Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.

Cerebral small vessel disease （CSVD） is a common disease with great impact on the health of the Chinese population. CSVD has insidious progression and is often neglected by both patients and physicians. In recent years， advances have been made in the research on CSVD from the aspects of risk factors， pathogenesis， clinical manifestations， and evaluation systems. In 2013， the international Standards for Reporting Vascular Changes on Neuroimaging （STRIVE） collaborative group standardized the definition and description of CSVD， and subsequently in 2021， our team released Chinese expert consensus on the diagnosis and treatment of cerebral small vessel disease 2021， which summarized the latest research findings in China and globally. In 2023， the international STRIVE collaborative group provided further updates on research advances in the field of CSVD. CSVD has similar clinical manifestations to neurodegenerative diseases， with a lack of significant specificity. Although genetic testing and brain tissue biopsy help to make a confirmed diagnosis to a certain extent， their application in clinical practice has been limited by technical and financial constraints. At present， neuroimaging techniques are mainly used to detect brain tissue lesions induced by CSVD and make a diagnosis. This article discusses the imaging markers for the diagnosis of CSVD and the imaging-based differential diagnosis of CSVD.
Diagnosis

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Objective:To investigate the clinical outcomes of minimally invasive lateral lumbar interbody fusion (LLIF) and the necessity to perform LLIF plus posterior direct decompression in the treatment of severe degenerative lumbar spinal stenosis (DLSS).Methods:In this prospective randomized, controlled trial, we assigned 71 patients, who were 50 to 80 years old, and diagnosed with severe DLSS (Schizas Classification grade C on magnetic resonance imaging), in a 1∶1 ratio to undergo either one-stage LLIF plus posterior internal fixation (treatment group) or CLIF plus posterior internal fixation with laminectomy (control group). Demographic and perioperative data were collected and compared. The clinical outcome measures included Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) score as well as visual analogue scale (VAS). Patients were followed up for at least 1 year.Results:The treatment group included 36 patients with 46 surgical levels, while the control group included 35 patients with 46 surgical levels. The baseline demographic data of the 2 groups were equivalent in preoperative central canal areas, spinal canal anteroposterior diameter, disc height, ODI, ZCQ score for symptom severity and physical function, as well as VAS scores for back and leg pain. The mean operative time, blood loss, drainage volume and hospital stay of the treatment group are significantly less than the control group (157.2±29.1 min vs. 180.6±26.8 min, 75.6±39.1 ml vs. 108.6±43.3 ml, 136.9±73.9 ml vs. 220.5±121.3 ml, 5.3±1.1 d vs. 6.6±2.3 d). There were 2 cases with dura tear and 1 case with wound infection in control group. Thus, the surgical trauma and complications of the control group were more than the treatment group. At 1-year follow-up, the mean ODI score of treatment group improved from 42.24%±10.70% preoperatively to 18.21%±11.49%, the mean ZCQ symptom severity from 2.89±0.38 to 1.61±0.41, the mean ZCQ physical function from 2.31±0.45 to 1.50±0.37, the mean VAS for back from 5.56±1.19 to 1.97±1.13 and the mean VAS for leg from 4.44±1.81 to 0.94±1.26. At 1-year follow-up, the mean ODI score of the control group improved from 43.65%±14.93% preoperatively to 17.36%±12.15%, the mean ZCQ symptom severity from 2.92±0.52 to 1.65±0.39, the mean ZCQ physical function from 2.37±0.52 to 1.55±0.39, the mean VAS for back from 5.63±1.40 to 2.34±1.47, and the mean VAS for leg from 4.37±2.14 to 0.83±1.20. The ZCQ satisfactory score of both groups were not significant different (1.25±0.45 vs. 1.26±0.43, t=0.07, P=0.944). The mean improvement rate of both groups for ODI, ZCQ symptom severity, ZCQ physical function, VAS back and VAS leg at 1-year follow-up were not significant different (55.43%±27.74% vs. 58.36%±25.06%, 43.07%±17.22% vs. 42.66%±12.95%, 32.25%±23.65% vs. 31.71%±23.24%, 62.65%±21.25% vs. 58.37%±22.44%, 78.94%±26.41% vs. 85.45%±20.53%). One adjacent segment disease was found in each group at 1 year follow-up. Conclusion:CLIF+ posterior internal fixation in the treatment of Schizas Grade C DLSS has satisfactory clinical outcome at 1-year follow-up. Laminectomy increases surgical trauma, but does not significantly improve the clinical outcome at 1-year follow-up.

