BACKGROUND:The incidence of inflammatory bowel disease has been steadily rising,accompanied by a lack of definitive therapeutic strategies.Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease,offering a glimmer of hope for afflicted patients.OBJECTIVE:To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease,aiming to provide insights for future research endeavors.METHODS:Utilizing the keywords"mesenchymal stem cells,MSCs,exosomes,extracellular vesicles,EVs,inflammatory bowel disease,IBD,ulcerative colitis,UC,Crohn's disease,CD"in English and their Chinese equivalents in CNKI and PubMed databases,a total of 89 eligible articles were selected for this review.RESULTS AND CONCLUSION:Currently,six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy:bone marrow-derived mesenchymal stem cells,adipose tissue-derived mesenchymal stem cells,perinatal tissue-derived mesenchymal stem cells,induced pluripotent stem cell-derived mesenchymal stem cells,embryonic stem cell-derived mesenchymal stem cells,and gingival mesenchymal stem cells.Five administration routes have been adopted,with intravenous and intraperitoneal injections being the most prevalent,followed by local,mesenteric,and intra rectal injections.Their therapeutic mechanisms encompass differentiation,regeneration,anti-inflammatory effects,immune modulation,neuroprotection,antioxidant stress response,homing,modulation of gut microbiota,autophagy,ferroptosis,and endoplasmic reticulum stress.While sharing functional similarities,mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials.Nevertheless,research into the specific properties of these mesenchymal stem cells remains limited,necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease.Additionally,the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.

Objective:To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES). Methods:A child presented at the Children′s Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1). Results:The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China. Conclusion:The c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.

OBJECTIVE: To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES). METHODS: A child presented at the Children's Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1). RESULTS: The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China. CONCLUSION The c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.
Humans ; Kinesins/genetics* ; Male ; Child, Preschool ; Intellectual Disability/genetics* ; Mutation ; Exome Sequencing ; X-Linked Intellectual Disability/genetics* ; Phenotype

BACKGROUND:The incidence of inflammatory bowel disease has been steadily rising,accompanied by a lack of definitive therapeutic strategies.Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease,offering a glimmer of hope for afflicted patients.OBJECTIVE:To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease,aiming to provide insights for future research endeavors.METHODS:Utilizing the keywords"mesenchymal stem cells,MSCs,exosomes,extracellular vesicles,EVs,inflammatory bowel disease,IBD,ulcerative colitis,UC,Crohn's disease,CD"in English and their Chinese equivalents in CNKI and PubMed databases,a total of 89 eligible articles were selected for this review.RESULTS AND CONCLUSION:Currently,six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy:bone marrow-derived mesenchymal stem cells,adipose tissue-derived mesenchymal stem cells,perinatal tissue-derived mesenchymal stem cells,induced pluripotent stem cell-derived mesenchymal stem cells,embryonic stem cell-derived mesenchymal stem cells,and gingival mesenchymal stem cells.Five administration routes have been adopted,with intravenous and intraperitoneal injections being the most prevalent,followed by local,mesenteric,and intra rectal injections.Their therapeutic mechanisms encompass differentiation,regeneration,anti-inflammatory effects,immune modulation,neuroprotection,antioxidant stress response,homing,modulation of gut microbiota,autophagy,ferroptosis,and endoplasmic reticulum stress.While sharing functional similarities,mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials.Nevertheless,research into the specific properties of these mesenchymal stem cells remains limited,necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease.Additionally,the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.

Objective:To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES). Methods:A child presented at the Children′s Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1). Results:The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China. Conclusion:The c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.

OBJECTIVE To identify the chemical components of Shenbai Jiedu Decoction(SBJDD),a traditional Chinese medi-cine(TCM)prescription clinically used for the treatment of colorectal adenoma(CRA),and explore the potential mechanism of SBJDD preventing and treating CRA carcinogenesis.METHODS An ultra-high performance liquid chromatography-time of flight-mass spectrometry(UPLC-Q-TOF-MS)method was established to detect the chemical components in the decoction of SBJDD and the plas-ma samples of rats after administration with SBJDD.Based on the network pharmacological method,SBJDD was screened for the poten-tial active ingredients at different stages of CRA carcinogenesis,and the mechanism of the anti-cancer effect of SBJDD was explored.In vitro experiments were also carried out to verify the mechanism of anti-colorectal cancer(CRC)action of SBJDD.RE-SULTS The detection data of UPLC-Q-TOF-MS showed that 152 components were found from SBJDD water extraction.41 chemical compounds were identified in plasma samples from rats administrated with SBJDD.Network pharmacology analysis indicated that during the CREI stage,the potential active ingredients in SBJDD,including epiberberine,and kushenol H,might affect target proteins such as PIK3CA,MAPK3 and PIK3CB.This,in turn,can influence signaling pathways like PI3K-AKT and Ras signaling pathways,and regulate biological processes like protein phosphorylation,and signal transduction.During the CRA stage,the potential active ingredi-ents from SBJDD,such as 3,7-dihydroxycoumarin,palmatine,and kushenol A,might affect target proteins such as AKT and EGFR.This can regulate the negative regulation of apoptotic process,and positive regulation of cell proliferation,and modify HIF-1,and Rap1 signaling pathways.During the progression of CRA carcinogenesis,potential active ingredients such as 3,7-dihydroxycouma-rin may interact with TP53,and impact the PI3K-AKT,and Thyroid hormone signaling pathways to regulate biological processes,in-cluding positive regulation of transcription from RNA polymerase Ⅱ promoter,and negative regulation of apoptotic process.In the CRC stage,core ingredients like p-coumaric acid may bind with proteins such as PRKCB.This binding may impact the signaling pathways that negatively affect EGFR tyrosine kinase inhibitor resistance,and PI3K-AKT signaling pathways.Additionally,it may regulate bio-logical processes,including negative regulation of apoptotic process,signal transduction,and protein phosphorylation.In vitro experi-ment results indicated that SBJDD inhibited the proliferation of HT29 cells and suppressed the expression of EGFR and PKC proteins.CONCLUSION The UPLC-Q-TOF-MS method is established to effectively separate the chemical constituents in SBJDD,which are mainly composed of alkaloids,organic acids and flavonoids components.Components from SBJDD dock with different targets during the carcinogenesis process of CRA and regulate cancer-related signaling pathways to exert therapeutic effects.

