both internal factors(healthy qi deficiency,viscus dysfunction,and qi,blood,and body fluid stagnation)and external factors(viral infection,environmental factors,and the six exogenous pathogens),driving tumor development,metastasis,and recurrence.Viral infection not only provides the material foundation for cancer toxin but also accelerates its maturation and spread through chronic inflammation and immune imbalance,forming a complex pathogen-esis of"viral toxicity-endogenous cancer toxin",which translates into a three-stage strategy of"prevention,treatment,and post-recovery prevention".This article systematically discusses the pathogenesis of major cancer toxins and their associated tumors.Inte-grating the cancer toxin theory,the article explores preventive and therapeutic strategies for virus-associated malignancies,providing a theoretical basis and practical reference for the integrated prevention and treatment of tumors using traditional Chinese and Western medicine.

OBJECTIVE To investigate of the regulatory effects of Budi Shenlian Recipe on gut microbiota and the phenotypic transition of tumor-associated macrophages(TAMs)in colorectal cancer(CRC)mice.METHODS Forty male BALB/c mice were divided into blank control group,model group,positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group(n=8).CRC-bearing models were established by subcutaneous injection of CT26 cells.Additionally,10 male BALB/c mice were divided into the Budi Shenlian Recipe fecal microbiota transplantation(BFMT)group and model fecal microbiota transplantation(MFMT)group(n=5).The gut microbiota of these mice was cleared using a mixed solution of quadruple antibiotics,followed by subcutaneous injection of CT26 cells to construct pseudo-germ-free CRC-bearing mice.Fecal samples from the model group and high-dose Budi Shenlian Recipe group were collected to prepare fecal microbiota solutions.The BFMT group received gavage with fecal microbiota solution from the high-dose Budi Shenlian Recipe group,while the MFMT group received gavage with fecal micro-biota solution from the model group.Tumor volume changes were observed and recorded.HE staining was used to assess pathological changes in tumor tissues.16S sequencing was performed to analyze changes in gut microbiota.Flow cytometry and immunofluorescence staining were used to evaluate the proportion of M1/M2 type TAMs in tumor tissues.ELISA was used to detect differences in TNF-α and IL-10 levels in tumor tissues.RESULTS Compared to the model group,the tumor volume of mice in the positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group grew more slowly(P<0.01).HE staining showed necrotic areas in tumor tissues and reduced mitotic figures in the positive control and Budi Shenlian Recipe groups compared to the model group.16S rRNA sequencing showed no significant differences in Chao1 and ACE indices between the high-dose Budi Shenlian Recipe group and the model group.PCoA analysis indicated a distinct microbial community structure between the blank group and mod-el group,with the microbial structure of CRC mice in the Budi Shenlian Recipe group closer to that of the blank group.Compared to the blank group,the model group showed a significant decrease in the proportion of Muribaculaceae,Muribaculum,Alloprevotella,and Prevotellaceae_UCG-001,and a significant increase in Lachnospiraceae_NK4A136_group,Bacteroides,and Helicobacter.After admin-istering Budi Shenlian Recipe to CRC mice,the community structure of some mice partially reverted to the level of the blank group.Transcriptome sequencing revealed that the most significant biological process(BP)among upregulated genes was the negative regulation of macrophage migration,suggesting that Budi Shenlian Recipe can reduce macrophage migration.Moreover,compared to the model group,the proportion of TAMs cells in the tumor tissues of the Budi Shenlian Recipe group significantly decreased(P<0.001).Simultaneously,compared to the model group,the proportion of M1 type TAMs in the Budi Shenlian Recipe group significant-ly increased(P<0.000 1),while the proportion of M2 type TAMs significantly decreased(P<0.05).Immunofluorescence analysis showed the same trend as flow cytometry.The content of TNF-α in tumor tissues of the Budi Shenlian Recipe group significantly in-creased(P<0.001),and IL-10 content significantly decreased(P<0.001).Additionally,compared to the MFMT group,the tumor volume in the BFMT group grew more slowly(P<0.0001).HE staining showed increased necrotic areas,sparser cell arrangement,and reduced pathological mitosis in the BFMT group.Furthermore,compared to the MFMT group,the proportion of TAMs cells in the tumor tissues of the BFMT group significantly decreased(P<0.01).Compared to the MFMT group,the proportion of M1 type TAMs cells in the BFMT group increased(P<0.000 1),while the proportion of M2 type TAMs cells decreased(P<0.01).Immunofluores-cence analysis further confirmed that Budi Shenlian Recipe fecal microbiota transplantation can reduce the proportion of TAMs in the tumor tissues of CRC mice and promote the conversion from M2 to M1 type,thereby reducing immune suppression in the tumor micro-environment.CONCLUSION Budi Shenlian Recipe can improve gut microbiota dysbiosis in CRC mice and exert anti-CRC effects by reducing tumor infiltration of TAMs and modulating the phenotypic transition of TAMs.There may be a certain correlation between these two effects.

