BACKGROUND:The 5-hydroxytryptamine system is one of the earliest-developing systems in mammals,playing crucial roles in diverse physiological processes throughout the entire life cycle.Traditionally,research on 5-hydroxytryptamine has primarily focused on its regulatory roles in physiological processes and central nervous system-related diseases.However,recent studies have also highlighted the significant roles of the 5-hydroxytryptamine system in the regenerative medicine.OBJECTIVE:To review the reparative functions of the central 5-hydroxytryptamine system in brain injury,spinal cord injury,and bone remodeling,as well as the roles of the peripheral 5-HT system in the regeneration and repair of tissues such as the liver,pancreas,intestines,and skin,thereby offering new insights into the development of therapeutic strategies in stem cell therapy,tissue engineering,and regenerative medicine.METHODS:A comprehensive literature search was conducted using the databases"PubMed"and"Google Scholar."The search terms included:"5-HT,""regeneration,""tissue repair,""5-HT and tissue repair,""brain injury,""spinal cord injury,""bone reconstruction,""liver regeneration,""enteric nerve regeneration,""tissue fibrosis,""pancreatic regeneration,""skin repair,"and"inflammation."Based on the inclusion and exclusion criteria,118 articles and books were finally included for review and analysis.RESULTS AND CONCLUSION:(1)The central 5-hydroxytryptamine system facilitates cellular regeneration in injuries such as brain damage,spinal cord injury,and bone remodeling,thereby promoting tissue repair following injuries.(2)The peripheral 5-hydroxytryptamine system plays a positive role in the repair of tissues such as the liver,pancreas,intestines,and skin.(3)However,the 5-hydroxytryptamine system also exhibits adverse effects in tissue repair and regeneration,such as promoting tissue fibrosis and exacerbating inflammation.Therefore,it should be used with caution.

BACKGROUND:The 5-hydroxytryptamine system is one of the earliest-developing systems in mammals,playing crucial roles in diverse physiological processes throughout the entire life cycle.Traditionally,research on 5-hydroxytryptamine has primarily focused on its regulatory roles in physiological processes and central nervous system-related diseases.However,recent studies have also highlighted the significant roles of the 5-hydroxytryptamine system in the regenerative medicine.OBJECTIVE:To review the reparative functions of the central 5-hydroxytryptamine system in brain injury,spinal cord injury,and bone remodeling,as well as the roles of the peripheral 5-HT system in the regeneration and repair of tissues such as the liver,pancreas,intestines,and skin,thereby offering new insights into the development of therapeutic strategies in stem cell therapy,tissue engineering,and regenerative medicine.METHODS:A comprehensive literature search was conducted using the databases"PubMed"and"Google Scholar."The search terms included:"5-HT,""regeneration,""tissue repair,""5-HT and tissue repair,""brain injury,""spinal cord injury,""bone reconstruction,""liver regeneration,""enteric nerve regeneration,""tissue fibrosis,""pancreatic regeneration,""skin repair,"and"inflammation."Based on the inclusion and exclusion criteria,118 articles and books were finally included for review and analysis.RESULTS AND CONCLUSION:(1)The central 5-hydroxytryptamine system facilitates cellular regeneration in injuries such as brain damage,spinal cord injury,and bone remodeling,thereby promoting tissue repair following injuries.(2)The peripheral 5-hydroxytryptamine system plays a positive role in the repair of tissues such as the liver,pancreas,intestines,and skin.(3)However,the 5-hydroxytryptamine system also exhibits adverse effects in tissue repair and regeneration,such as promoting tissue fibrosis and exacerbating inflammation.Therefore,it should be used with caution.

BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

BACKGROUND:As a degradable scaffold material for bone tissue engineering,lactic acid is widely used in tissue regeneration and repair research,and plays an important role in promoting tissue healing,new bone formation and angiogenesis. OBJECTIVE:To observe the effect of lactic acid degradation products on osteoclasts and to investigate the effects of lactic-interfered osteoclast conditioned medium on the proliferation,migration and tube-forming capacity of human umbilical vein endothelial cells. METHODS:(1)The mouse monocyte macrophage cell line RAW264.7 at logarithmic growth period was selected,and adherent cells were cultured in the osteoclast induction medium(DMEM medium with nuclear factor-κB receptor-activating factor ligand and 10%fetal bovine serum)containing different concentrations of lactic acid(0,5,10,20 mmol/L).After 5 days of culture,tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining were conducted.After 24 hours of culture,RT-PCR was used to detect the mRNA expression of tartrate-resistant acid phosphatase 5.(2)RAW264.7 cells at logarithmic growth period were selected and adherent cells were divided into two groups.Control group was cultured in the osteoclast induction medium,while experimental group was cultured in the osteoclast induction medium containing 10 mmol/L lactic acid.After 5 days of culture,the medium in each group was removed and the cells in the two groups were cultured in the serum-free DMEM medium for another 24 hours.Cell supernatant was then collected and used as the conditioned medium after mixed with an equal volume of DMEM medium containing 10%fetal bovine serum.Human umbilical vein endothelial cells at the logarithmic growth phase were taken and separately co-cultured with the conditioned medium of the control and experimental groups.The proliferation,migration and tube-forming ability of human umbilical vein endothelial cells were observed by cell counting kit-8 assay,migration assay,scratch assay and tube-forming assay.The mRNA and protein expression of angiogenesis-related genes and proteins were observed by RT-PCR and western blot. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and cytoskeletal fibrillar actin staining showed that 5 and 10 mmol/L lactic acid promoted osteoclastic differentiation of RAW264.7 cells and the promoting effect of 10 mmol/L lactate was more significant.RT-PCR results showed that the expression of tartrate-resistant acid phosphatase-5 mRNA of osteoclast-related genes was the highest when the lactic acid concentration was 5,10,and 20 mmol/L(P<0.05),especially 10 mmol/L.Compared with the control group,the proliferation,migration and tube-forming abilities of human umbilical vein endothelial cells were significantly increased in the experimental group(P<0.05).Compared with the control group,the expression levels of vascular endothelial growth factor and angiogenin 1 mRNA and protein were increased in the experimental group(P<0.05).To conclude,lactate-induced osteoclast conditioned medium could promote the angiogenesis of endothelial cells,and the mechanism may be related to the promotion of the expression of vascular endothelial growth factor and angiogenin 1.

BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

BACKGROUND:The diabetic microenvironment can cause excessive M1 polarization of macrophages,and this hyperglycemic inflammatory state can inhibit osteogenic differentiation of bone marrow mesenchymal stem cells,thus affecting the healing of diabetic bone defects.Studies have indicated that mogroside V possesses anti-inflammatory,antioxidant,and hypoglycemic properties.However,its potential to modulate M1 polarization of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition remains unclear. OBJECTIVE:To explore the effect of mogroside V on regulating M1 macrophage polarization and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition. METHODS:Murine diabetic models were established using C57BL/6 mice.Bone marrow-derived macrophages were isolated from tibia and fibula of normal and diabetic mice,and cultured in low-glucose and high-glucose media.Then M1 polarization of bone marrow-derived macrophages was induced using lipopolysaccharide and interferon-γ.Bone marrow-derived macrophages were treated with 160,320,and 640 μmol/L mogroside V.Flow cytometry was employed to determine the proportion of F4/80+CD86+cells.qRT-PCR was utilized to assess mRNA expression levels of inducible nitric oxide synthase,interleukin 1β,and interleukin 6.ELISA was employed to evaluate tumor necrosis factor-α secretion in bone marrow-derived macrophage supernatants.Bone marrow mesenchymal stem cells were isolated from tibia and fibula of C57BL/6 suckling mice,and induced osteogenic differentiation using low-or high-glucose osteogenic induction medium.Bone marrow mesenchymal stem cells were treated with M1 macrophage-conditioned mediums with or without 320 μmol/L mogroside V in osteogenic differentiation process.qRT-PCR was employed to assess the mRNA expression of alkaline phosphatase,Runt-related factor 2,osteocalcin,and osteopontin on day 14 after osteogenic induction.Alizarin red staining and quantitative analysis were conducted to evaluate calcium deposition on day 21 after osteogenic induction. RESULTS AND CONCLUSION:(1)Flow cytometry results showed that with the treatment of 320 and 640 μmol/L mogroside V,the proportion of F4/80+CD86+bone marrow-derived macrophages was significantly lower than that in the high-glucose control group(P<0.05).(2)qRT-PCR results showed that with the treatment of 160,320,and 640 μmol/L mogroside V,the mRNA expression levels of inducible nitric oxide synthase and interleukin 6 were significantly lower than that in the high-glucose control group(P<0.05).With the treatment of 320 and 640 μmol/L mogroside V,the mRNA expression level of interleukin 1β was significantly lower than that in the high-glucose control group(P<0.05).(3)ELISA results exhibited that with the treatment of 160,320,and 640 μmol/L mogroside V,the tumor necrosis factor-α secretion level was significantly lower than that in the high-glucose control group(P<0.05).(4)With the treatment of 320 μmol/L mogroside V,calcium salt deposition was increased in bone marrow mesenchymal stem cells under high glucose and inflammatory conditions(P<0.05),and the mRNA relative expression levels of alkaline phosphatase,Runt-related factor 2,and osteopontin were increased(P<0.05).These findings indicate that mogroside V can promote osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting the M1 polarization of bone marrow-derived macrophages under high glucose and inflammatory conditions and reducing the generation of inflammatory factors.

