Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

Objective:To investigate the differences in clinical and imaging characteristics of patients with recent small subcortical infarct (RSSI) stratified by different etiological subtypes.Methods:A retrospective, consecutive analysis was conducted on 696 RSSI patients admitted to the West China Hospital, Sichuan University, from January 2019 to May 2024. Based on clinical and imaging data, patients were stratified into 3 etiological subgroups: presumed cerebral small vessel disease (CSVD)-related RSSI, coexisting carrier large artery stenosis, and coexisting proximal extracranial/intracranial large artery stenosis. The clinical characteristics, vascular risk factors, infarct imaging features, and CSVD markers were compared across the 3 groups. Additionally, the differences in clinical and imaging features based on the location of infarcts (anterior vs posterior circulation) and infarct size (<15 mm vs ≥15 mm) were examined. Results:Among the 696 patients, 557 (80.0%) had presumed CSVD-related RSSI, 68 (9.8%) had coexisting carrier large artery stenosis, and 71 (10.2%) had coexisting proximal extracranial/intracranial large artery stenosis. The patients with presumed CSVD-related RSSI were the youngest [60 (53, 69) years], followed by those with coexisting carrier large artery stenosis [64 (55, 69) years] and those with coexisting proximal extracranial/intracranial large artery stenosis [69 (55, 75) years; H=9.523, P=0.013]. Among RSSI patients with coexisting proximal extracranial/intracranial large artery stenosis, the proportion of those with diabetes (38/71, 53.5%) was the highest, whereas the proportion was 210/557 (37.7%) in the presumed CSVD-related group and 31/68 (45.6%) in the group with coexisting carrier large artery stenosis (χ 2=8.027, P=0.023). Patients with RSSI combined with proximal extracranial/intracranial large artery stenosis had more infarction sites in the pons and a higher proportion of proximal infarction. However, there were no significant differences among the 3 groups in terms of infarct size, or CSVD imaging markers. In the anterior versus posterior circulation comparison, patients with posterior circulation RSSI ( n=360) had a significantly higher age of onset [63(55, 72) years vs 60(52, 59) years, U=51 335.500, P<0.001], had higher prevalence of hypertension and diabetes, and showed higher NIHSS scores [3(2, 6) vs 3(1, 5), U=57 840.500, P=0.028]. The anterior circulation group ( n=366) showed a higher proportion of lacunas [152/336 (45.2%) vs 118/360 (32.8%), χ2=11.364, P<0.001], while the posterior circulation group had a greater prevalence of severe perivascular spaces in the basal ganglia [254/360 (70.6%) vs 203/336 (60.4%), χ2=7.879, P=0.005] and deep white matter hyperintensities grading≥2 [124/360 (34.4%) vs 90/336 (26.8%), χ2=4.787, P=0.029]. There were no statistically significant differences in the distribution of infarcts between anterior and posterior circulations or in CSVD imaging markers between RSSI patients with infarction lesions ≥15 mm ( n=290) and <15 mm ( n=406). Conclusions:Approximately 20% of RSSI cases are related to large artery stenosis. These patients tend to be older at onset and have a higher prevalence of diabetes. Compared to presumed CSVD-related RSSI cases, RSSI cases related to large artery stenosis show no significant differences in infarct imaging features and CSVD imaging markers, suggesting that large artery stenosis in RSSI may be an epiphenomenon rather than a direct causative factor.

