GNE myopathy is a progressive distal myopathy typically manifested in late teens to thirties. We described the effects of bilateral upper-extremity hybrid assistive limb (HAL) rehabilitation in patients with GNE myopathy. We described a case series of 6 patients with GNE myopathy. Among them, five patients underwent bilateral upper-extremity HAL rehabilitation during a two-week hospitalization. The rehabilitation program consisted of elbow flexion-extension exercises with gradually adjusted assistance levels. HAL rehabilitation resulted in significant improvements in upper extremity strength scores (p = 0.0311), and overall upper limb motor function assessed by Simple Test for Evaluating Hand Function (STEF) (p = 0.0014). No significant changes in creatine kinase (CK) levels were observed, indicating that the exercise intensity did not cause muscle damage. Patients reported functional improvements including increased ability to perform daily activities requiring elbow flexion. While further research is needed to assess long-term effects and underlying mechanisms, these findings suggest potential benefits of HAL rehabilitation for neuromuscular diseases with upper-limb weakness.

Since BRCA1/2 genetic testing has been covered by public insurance for certain breast cancer patients in Japan from April 2020, it has led to a rapid increase in testing frequency and the identification of many BRCA1/2 pathogenic variant (PV) carriers. BRCA1/2 PV carriers in Japan are reported to be also more susceptible to esophageal, gastric, and biliary tract cancers. We retrospectively analyzed 337 breast cancer patients who underwent BRCA1/2 genetic testing at Tohoku University Hospital. We extracted medical records such as past medical histories and family histories of malignancies based on questionnaires written by patient himself at first visit to our department. Compared to non-PV patients (n = 304), BRCA1/2 PV patients (n = 33) tended to have higher family history of breast cancer (P = 0.098) and had significantly higher family history of ovarian cancer (P = 0.005). However, pancreas, prostate, esophagus, gastric, and biliary tract cancer are not significantly more prevalent with family history among BRCA1/2 PV patients than non-PV patients. In following up on breast cancer patients with BRCA1/2 PV, at present, although there is a suggestion that esophageal, gastric, and biliary tract cancers are more likely to occur, the number of cases remains small, and it is not easy to perform these cancer screening on all BRCA1/2 PV cases.

Polycystic ovary syndrome (PCOS) affects the health of many females of childbearing age. PCOS cannot be completely cured at present, so it is very important to study the pathogenesis. miR-126-3p expression was detected by RT-qPCR. The receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic value. In human ovarian granulosa-like tumor cell line (KGN) cells, miR-126-3p and solute carrier family 7 member 5 (SLC7A5) were overexpressed or inhibited by transfection. The target of miR-126-3p was forecasted using the miRDB database. The correlation of the two in PCOS was proved using Pearson correlation analysis. miR-126-3p and SLC7A5 were knocked down in KGN cells to detect the function of both in PCOS. miR-126-3p was reduced and had a high diagnostic value in PCOS. In KGN cells, overexpressed miR-126-3p increased the proliferation and decreased the apoptosis, while inhibited miR-126-3p decreased the proliferation and increased the apoptosis. SLC7A5 in PCOS was increased and was negatively regulated by miR-126-3p. In KGN cells, the simultaneous overexpression of SLC7A5 and miR-126-3p decreased the proliferation and increased the apoptosis compared with the overexpression of miR-126-3p. miR-126-3p decreased and had a diagnostic value in PCOS. In KGN cells, SLC7A5 was the target gene of miR-126-3p, with which it exhibited a negative correlation.