The European Society for Medical Oncology Asia Congress 2024 was held in Singapore from December 6 to 8,2024.The conference unveiled several groundbreaking studies in the field of hepatobiliary and pancreatic tumors,covering clinical applications related to neoadjuvant and adjuvant therapies,translational treatments,later-line therapies,and tumor biomarkers.These studies provide new insights into the clinical diagnosis and treatment of hepatobiliary and pancreatic malignancies and drive the development of related fields.This article focuses on the key topics in hepatobiliary and pancreatic malignancies presented at the conference,aiming to interpret the latest advances in the field and explore the hot issues and future directions for development in this area.

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.

Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous pancreatic tumors with insidious clinical manifestations.They have a high propensity for distant metastasis,with liver metastases being the most common,significantly impacting patient prognosis.Despite extensive research on treating pNEN with liver metastases in recent years,many controversies and gaps remain.With the advancement of multidisciplinary treatment approaches,therapeutic strategies for pNEN liver metastases have been continuously refined,encompassing surgical resection,local therapies(such as radiofrequency ablation and transarterial interventions),and systemic treatments(including chemotherapy,targeted therapy,immunotherapy,radionuclide therapy,and endocrine therapy).Combination therapy has become an emerging trend.Radical surgery remains the preferred option for resectable cases,while for inoperable or treatment-intolerant patients,a rational combination of local and systemic therapies can improve survival outcomes.Additionally,endocrine therapy is crucial in symptom relief and quality-of-life improvement for patients with functional pNEN.Multidisciplinary collaboration in formulating individualized treatment plans can significantly enhance patient prognosis.This review summarizes recent advancements in treating pNEN liver metastases,providing a reference for clinical decision-making.

Leukemia is a common malignant tumor of the blood system,and the accuracy of ICD coding plays a key role in medical record management and DRG grouping.Currently,in clinical practice,both French-American-British(FAB)classifi-cation and World Health Organization(WHO)classification are used for leukemia classification.With the introduction of MICM(morphology,immunology,genetics and molecular biology)technology,the leukemia classification system has become more re-fined,which also increases the complexity of medical record coding.Therefore,medical record coders need to keep up with the forefront of medical development,thoroughly understand the latest classification standards of leukemia,systematically summarize the coding points and ideas for myeloid leukemia,lymphoid leukemia and unclassified leukemia,and clarify the situation where leukemia is coded as the main diagnosis.In the context of DRG payment reform,clinical doctors should accurately fill in the dis-ease diagnosis and surgical operation information on the medical record cover,and when coding the medical record cover,the co-der needs to comprehensively consider the three principles of selecting the main diagnosis and the local DRG grouping rules to en-sure the accurate selection of the main diagnosis,thus improving the accuracy of DRG admission and providing a reliable basis for the rational allocation of medical resources.