AIM:This study aims to investigate the functions of interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in adenomyosis(ADM),and to assess the therapeutic potential of JAK2 inhibitor AG490.METHODS:(1)Neonatal female mice were randomly divided into 2 groups:control group and ADM group.An ADM mice model was established by tamoxifen.Additionally,Western blot was employed to detect the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins.(2)Human endometrial adenocarcinoma Ishikawa cells were treated with AG490,and Western blot was performed to evaluate the expression of the proteins related to IL-6/JAK2/STAT3 signaling pathway,epithelial-mesenchymal transition(EMT),cell migration and cell proliferation.Besides,wound-healing and Transwell assays were carried out to investigate the cell migration and inva-sion.Colony formation and EdU assays were employed to investigate the cell proliferation,and flow cytometry analysis was performed to investigate the cell apoptosis.(3)The ADM mice were randomly divided into 2 groups:ADM group and AG490 group.The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in uterine tissues was detected by Western blot.Besides,Western blot and immunohistochemistry were employed to detect the expression of the proteins re-lated to cell EMT,migration and proliferation.Cell apoptosis in uterine tissues was detected by TUNEL assay.RE-SULTS:(1)The expression of IL-6/JAK2/STAT3 signaling pathway-related proteins exhibited an increasing trend in ADM mice(P<0.05).(2)Treatment with AG490 significantly suppressed the expression of IL-6/JAK2/STAT3 signaling pathway-related proteins in Ishikawa cells(P<0.05).The protein level of E-cadherin showed an increasing trend(P<0.01),while the expression levels of N-cadherin,vimentin and Slug showed a decreasing trend(P<0.05)in Ishikawa cells after AG490 treatment.Besides,the expression of MMP-2 and MMP-9 was down-regulated(P<0.05),and the capa-bilities of cell migration and invasion were suppressed in AG490-treated Ishikawa cells(P<0.05).The expression levels of Bcl-2 and cyclin D1 exhibited a decreasing trend(P<0.05),and the expression level of Bax increased(P<0.05)in Ishikawa cells after treatment with AG490.Additionally,AG490 inhibited Ishikawa cell proliferation,and enhanced the cell apoptosis(P<0.01).(3)The p-JAK2/JAK ratio and the IL-6 expression exhibited a decreasing trend in AG490 group(P<0.01).Moreover,the expression of E-cadherin was up-regulated(P<0.05),while the expression of N-cadherin,vi-mentin,Snail,Slug and Twist was down-regulated(P<0.05)in ADM mice after treatment with AG490.Compared with ADM group,the expression of MMP-2 and MMP-9 decreased in AG490 group(P<0.05),alongside the down-regulated Bcl-2/Bax ratio and PCNA expression(P<0.01).Besides,the cell apoptosis was enhanced by AG490.CONCLUSION:The IL-6/JAK2/STAT3 signaling pathway is aberrantly activated in ADM and facilitates endometrial cell EMT,prolifera-tion,invasion and migration.Additionally,AG490 inhibits the progression of ADM by blocking the IL-6/JAK2/STAT3 sig-naling pathway.

This paper introduces Professor LIU Zhibin 's clinical experience in the treatment of subjective tinnitus with acupuncture based on the "kidney-bone-brain" axis. Professor LIU proposes that the disease is most closely related to the kidney and brain. The lesion is located in the brain, and the pathogenesis is kidney essence deficiency, marrow sea loss, and ear orifice dystrophy. The "kidney-bone-brain" shows close correlation in physiological function, pathological changes and treatment. According to the "kidney-bone-brain" axis, Professor LIU proposes that the treatment of subjective tinnitus should be tonifying kidney qi, tonifying essence and filling marrow, and the principle of local acupoint selection, touching bone acupuncture, matching distal acupoints and proximal acupoints, tonifying kidney and benefiting brain should be adopted. The acupoints of Tinggong (SI19) and Yifeng (TE17) are selected to be treated with touching bone acupuncture, combined with Taixi (KI3), Shenshu (BL23), Baihui (GV20) and Shenting (GV24), so as to achieve common benefit of kidney, bone and brain, and multi-angle treatment.
Humans ; Acupuncture Therapy/history* ; Tinnitus/physiopathology* ; Acupuncture Points ; Kidney/physiopathology* ; Brain/physiopathology* ; Bone and Bones/physiopathology* ; Female ; Male ; Adult ; Middle Aged

Objective:To investigate the differences in clinical and imaging characteristics of patients with recent small subcortical infarct (RSSI) stratified by different etiological subtypes.Methods:A retrospective, consecutive analysis was conducted on 696 RSSI patients admitted to the West China Hospital, Sichuan University, from January 2019 to May 2024. Based on clinical and imaging data, patients were stratified into 3 etiological subgroups: presumed cerebral small vessel disease (CSVD)-related RSSI, coexisting carrier large artery stenosis, and coexisting proximal extracranial/intracranial large artery stenosis. The clinical characteristics, vascular risk factors, infarct imaging features, and CSVD markers were compared across the 3 groups. Additionally, the differences in clinical and imaging features based on the location of infarcts (anterior vs posterior circulation) and infarct size (<15 mm vs ≥15 mm) were examined. Results:Among the 696 patients, 557 (80.0%) had presumed CSVD-related RSSI, 68 (9.8%) had coexisting carrier large artery stenosis, and 71 (10.2%) had coexisting proximal extracranial/intracranial large artery stenosis. The patients with presumed CSVD-related RSSI were the youngest [60 (53, 69) years], followed by those with coexisting carrier large artery stenosis [64 (55, 69) years] and those with coexisting proximal extracranial/intracranial large artery stenosis [69 (55, 75) years; H=9.523, P=0.013]. Among RSSI patients with coexisting proximal extracranial/intracranial large artery stenosis, the proportion of those with diabetes (38/71, 53.5%) was the highest, whereas the proportion was 210/557 (37.7%) in the presumed CSVD-related group and 31/68 (45.6%) in the group with coexisting carrier large artery stenosis (χ 2=8.027, P=0.023). Patients with RSSI combined with proximal extracranial/intracranial large artery stenosis had more infarction sites in the pons and a higher proportion of proximal infarction. However, there were no significant differences among the 3 groups in terms of infarct size, or CSVD imaging markers. In the anterior versus posterior circulation comparison, patients with posterior circulation RSSI ( n=360) had a significantly higher age of onset [63(55, 72) years vs 60(52, 59) years, U=51 335.500, P<0.001], had higher prevalence of hypertension and diabetes, and showed higher NIHSS scores [3(2, 6) vs 3(1, 5), U=57 840.500, P=0.028]. The anterior circulation group ( n=366) showed a higher proportion of lacunas [152/336 (45.2%) vs 118/360 (32.8%), χ2=11.364, P<0.001], while the posterior circulation group had a greater prevalence of severe perivascular spaces in the basal ganglia [254/360 (70.6%) vs 203/336 (60.4%), χ2=7.879, P=0.005] and deep white matter hyperintensities grading≥2 [124/360 (34.4%) vs 90/336 (26.8%), χ2=4.787, P=0.029]. There were no statistically significant differences in the distribution of infarcts between anterior and posterior circulations or in CSVD imaging markers between RSSI patients with infarction lesions ≥15 mm ( n=290) and <15 mm ( n=406). Conclusions:Approximately 20% of RSSI cases are related to large artery stenosis. These patients tend to be older at onset and have a higher prevalence of diabetes. Compared to presumed CSVD-related RSSI cases, RSSI cases related to large artery stenosis show no significant differences in infarct imaging features and CSVD imaging markers, suggesting that large artery stenosis in RSSI may be an epiphenomenon rather than a direct causative factor.