Intra-abdominal complications related to spinal surgery are uncommon but may result in serious morbidity. Prone positioning, often used in scoliosis correction procedures, has been implicated in compression-induced injuries of visceral organs, particularly in patients with anatomical deformities such as thoracic asymmetry and lumbar lordosis. We report a rare case of concurrent liver injury, pancreatic damage, and renal dysfunction following posterior spinal fusion in a 12-year-old male with idiopathic scoliosis. Despite intraoperative decompression precautions and stable hemodynamics, the patient developed acute abdominal symptoms and elevated hepatic, pancreatic enzymes, and creatinine indicating renal damage on postoperative day 1. Imaging revealed a liver contusion, ascites, and reduced enhancement of the left kidney, suggestive of organ compression. Renal findings were attributed to venous congestion likely caused by compression of the left renal vein between the aorta and the superior mesenteric artery, resembling nutcracker syndrome. Conservative management led to rapid clinical improvement, with full recovery observed by postoperative day 18. This case highlights the importance of recognizing position-related organ injury during scoliosis surgery. Awareness of risk factors—including low body mass index and skeletal deformities—and early assessment of blood flow are essential for accurate diagnosis and appropriate management. Preoperative simulation of prone positioning may help mitigate the risk in anatomically vulnerable patients.

ACTR2 is highly expressed and autophagy is enhanced in adriamycin (ADR)-induced nephropathic rats, and KLF5/ITCH is predicted to be the upstream axis of ACTR2. Accordingly, we investigated the regulation of excessive autophagy by KLF5/ITCH/ACTR2 in inflammatory ADR-induced podocytes and preliminarily elucidated the molecular mechanisms of podocyte injury. ADR was used to establish a rat model of nephropathy as well as a model of podocyte injury. Proteinuria, albumin, serum creatinine, triglyceride and total cholesterol levels, histopathologic staining were assessed. Transmission electron microscopy was applied to observe autophagy, and Western blot to detect protein levels in vivo. Quantitative real-time polymerase chain reaction, Western blot, flow cytometry, Co-immunoprecipitation, chromatin immunoprecipitation, dual luciferase reporter genes, and bioinformatics analyses were performed for in vitro mechanistic and functional exploration. ADR rat model was successfully constructed, showing abnormal biochemical indices, pathological damage and autophagic vesicle formation, increased expressions of autophagy-related proteins and ACTR2 protein, and decreased expressions of KLF5 and ITCH. ACTR2 silencing reversed ADR-induced apoptosis and inflammatory factors, decreased LC3 II/LC3 I, Beclin 1, Bax and C-caspase 3 levels, and elevated Bcl-2 level in vitro. KLF5 activated ITCH to promote ubiquitinated degradation of ACTR2. KLF5 overexpression attenuated the promoting effects of ACTR2 on autophagy, apoptosis, and inflammation in podocytes. The mechanism by which KLF5 protects podocytes from injury is to promote ITCH transcription, thereby facilitating ITCH-mediated ubiquitination of ACTR2 and inhibiting podocyte autophagy.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmia syndrome often caused by biallelic variants in the TECRL gene. This study reviews a Chinese family with two generations and six members affected by CPVT. The proband experienced syncope, loss of consciousness after exercise, and recurrent seizures, with electrocardiograph showing prolonged QTc interval and extreme ventricular tachycardia. Her elder sister died of syncope and cardiac arrest after exercise. Genetic analysis identified compound heterozygous variants in the TECRL gene: c.587G>A (p.Arg196Gln) and c.868C>T (p.Pro290Ser), inherited from each parent. Other family members without symptoms only carried one heterozygous variant. The p.Arg196Gln variant was previously reported, but p.Pro290Ser was a novel variant. Molecular dynamics simulations and Western blot analysis suggested that the structural stability and expression levels of the mutant protein were altered. This study underscores the significance of molecular diagnostics in patients experiencing syncope or cardiac arrest triggered by environmental changes or exercise, as early detection can facilitate personalized care and targeted treatment.

