Immune-mediated myocarditis is a rare but life-threatening complication of immune checkpoint inhibitor therapy. We report a case of a patient with high-grade urothelial carcinoma and lymph node metastasis. After exhibiting cisplatin intolerance postoperatively, the patient received dual immunotherapy. On day 19 of treatment, following physical exertion, the patient developed progressive chest tightness and dyspnea, accompanied by markedly elevated cardiac biomarkers (troponin Ⅰ: 550.7 pg/mL; creatine kinase: 9 669 U/L). Multidisciplinary evaluation confirmed the diagnosis of grade 4 immune-mediated myocarditis. Immediate discontinuation of immunotherapy was followed by intensive care unit admission for hormonal shock therapy and additional symptomatic management. After two months of targeted management, both clinical symptoms and laboratory parameters normalized. The patient remained stable with no cardiac sequelae during three-month post-discharge follow-up.

Immune-mediated myocarditis is a rare but life-threatening complication of immune checkpoint inhibitor therapy. We report a case of a patient with high-grade urothelial carcinoma and lymph node metastasis. After exhibiting cisplatin intolerance postoperatively, the patient received dual immunotherapy. On day 19 of treatment, following physical exertion, the patient developed progressive chest tightness and dyspnea, accompanied by markedly elevated cardiac biomarkers (troponin Ⅰ: 550.7 pg/mL; creatine kinase: 9 669 U/L). Multidisciplinary evaluation confirmed the diagnosis of grade 4 immune-mediated myocarditis. Immediate discontinuation of immunotherapy was followed by intensive care unit admission for hormonal shock therapy and additional symptomatic management. After two months of targeted management, both clinical symptoms and laboratory parameters normalized. The patient remained stable with no cardiac sequelae during three-month post-discharge follow-up.

Gastric cancer is one of the most common malignant tumors of the digestive tract globally, causing a heavy burden on society due to its high incidence and mortality rates. Patients with gastric cancer and peritoneal metastasis suffer poor prognosis, and peritoneal metastasis is a major factor in the recurrence and metastasis of gastric cancer. Currently, the diagnosis of peritoneal metastasis mainly relies on contrast-enhanced CT, PET-CT, and other imaging techniques, but these technologies have a limited capability to detect small lesion of peritoneal metastases. Laparoscopic exploration is still considered as the most reliable method to diagnose peritoneal metastasis of gastric cancer. It allows direct visualization of the abdominal cavity and peritoneal regions, facilitating the detection of metastases. Furthermore, it enables the collection of histological or cytological specimens for definitive pathological diagnosis. However, the area formed by the parietal peritoneum and visceral peritoneum is large and has many folds in space. To explore the tumor and peritoneum as comprehensively as possible, our team has proposed the "Four-Step Procedure" of laparoscopic exploration for gastric cancer to standardize the operation process of laparoscopic exploration, which is characterized by its safety, comprehensiveness, precision and ease of implementation. This article primarily discusses the limitation of routine clinical techniques in diagnosing peritoneal metastasis in gastric cancer and introduce the significant value of the "Four-Step Procedure" in diagnosing peritoneal metastasis in gastric cancer.

The clinical data and genetic characteristics of one child with mental retardation-56 (MRD56) diagnosed at the Department of Neonatology, Foshan Fosun Chancheng Hospital in October 2021 were retrospectively analyzed.The patient was admitted to the hospital with " 34 + 2 weeks of preterm birth, shortness of breath, and dyspnea for 0.5 hours". In the neonatal period, the patient had special facial features, hypotonia, weaning and feeding difficulties, laryngeal stridor.In infancy, the patient showed global psychomotor development delay, intellectual disability, epilepsy, etc.Magnetic resonance imaging of the brain showed delayed myelination and dysplasia of the cerebellum and corpus callosum.Whole-exome sequencing showed that the CLTC gene had a new missense mutation c.3334T>C (p.Trp1112Arg), and MRD56 was confirmed.A total of 32 cases of MRD56 were reported worldwide, with special facial features, intellectual disability, and psychomotor retardation as the main clinical manifestations.The cause is a mutation in the CLTC gene, which leads to abnormality in the structure of the clathrin encoded, thus affecting neurotransmitter transmission.This is the first report of MRD56 caused by the CLTC gene mutation in China, and a new clinical phenotype has been discovered.The finding enriches the phenotypic spectrum of the disease and provides a basis for clinicians to understand and study the disease.

