ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.

To understand the background of Escherichia coli(E.coli)carried by artificially bred sika deer and the biological characteristics of the isolated strains,such as drug resistance and pathogenicity,in April 2024,we collected 184 fresh deer fecal samples from four deer farms in Luxiang Township,Shuangyang District,Changchun City,Jilin Province,for isolation and cultivation of E.coli.The isolates were tested for drug resistance and biochemical identification with a BD PhoenixTM-100 Automated Microbiology System.The virulence genes were detected with PCR,and the strains were molecularly typed with ERIC-PCR.A total of 165 E.coli strains were isolated from 184 samples of deer feces,with an isolation rate of 89.67%.Twenty strains had a drug resistance phenotype,and the drug resistance rate was 12.12%;these strains included 15 strains of multi-drug resistant bacteria and 11 strains of ESBL-producing bacteria.Virulence gene detection indicated that the sika deer isolates carried multiple diarrhea-associated virulence genes,such as EAST-1(12.12%),eae(1.21%),stx1(7.88%),stx2(7.27%),and STa(1.82%).ERIC-PCR demonstrated that the isolates showed high polymorphism.The ESBL-producing E.coli carried by sika deer are likely to spread drug resistance in the community and livestock population.Some isolates carried multiple diarrhea-associated virulence genes,thus posing a human transmission risk.Therefore,monitoring of drug resistance and virulence genes must be strengthened,and antibiotics must be used reasonably during the breeding process to avoid excessive use and misuse.

Aim To infer novel therapeutic and phar-macological targets related to lung cancer treatment through multiomics approaches,so as to provide new directions for developing more personalized and effec-tive treatment strategies.Methods Genome-wide as-sociation study(GWAS)data analysis,pan-cancer,single-cell,transcriptomics,and protein-protein interac-tion analysis were employed in this study.Results We analyzed biomarkers and therapeutic targets associ-ated with lung cancer.The study identified key bio-markers closely related to lung cancer progression and explored the interrelationships between these biomark-ers and viral infections.According to KEGG pathway annotation,the number of genes related to metabolic processes increased significantly.In particular,metab-olites such as alanine and isoleucine emerged as pivotal factors in therapeutic interventions.The IgD+CD24+and IgD+CD24-B cell subsets were identified as cen-tral elements in immune evasion and treatment re-sponse.Concurrently,the Lachnospiraceae and Prevo-tella were shown to modulate host immune responses and the tumor microenvironment by regulating short-chain fatty acid levels,thereby opening novel avenues for cancer research.Conclusions Through mul-tiomics analysis combined with transcriptomics and pro-teomics analysis,we identify several potential therapeu-tic targets for lung cancer,providing key insights for developing novel treatment strategies.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.