Objective: To analyze the phylogenetic characteristics of VP1 gene of Coxsackievirus A10 (CVA10) isolates from 2004 to 2023, and to understand the genetic evolution and epidemic trends of CVA10, so as to provide references for the prevention and control of hand, foot, and mouth disease. Methods: The full-length sequences of the VP1 region of CVA10 isolates were retrieved from the BV-BRC database before December 15, 2024. Gene typing, sequence analysis, evolutionary analysis, and amino acid mutation site analysis were conducted using bioinformatics software. Results: A total of 1 253 CVA10 isolates VP1 region nucleotide full-length sequences from 2004 to 2023 were included, with 9 strains from 2004 to 2008, 338 strains from 2009 to 2012, and 906 strains from 2013 to 2023. China had the highest number of CVA10 isolates, with 1 143 strains accounting for 91.22%, and the predominant genotype was C3. Compared to the prototype strain, the nucleotide sequence homology of the VP1 region of CVA10 isolates ranged from 74.94% to 77.63%, while the amino acid sequence homology ranged from 88.59% to 93.62%. The third codon position preferred cytosine and thymine. The top three most abundant amino acids were threonine, alanine, and valine. The average relative synonymous codon usage of 30 amino acid codon groups was greater than 1. The average amino acid substitution entropy value was 0.04, with four amino acid mutation-prone sites identified, and the mutation-prone rate was 1.35%. Conclusions From 2004 to 2023, the majority of CVA10 isolates were primarily sourced from China, with genotype C3 being the predominant circulating strain in China. The nucleotide homology between the CVA10 isolates and the prototype strain was relatively low, and mutation-prone sites were identified, indicating that enhanced monitoring of viral variation is necessary.

Objective To explore the effects of sacral neuromodulation (SNM) on urodynamic parameters during the storage phase in patients with neurogenic bladder (NB), so as to provide reference for evaluating the efficacy of SNM. Methods A total 49 NB patients undergoing SNM at our hospital during Oct.2012 and May 2025 were enrolled. Baseline data and video-urodynamic parameters were collected. Changes in maximum cystometric capacity, maximum detrusor pressure during storage phase, and bladder compliance before and after treatment were assessed. Improvements in detrusor overactivity (DO) and vesicoureteral reflux (VUR) were also analyzed. Results Among the 49 patients,27 were male and 22 were female, with a mean age of (37.41±15.15) years, a median disease duration of 5.0 (2.0,15.5) years, and a median follow-up of 11 (1,32) months. Up to 37 patients (75.5%) received permanent sacral nerve pulse generator implantation (permanent implant group), while the remaining 12 were classified as the non-permanent implant group. Before and after the test period, all patients showed a significant increase in maximum cystometric capacity [ (218.0 (93.0,358.5) mL vs.300.0 (238.5, 400.0) mL, P<0.001], a decrease in maximum detrusor pressure during the filling phase [32.0 (13.5,71.0) cmH_2 O vs. 20.0 (9.0,50.0) cmH_2 O, P<0.001], and an improvement in bladder compliance [11.8 (8.3,25.6) mL/cmH_2 O vs.26.7 (8.6,44.1) mL/cmH_2O, P<0.001]. In the permanent implant group, comparisons before and after the test period showed an increase in maximum bladder capacity [ (239.16±147.23) mL vs. (312.24±121.83) mL, P<0.001], a decrease in maximum detrusor pressure during filling[32.0 (15.0,58.0) cmH_2 O vs.15.0 (9.0,41.0) cmH_2 O, P<0.05], and improved bladder compliance [10.8 (8.3,23.6) mL/cmH_2 O vs.28.6 (8.6,41.4) mL/cmH_2 O, P<0.001]. No statistically significant differences in these parameters before and after the test period were observed in the non-permanent implant group (P>0.05). A total of 17 patients in the permanent implant group underwent follow-up video urodynamics. Compared to pre-test values, significant improvements were observed in maximum detrusor pressure during filling, and bladder compliance both at the end of the test period and at the last follow-up (P<0.05). However, no statistically significant differences were found in maximum cystometric capacity, maximum detrusor pressure during filling, and bladder compliance between the end of the test period and the last follow-up (P>0.05). Among the 49 patients,21 had DO and 20 had VUR. Both DO and VUR showed improvement after the test period and at the last follow-up. Conclusion SNM can effectively improve storage function in NB patients, ameliorate detrusor overactivity and bladder compliance, and relieve or eliminate VUR in some patients. Long-term follow-up confirms that SNM provides stable therapeutic effects, demonstrating significant clinical value.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