Objective:To analyze the lower limb muscle synergy patterns during the jump landing/cutting in patients with functional ankle instability(FAI),those who have experienced an ankle sprain without instability(Coper),and healthy controls(CON).Method:Twelve populations were recruited for each of the FAI,Coper,and CON groups(male/female ratio and whether the injured side was the favorable side were matched among groups).Kinematic,kinetic and sur-face electromyography(sEMG)data were collected from the unilateral lower limb during the jumping landing/cutting maneuver.Muscle synergy analysis was conducted using a non-negative matrix decomposition algorithm to extract parameters including the number of synergies,variance accounted for(VAF),synergy vectors,and activation coefficients.Result:Four synergy patterns existed in all three groups.Synergy l mainly activated the hip and knee exten-sors,contributing to impact absorption during landing.Synergy 2 mainly activated the knee extensors and ankle plantarflexors,functioning during both landing absorption and force generation in the lateral cut.Synergy 3 mainly activated the knee flexors and ankle plantarflexors,playing a role in the lateral cut force phase.Syner-gy 4 mainly activated the tibialis anterior muscle,contributing during the early landing phase and at the end of the lateral cut force generation phase,with a primary role in ankle stabilization.There was no significant difference in the number of synergies among the three groups,but the VAF-l(the VAF value when the num-ber of synergy is 1)of FAI group was significantly higher than the other two groups(P＜0.05).In the synergy vectors,the FAI and Coper groups showed increased activation weights for the periprosthetic muscles,reduced activation weights for the ankle plantarflexors and extensor digitorum brevis,and greater activation weights for the tibialis anterior muscles(P＜0.05).In terms of activation coefficients,the Coper group exhibited an earlier peak activation of synergy 2 and synergy 3(P＜0.05).Conclusion:Differences in ankle stabilization did not affect the number of muscle synergies in the lower ex-tremity,but muscle contributions within each synergy were altered in patients with FAI,indicating a compensa-tory strategy that relied more on proximal muscle while reducing the functional contributions of foot muscles to impact absorption and force generation.In the Coper group,reduced ankle muscle activation was compen-sated for by central adjustment of activation coefficient.

BACKGROUND:Anybody musculoskeletal modeling system uses mathematical modeling techniques to simulate the relationship between human bones,muscles,and the environment,allowing for the study of inverse dynamics of the human body and obtaining indicators such as lower limb joint forces.OBJECTIVE:To analyze the stress distribution patterns of lower limb joints during the practice of Tai Chi movements,thereby exploring the scientific training and exercise value of Tai Chi.METHODS:Eight Tai Chi master-level athletes were selected from the Wushu College of Beijing Sport University for data collection,including seven sets of stepping movements and CT scans of the right femur.The BTS infrared capture system and Kistler three-dimensional force platform were used to collect kinematic and mechanical data of the seven sets of stepping movements in Tai Chi(Eight Methods and Five Steps).The Anybody 7.2 musculoskeletal model's multi-body dynamics simulation technology was utilized to calculate lower limb joint dynamic parameters,and Workbench 19.2 was used to perform stress analysis on the femur.RESULTS AND CONCLUSION:(1)Using Workbench software,the stress results of the femur for seven sets of movements were obtained.The peak stress values of the seven sets of movements in descending order were:Retreat and Rollback(22.00 MPa),Retreat and Pluck(19.379 MPa),Left and Right Shift Step Squeeze and Press(9.35 MPa),Left and Right Shift Step Elbow Lean(6.30 MPa),Forward Step and Expand(4.68 MPa),Forward Step and Pull(2.57 MPa),and Middle Fixed Standalone Position(0.31 MPa).(2)In the seven sets of stepping movements,the two backward stepping movements resulted in the greatest stress on the femur(P＜0.05),and the maximum stress positions on the femur were different during the movement of the seven sets of actions.(3)It is concluded that during the seven sets of stepping movements in Tai Chi(Eight Methods and Five Steps),stress threshold and maximum stress position of the femur will vary with different movements in five directions(seven sets of movements).Continuous training can comprehensively stimulate the femoral body.Forward stepping movements have a greater impact on the front and upper lateral side of the femoral body,while backward stepping movements have a greater impact on the back and inner side of the femoral body.Left and right lateral stepping movements mainly involve symmetrical stress on both sides of the femoral body.(4)Beginners should train targeted according to the stress characteristics of different stepping movements.During forward and backward stepping movements,attention should be paid to the rotational force of Tai Chi,and during left and right lateral stepping movements,attention should be paid to the medial counterforce.Beginners should focus on the Tai Chi training steps that correspond to their own weaknesses to achieve better exercise outcomes.