Objective To investigate the effect of combination therapy of evolocumab and statins on blood lipids,liver and renal functions and occurrence of cardiovascular events in elderly patients with multi-vessel coronary heart disease(CHD).Methods A total of 108 elderly patients with multi-vessel CHD admitted to our hospital from January 2022 to January 2023 were enrolled and randomly divided into statin group(54 cases)and combination group(atorvastatin+evolocumab,54 cases).The clinical efficacy,changes in blood lipids before and after treatment[TC,LDL-C and LP(a)],angina pectoris status[attack frequency and duration,Seattle angina questionnaire(SAQ)score],indicators of liver and renal functions(Scr,ALT,AST),endothelial function indi-cators(NO,ET-1),blood-related biochemical indicators[proprotein convertase subtilisin/kexin type 9(PCSK9),soluble intercellular adhesion molecule-1(sICAM-1)],and incidence rates of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 1 year were com-pared between the two groups.Results The total efficacy was significantly higher in the combina-tion group than the statin group(94.4％vs 81.5％,P＜0.05).There were no statistical differences in the levels Scr,ALT and AST in both groups before and after treatment(P＞0.05).After treat-ment,the levels of TC,LDL-C and Lp(a),frequency and duration of angina attack,and levels of ET-1,PCSK9 and sICAM-1 were significantly decreased,while SAQ score and NO level were ob-viously increased in both groups(P＜0.01).The combination group had notably lower frequency and shorter duration of angina attack,reduced levels of TC,LDL-C and Lp(a),and ET-1,PCSK9 and sICAM-1,and higher SAQ score and elevated NO level when compared with the statin group(P＜0.01).No statistical difference was seen in the incidence of adverse drug reactions between the two groups(13.0％vs 9.3％,P＞0.05).Within 1 year after treatment,the incidence of MACE in the combination group was notably lower than that in the statin group(3.7％vs 16.7％,P＜0.05).Conclusion Evolocumab has a significant lipid-lowering effect on elderly patients with multi-vessel CHD.It can significantly promote lipid metabolism,alleviate angina pectoris symp-toms,and improve vascular endothelial function and the prognosis outcomes,with good safety,which is worthy of application.

Regaining offspring is the most common medical demand for families who lost their only-child in China. However, couples who lost their only-child are often unable to have children naturally due to their old age. With the maturity of assisted reproductive technology (ART), embryo donation is a potentially effective method to help families regain their offspring. However, there is still lack of corresponding laws and operating standards in our country. This article reviews the research progress of embryo donation at home and abroad, and the experience of ART in our hospital, and discusses the feasibility of using ART to regain offspring of families who lost their only child, as well as the medical and ethical issues that need to be considered in practical operation, so as to provide reference for relevant departments.