This study aimed to identify mutations in the human insulin receptor gene (INSR) and investigate their role in the pathogenesis of severe insulin resistance syndrome. Sanger sequencing of the INSR gene was performed on a patient clinically suspected of having type A insulin resistance syndrome admitted to the Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital. Upon identifying mutations, relevant exons were sequenced in her first-degree relatives. Additionally, control groups consisting of individuals with type 2 diabetes and those with normal glucose tolerance were screened for the mutation detected in the patient. Functional predictions of the INSR protein were made using MutationTaster, SIFT, and PolyPhen2 software. A previously unreported heterozygous missense mutation, c.3652G/A (Asp1218Asn), in exon 20 was identified in both the proband and her father. This mutation was not present in any of the control individuals. Multiple prediction tools indicate that this mutation likely disrupts gene/protein structure or function. The c.3652G/A (Asp1218Asn) heterozygous mutation in INSR is a novel variant that plays a significant role in the pathogenesis of severe insulin resistance in this Chinese family.

Objective:To investigate the clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL).Methods:Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People′s Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases.Results:There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months.Conclusions:AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.

Objective To compare the technical indicators and clinical effect of catheter-directed thrombolysis(CDT)via two types of non-popliteal venous access in the treatment of acute mixed-type lower extremity deep vein thrombosis(DVT).Methods The clinical data of 119 patients with acute mixed-type lower extremity DVT,who were admitted to the Affiliated Jiangning Hospital of Nanjing Medical University and the Affiliated Nanjing Hospital of Nanjing Medical University of China to receive CDT treatment from January 2016 to June 2022,were retrospectively analyzed.Of the 119 patients,CDT via deep calf vein access was carries out in 45(calf vein group)and CDT via healthy-side femoral venous access was performed in 74(femoral vein group).The success rate of vascular puncture,success rate of catheterization technique,number of successful CDT venous puncturing,time spent for sheath placement,time spent for catheterization,thrombolysis time,used amount of thrombolytic agent and associated complications(including vein puncturing and anticoagulant thrombolysis-related complications),the thrombolytic effect of different anatomical segments,and the clinical efficacy during the follow-up period for at least 12 months were compared between the two groups.Results Successful catheterization via deep calf vein access and via healthy-side femoral vein access was obtained in 31 and 58 CDT patients respectively,with a technical success rate of 68.89％(31/45)and 78.38％(58/74)respectively,the difference between the two groups was not statistically significant(P=0.248).In 26 patients(67.74％)of the calf vein group,more than two times of puncturing were needed before the sheath placement could be successfully achieved.The time spent for sheath placement in the femoral vein group was(1.84±0.87)min,which was remarkably shorter than(10.52+6.13)min in the calf vein group(P＜0.001),but the time spent for catheterization in the femoral vein group was(41.60±13.31)min,which was obviously longer than(20.06+4.46)min in the calf vein group(P＜0.001).The thrombolysis time in the femoral vein group and the calf vein group was(5.34+1.43)days and(5.06±1.18)days respectively(P=0.354),and the used amount of thrombolytic agent in the femoral vein group was(352.16±71.98)×104 U,which was prominently larger than(284.68±77.64)× 104 U in the calf vein group(P＜0.001).The last follow-up check showed that the patency rate of the popliteal vein in the calf vein group was significantly higher than that in the femoral vein group(P=0.037).No statistically significant differences in the incidence of post-thrombotic syndrome(PTS)and the mean VEINES-QOL/Sym scores existed between the two groups(all P＞0.05).Conclusion Compared with CDT via healthy-side femoral vein access,CDT via deep calf vein access can better remove the thrombus in the popliteal vein and superficial femoral vein,and improve the femoropopliteal vein patency rate,although it has no obvious advantages in reducing the occurrence of PTS and in improving the VEINES-QOL/Sym score,moreover,the deep calf vein puncture and sheath placement require a high-level technique.

Tissue resident memory T(TRM)cells are a class of memory T cells with long life span and non-lymphoid resident characteristics.TRM cells are the first line of defense against secondary infections in human.TRM cells can restrict the transmission of viruses as well as combat against viruses.Rapid evolution of severe acute respiratory syn-drome coronavirus 2(SARS-CoV-2)and post-COVID-19 syndrome could lead to a series of symptoms such as pulmonary fi-brosis,resulting in long-term fall in quality of life.Many studies focused on enhancing the ability to cope with the mutation of SARS-CoV-2 and reducing the incidence of post-COVID-19 syndrome.The relationship between TRM cells and SARS-CoV-2 infection or therapy still remain unknown.It is significant to investigate TRM cells divergence and functions for the development of vaccines.We review the functions and residence properties of TRM cells,as well as their roles in SARS-CoV-2 infection and post-COVID-19 syndrome.In this review,we are dedicated to deepen our understanding of the immune process in SARS-CoV-2 infection and provide a new prospect for the prevention and treatment of post-COVID-19 syndrome.

