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.

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

Objective To compare the anesthetic effects of remazolam and dexmedetomidine assisted sedation in the operation of finger replantation under ultrasound guided brachial plexus block.Methods 60 patients undergoing severed finger replantation were randomly divided into remazolam group(group R)and a dexmedetomidine group(group D)by random number table method,with 30 cases in each group.Both groups received a single brachial plexus block under ultrasound guidance.Group R was injected with remazolam 0.1 mg/kg,followed by 1 mg/(kg·h)pump until 10 min before the end of the operation.In group D,a load dose of 0.5 μg/kg of dexmedetomidine was injected,followed by continuous infusion at a rate of 0.5 μg/(kg·h)until 10 min before the end of surgery.The MAP,HR and SpO2 values of the two groups were compared when the patients entered the room(T0),the wound was cleaned and disinfected(T1);the tourniquet was upper(T2);the operation began(T3);the tourniquet was relaxed(T4);and the operation ended(T5).MOAA/S scores and BIS values were compared between the two groups at different time.The time from the beginning of medication to the absence of consciousness and the time of consciousness recovery after drug withdrawal were compared between the two groups.Blood lactic acid(Lac)before applying tourniquet and 15 min after relaxing tourniquet were compared between the two groups.The occurrence of intraoperative adverse reactions was recorded in the two groups.Results The MAP of patients in group R had little fluctuation at each time during the operation,and the MAP of patients in group D was significantly increased at T1,T2,T3 and T0 moments and at the same time as that in group R(P<0.05);HR in group R was stable at all times,and HR in group D significantly slowed down at T1,T2 and at the same time with group R(P<0.05).Patients in both groups achieved ideal sedation during the operation(MOAA/S score≤3 points),and the MOAA/S score of patients in group R at T5 minutes after drug withdrawal was higher than that at other moments of the same group and group D(P<0.05);the BIS value of group R was higher than that of group D(P<0.05).The loss time and recovery time of consciousness in group R were shorter than those in group D(P<0.05).The incidence of intraoperative hypertension and bradycardia in group D was significantly higher than that in group R,and the incidence of respiratory depression in group R was higher than that in group D(P<0.05).There was no significant change in lactate value between the two groups(P>0.05).Conclusion Remazolam and dexmedetomidine can satisfy sedation in brachial plexus nerve block for replantation of severed finger under ultrasound guidanc.Compared with dexmedetomidine,remazolam has better sedation control,stable hemodynamics,low incidence of circulatory adverse events.

Objective To investigate the mechanism of maslinic acid on pyroptosis and inflammato-ry response in myocardial ischemia/reperfusion(IR)injury.Methods H9C2 cardiomyocytes were randomly divided into control group,control+maslinic acid group,hypoxia reoxygenation(HR)group,and HR+maslinic acid group.Cellular model of HR injury was constructed by hypoxia for 4 h and then reoxygenation for 12 h.Forty-eight male SD rats were randomly divided into Sham group,IR group,IR+maslinic acid group,IR+maslinic acid+Tri group(n=12).Rat model of myocardial IR injury was established by ligating the left anterior descending branch for 30 min followed by reperfusion for 2 h.The viability of cardiomyocytes was detected,the levels of LDH,CK-MB,IL-1β and IL-18 in the supernatant of cardiomyocytes and rat serum samples were detec-ted in each group.Drug-molecular docking was performed to predict the binding site and binding force of maslinic acid and NOD-like receptor thermal protein domain-associated protein 3(NLRP3).Western blotting was used to detect IκBα,NF-κB P65,NLRP3,apoptosis-associated speck-like protein(ASC),and gasdermid D-N terminal(GSDMD-N)in each group of cardiomyo-cytes and myocardial tissues.Results Compared with the Control group,significantly reduced cell viability,enhanced protein levels of p-IκBα,p-NF-κB P65 and higher releases of LDH,IL-1β and IL-18 were observed in the HR group(P＜0.05).Maslinic acid treatment reversed HR-induced changes in above indicators(P＜0.05).Compared with the Sham group,the protein levels of p-IκBα,p-NF-κB P65,NLRP3,ASC,GSDMD-N and the releases of serum CK-MB,LDH,IL-1βand IL-18 were significantly increased in the IR group(P＜0.05).Maslinic acid treatment also reversed above indicators induced by IR injury(P＜0.05).The protein levels of p-IκBα,p-NF-κB P65,NLRP3,ASC and GSDMD-N were significantly increased,and the releases of serum CK-MB,LDH,IL-1β and IL-18 were also elevated in the IR+maslinic acid+Tri group than the IR+maslinic acid group(1681.00±136.20 U/L vs 1251.00±213.60 U/L,1776.00±185.80 U/L vs 1330.00±172.50 U/L,4.32±0.45 vs 2.95±0.26,3.89±0.20 vs 2.47±0.29,P＜0.05).Conclusion Maslinic acid can show target intervention in NLRP3 activity,thereby inhibiting inflammatory re-sponse and cell pyroptosis,and ultimately attenuate myocardial IR injury effectively.

