To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

The SEPN1 gene encodes selenoprotein N,and mutations in this gene can cause SEPN1-re-lated myopathy(SEPN1-RM).SEPN1-RM is an extremely rare and complex congenital myopathy with an in-sidious onset and slow progression,often leading to multi-system involvement.The main clinical manifestations include axial and proximal muscle weakness,early respiratory dysfunction,and spinal deformities.This article reports the diagnosis and treatment conditions for a pediatric patient carrying novel mutation in SEPN1 gene who underwent spinal orthopedic fusion surgery.After detailed multidisciplinary evaluation,adequate preoperative preparation,and meticulous perioperative management,the patient successfully underwent high-risk spinal or-thopedic surgery and recovered well.Based on the patient's diagnosis,perioperative management,and follow-up,combined with the latest domestic and international literature,this article systematically discusses the diag-nostic and therapeutic characteristics of this rare disease.The aim is to enhance clinicians'understanding of such diseases and to provide evidence-based support and reference for perioperative comprehensive management for such diseases.

Objective:To evaluate the clinical efficacy of methylation sensitive-high resolution melting curve (MS-HRM) detection of IFN-induced protein 44-like (IFI44L) gene methylation in the diagnosis of systemic lupus erythematosus (SLE), as well as the relationship between IFI44L gene markers and the early onset of SLE.Methods:From February 2020 to September 2022, the MS-HRM was used to detect the methylation level of the IFI44L gene in peripheral blood mononuclear cells of 602 SLE patients and 524 other autoimmune disease patients (excluding SLE) from Beijing Peking Union Medical College Hospital, Guangdong Provincial People′s Hospital, and Shenzhen People′s Hospital, totaling 1 126 patients. Compared with the 2012 SLICC criteria, the suspected cases were followed up for 6 months until the onset and clinical diagnosis of SLE were confirmed. The measurement data of normal distribution were expressed as mean±SD, and the consistency analysis was performed using the Kappa consistency test. The clinical diagnostic efficacy indicators were calculated using the receiver operating characteristic (ROC) curve. Results:RR (95% CI) of early suspected cases was 17.06 (9.43, 30.82). The results of IFI44L gene methylation level were in good agreement with the 2012 SLICC criteria, and the sensitivity, specificity and total coincidence rate were 90.53%, 92.56% and 91.47%, respectively. The Kappa value (95% CI) was 0.829(0.796, 0.862) ( P<0.001). The diagnostic efficiency of IFI44L gene methylation level ( Kappa value 0.817) was superior to anti-nuclear antibody, anti-SM antibody and anti-dsDNA antibody ( Kappa value 0.418, 0.216 and 0.440, respectively). The Kappa values (95% CI) of methylation between MS-HRM and pyrosequencing was 0.861(0.806, 0.916), P<0.001. Conclusion:The hypomethylation of IFI44L gene methylation level detected by MS-HRM is closely related to the occurrence and development of SLE, and its diagnostic performance is better than that of three autoantibodies in SLE diagnosis, which can be used for the early diagnosis of SLE.