Objective To explore related factors of intra-amniotic infection(IAI)during the delivery period in pregnant women with gestational diabetes mellitus(GDM),and to analyze the predictive value of these related factors for IAI.Methods A retrospective study was conducted on 360 GDM pregnant women,including 120 cases with IAI(IAI group)and 240 pregnant women with GDM who did not develop IAI(control group).Clinical data,fetal monitoring during labor,placental pathology,pregnancy outcomes and glycosylated hemoglobin(HbA1c)results were collected for both groups.Multivariate Logistic regression was used to investigate influencing factors of IAI.The predictive value of combined HbA1c levels,parity and rupture time for IAI was evaluated using receiver operating characteristic(ROC)curves,and the area under the curve(AUC)was calculated.Results In the IAI group,the proportion of primigravida,first-time delivery,artificial rupture of membranes,oxytocin use,rupture time and HbA1c levels were significantly higher than those in the control group(P＜0.05).The IAI group had a smaller gestational age at delivery,higher rates of forceps-assisted delivery,cesarean section and amniotic fluid contamination(P＜0.05).In the IAI group,the proportion of abnormal intrapartum baseline fetal heart rate and the incidence of late decelerations were higher than those in the control group(P＜0.05),while the incidence of variable deceleration and the proportion of category Ⅱ fetal heart rate monitoring were lower in the IAI group than those in the control group(P＜0.05).There were no significant differences in baseline variability or acceleration of fetal heart rate between the two groups(P＞0.05).The proportions of mild neonatal asphyxia and neonatal transfer to intensive care were high in the IAI group than those of the control group(P＜0.05).Multivariate Logistic regression showed that elevated HbA1c levels(OR=3.342,95%CI:1.539-7.257)and prolonged rupture time(OR=1.001,95%CI:1.000-1.001)were independent risk factors for IAI in GDM pregnant women,while multiparity was a protective factor(OR=0.113,95%CI:0.046-0.278).The AUC for predicting IAI during labor by combining HbA1c,parity and rupture time was 0.819(95%CI:0.772-0.865),with a sensitivity of 0.742 and specificity of 0.767.Conclusion HbA1c levels,rupture time and parity are independent influencing factors for IAI during labor in pregnant women with GDM.The combination of these three factors has high clinical value in predicting IAI in GDM patients.

Objective To investigate the early clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) via left intercostal small incision for multivessel coronary artery disease. Methods The patients who received off-pump CABG in the Central China Fuwai Hospital of Zhengzhou University from June 2021 to June 2023 were enrolled. Patients were divided into two groups according to the operative technique used, including a traditional midline sternotomy group and a left intercostal small incision group. The clinical data of the two groups were compared. Results A total of 143 patients were enrolled, including 70 patients in the traditional midline sternotomy group and 73 patients in the left intercostal small incision group. The age of the patients in the left intercostal small incision group and the traditional midline sternotomy group was (63.8±8.0) years and (63.0±7.8) years, respectively; the proportions of males were 69.9% and 74.3%, respectively. The differences were not statistically significant (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the left intercostal small incision group were converted to thoracotomy. The patients in the left intercostal small incision group showed less postoperative drainage within postoperative 24 hours [(239.4±177.7) mL vs. (338.0±151.9) mL, P<0.001], lower perioperative blood transfusion rate [32.9% (24/73) vs. 51.4% (36/70), P=0.028], higher postoperative myoglobin level within postoperative 24 hours [366.1 (247.9, 513.0) ng/mL vs. 220.8 (147.2, 314.9) ng/mL, P<0.001], shorter intensive care unit stay [45.5 (31.5, 67.5) h vs. 68.0 (46.0, 78.5) h, P=0.001] and postoperative hospital stay [(10.8±4.0) d vs. (13.1±5.3) d, P=0.028] compared to the traditional midline sternotomy group. There was no significant difference in the incidence of major adverse cardiac and cerebrovascular event between the two groups [2.7% (2/73) vs. 2.9% (2/70), P=1.000]. Conclusion Compared to the full median sternotomy, MICS CABG leads to a good clinical result with smaller trauma, faster overall recovery, and less perioperative blood transfusion.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.