Objective:To investigate the efficiency and safety of traditional growing rod in the treatment of early onset dystrophic scoliosis secondary to type 1 neurofibromatosis (NF1-DS) with intraspinal rib head in children.Methods:From September 2006 to May 2020, this study recruited 20 children with intraspinal rib head with early onset NF1-DS who had received traditional growing rods. There were 13 boys and 7 girls and the age of the initial operation was 7.0±1.6 years (range, 4.1-9.8 years). There were 7 cases of simple left chest bend, 9 cases of simple right chest bend, and 4 cases of double chest bend; 13 patients had varying degrees of kyphosis deformity. Two children had neurological symptoms before surgery, American Spinal Injury Association Impairment Scale (AIS) were grade D. The proportion of the intraspinal rib head (IRP), the Cobb angle of the main chest bend, apical vertebra rotation (AVR), apical vertebral translation (AVT), trunk shift (TS) and sagittal TK, lumbar lordosis (LL), sagittal balance and T 1-S 1 height were measured before and after first time internal fixation and at last follow-up, and the complications were also evaluated. Results:All 20 patients were followed up and the average follow-up time was 41.6±23.8 months (range, 24-99 months). A total of 85 operations was conducted including 63 protrude operations. After operation, the IRP was significantly lower than that before operation (preoperative 33.1%±17.5% vs. postoperative 22.2%±11.3%, P<0.001) and no significant correction loss was found at last follow-up 23.7%±12.4% ( P>0.05). The mean Cobb angle decreased from 75.9°±26.7° preoperatively to 45.0°±18.5° postoperatively ( P<0.001) and there was still significant improvement at the last follow-up (41.0°±17.2°) compared with postoperatively ( P<0.05). The AVR was significantly reduced after surgery compared with preoperatively (33.0°±10.1° vs. 39.3°±13.3°, P<0.001), and the last follow-up (40.1°±11.4°) was significantly improved compared with postoperative ( P=0.005). The T 1-S 1 height increased from 259.8±70.7 mm preoperatively to 296.9±78.4 mm postoperatively ( P=0.001), and at the last follow-up 296.9±78.4 mm was still significantly higher than after operation ( P<0.001), with an average annual increase of 12.4±3.2 mm. Significant correction of AVT, TK, LL and sagittal balance were noted after initial surgery ( P<0.05), and no significant correction loss was found at last follow-up ( P>0.05). There were 10 complications in 7 cases. There were 5 complications of pedicle screw loosening, 1 complication of bolt droping, 2 complications of broken rod, 1 complication of distal junctional kyphosis and 1 complication of adding-on phenomenon. 2 cases with nerve injury were recover after operation (AIS grading E). None of the children had new neurological complications during growth rod insertion and multiple stretching during follow-up. Conclusion:For children with early onset NF1-DS with intraspinal rib head, if the preoperative AIS grade is D or E, traditional growing rod technique is relatively safe and effective and can make the intraspinal rib head remove from the spinal canal partly.

We presented an adolescent with recurrent intracranial hemorrhage and skin lesion. The diagnosis was unclear and the treatment was difficult. Through a multidisciplinary effort type Ⅰ interferon disease was suspected and later, an interferon-stimulated gene was further detected. Considering the high morbidity and fatality rate of recurrent intracranial hemorrhage, tofacitinib and hydroxychloroquine were administered. After treatment, the livedo reticularis was significantly regressed. Unfortunately, the intracranial hemorrhage recurred due to a pre-existing cerebral aneurysm, leading to death of the patient. The diagnosis and treatment of this case highlight the importance of multidisciplinary collaboration in the diagnosis and treatment of difficult and rare diseases.