Objective To investigate the mechanism of action of the Astragalus-Chinese yam combination in treating cancer-related fatigue(CRF)in mice.Methods The active components and related targets of Astragalus-Chinese yam were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform.CRF-associated targets were identified using the GeneCards database.Intersecting targets were analyzed using the DAVID database for gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses.A network diagram depicting"drug-active component-intersecting targets-disease"was constructed using Cytoscape software,and a protein-protein interaction network was created to identify the top five core target proteins based on degree values.Molecular docking simulations were performed using Autodock Vina software.Twenty-five mice were divided randomly into a blank group and a modeling group in a 1∶4 ratio.After successfully establishing the CRF model using Lewis lung cancer cells,mice in the modeling group were further divided into model,Chinese yam(0.2 g/kg),Astragalus(0.6 g/kg),and Astragalus-Chinese yam combination groups(0.3+0.1 g/kg)(n=5 mice per group).The treatments were administered by gavage twice daily for 14 consecutive days.Grip-strength and forced-swimming tests were conducted.The mice were then euthanized and tissues were collected.The gastrocnemius muscles were weighed and stained with hematoxylin and eosin to reveal the muscle fiber morphology.Results A total of 23 effective active components of Astragalus-Chinese yam were identified through network pharmacology analysis,with 199 intersecting drug-disease targets.These targets mainly participated in biological processes such as protein phosphorylation through cellular components(cytoplasm,membrane,nucleus)and performed molecular functions such as protein binding.A total of 155 signaling pathways,including pathway in cancer and the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,were involved in CRF.The critical targets of Astragalus-Chinese yam for CRF included serine/threonine kinase,tumor necrosis factor,epidermal growth factor receptor,B-cell lymphoma 2,and caspase 3.The active components quercetin and diosgenin interacted with the highest number of targets and demonstrated binding energies＜-5.0 kJ/mol with the five core targets,indicating strong ligand-receptor binding affinity.Mice in the Chinese yam and Astragalus groups exhibited increased grip strength and prolonged swimming times compared with the model group.Gastrocnemius muscle volume and mass were increased,with well-organized muscle fibers and clear boundaries,and the effects were even more pronounced in the Astragalus-Chinese yam combination group.Conclusions Astragalus-Chinese yam treats CRF via a multi-target,multi-pathway approach,enhancing muscle strength and endurance in mice,improving gastrocnemius muscle volume and mass,and alleviating muscle atrophy,thereby mitigating the associated symptoms of CRF in mice.

OBJECTIVE To investigate of the regulatory effects of Budi Shenlian Recipe on gut microbiota and the phenotypic transition of tumor-associated macrophages(TAMs)in colorectal cancer(CRC)mice.METHODS Forty male BALB/c mice were divided into blank control group,model group,positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group(n=8).CRC-bearing models were established by subcutaneous injection of CT26 cells.Additionally,10 male BALB/c mice were divided into the Budi Shenlian Recipe fecal microbiota transplantation(BFMT)group and model fecal microbiota transplantation(MFMT)group(n=5).The gut microbiota of these mice was cleared using a mixed solution of quadruple antibiotics,followed by subcutaneous injection of CT26 cells to construct pseudo-germ-free CRC-bearing mice.Fecal samples from the model group and high-dose Budi Shenlian Recipe group were collected to prepare fecal microbiota solutions.The BFMT group received gavage with fecal microbiota solution from the high-dose Budi Shenlian Recipe group,while the MFMT group received gavage with fecal micro-biota solution from the model group.Tumor volume changes were observed and recorded.HE staining was used to assess pathological changes in tumor tissues.16S sequencing was performed to analyze changes in gut microbiota.Flow cytometry and immunofluorescence staining were used to evaluate the proportion of