Anticancer drugs are important causes of kidney injury in cancer patients. Once kidney injury occurs, it will affect anticancer therapy and patient prognosis. Thus, the Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made a particular discussion on the prevention and management of anticancer drug-induced kidney injury. This article focuses on interpreting the management of kidney injury related to cytotoxic anticancer drugs, targeted therapies, and immune checkpoint inhibitors to more effectively guide clinical practice.

The pathogenesis of diabetic peripheral neuropathy(DPN)is driven by environmental factors,which can induce epigenetic changes and make it a bridge between environment and gene expression.Hyperglycemia causes changes in DNA methylation,abnormal regulation of enzyme activity involved in his tone modification,and is associated with chromatin structural modification,leading to alterations in DPN gene expression.This article reviews the research progress of epigenetic effects on DPN.

Objective Based on the network pharmacology and animal experiments,to investigate the protective effect and possible molecular mechanism of ethanol extract from Atractylodes lancea on liver function in mice with liver fibrosis induced by bile duct ligation.Methods The main active ingredients atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅱ from Atractylodes lancea were selected,which had been verified by literature and experiments,and the targets of these active ingredients were obtained through the SwissTargetPrediction database.The liver fibrosis disease targets were obtained through On-line Mendelian Inheritance in Man (OMIM),DisGeNET and GeneCards databases.The targets were added to the Wei Sheng Xin platform to find the intersection target for Atractylodes lancea in treating liver fibrosis.Cytoscape 3.10.1 was used to construct the "drug-component-target-disease" network diagram and protein-protein interaction core target network diagram.GO functional enrichment analysis and KEGG pathway analysis were performed,and molecular docking was performed between active components and core targets.Liver fibrosis was induced in mice by bile duct ligation,and liver function markers were measured.Results A total of 91 corresponding targets of atractylodin,atractylenolide Ⅰ,Ⅱ and Ⅲ and 9296 liver fibrosis disease targets were obtained,including 74 intersecting targets and 31 core targets.KEGG enrichment analysis showed that the main signaling pathways involved included inflammatory pathways such as epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt).Molecular docking results showed that the active ingredients had strong binding activity with the core target protein.The results of animal experiments showed that,compared with the sham surgery group,the model group displayed notable,the liver index,spleen index,activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST),degree of liver fibrosis,mRNA and protein expression of α-smooth muscle actin (α-SMA) and recombinant collagen type Ⅰ alpha 1 (COL1A1),and mRNA of recombinant collagen type Ⅳ alpha 2 (COL4A2) were significantly increased,and the thymus index was sigficantly decreased (P<0.05);compared with the model group,the liver injury of mice in the Atractylodes lancea administration group reduced liver injury,its liver index,spleen index,activity of serum ALT and AST,degree of liver fibrosis,mRNA and protein expression of α-SMA and COL1A1,and mRNA of COL4A2 were significantly decreased,and the thymus index was sigficantly increased (P<0.05).Conclusion Atractylodes lancea can improve liver function and alleviate tissue pathological damage in mice with liver fibrosis,which may be related to activating pathways such as PI3K/Akt,inhibiting oxidative stress and inflammatory reactions,and intervening in liver fibrosis.

Anticancer drugs are important causes of kidney injury in cancer patients. Once kidney injury occurs, it will affect anticancer therapy and patient prognosis. Thus, the Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made a particular discussion on the prevention and management of anticancer drug-induced kidney injury. This article focuses on interpreting the management of kidney injury related to cytotoxic anticancer drugs, targeted therapies, and immune checkpoint inhibitors to more effectively guide clinical practice.