Bladder cancer (BCa) is a malignancy in the genitourinary tract. Aerobic glycolysis is involved in the progression and chemoresistance of BCa. Oxymatrine is an alkaloid from the root of Sophora flavescens Ait. and possesses anticancer properties. This study aimed to validate whether oxymatrine can inhibit BCa progression by regulating glycolysis. The effects of oxymatrine on BCa cellsin vitro were evaluated using CCK-8 assays, colony formation assays, wound healing assays, and transwell assays. To determine the levels of lactate production and glucose consumption, a lactate assay kit and a glucose assay kit were used. Pyruvate kinase M2 (PKM2) and glucose transporter type 1 (GLUT1) expression levels were measured using immunoblotting, immunofluorescent staining, and immunohistochemistry analysis. A mouse model of BCa was constructed to explore the impact of oxymatrine (40 mg/kg) combined with cisplatin (5 mg/kg) on BCa in vivo. Oxymatrine suppressed BCa cell viability, proliferation, migration, and invasion. Oxymatrine attenuated glycolysis and downregulated the expression of PKM2 and GLUT1 in BCa cells. Overexpression of PKM2 reversed the suppressive effects of oxymatrine on the malignant phenotypes of BCa cells, while silencing PKM2 further enhanced them. Moreover, oxymatrine (40 mg/kg) or cisplatin (5 mg/kg) restrained BCa tumor growth and PKM2 expression in vivo, and these effects were further enhanced by the combination treatment with oxymatrine and cisplatin. Overall, oxymatrine inhibits cell growth and enhances cisplatin sensitivity in BCa by attenuating PKM2-mediated glycolysis, suggesting that oxymatrine is a potential anti-BCa agent.

Iron is required for the synthesis of neurotransmitters that influence emotion and behavior. This study examined the relationship between iron intake and mental health in older adults using data from the Yamagata Cohort study, which included a total of 6,184 individuals (3,256 men and 2,928 women) aged 65 years or above. Mental health was evaluated using the Kessler 6 scale (K6). Participants were divided into two groups based on the K6 score: those with a score < 9 and those with a score ≥ 9. Based on iron intake, male participants were divided into two groups: those with an iron intake of < 6 mg/day or more; female participants were classified as those with an iron intake of < 5 mg/day or more. In logistic regression analysis, after adjusting for 10 factors, including age, hypertension, diabetes, dyslipidemia, alcohol consumption history, smoking history, marital status, total energy intake per day, body mass index, and hemoglobin level, the number of men with suspected depression was significantly higher among those with an iron intake of < 6 mg/day. No significant differences were observed among women. These results suggest a potential association between increased iron intake and improved mental health among male older adults.

Low-dose dexamethasone is widely used in perioperative settings for its antiemetic and analgesic effects. The present study aimed to investigate the impacts of low-dose dexamethasone on cell kinetics, cytokine productions and cytotoxic activity of natural killer (NK) cells in lymphoid organs. Female Balb/c mice were intraperitoneally administered normal saline (Group N), low-dose dexamethasone (0.1 mg/kg) (Group L), or high-dose dexamethasone (20 mg/kg) (Group H). Measurement of cell counts of thymocytes and splenocytes, and phenotypic analyses of the lymphocytes and the cytotoxicity of NK cells in the splenocytes using flow cytometry were performed. The production of cytokines in the splenocytes ex vivo was measured by ELISA. There was a marked decrease in the number of lymphocytes in Group H, while the number of splenocytes was significantly increased in Group L compared to Group N at 24 hours after administration (p = 0.019). The production of IFN-γ was dose-dependently decreased by dexamethasone. The proportions of double-positive thymocytes and CD4⁺ splenocytes were reduced in Group H, but there were no significant changes in lymphocyte subsets between Groups N and L until 48 hours after administration. The cytotoxicity of NK cells in Group L was increased compared to that in Group N at 24 and 48 hours (p = 0.008 and p = 0.018, respectively). Low-dose dexamethasone augmented immune cell mobilization and upregulated cytotoxicity of NK cells while suppressing cytokine production. These results suggested that low-dose dexamethasone have conflicting immunological effects and transiently enhances innate immunity such as NK cell function.