M1/M2 type TAMs in tumor tissues.ELISA was used to detect differences in TNF-α and IL-10 levels in tumor tissues.RESULTS Compared to the model group,the tumor volume of mice in the positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group grew more slowly(P<0.01).HE staining showed necrotic areas in tumor tissues and reduced mitotic figures in the positive control and Budi Shenlian Recipe groups compared to the model group.16S rRNA sequencing showed no significant differences in Chao1 and ACE indices between the high-dose Budi Shenlian Recipe group and the model group.PCoA analysis indicated a distinct microbial community structure between the blank group and mod-el group,with the microbial structure of CRC mice in the Budi Shenlian Recipe group closer to that of the blank group.Compared to the blank group,the model group showed a significant decrease in the proportion of Muribaculaceae,Muribaculum,Alloprevotella,and Prevotellaceae_UCG-001,and a significant increase in Lachnospiraceae_NK4A136_group,Bacteroides,and Helicobacter.After admin-istering Budi Shenlian Recipe to CRC mice,the community structure of some mice partially reverted to the level of the blank group.Transcriptome sequencing revealed that the most significant biological process(BP)among upregulated genes was the negative regulation of macrophage migration,suggesting that Budi Shenlian Recipe can reduce macrophage migration.Moreover,compared to the model group,the proportion of TAMs cells in the tumor tissues of the Budi Shenlian Recipe group significantly decreased(P<0.001).Simultaneously,compared to the model group,the proportion of M1 type TAMs in the Budi Shenlian Recipe group significant-ly increased(P<0.000 1),while the proportion of M2 type TAMs significantly decreased(P<0.05).Immunofluorescence analysis showed the same trend as flow cytometry.The content of TNF-α in tumor tissues of the Budi Shenlian Recipe group significantly in-creased(P<0.001),and IL-10 content significantly decreased(P<0.001).Additionally,compared to the MFMT group,the tumor volume in the BFMT group grew more slowly(P<0.0001).HE staining showed increased necrotic areas,sparser cell arrangement,and reduced pathological mitosis in the BFMT group.Furthermore,compared to the MFMT group,the proportion of TAMs cells in the tumor tissues of the BFMT group significantly decreased(P<0.01).Compared to the MFMT group,the proportion of M1 type TAMs cells in the BFMT group increased(P<0.000 1),while the proportion of M2 type TAMs cells decreased(P<0.01).Immunofluores-cence analysis further confirmed that Budi Shenlian Recipe fecal microbiota transplantation can reduce the proportion of TAMs in the tumor tissues of CRC mice and promote the conversion from M2 to M1 type,thereby reducing immune suppression in the tumor micro-environment.CONCLUSION Budi Shenlian Recipe can improve gut microbiota dysbiosis in CRC mice and exert anti-CRC effects by reducing tumor infiltration of TAMs and modulating the phenotypic transition of TAMs.There may be a certain correlation between these two effects.

Objective To investigate the clinical value of serum leucine-rich α-2-glycoprotein 1(LRG1),uncoupling protein 2(UCP2)and sestrin2 in evaluating the cognitive status and prognosis of patients with acute ischemic stroke(AIS).Methods A total of 164 AIS patients who were treated and hospitalized in the Department of Neurology of our hospital from April 2020 to May 2023 were selected as the study subjects.According to the Chinese version of the Montreal cognitive assessment scale(MoCA),the patients were divided into cognitive impairment group and non-cognitive impairment group.The levels of serum LRG1,UCP2 and Sestrin2 were compared between the two groups.Pearson correlation analysis was used to test the correlation between serum LRG1,UCP2 and Sestrin2 and MoCA score.After discharge,the patients were followed up for 3 months.The mRS was used to divide the patients into poor prognosis group and good prognosis group.The data and serum levels of LRG1,UCP2 and Sestrin2 were compared between the two groups.Multivariate Logistic regression analysis was used to explore the prognostic factors of AIS patients.ROC curve was constructed to evaluate the predictive efficacy of serum LRG1,UCP2 and Sestrin2 alone and in combination on cognitive status and prognosis of