Objective:To investigate the influence of different degrees of facet joint arthropathy on the indirect decompression effect of crenel lumbar interbody fusion (CLIF), and the clinical outcomes of CLIF for the treatment of lumbar spinal stenosis with severe facet joint arthropathy (grade 3).Methods:This study reviewed a total of 269 surgical segments in 156 patients with lumbar spinal stenosis treated with CLIF technique from November 2016 to February 2020. According to preoperative CT images, the facet joint was graded according to Pathria classification. There are 19 segments with grade 0, 156 segments with grade 1, 67 segments with grade 2, and 27 segments with grade 3. Radiographic parameters included disc angle, anterior and posterior disc height, and bilateral intervertebral foramen height on CT, and the midsagittal canal diameter and axial central canal area. In 30 patients with at least one segment of grade 3, the clinical efficacy was assessed using visual analogue scale (VAS) and Oswestry disability index (ODI).Results:The average the anterior and posterior intervertebral space height, intervertebral space angle, height of bilateral intervertebral foramina, spinal canal sagittal diameter and spinal canal area were significantly improved after the operation of grade 3 facet joint degeneration segment compared to preoperation. The preoperative mean spinal canal sagittal diameter and spinal canal area of grade 3 facet joint degeneration segment were significantly less than grade 1 and grade 2. The average change of spinal canal area after grade 3 articular degeneration was significantly less than that of grade 1 and 2, but there was no significant difference with that of grade 0. The posterior decompression rate was 55.56% (15/27) for grade 3, 35.82% (24/67) for grade 2, 16.03% (25/156) for grade 1, and 21.05% (4/19) for grade 0. The posterior decompression rate of grade 3 articular process degeneration was significantly higher than that of other grades ( P<0.001). Severe lateral recess stenosis and 24.24% of severe intervertebral foraminal stenosis were found in 81.48% of grade 3 degenerative segment. The 23 patients were followed up with an average of 21.62±6.52 months, and the average improvement of ODI was 24.10%±11.09%; the average VAS for leg pain and back pain were improved significantly. Conclusion:The degrees of facet joint degeneration do not prevent intervertebral space distraction of CLIF. However, because segments with severe facet joint arthropathy were usually associated with severe spinal canal stenosis, CLIF had a high rate of second-stage posterior decompression in the treatment of lumbar spinal stenosis with severe facet joint arthropathy.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

This study aimed to investigate the ameliorative effects of 60% ethanol elution fraction (ESMW) from Si Miao Wan on the hepatic lipid accumulation and its mechanism.TG kit, BODIPY fluorescence staining, QPCR, WB, oil red O staining, and AMPKα knockdown were used to detect the ability of ESMW to improve lipid accumulation in hepatocytes stimulated with free fatty acid.Furthermore, the effects of ESMW on the oral glucose tolerance, serum biochemical indexes, TG content in liver tissue, the expressions of mRNA and protein related to lipid metabolism in liver tissue were studied in mice fed with high fat diet to verify the mechanism of ESMW fraction on hepatic lipid accumulation.The results showed that ESMW inhibited lipid accumulation induced by free fatty acids by regulating AMPK signaling pathway, and that ESMW significantly improved the lipid metabolism of mice fed with high fat diet, with relation to AMPK signaling pathway.