AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγ pathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1β measured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1α and PPARγ detected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P＜0.01);decreased platform crossing times and target quadrant residence time(P＜0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1β and IL-18(P＜0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P＜0.05,P＜0.01);increased platform crossing times and target quadrant residence time(P＜0.05,P＜0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1β and IL-18(P＜0.05,P＜0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.05,P＜0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning and memory impairment by activating the SIRT1/PGC-1α/PPARγ signaling pathway.

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

Objective:To explore the clinicopathological characteristics and prognosis of fumarate hydratase-deficient uterine leiomyoma (FH-dUL).Methods:Clinical data and follow-up information for 117 patients with FH-dUL diagnosed through surgical pathology and immunohistochemistry in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2024, were collected. A control group of 130 patients with common uterine leiomyomas was also included. The differences between the two groups in clinical, imaging, and pathological characteristics were compared. Additionally, recurrence rates, fertility outcomes for FH-dUL patients, and the incidence of renal cancer in FH germline mutation carriers were monitored.Results:(1) Comparison of clinicopathological characteristics: the median age of 117 FH-dUL patients was 35 years, and the median age at first diagnosis of uterine leiomyomas was 29 years, both significantly younger than the control group (41 and 36 years; both P<0.01). The FH-dUL group showed significantly higher incidences of uterine myomectomy, multiple leiomyomas, diffusion restriction on pelvic magnetic resonance imaging diffusion weighted imaging, and typical pathological features (candelabra-like vessels, bizarre nuclei, cytoplasmic eosinophilic globules, perinuclear halo, cellular atypia) and higher ultrasound blood flow score (all P<0.05). Of the 30 FH-dUL patients who underwent genetic testing, 9 had germline mutations, 3 had somatic mutations, and 6 had mutations of unclear origin. Among the 9 FH gene germline mutation patients, 2 had already developed renal cell carcinoma. (2) Recurrence analysis: among the 56 patients who underwent uterine myomectomy, 22 (39.3%, 22/56) experienced recurrence during follow-up, compared to 12 (21.8%, 12/55) of the 55 patients in the control group, the difference between the two groups was statistically significant ( P=0.046). Multivariate binary logistic regression analysis showed that cellular leiomyomas ( OR=9.489, 95% CI: 1.740-51.755; P=0.009) and multiple uterine leiomyomas ( OR=10.709, 95% CI: 1.354-84.683; P=0.025) were significant risk factors for recurrence in FH-dUL. (3) Fertility analysis: among the 66 FH-dUL patients who underwent fertility-preserving surgery, 16 had the intention to have fertility desire, only 2 (2/16) completed their fertility plans during follow-up. Conclusions:Clinicopathological features and imaging features help to differentiate FH-dUL from common type uterine fibroids, but lack specificity, and the diagnosis of FH-dUL is based on immunohistochemistry. The recurrence rate after resection of FH-dUL is high, and cellular and multiple leiomyomas are important predictors of recurrence. It is crucial to perform genetic testing, genetic counseling, drug treatment to prevent recurrence, fertility guidance, and long-term comprehensive management after surgery for FH-dUL management.

OBJECTIVE: To investigate the short-and med-term clinical efficacy of unicompartmental knee arthroplasty(UKA)for the treatment of medial knee osteoarthritis (OA) in elderly patients with anterior cruciate ligament deficiency(ACLD). METHODS: A retrospective analysis was conducted on 31 patients aged over 75 years old with primary medial knee OA and ACLD who underwent UKA between January 2018 and December 2022. The cohort included 12 males and 19 females, aged from 75 to 91 years with an average age of (79.56±4.54) years, with 13 left knee, 16 right knee, and 2 bilateral knees. Clinical outcomes were assessed preoperatively and at final follow-up using the visual analogue scale (VAS), Hospital for Special Surgery(HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA), and tibial component posterior slope angle (TCPSA). Complications such as infection, prosthesis wear, prosthesis loosening, and dislocation were also recorded. RESULTS: All 31 patients were followed up from 12 to 63 months with an average of (28.34±10.56) months. The average postoperative TCPSA was (4.83±1.31)° ranged from 2.5° to 6.8°. At the final follow-up, there was significant improvement in VAS (3.24±0.53) vs. (6.59±0.69), HSS score (85.19±4.45) vs. (64.38±5.94), ROM (118.83±5.38)° vs. (98.85±4.08)°, and HKA (176.83±5.16)° vs. (169.57±6.28)° compared to preoperative values (P<0.05). No cases of infection, prosthesis loosening, or dislocation were reported. CONCLUSION UKA provides favorable short-and mid-term outcomes for elderly patients with medial knee OA and ACLD . However, long-term clinical efficacy needs further investigation through extended follow-up.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Osteoarthritis, Knee/physiopathology* ; Retrospective Studies ; Aged, 80 and over ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/surgery*

Objective To explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

In patients with chronic kidney disease(CKD),the incidence of cardiovascular events and the mortality rate are significantly higher than those in the general population.Approximately 85% of end-stage CKD patients develop hyperhomocysteinemia(HHcy)due to impaired renal function.It is not yet fully determined whether HHcy merely acts as a biomarker of CKD or plays a role in the pathogenesis.Although supplementation with folic acid and other B vitamins(B6 and B12)has been proven to lower the plasma level of total homocysteine,their effectiveness in slowing CKD progression or reducing cardiovascular complications remains uncertain.This article reviews the latest research progress in the relationship between HHcy and CKD,aiming to give new insights into the prevention and treatment of CKD and its complications.
Humans ; Hyperhomocysteinemia/complications* ; Renal Insufficiency, Chronic/complications*

