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.

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

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.

Objective To investigate the clinical efficacy of Tongfu Xiefei Formula in treating patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)based on the theory of simultaneous treatment of lung and intestine,and to observe its effects on serum inflammatory cytokines.Methods A retrospective study was conducted on 134 AECOPD patients treated at the Department of Pulmonary Diseases of Traditional Chinese Medicine,Tangshan Hospital of Traditional Chinese Medicine from December 2020 to December 2022.The patients were divided into an observation group and a western medicine group based on the treatment plans,with 67 cases in each group.The western medicine group received conventional western medical treatment,while the observation group was given Tongfu Xiefei Formula orally in addition to the western medical treatment.The course of treatment covered 2 weeks.Before and after treatment,the two groups were observed in the changes of the modified Medical Research Council(mMRC)dyspnea scale scores,COPD Assessment Test(CAT)scores,lung function indicators,arterial blood gas analysis indicators,and serum inflammatory cytokine levels.The clinical efficacy,total incidence of adverse reactions,and hospitalization time were compared between the two groups.Results(1)After 2 weeks of treatment,the total effective rate in the observation group was 95.52%(64/67),compared to 79.10%(53/67)in the western medicine group.The intergroup comparison(tested by the chi-square test)showed that the efficacy of the observation group was significantly superior to that of the western medicine group(P＜0.01).(2)After treatment,the mMRC scores and CAT scores in both groups were significantly decreased(P＜0.05),and the decrease in the observation group was significantly superior to that in the western medicine group(P＜0.01).(3)After treatment,lung function indicators of the forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and their ratio(FEV1/FVC)in both groups were significantly increased(P＜0.05),and the increase in the observation group was significantly superior to that in the western medicine group(P＜0.01).(4)After treatment,the oxygen saturation(SaO2)and arterial oxygen partial pressure(PaO2)levels in both groups significantly increased(P＜0.05),while the arterial carbon dioxide partial pressure(PaCO2)level was significantly decreased(P＜0.05).The increase in SaO2 and PaO2 levels and the decrease in PaCO2 level in the observation group were significantly superior to those in the western medicine group(P＜0.01).(5)After treatment,the levels of serum inflammatory cytokines of tumor necrosis factor α(TNF-α),C-reactive protein(CRP),and interleukin-6(IL-6)in both groups were significantly decreased(P＜0.05),and the decrease in the observation group was significantly superior to that in the western medicine group(P＜0.01).(6)The total incidence of adverse reactions in the observation group was 2.99%(2/67),compared to 5.97%(4/67)in the western medicine group,with no statistically significant difference between the two groups(P＞0.05).(7)The observation group had a significantly shorter hospitalization time than the western medicine group,and the difference was statistically significant(P＜0.05).Conclusion Tongfu Xiefei Formula,formulated based on theory of simultaneous treatment of lung and intestine,is effective and safe on relieving symptoms such as dyspnea in AECOPD patients,improving lung function,correcting arterial blood gas disorders,inhibiting the release of inflammatory factors,shortening treatment time,while causing no serious adverse reactions.

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.

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.

OBJECTIVE To analysis the structures of the impurities in aciclovir tablets and the compulsory degradation samples by high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry technology (HPLC-Q-Exactive Orbitrap-MS). METHODS The HPLC separation was carried out on a Waters Xbridge BEH Shield RP18 (4.6 mm×250 mm, 5 μm) by the gradient elution with a mobile phase consisting of 10 mmol·L–1 ammonium formate solution (0.15% formic acid)(A) and 10 mmol·L–1 ammonium formate solution(0.15% formic acid)-acetonitrile(50∶50)(B), and the detection wavelength was 254 nm. The Q-Exactive Orbitrap-MS was used to determine the precise first-order molecular weight and second-order fragment ions of these impurities, and the structures were identified. RESULTS Aciclovir and its impurities were well separated, and 8 major impurities with content>0.1% were detected and identified in aciclovir tablets and the compulsory degradation samples. Among them, 4 were the impurities listed in the European Pharmacopeia 10.0, and the others were unknown impurities identified for the first time. CONCLUSION The LC-MS/MS method can effectively identify the impurities in aciclovir tablets, which is significant for the production process optimization and quality control.

AIM:To observe how total flavonoids of Pterocarya hupehensis Skan(PHSTF)affects the migra-tion and invasion of human rheumatoid fibroblast-like synoviocyte line MH7A.METHODS:The MH7A cells were divided into control group(without any treatment),low-,medium-and high-dose(6.25,12.5 and 25 mg/L,respectively)PHSTF groups,phosphatidylinositol 3-kinase(PI3K)inhibitor 740Y-P(10 μmol/L)group,and 740Y-P(10 μmol/L)+high-dose(25 mg/L)PHSTF group.The viability of the MH7A cells was determined by CCK-8 assay,while the migration and inva-sion were assessed by scratch and Transwell assays.The protein levels of matrix metalloproteinase-2(MMP-2),MMP-9,PI3K,p-PI3K,AKT and p-AKT were detected by Western blot.RESULTS:Compared with control group,the cell via-bility in PHSTF treatment groups was reduced(P<0.05),the cell wound healing area was significantly decreased(P<0.01),migratory and invasive cells in the lower chamber were significantly reduced(P<0.01),and the protein expres-sion of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT were decreased(P<0.01).Compared with high-dose PHSTF group,the addition of PI3K/AKT pathway agonist 740Y-P significantly increased the migration and invasion ability of MH7A cells(P<0.01)and elevated the protein expression of MMP-2 and MMP-9 and the ratios of p-PI3K/PI3K and pAKT/AKT(P<0.01)under the treatment with PHSTF.CONCLUSION:Total flavonoids of Pterocarya hupehensis Skan could inhibit the migration and invasion of MH7A cells by regulating the PI3K/AKT signaling pathway.

