Methods: This study enrolled 40 patients with AIS, 20 patients with congenital scoliosis (CS), and 20 patients with spinal degenerative disease (SDD). All patients underwent open posterior surgery in our hospital, and a paravertebral muscle (multifidus muscle) biopsy was performed intraoperatively. This study included many indexes that describe muscle, especially dystrophin staining. The above pathological results were compared among the AIS, CS, and SDD groups. The correlation between the Cobb angle and Nash–Moe classification and the above pathological results was analyzed in patients with AIS. Results: Significant reductions in the dystrophin staining of dystrophin-1 (p<0.001), dystrophin-2 (p<0.001), and dystrophin-3 (p<0.001) were observed in the AIS group than in the CS and SDD groups. The higher the Nash–Moe classification in the AIS group, the more significant the loss of dystrophin-2 (p=0.042) in the convex paraspinal muscles. Additionally, a significantly positive correlation was observed between the reductions of dystrophin-2 on the concave side of the AIS group and Cobb angle (p=0.011). Conclusions Dystrophin protein deficiency in the paraspinal muscles plays a crucial role in AIS formation and progression. The severity of scoliosis in patients with AIS is correlated with the extent of dystrophin loss in the paravertebral muscles. Therefore, dystrophin dysfunction may be relevant to AIS occurrence and development.

Objective To identify genetic regulators of ionizing radiation(IR)sensitivity through clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated nuclease 9(Cas9)genome-wide screening.Methods A specialized single guide RNA(sgRNA)library was developed targeting 987 stress-response regulatory genes identified through Kyoto Encyclopedia of Genes and Genomes(KEGG),Reactome and gene ontology(GO)databases,followed by construction of sgRNA plasmids and packaging into a lentiviral library.Using colon adenocarcinoma Caco-2 cells as a model system,the Cas9-stable transgenic line was established via lentiviral transduction and antibiotic selection.Library-transduced cells underwent puromycin selection,followed by γ-irradiation(dose optimized via preliminary experiments).Post-irradiation phenotypic selection was conducted after 14 days,with subsequent next-generation sequencing of surviving cell populations to identify enriched/depleted sgRNAs.Candidate genes were functionally validated through orthogonal assays:cell counting kit-8(CCK-8)proliferation analysis,clonogenic survival assays and flow cytometric quantification of reactive oxygen species(ROS)and apoptotic markers.Results The optimized screening platform identified 281 radiation response genes(165 radiosensitive and 116 radioprotective candidates).Functional validation revealed Bcl2-associated athanogene 3(BAG3)knockdown significantly enhanced radioresistance.Proliferation was increased 1.2-1.5 fold,clonogenic survival improved 1.5-2.0 fold,and ROS was reduced by 13％-25％coupled with 32％-73％apoptosis attenuation compared to control groups.Conclusion The integrated CRISPR/Cas9 screening platform effectively identifies novel radiation response regulators,as evidenced by the discovery of BAG3 as a critical radiosensitivity determinant.This high-throughput functional genomics approach provides a robust methodology for systematically mapping molecular determinants of cellular radiation response,with potential applications in both mechanistic studies and therapeutic target discovery.

Uncontrolled hemorrhage is the leading cause of potentially survivable combat casualty death,dominated by non-compressible hemorrhage in the torso and junctional areas.Rapid hemostasis using war trauma dressings is the mainstay of treatment for such casualties.The article reviews the research progress of novel hemostatic dressings for war trauma,including novel improved dressings,multifunctional dressings,electrospinning wound dressings,and smart dressings in order to provide references for the research on war trauma dressings.

ObjectiveTo construct a comprehensive evaluation indicator system for clinical practice guidelines of traditional Chinese medicine （TCM） that is scientific， systematic， and reflects the characteristics of TCM. MethodsA systematic search was conducted in Chinese and English databases， including CNKI， Wanfang， VIP， SinoMed， PubMed， Embase， and Cochrane Library， to include literature on domestic and international guideline evaluation tools and TCM-related research. Document analysis and CiteSpace were utilized for keyword co-occurrence and clustering analysis. ResultsA total of 65 relevant studies were included， from which seven core thematic domains were identified. Based on the research objectives， a two-step construction strategy was adopted： first， an external evaluation framework was established by referencing international tools to cover methodological rigor and procedural standardization； second， an internal evaluation framework was developed to reflect the distinctive features of TCM clinical practice， including syndrome differentiation and efficacy feedback. Through expert consensus， the indicator system was refined， resulting in a dual-layered structure comprising 8 primary indicators， 22 secondary indicators， and 62 evaluation criteria. ConclusionThe comprehensive evaluation system for TCM clinical practice guidelines， based on bibliometric analysis and core element extraction， integrates both theoretical integrity and practical applicability. This study provides a preliminary research foundation for further optimization， validation， and development of a refined comprehensive evaluation system.