Early identification and treatment optimization for the patients with primary aldosteronism are crucial to minimizing the enhanced cardiovascular risks. However, the natural course of primary aldosteronism development remains unclear. An 18-year-old man visited our outpatient clinic for hypertension. At baseline, confirmatory testing ruled out primary aldosteronism, and computed tomography showed normal adrenal glands. During subsequent outpatient follow-up, his blood pressure gradually increased despite treatment with multiple antihypertensive medications. At his 7^th-year visit, he eventually presented severe hypokalemia with a right adrenal tumor. Endocrinological evaluation revealed hyperaldosteronism along with suppressed renin activity, suggesting primary aldosteronism. Subsequent diagnostic procedures, including the captopril challenge test and adrenal venous sampling, confirmed the diagnosis of primary aldosteronism due to the right adrenal tumor. The patient underwent right adrenalectomy, leading to remission of primary aldosteronism. Histopathological analysis confirmed the resected adrenal tumor as a KCNJ5-mutated aldosterone-producing adenoma. Notably, plasma steroid profiling retrospectively revealed elevated peripheral 18-oxocortisol levels, a biomarker of KCNJ5-mutated aldosterone-producing adenomas, before the diagnosis of primary aldosteronism. This case clearly demonstrated a natural course of unilateral primary aldosteronism and highlights the potential utility of steroid profiling as part of the diagnostic strategy for primary aldosteronism.

The severity of sepsis-induced hepatic injury severely impacts disease progression and prognosis. Hence, this study investigates the role of adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSCs-exo) in mitigating hepatic injury during sepsis. An in vitro model of sepsis-induced hepatic injury was established by stimulating HepG2 cells with lipopolysaccharide (LPS). ADSCs were either co-cultured with LPS-injured HepG2 cells or used to isolate exosomes for subsequent treatment. The characteristics of ADSCs-derived exosomes were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. ADSCs-exo uptake by hepatocytes was assessed via PKH67 labeling. Cell viability, apoptosis, and lactate dehydrogenase (LDH) release were evaluated using Cell Counting Kit-8, flow cytometry, and commercial assays, respectively. The involvement of the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was further investigated. Both ADSCs and ADSCs-exo notably attenuated LPS-induced hepatocyte injury, as evidenced by lowered LDH release, enhanced cell viability, and suppressed apoptosis. ADSCs-exo were internalized by HepG2 cells. Treatment with ADSCs-exo led to a notable downregulation of phosphorylated JAK2 and STAT3. Moreover, pharmacological activation of the JAK2/STAT3 pathway partially reversed the protective effects of ADSCs-exo. Collectively, ADSCs-exo alleviate LPS-induced hepatocyte injury by inhibiting activation of the JAK2/STAT3 signaling pathway. These findings underscore the potential of ADSCs-exo as a promising cell-free therapeutic strategy for sepsis-associated liver injury.

Acute pancreatitis (AP) is marked by severe inflammatory injury to pancreatic acinar cells, with pyroptosis playing a critical role in its progression. Disulfiram (DSF), traditionally prescribed for alcohol dependence, has recently attracted attention for its anti-inflammatory potential. In this study, caerulein-stimulated AR42J cells were used to model AP in vitro and to evaluate whether DSF could alleviate cellular injury and inflammatory responses. Treatment with DSF improved cell viability, suppressed lactate dehydrogenase release, and significantly reduced pro-inflammatory cytokines IL-1β and IL-18. Mechanistic analyses revealed that DSF downregulated NLRP3, cleaved Caspase-1, and the active fragment of gasdermin D (GSDMD), indicating inhibition of the NLRP3/Caspase-1/GSDMD pyroptotic pathway. Additional experiments showed that pharmacological inhibition of Caspase-1 enhanced the beneficial effects of DSF, while GSDMD overexpression counteracted them, confirming the centrality of this pathway to DSF’s protective action. These findings suggest that DSF modulates inflammasome-driven pyroptotic signaling in pancreatic acinar cells under inflammatory conditions and may warrant further investigation in more complex in vivo models of acute pancreatitis.