Gastric cancer is one of the most common malignant tumors of the digestive tract globally, causing a heavy burden on society due to its high incidence and mortality rates. Patients with gastric cancer and peritoneal metastasis suffer poor prognosis, and peritoneal metastasis is a major factor in the recurrence and metastasis of gastric cancer. Currently, the diagnosis of peritoneal metastasis mainly relies on contrast-enhanced CT, PET-CT, and other imaging techniques, but these technologies have a limited capability to detect small lesion of peritoneal metastases. Laparoscopic exploration is still considered as the most reliable method to diagnose peritoneal metastasis of gastric cancer. It allows direct visualization of the abdominal cavity and peritoneal regions, facilitating the detection of metastases. Furthermore, it enables the collection of histological or cytological specimens for definitive pathological diagnosis. However, the area formed by the parietal peritoneum and visceral peritoneum is large and has many folds in space. To explore the tumor and peritoneum as comprehensively as possible, our team has proposed the "Four-Step Procedure" of laparoscopic exploration for gastric cancer to standardize the operation process of laparoscopic exploration, which is characterized by its safety, comprehensiveness, precision and ease of implementation. This article primarily discusses the limitation of routine clinical techniques in diagnosing peritoneal metastasis in gastric cancer and introduce the significant value of the "Four-Step Procedure" in diagnosing peritoneal metastasis in gastric cancer.