To study the clinical effect of non-ampullary duodenal mucosal lesions treated by endoscopic resection. A retrospective analysis was performed on the data of 58 cases of duodenal non-ampullary mucosal lesions treated by endoscopic resection from January 2016 to June 2019 from 3 hospitals. Among 58 cases, 27 lesions (46.6%) were located in the duodenal bulb and 31 (53.4%) in the duodenal descending part (including the ball-drop boundary). Forty-six patients (79.3%) received endoscopic mucosal resection, 7 (12.1%) received endoscopic submucosal dissection and 5 (8.6%) received pre-cut endoscopic mucosal resection. Few postoperative complications were found except for 1 case of intraoperative bleeding, 1 case of delayed bleeding 2 days after surgery, 1 case of lesion residual and 2 cases of postoperative abdominal pain. No perforation occurred. Endoscopic treatment of non-ampullary duodenal mucosal lesions is safe and effective.

Objective:To introduce the Burnt Hand Outcome Tool (BHOT) into China to conduct sinicization, cross-cultural debugging, and test the reliability and validity, thus provide a reference for the evaluation of treatment effect and making of medical decisions of hand burn patients.Methods:The cross-sectional research was conducted. After obtaining the authorization of the original author, the Brislin translation mode was used to literally translate, synthesize, back-translate, and be checked by experts to form the Chinese version of BHOT (C-BHOT) 2. Ten experts in the field of burn rescue and treatment were invited by purpose sampling method to conduct cross-cultural debugging to form C-BHOT 3. A total of 21 hand burn patients who were treated in General Hospital of Ningxia Medical University from January to March 2020 and conformed to the inclusion criteria were selected by accidental sampling method for pre-testing. Then the final version of C-BHOT 4 was formed. Hospitalized patients who met the selection criteria were recruited using accidental sampling, multi-site and cross-regional survey method from May 2020 to March 2021 in General Hospital of Ningxia Medical University, the First Affiliated Hospital of Air Force Medical University, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), and the First Affiliated Hospital of Nanchang University. The survey was performed with the general information questionnaire and C-BHOT 4. Critical ratio method and correlation coefficient method were used for item analysis, Cronbach's α coefficient test tool was used to test internal consistency, test-retest reliability was used to judge the stability of the tool, content validity index analysis tool was used to analyze the content validity, and exploratory factor analysis was used to test the validity of the structure. Data were statistically analyzed with independent sample t test or Pearson correlation analysis. Results:After the sinicization, cross-cultural debugging, and pre-testing, C-BHOT 4 was formed with a total of 20 items. All items were adjusted to positive scoring, and 7 modifications were made on the basis of the original tool. A total of 353 questionnaires were issued in the formal survey, and 344 valid questionnaires were returned, with an effective response rate of 97.45%. In the 344 patients, there were more male patients (297 patients) than female patients (47 patients), with ages of 23 to 57 years. The critical ratios of each item in the item analysis ranged from 5.48 to 12.59 ( P<0.05). There were statistically significant differences in the scores between patients in high-score group and low-score group ( t=-10.72--2.84, P<0.05 or P<0.01). There was significant positive relationship among the scores of each two items and between scores of each item and the overall tool score ( r=0.68-0.71, 0.47-0.63, P<0.05 or P<0.01). In reliability test, the Cronbach's α coefficient of the whole tool was 0.837, and the test-retest reliability was 0.702-0.793. In validity test, the content validity index of whole tool was 0.923. The exploratory factor analysis extracted 3 common factors, and the cumulative variance contribution rate was 76.162%. The comparative fit index in the confirmatory factor analysis was 0.924. Conclusions:After the BHOT tool being sinicized, cross-culturally debugged, pre-tested, and tested for reliability and validity, it was verified that C-BHOT 4 has good reliability and validity in assessing the outcome of Chinese hand burn patients, and therefore can be used as an effective tool for the evaluation.

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.