The construction of first-class universities and disciplines is a major strategic initiative of the Communist Party of China Central Committee and the State Council,and an important task for building a world-class higher education powerhouse.Forensic medicine was officially listed as a first-level discipline under the medical category in 2022,presenting unprecedented historical opportunities for the development of forensic medicine.Facing this significant strategic opportunity,this paper sorts out the disciplinary system of forensic medicine,carries out forward-looking planning for the develop-ment of the discipline,and looks forward to the development vision of the discipline:(1)Establish an organically connected three-stage forensic medicine talent training system to cultivate applied and innovative talents that meet the needs of China's socialist modernization construction;(2)Establish a unified standardized forensic practice qualification examination system,organically connect talent training with professional qualification examination,and optimize the professional development path of forensic medicine;(3)Widely intersect,integrate and transform forensic medicine with other multiple disciplines,expand and enrich the second-and third-level disciplinary systems of forensic medicine,and build a world-class forensic medicine discipline with Chinese characteristics.

Objective:To explore the clinicopathological characteristics and prognosis of fumarate hydratase-deficient uterine leiomyoma (FH-dUL).Methods:Clinical data and follow-up information for 117 patients with FH-dUL diagnosed through surgical pathology and immunohistochemistry in the First Affiliated Hospital of Nanjing Medical University from January 2020 to December 2024, were collected. A control group of 130 patients with common uterine leiomyomas was also included. The differences between the two groups in clinical, imaging, and pathological characteristics were compared. Additionally, recurrence rates, fertility outcomes for FH-dUL patients, and the incidence of renal cancer in FH germline mutation carriers were monitored.Results:(1) Comparison of clinicopathological characteristics: the median age of 117 FH-dUL patients was 35 years, and the median age at first diagnosis of uterine leiomyomas was 29 years, both significantly younger than the control group (41 and 36 years; both P<0.01). The FH-dUL group showed significantly higher incidences of uterine myomectomy, multiple leiomyomas, diffusion restriction on pelvic magnetic resonance imaging diffusion weighted imaging, and typical pathological features (candelabra-like vessels, bizarre nuclei, cytoplasmic eosinophilic globules, perinuclear halo, cellular atypia) and higher ultrasound blood flow score (all P<0.05). Of the 30 FH-dUL patients who underwent genetic testing, 9 had germline mutations, 3 had somatic mutations, and 6 had mutations of unclear origin. Among the 9 FH gene germline mutation patients, 2 had already developed renal cell carcinoma. (2) Recurrence analysis: among the 56 patients who underwent uterine myomectomy, 22 (39.3%, 22/56) experienced recurrence during follow-up, compared to 12 (21.8%, 12/55) of the 55 patients in the control group, the difference between the two groups was statistically significant ( P=0.046). Multivariate binary logistic regression analysis showed that cellular leiomyomas ( OR=9.489, 95% CI: 1.740-51.755; P=0.009) and multiple uterine leiomyomas ( OR=10.709, 95% CI: 1.354-84.683; P=0.025) were significant risk factors for recurrence in FH-dUL. (3) Fertility analysis: among the 66 FH-dUL patients who underwent fertility-preserving surgery, 16 had the intention to have fertility desire, only 2 (2/16) completed their fertility plans during follow-up. Conclusions:Clinicopathological features and imaging features help to differentiate FH-dUL from common type uterine fibroids, but lack specificity, and the diagnosis of FH-dUL is based on immunohistochemistry. The recurrence rate after resection of FH-dUL is high, and cellular and multiple leiomyomas are important predictors of recurrence. It is crucial to perform genetic testing, genetic counseling, drug treatment to prevent recurrence, fertility guidance, and long-term comprehensive management after surgery for FH-dUL management.

AIM To investigate the effects of Huazhuo Jiedu Shugan Formula(HJSGF)on improving learning and memory impairment in a rat model of vascular dementia(VD)via SIRT1/PGC-1α/PPARγ pathway.METHODS The SD rats were randomly divided into the sham control group,the model group,the donepezil group(0.5 mg/kg),and the low-,medium-and high-dose HJSGF groups(2.7,5.4,10.8 g/kg),with 10 rats in each group.The VD rat models established by bilateral common carotid artery permanent ligation(2-VO)had their neurological behavior assessment using the Longa5-point scale,and their modeling success confirmed by the Morris water maze test and their 3-week corresponding dosing of drugs by gavage afterward.After the drug administration,the rats had their spatial memory ability tested through behavioral experiments;their serum levels of IL-18 and IL-1β measured by ELISA;their histopathological changes and neuronal morphology in the hippocampal CA1 region observed by HE staining and Nissl staining;and their hippocampal protein expressions of SIRT1,PGC-1α and PPARγ detected by immunohistochemistry and Western blot.RESULTS Compared with the sham control group,the model group showed prolonged escape latency(P＜0.01);decreased platform crossing times and target quadrant residence time(P＜0.01);disorganized arrangement of hippocampal CA1 neurons,nuclear condensation,reduced Nissl bodies,increased secretion and protein expressions of IL-1β and IL-18(P＜0.01);and reduced hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.01).Compared with the model group,the groups intervened with donepezil or HJSGF showed shortened escape latency(P＜0.05,P＜0.01);increased platform crossing times and target quadrant residence time(P＜0.05,P＜0.01);alleviated damage of the hippocampal CA1 region,reduced secretion and protein expressions of IL-1β and IL-18(P＜0.05,P＜0.01);and elevated hippocampal protein expressions of SIRT1,PGC-1α and PPARγ(P＜0.05,P＜0.01).CONCLUSION HJSGF may alleviate the inflammatory responses in VD rats and therefore improve their learning and memory impairment by activating the SIRT1/PGC-1α/PPARγ signaling pathway.