OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Chronic obstructive pulmonary disease(COPD)is one of the most common chronic lung diseases,which is characterized by chronic irreversible airway obstruction.Chronic airflow restriction causes a decrease in oxygen supply to the brain,which inevitably leads to a series of changes in brain function and structure.In recent years,many magnetic resonance imaging(MRI)technology has been applied to explore the brain function and structure of COPD.Resting-state functional MRI,voxel-based morphometry,and diffusion tensor imaging are reviewed in this article to discuss the recent research progress of brain function and structure imaging study in COPD.

Objective:To explore the funding status and research hotspots of the National Natural Science Foundation of China (NSFC) for projects in the field of TCM for the prevention and treatment of heart failure.Methods:The research projects of TCM in the prevention and treatment of heart failure funded were retrieved from NSFC Big Data Knowledge Management Service Platform from January 1, 2010 to December 31, 2023. Excel 2022 software was used to analyze the data of the number of funded projects, the amount of funding, the supporting units and the regions. VOSviewer 1.6.20 software was used to analyze the co-occurrence of keywords with frequency≥3.Results:A total of 202 research projects were funded with a total funding amount of 89.8 million RMB, and the number and amount of projects showed a fluctuating upward trend. The funding categories were mainly general programs and youth science foundation projects. There were 42 supporting units involved, and TCM universities and colleges were the main recipients of funding. Regional distribution was uneven, mainly in Beijing, Shanghai, Guangdong and other regions. There were 17 secondary discipline codes involved, and the discipline categories were concentrated in Internal Medicine of TCM (H3108), Clinical Basis of Integrative Medicine (H3302) and Cardiovascular Pharmacology of Chinese Medicine (H3209). Therapeutic modalities covered compounding, monomers, proprietary Chinese medicines, and drug pairs, and research hotspots included aspects of myocardial energy metabolism remodeling, mitochondrial autophagy, macrophage polarization, endoplasmic reticulum stress, calcium homeostasis, ferroptosis, exosomes, micro-RNAs, and so on.Conclusion:NSFC has provided strong support to the research in the field of TCM for heart failure. In the future, the supporting units should pay attention to the interdisciplinary integration and development to promote the vigorous development of TCM.

Hypokalemic periodic paralysis(HypoPP)is a very rare but potentially life-threatening condition,often attacking suddenly,usually triggered by overeating or vigorous exercise,which complicates disease prevention and treatment and significantly lowers patients' quality of life.With the deepening of modern traditional Chinese medicine(TCM)research on the spleen's role in water metabolism and the kidney's function in storage,and with the achievements in western medicine's microscopic understanding of the disease,it has been found that TCM can utilize the micro-level physiological and pathological insights of modern medicine to elucidate the pathogenesis of diseases,thereby facilitating the establishment of a TCM management model for high-risk factors of diseases.This article explored the relationship between potassium balance and HypoPP from the perspective of spleen-kidney correlation.It is proposed that spleen failing in transportation and kidney failing in storing essence may lead to potassium imbalance,which constitutes a key pathogenesis of HypoPP.Prevention and treatment should focus on strengthening the middle energizer and simultaneously reinforcing kidney essence.Clinically,modified Buzhong Yiqi Decoction plus Da Buyin Pills has shown favorable therapeutic effects.The approach of making diagnosis and treatment of HypoPP based on potassium balance and from the perspective of spleen-kidney correlation may provide novel insights for its TCM prevention and management.

Hepatitis B virus(HBV)infection is worldwide and poses a serious threat to human health.Existing conventional therapeutic drugs(e.g.,interferon-alpha,nucleoside analogs)can inhibit intrahepatic replication of HBV,but it is difficult to remove HBV covalently closed circular DNA(cccDNA)from the nucleus of hepatocytes,resulting in the virus not being easily cleared and the formation of a chronic infection that is difficult to cure.However,the emergence of targeted drugs is expected to destroy cccDNA making a cure for HBV infection possible.To achieve this,in vitro cell models of HBV infection and replication are needed to screen for targeted drugs.In recent years,in vitro cell models for HBV research have made fundamental progress,providing a platform for a better understanding of virus-host interactions,in vitro studies of the HBV life cycle,and the screening and evaluation of novel antiviral drugs.In this review,the research progress of HBV infection and replication cell models,and the characteristics and limitations of different cell models are reviewed,aiming to provide a basis for exploring the mechanism of complex chronic HBV infection,screening targeted drugs and selecting suitable HBV cell models in vitro.

Objective To evaluate the therapeutic efficacy of endoscopic total thyroidectomy performed via a combined transoral and submental approach in patients with thyroid cancer Methods This study enrolled 227 patients diagnosed with papillary thyroid carcinoma(PTC)who underwent total thyroidectomy combined with unilateral central lymph node dissection at the Department of Thyroid and Hernia Surgery,the First Affiliated Hospital of Gannan Medical University,between October 2019 and March 2024.Of these patients,68 were treated using the fully endoscopic combined transoral and submental approach(endoscopic group),whereas 159 underwent the conventional open anterior cervical approach(open group).A retrospective analysis was performed to evaluate and compare the therapeutic outcomes between the two groups.Results Surgical procedures were successfully completed in both groups without complications,and no additional incisions were required in the endoscopic group.Compared with the open surgery group,the endoscopic group had a longer operative duration,reduced intraoperative blood loss,and greater total postoperative drainage volume.Furthermore,on the first postoperative day,patients in the endoscopic surgery group exhibited lower levels of serum calcium and intact parathyroid hormone(iPTH).The incidence of temporary parathyroid dysfunction was significantly higher in the endoscopic group(51.47%)than in the open surgery group(30.82%),and this difference was statistically significant(P<0.05).No significant differences were found between the two groups regarding preoperative serum iPTH levels,preoperative serum calcium levels,number of dissected lymph nodes,incidence of temporary recurrent laryngeal nerve injury,postoperative hemorrhage,incision infection,or submental sensory loss(P>0.05).Conclusions Compared with traditional open surgery,total thyroidectomy via TOETSMVA under full endoscopy demonstrates comparable efficacy and favorable long-term safety.However,it is associated with a higher risk of transient hypoparathyroidism in the short term,highlighting the necessity for enhanced intraoperative protection of the parathyroid glands.

Objective:To explore the effect of self-compassion-based writing on prosocial behavior in college students with different self-construals.Methods:A total of 182 college students were recruited,and the Self-Con-structional Scales were used to determine the self-construal types(independent or interdependent).Participants were then assigned to either a self-compassion-based writing group(n=91)or a non-self-compassion daily writing group(n=91)and completed writing tasks according to the respective instructions.Prosocial behavior was evaluated with the Prosocial Tendencies Measure(PTM),situational judgment tests,and donation amounts.Results:The evaluation results from the PTM showed that prosocial behavior was significantly higher in individuals with interdependent self-construal compared to those with independent self-construal(P＜0.001),the main effect of the group type was not statistically significant(P＞0.05).The evaluation results from situational judgment tests showed that prosocial behavior was significantly higher in individuals with interdependent self-construal compared to those with independ-ent self-construal(P＜0.001),the self-compassion-based writing group demonstrated significantly more prosocial behavior than the non-self-compassion daily writing group(P＜0.05).The evaluation results from donation a-mounts showed that the main effect of self-construal type was not statistically significant(P＞0.05),the self-com-passion-based writing group demonstrated significantly more prosocial behavior than the non-self-compassion daily writing group(P＜0.05).Conclusion:Compared to daily writing,self-compassion-based writing could effectively increase prosocial behavior in college students,regardless of their self-construal type.