AIS patients.Results There were 115 cases in the non-cognitive impairment group and 49 cases in the cognitive impairment group.The serum levels of LRG1 and UCP2 in the non-cognitive impairment group were significantly higher than those in the cognitive impairment group,while the Sestrin2 level was significantly lower than that in the cognitive impairment group(all P＜0.05).Serum LRG1 and UCP2 levels were positively correlated with MoCA score,while Sestrin2 level was negatively correlated with MoCA score(all P＜0.05).The area under the curve(AUC)of serum LRG1,UCP2 and Sestrin2 in cognitive status of AIS patients was 0.723,0.689 and 0.789,respectively,while the AUC of the combined detection of the three reached 0.892,and the 95％CI of the AUC of all indicators did not contain 0.5(all P＜0.05).There were 134 cases in the good prognosis group and 30 cases in the poor prognosis group.The NIHSS score,mRS score and Sestrin2 level in the good prognosis group were significantly lower than those in the poor prognosis group,while the MoCA score,LRG1 and UCP2 levels were significantly higher than those in the poor prognosis group(all P＜0.05).The increase of NIHSS score(OR=1.419),mRS score(OR=1.153)and serum Sestrin2 level(OR=1.462)were risk factors affecting the prognosis of AIS patients,while the increase of MoCA score(OR=0.657),serum LRG1 level(OR=0.756)and UCP2 level(OR=0.733)were protective factors affecting the prognosis of AIS patients(all P＜0.05).From the AUC value,the combination of the three(0.899)was significantly higher than Sestrin2(0.755),LRG1(0.730)and UCP2(0.712).The combination of sensitivity,specificity and Youden index was also significantly higher than other single indicators(all P＜0.05).Conclusion The combined detection of serum LRG1,UCP2 and Sestrin2 shows higher efficiency than single detection in the evaluation of cognitive status and prognosis of AIS patients,and its AUC,sensitivity,specificity and other indicators are better,providing more accurate and reliable evaluation basis for clinical practice.

Objective To investigate the effect of combination therapy of evolocumab and statins on blood lipids,liver and renal functions and occurrence of cardiovascular events in elderly patients with multi-vessel coronary heart disease(CHD).Methods A total of 108 elderly patients with multi-vessel CHD admitted to our hospital from January 2022 to January 2023 were enrolled and randomly divided into statin group(54 cases)and combination group(atorvastatin+evolocumab,54 cases).The clinical efficacy,changes in blood lipids before and after treatment[TC,LDL-C and LP(a)],angina pectoris status[attack frequency and duration,Seattle angina questionnaire(SAQ)score],indicators of liver and renal functions(Scr,ALT,AST),endothelial function indi-cators(NO,ET-1),blood-related biochemical indicators[proprotein convertase subtilisin/kexin type 9(PCSK9),soluble intercellular adhesion molecule-1(sICAM-1)],and incidence rates of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 1 year were com-pared between the two groups.Results The total efficacy was significantly higher in the combina-tion group than the statin group(94.4％vs 81.5％,P＜0.05).There were no statistical differences in the levels Scr,ALT and AST in both groups before and after treatment(P＞0.05).After treat-ment,the levels of TC,LDL-C and Lp(a),frequency and duration of angina attack,and levels of ET-1,PCSK9 and sICAM-1 were significantly decreased,while SAQ score and NO level were ob-viously increased in both groups(P＜0.01).The combination group had notably lower frequency and shorter duration of angina attack,reduced levels of TC,LDL-C and Lp(a),and ET-1,PCSK9 and sICAM-1,and higher SAQ score and elevated NO level when compared with the statin group(P＜0.01).No statistical difference was seen in the incidence of adverse drug reactions between the two groups(13.0％vs 9.3％,P＞0.05).Within 1 year after treatment,the incidence of MACE in the combination group was notably lower than that in the statin group(3.7％vs 16.7％,P＜0.05).Conclusion Evolocumab has a significant lipid-lowering effect on elderly patients with multi-vessel CHD.It can significantly promote lipid metabolism,alleviate angina pectoris symp-toms,and improve vascular endothelial function and the prognosis outcomes,with good safety,which is worthy of application.