Objective To retrospectively study the characteristics and short-term outcomes of patients with decompensated liver cirrhosis accompanied by diastolic cardiac dysfunction,and to inform the clinical diagnosis and treatment of decompensated liver cirrhosis.Methods We retrospectively analyzed the clinical data of patients with liver cirrhosis and diastolic heart dysfunction admitted to Nanfang Hospital of Southern Medical University from April 1,2019 to July 31,2023.The patients were divided into compensated cirrhosis group(n=37)and decompensated cirrhosis group(n=226),and those with decompensated cirrhosis were further divided into subgroups of patients with heart dysfunction(n=84)and patients without heart dysfunction(n=142).We compared two groups using the independent samples t-test and Mann-Whitney U test for continuous data in normal distribution and data in skewed distribution,respectively;compared multiple groups using the Kruskal-Wallis H test,with subsequent paired comparisons using the Wilcoxon test;compared categorical data between two groups using the chi-square test or corrected chi-square test;identified the factors affecting patient survival using a Logistic regression model;and plotted Kaplan-Meier survival curves,with inter-group comparisons using the log-rank test.Results A total of 263 eligible patients were ultimately included,among whom 226 patients were diagnosed with decompensated liver cirrhosis(84 patients with diastolic dysfunction).Between the diastolic dysfunction group and non-diastolic dysfunction group,significant differences were detected in age(t=-4.566,P<0.05),activated partial thromboplastin time(Z=-3.026,P<0.05),prothrombin time(Z=-2.450,P<0.05),international normalized ratio(Z=2.779,P<0.05),and the proportion of moderate esophageal varices(χ2=4.273,P<0.05).During hospitalization,35 patients experienced new or aggravated ascites(18 with cardiac dysfunction and 17 without cardiac dysfunction),6 patients experienced new gastroesophageal variceal bleeding,and 9 patients experienced new or aggravated hepatic encephalopathy(3 with cardiac dysfunction and 6 without cardiac dysfunction).Jaundice was the most common decompensation event upon admission,and electrophysiological abnormalities were the most common electrocardiogram findings upon admission.During the 90-day follow-up period,30 individuals(12 with cardiac dysfunction and 18 without cardia dysfunction)died.The logistic regression analysis showed that age(odds ratio[OR]=1.075,95%confidence interval[CI]:1.033-1.119,P<0.001),N-terminal pro-B-type natriuretic peptide(NT-proBNP,OR=0.996,95%CI:0.992-0.999,P=0.016),and mild/moderate ascites(OR=0.270,95%CI:0.092-0.789,P=0.017)were independent predictive factors for cirrhotic cardiomyopathy.Conclusion Timely attention should be paid to elderly patients with decompensated liver cirrhosis and diastolic heart dysfunction who have a decline in NT-proBNP and mild to moderate ascites.Symptomatic treatment such as diuretics may improve diastolic heart dysfunction.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective To establish a model of radiation-induced myocardial fibrosis in mice, and study the effect of TGF-β/SMAD pathway on radiation-induced myocardial fibrosis in mice and the protective effect of pirfenidone capsules (PFD) on radiation-induced myocardial fibrosis. Methods Male C57BL/6J mice were randomly divided into control group, irradiation group, and drug intervention groups (low-dose PFD + irradiation group and high-dose PFD + irradiation group). After radiation exposure, the control group and the irradiation group were given sodium carboxymethyl cellulose by gavage, while the low-dose PFD + irradiation group and the high-dose PFD + irradiation group were given PFD at 150 and 300 mg/kg daily by gavage for 12 consecutive weeks, respectively. The body weights of mice were measured and recorded weekly. The pathological changes of heart tissues in mice were observed by H&E and Masson’s trichrome staining. The expression levels of TGF-β, SMAD2, and SMAD3 mRNAs in mouse heart tissues were detected by RT-PCR. The expression levels of TGF-β, SMAD2, and SMAD3 proteins in mouse heart tissues were detected by Western blot. The expression levels of CK and CK-MB in mouse heart tissues were detected by blood biochemical tests. Results H&E and Masson’s trichrome staining showed severe myocardial fibrosis in the irradiation group compared with the control group. Compared with the irradiation group, the two groups with drug intervention showed reduced heart disease and myocardial fibrosis. RT-PCR and Western blot showed that the expression levels of TGF-β, SMAD2, and SMAD3 were up-regulated in the irradiation group compared with the other three groups (P < 0.05). The expression levels of TGF-β, SMAD2, and SMAD3 were down-regulated in the two groups treated with PFD compared with the irradiation group (P < 0.05). The expression levels of CK and CK-MB in mouse heart tissues were down-regulated in the two groups treated with PFD compared to irradiation group (P < 0.05). Conclusion Radiation has long-term effects on normal heart tissue, causing myocardial damage and promoting myocardial fibrosis. The up-regulation of TGF-β/SMAD pathway is related to the formation of radiation-induced myocardial fibrosis. PFD can mitigate the progression of myocardial fibrosis and protect heart tissue by down-regulating TGF-β/SMAD pathway.