Objective To compare the safety and efficacy of various brachial plexus block techniques using local anesthesia(LA)in patients undergoing their first radiocephalic arteriovenous fistula(RCAVF)surgery.Methods Patients were randomly allocated into three groups:LA,interscalene brachial plexus block(ISBPB),and axillary brachial plexus block(ABPB).Ultrasound was utilized to evaluate the pre-and post-anesthesia changes in vessel diameter and blood flow.Postoperative follow-up assessments were performed at three days and three months to determine fistula patency.Results Immediate patency rates were 92.52％(LA),96.26％(ISBPB),and 95.33％(ABPB),with no statistically significant differences among the groups(χ2=1.615,P=0.446).However,at three months,primary patency rates differed significantly among the groups(χ2=22.691,P<0.001).Specifically,the ISBPB group(83.18％)exhibited significantly higher patency compared to the LA group(57.01％)(χ2=17.477,P<0.001).Similarly,the ABPB group(80.37％)demonstrated better patency than the LA group(χ2=13.580,P<0.001).Regarding respiratory complications,they were more prevalent in the ISBPB group(15.89％)compared to the LA group(2.80％)(χ2=9.761,P=0.002)and the ABPB group(0.93％)(χ2=14.377,P<0.001).No significant difference was observed between the LA and ABPB groups in terms of respiratory complications(χ2=1.019,P=0.313).Conclusions Both ISBPB and ABPB demonstrated superior primary patency compared to LA.Nevertheless,ABPB exerted a lesser impact on respiratory function and provided a more comfortable surgical experience for ESRD patients.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

BACKGROUND:With the continuous improvement of artificial biological materials and surgical techniques,total knee arthroplasty has become the preferred way to improve the quality of life of patients with knee osteoarthritis. However,patients with knee osteoarthritis have severe pain after knee arthroplasty,and there is no good treatment at present. Electroacupuncture therapy is a low-cost option for pain relief and has wide application prospects in combination with preemptive analgesia.OBJECTIVE:To investigate the effect of opposing needling acupuncture with preemptive analgesia on postoperative analgesia after initial unilateral total knee arthroplasty in patients with knee osteoarthritis.METHODS:Using a randomized controlled design,120 participants were selected from Shanghai Guanghua Hospital of Integrative Medicine. All of them received the initial unilateral total knee arthroplasty. The patients were divided into three groups by using the statistical software SPSS 25:pre-electroacupuncture group,post-electroacupuncture group,and sham group,with 40 patients in each group. In pre-electroacupuncture group,opposing needling acupuncture was performed 1 day before operation,30 minutes before anesthesia induction,and 1-3 days after operation. In post-electroacupuncture group,opposing needling acupuncture was performed with the same acupoints and parameters 1-3 days after operation,thus the sham electroacupuncture was performed 1 day before operation and 30 minutes before anesthesia induction. The sham group was treated with the same acupuncture point parameters with five times of sham electroacupuncture. The improvement of numerical rating scale after operation,the consumption of remifentanil and propofol used during operation,the time when patient first used the patient-controlled analgesia,the number of postoperative nausea and vomiting,the increase rate of thigh circumference,and the success rate of blind method were compared among the three groups.RESULTS AND CONCLUSION:(1) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale at rest between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced;the improvement of numerical rating scale at rest in sham group on day 7 after operation was significantly reduced (P<0.05). (2) Compared with the pre-electroacupuncture group,the improvement of numerical rating scale score between post-electroacupuncture group and sham group on day 4 after operation was significantly reduced (P<0.05),and the improvement of numerical rating scale with movement on day 7 after operation was not significant among the three groups (P>0.05). (3) Compared with the pre-electroacupuncture group,the remifentanil consumption was significantly increased in post-electroacupuncture group and sham group (P<0.05). (4) Compared with the pre-electroacupuncture group,the first time used the patient-controlled analgesia pump was significantly shortened in post-electroacupuncture group and sham group (P<0.05). (5) Compared with the pre-electroacupuncture group,the number of postoperative nausea was increased in post-electroacupuncture group and sham group (P<0.05). (6) Compared with the pre-electroacupuncture group,the increase rate of thigh circumference in post-electroacupuncture group and sham group was significantly increased on day 3 and day 7 after operation (P<0.05). Compared with the post-electroacupuncture group,the increase rate of thigh circumference in sham group was significantly increased on day 3 and day 7 after operation (P<0.05). (7) There was no significant difference in the success rate of blind method among the three groups (P>0.05). (8) The artificial knee prosthesis has good biocompatibility. To conclude,opposing needling acupuncture with preemptive analgesia can relieve acute pain after total knee arthroplasty,reduce the consumption of intraoperative anesthesia,prolong the time of postoperative analgesia,alleviate postoperative adverse reactions,and reduce the increase rate of thigh circumference.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.