AIM:To investigate the impact of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on the migration,invasion,and ferroptosis of non-small-cell lung cancer A549 cells.METHODS:The A549 cells were divided into control group,low-,medium-and high-dose(100,150 and 200 μg/mL)PHSTF groups,ferroptosis inhibitor liprox-statin-1(Lip-1)group,and high-dose PHSTF combined with Lip-1 group,each cultured in corresponding media.Cell via-bility was assessed using the CCK-8 assay,while cell migration and invasion abilities were determined through scratch and Transwell assays.Cell lipid peroxidation levels were measured using the glutathione(GSH)assay kit.RT-qPCR was em-ployed to assess the mRNA expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while Western blot was utilized to examine the protein expression of SLC7A11,GPX4,Kelch-like epichlorohy-drin-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RE-SULTS:Compared with control group,PHSTF significantly diminished the viability of A549 cells in a time-and dose-de-pendent manner(P＜0.01),and the cell migration and invasion were also reduced(P＜0.01),along with a significant de-crease in GSH level(P＜0.01).Treatment with PHSTF inhibited the mRNA and protein expression levels of ferroptosis-re-lated proteins,including SLC7A11 and GPX4(P＜0.01),suppressed the protein expression of Nrf2 and HO-1(P＜0.01),and enhanced the expression of Keap-1(P＜0.01).The Lip-1 partially restored the decrease in cell viability in-duced by PHSTF(P＜0.01),significantly up-regulated the protein expression levels of SLC7A11,GPX4,Nrf2 and HO-1,and suppressed the protein expression of Keap-1(P＜0.01).CONCLUSION:Total flavonoids of Pterocarya hupehen-sis Skan can inhibit the migration and invasion of non-small-cell lung cancer A549 cells,and induce the cell ferroptosis by regulating the Keap-1/Nrf2/HO-1 pathway.

Objective:To investigate the clinical outcomes and efficacy of trabecular metal (TM) cones for the reconstruction of metaphyseal bone defects in revision total knee arthroplasty.Methods:A retrospective analysis was conducted on 46 patients (47 knees), who underwent revision total knee arthroplasty with TM cones for metaphyseal defect reconstruction from July 2015 to August 2023. The cohort comprised 12 males and 34 females, ranging from 41 to 83 years of age, with a mean of 68.65 ± 9.09 years. Body mass index (BMI) ranged from 19.5 to 36.0 kg/m 2, averaging 27.20±4.50 kg/m 2. Bone defects were stratified according to the Anderson Orthopedic Research Institute (AORI) classification, including 64 sides (AORI T2B type 20 sides, T3 type 16 sides, F2B type 11 sides, F3 type 17 sides) which were addressed with 67 cones. Evaluations during follow-up included range of motion (ROM), visual analogue scale (VAS) for pain, and the American Knee Society Score (KSS). Long leg radiographs and knee X-rays were reassessed for femorotibial angle (FTA) and joint alignment, osseointegration of the TM cones, and any complications were documented. Results:The average follow-up duration was 46.22±26.55 months (range 16-103 months). The KSS knee score significantly improved from 29.22±19.79 preoperatively to 88.22±6.01 at the final follow-up ( F=258.118, P<0.001). Similarly, the KSS function score saw a marked increase from a preoperative average of 7.65±8.21 to 56.30±6.10 at the final follow-up ( F=354.711, P<0.001). VAS scores significantly decreased from 5.35±1.50 preoperatively to 0.28±0.50 at the final follow-up ( F=300.934, P<0.001). ROM improved from 67.72°±34.62° preoperatively to 85.33°±9.15° at the final follow-up ( F=7.798, P<0.001), and the FTA improved from 179.24°±10.30° preoperatively to 174.39°±1.69° at the final follow-up, a statistically significant enhancement ( F=9.123, P<0.001). Osseointegration was observed in 95.5% of the cases (64/67 cones). There were no instances of osteolysis or aseptic loosening observed, indicating stable prosthetic fixation. Complications were minimal, with one reported case of a femoral shaft fracture, which was successfully treated with internal fixation, resulting in satisfactory healing at 6 months. At the last follow-up (3 years after operation), the patient could walk at home with a walker and the other patients had no complications such as periprosthetic joint infection, dislocation and periprosthetic fracture. Conclusion:The application of trabecular metal cones in revision total knee arthroplasty provides an effective solution for the reconstruction of severe metaphyseal bone defects, enhancing prosthetic stability and restoring the knee joint's mechanical alignment. The trend towards successful osseointegration in the TM cones is promising, and a significant improvement in knee joint function has been observed.