Objective To investigate the effect of lateral wedge insoles (LWI) with different heights on lower limb biomechanical characteristics during single-leg landing in patients with chronic ankle in? stability (CAI). Methods Thirty CAI undergraduates (15 males and 15 females) were recruited. All participants were required to perform a single-leg landing task from a height of 30 cm. They first un? derwent the test with flat insoles (FI),followed by tests with 3 mm and 6 mm LWI in a randomized order. A Qualisys 3D motion capture system and Kistler force platform were used to synchronously col? lect data. Kinematic and kinetic data of the lower limb tri-joints (hip,knee and ankle) were ana? lyzed from the moment of ground contact to the body stabilization phase. Results(1) Kinematically,compared with the FI group,the 3 mm and 6 mm LWI groups showed greater hip and knee flexion angles (P<0.001),smaller hip adduction (P<0.05,P<0.01),ankle plantarflexion (P<0.05,P<0.001),and knee valgus angles (P<0.05,P<0.001) at the moment of ground contact. The 6 mm LWI group had larger hip/knee flexion angles (P<0.001) and smaller ankle plantarflexion angles (P<0.001) at contact than the 3 mm LWI group. Additionally,compared with the FI group,the 6 mm LWI group showed significantly smaller ankle eversion angles (P<0.05). The 6 mm LWI group showed larger peak knee flexion angle (P<0.05) and peak ankle eversion angle (P<0.01) than the FI group,while the 3 mm LWI group also had a greater peak ankle eversion angle (P<0.05) than the FI group. Meanwhile,the 3 mm and 6 mm LWI groups had a larger knee flexion-extension range of motion (ROM)(P<0.05,P<0.01) but smaller ankle flexion-extension ROM (P<0.001) than the FI group. The 6 mm LWI group showed a significantly greater hip adduction-abduction ROM (P<0.001,P<0.05) than the other groups,with a smaller ankle plantar flexion-extension ROM (P<0.05) than the 3 mm LWI group. (2) The peak vertical ground reaction force (peak vGRF) of the LWI groups was signifi? cantly lower than the FI group (P<0.01),with that of the 6 mm LWI group significantly lower than the 3 mm LWI group (P<0.001). Moreover,there were significantly greater peak hip flexion moment (P<0.01) and smaller peak ankle plantarflexion moment of the LWI groups than the FI group (P<0.001),with a smaller peak ankle plantarflexion moment of the 6 mm LWI group than the 3 mm LWI group (P<0.05). (3) Significantly greater subjective comfort was observed in the 6 mm LWI group than the FI group (P<0.01). Conclusion LWI can improve landing patterns in CAI patients,re? duce their ground reaction forces,and lower the risk of ankle sprain. The 6 mm LWI outperforms the 3 mm LWI in improving flexion angles of the lower limb tri-joints at ground contact,ankle flexion-ex? tension ROM,peak vGRF,and peak ankle plantarflexion moment during single-leg landing tasks. Therefore,LWI can be used as a wearable protective device during rehabilitation to prevent recurrent ankle sprains among such patients.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Objective To explore the risk factors for the recurrence of autoimmune pancreatitis(AIP),so as to provide a new reference for its clinical treatment.Methods The clinical data of 198 AIP patients admitted to The First Affiliated Hospital of Naval Medical University from 2014 to 2021 were collected,including 164 patients with type 1 AIP and 34 patients with type 2 AIP.Based on the recurrence status of AIP,the patients were categorized into recurrence group(38 cases)and non-recurrence group(160 cases),and differences between the 2 groups were analyzed.Patients with definite duration of glucocorticoid maintenance therapy were further screened,and logistic regression model and Spearman rank correlation analysis were used to analyze the risk factors of AIP recurrence.Results During the follow-up period,19.19％(38/198)of AIP patients experienced a relapse.The 1-,3-,and 5-year cumulative recurrence rates were 6.57％,9.09％,and 12.63％,respectively,with type 1 AIP demonstrating a significantly higher recurrence rate than type 2 AIP(21.95％[36/164]vs 5.88％[2/34],P=0.030).Univariate logistic regression analysis showed that serum low density lipoprotein-cholesterol level(odds ratio[OR]=0.544,95％confidence interval[CI]0.321-0.924,P=0.024)and the duration of glucocorticoid maintenance therapy(OR=0.797,95％CI 0.704-0.902,P＜0.001)were the potential factors of AIP recurrence in 112 patients with definite data on the duration of glucocorticoid maintenance therapy.Multivariate logistic regression analysis showed that the duration of glucocorticoid maintenance therapy was independently associated with AIP recurrence(OR=0.813,95％CI 0.713-0.926,P=0.002).Spearman rank correlation analysis further demonstrated a negative correlation between the duration of glucocorticoid maintenance therapy and AIP recurrence(r=-0.545,P＜0.001).Additionally,receiver operating characteristic curve analysis indicated that the duration of glucocorticoid maintenance therapy had good predictive effect on AIP recurrence,with an area under curve value of 0.873(95％CI 0.800-0.945,P＜0.001).Conclusion Long-term regular glucocorticoid therapy is an independent protective factor against AIP recurrence,and it can significantly reduce the recurrence of AIP.