Objective To explore the trend in self-management efficacy and exercise compliance among patients within 6 months after radical resection of lung cancer and analyse the predictive correlation between the factors to provide references for improvement of exercise compliance in patients after lung cancer surgery.Methods Convenience sampling was used to select patients who had surgery of radical resection of lung cancer for the first time in the departments of thoracic surgery of two Grade IIIA hospitals in Nanchong between December 2022 and May 2023.The Chinese-version strategies used by people to promote health(C-SUPPH)and exercise compliance scale were employed to assess the self-management efficacy and patient exercise compliance at four time points:1 day before discharge(T1)and 1 month(T2),3 months(T3)and 6 months(T4)after surgery.A cross-lagged model was constructed to analyse the causal correlation between self-management efficacy and exercise compliance.Results Within 6 months after surgery,both of self-management efficacy and exercise compliance in the patients after radical resection of lung cancer were seen initially increased and then decreased(P<0.05).The cross-lagged model revealed that self-management efficacy and exercise compliance during the early postoperative period(TI-T2)exhibited reciprocal causation(β=0.254,P=0.003;β=0.332,P=0.007).Between T2 and T3,higher self-management efficacy positively predicted an increased exercise compliance(β=0.286,P<0.001).However,during T3 and T4,no predictive relationship was observed between the indicators(P>0.05).Conclusion The self management efficacy of patients after lung cancer sugery is at middle level and their exercise compliance is at low level.This study indicates that the initial levels of self-management efficacy and exercise compliance among patients after radical resection of lung cancer do not necessarily reflect a long-term trend.The predictive correlation between the two factors also varies over the time.Healthcare providers should consider the dynamic changes and individual differences across different stages after surgery,and implement timely and targeted intervention.

Objective To evaluate the acceptability and effectiveness of different doses of midazolam oral solution in sedating infants during echocardiographic studies.Methods Two hundred and fourty patients aged 1 to 3 years who underwent echocardiographic study in sedation in our hospital were enrolled in this study.After recording the baseline data of all infants,they were randomly divided into four groups:0.3 mg·kg-1 midazolam oral solution group(M1 group),0.5 mg·kg-1 midazolam oral solution group(M2 group),0.7 mg·kg-1 midazolam oral solution group(M3 group)and 0.5 mL·kg-1 10%chloral hydrate administrated rectally group(C group),60 case per group,and the sedation was performed in the corresponding method of each group.The 5-point facial hedonic and Ramsay scales were used to evaluate acceptability and effectiveness in sedation.The onset time and duration time of sedation were recorded.Results Compared with the C group,the 5-point facial hedonic scale scores in M1,M2,and M3 groups increased during sedation(F=17.50,P<0.017).The onset time of sedation in the M1 and M2 groups was longer than that in the C group(P<0.017),and the duration time of sedation in the M1 and M2 groups was shorter than that in the C group(P<0.017).There was no significant difference in the onset time(P=0.85)and duration time(P=0.50)of sedation between the M3 and C groups.The onset time of sedation in the M1and M2groups was longer than that in the M3 group(P<0.017),and the duration time of sedation in the M1 and M2 groups were shorter than that in the M3 group(P<0.017).Conclusions The acceptability of infants with midazolam oral solution sedation under echocardiographic study was better than that of 10%chloral hydrate administrated rectally.There were fewer adverse reactions with the midazolam oral solution.The 0.7 mg·kg-1 midazolam oral solution had a rapid onset of sedation and definite effect.

Brain edema belongs to the category of "stroke" and "true headache", while Traditional Chinese Medicine mostly understands its core disease mechanisms from the perspectives of stasis, deficiency, and heat, and mostly treats the disease by using warming yang to induce diuresis and eliminating stasis to remove water. Wuling Powder has been lauded as the "first party to typhoid and relieving diuresis", which is used to cure clearing damp and promoting diuresis and warming yang and transforming qi, and has been clinically used in the treatment of brain edema caused by various causes such as head trauma, intracerebral hemorrhage, cerebral infarction, and intracranial space occupying, all with remarkable efficacy. Wuling Powder improves cellular energy supply, scavenges excess oxygen radicals and calcium ions in brain tissue, and reduces the damage to brain tissue caused by vascular inflammatory factors and regulates aquaporins and vascular endothelial growth factor, thereby achieving therapeutic effects.

Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller mo-lecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting ther-apeutics for HCC treatment with low toxic side effects.