Creating intervertebral disc degeneration (IDD) models is paramount for basic research. The investigation was to identify the commonalities and distinctions between two strategies for provoking IDD: the cervical dorsal muscles resection (CMS) and the facet joints resection (FR). Thirty-two 3-month-old male Sprague Dawley rats were randomly split into four groups: FR, CMS and two shams. For the CMS group, the cervical dorsal muscles was excised, whereas, the FR cohort sawed the bilateral facet joints of C5/6. Twelve weeks postprocedure, C5/6 intervertebral discs were collected, and the bone microstructure of C5 vertebrae were analyzed by Micro-CT, as well as the defect rates of C5/6 vertebral endplates and the intervertebral disc height (IDH) of C5/6. Finally, histological staining was employed to evaluate the disc degeneration scores (DDS). Twelve weeks post operatively, both CMS and FR groups demonstrated significant IDD, with the pronounced deterioration of vertebral endplates, a diminished intervertebral height, and a notably elevated disc degeneration score within the model rats. Yet, the two models also exhibited distinct features. Primarily, the FR rats showed a significant boost in vertebral bone volume fraction, a trend not visible in the CMS rats. Additionally, the CMS rats presented more advanced endplate deterioration. Lastly, the CMS rats revealed a reduced IDH and an elevated DDS in comparison to the FR rats. Both CMS and FR prove successful in causing IDD. Nonetheless, a comparison of the two models revealed a more profound degeneration of the intervertebral disc in CMS rats relative to FR counterparts.

Dexmedetomidine-containing anesthetic regimes improve satisfaction and reduce postoperative mental disorders, but relevant evidence in patients who undergo painless induced abortion is scarce. This study intended to compare the effect of dexmedetomidine combined with propofol and propofol alone on postoperative anxiety and depression, efficacy, and satisfaction in patients who underwent painless induced abortion. A total of 142 patients who underwent painless induced abortion were divided into the Dexmedetomidine plus propofol group (N = 65) and Propofol group (N = 77) according to the actual anesthesia method. In the Dexmedetomidine plus propofol group, 0.3-0.6 μg/kg dexmedetomidine was intravenously pumped within 10 minutes before anesthesia induction. In both groups, 2.0 mg/kg propofol was intravenously administrated for anesthesia induction, and 20-40 mg of propofol was added each time for anesthesia maintenance during surgery. Awake time (7.5 ± 3.1 vs. 8.8 ± 3.2 min) (P = 0.017) and propofol dose (124.7 ± 22.1 vs. 139.8 ± 23.5 mg) (P < 0.001) were decreased in the Dexmedetomidine plus propofol group compared to the Propofol group. Postoperative Hospital Anxiety and Depression (HADS)-anxiety score was numerically lower in the Dexmedetomidine plus propofol group than in the Propofol group (5.2 ± 2.3 vs. 5.9 ± 2.8) (P = 0.087). The overall satisfaction rate was higher in the Dexmedetomidine plus propofol group than in the Propofol group (87.7% vs. 72.7%) (P = 0.028), which was further validated by multivariate logistic regression analysis. In conclusion, dexmedetomidine plus propofol improves satisfaction compared to propofol alone in patients receiving painless induced abortion.

In Japan, the measles-mumps-rubella (MMR) vaccine faced voluntary withdrawal in 1993 due to concerns about aseptic meningitis, resulting in a low nationwide mumps vaccination rate of 30-40%. Responding to this, Nagoya City (population 2.32 million) and Sendai City (population 1.09 million) introduced mumps vaccination subsidies for children aged 1-5 in 2010 and for those aged 1-2 in 2013, respectively. Sendai City, with a lower age limit of 2, reached a 97% vaccination rate within just three years. After intensive interviews with stakeholders, we attribute the success of Sendai City to collaborative efforts among pediatric association leadership, citizens and municipal health center. Trust was established through citizen petitions and effective communication strategies involving the media. These efforts rapidly increased immunization rates, underscoring the significance of local vaccine initiatives despite the voluntary vaccination policy mandated by national regulations.