This study elucidated the structure-activity relationships (SAR) of three distinct opioid ligand series at the μ-opioid receptor (μ-OR) and investigated the ligand-dependent role of arrestin in downstream signaling. Radioligand binding assays across 13 compounds revealed that high-affinity μ-OR binding is not restricted to a single chemical scaffold. For fentanyl analogs, SAR analysis identified four key structural determinants: the N-phenethyl group (R1) is essential for μ-OR binding, the piperidine 4-position (R2) is sterically constrained and tolerates only small substituents such as carbomethoxy, the acyl side chain (R3) tolerates diverse chemical modifications including alkyl, alkoxy, and heteroaryl groups without substantial loss of affinity, and para-substitution on the phenethyl ring (R4) with electron-withdrawing groups like fluorine is well-tolerated. Analysis of non-fentanyl scaffolds (2-Methyl AP-237, W-15, and brorphine) demonstrated that specific side-chain functionalization, rather than core scaffold architecture, primarily determines binding potency. Comparison of classical opioids further revealed that structural flexibility, exemplified by methadone, can confer superior binding affinity compared to the rigid morphine scaffold. Consistent with this structural diversity, the contribution of arrestins to ERK activation varied substantially across compounds, suggesting that μ-OR-biased signaling is not dictated exclusively by intrinsic receptor properties but emerges from the interplay between receptor conformation and ligandspecific structural features. Collectively, our results provide a molecular framework for understanding opioid pharmacology with important implications for rational drug design aimed at minimizing adverse effects while maintaining analgesic efficacy.

Objective To investigate the renal function recovery and perioperative risk factors for chronic kidney disease in patients after acute Stanford type A aortic dissection (ATAAD) repair. Methods A retrospective study was conducted on patients who underwent ATAAD repair at the Xiamen Cardiovascular Hospital, Xiamen University from 2020 to 2021, and their clinical data were analyzed. Results A total of 255 patients were included, with 200 males and 55 females, and an average age of (52.80±12.46) years. The incidence of acute kidney injury (AKI) after ATAAD repair was 43.9%. Dissection involving the renal artery [OR=2.144, 95%CI (1.234, 3.765), P=0.007], intraoperative urine output [OR=0.761, 95%CI (0.625, 0.911), P=0.004], and intraoperative red blood cell transfusion [OR=1.288, 95%CI (1.088, 1.543), P=0.004] were significantly associated with early AKI after ATAAD repair. Long-term renal function follow-up data were available for 232 patients, among whom 40 (17.2%) patients developed chronic kidney disease (CKD). Independent predictors for CKD included lower body mass index [OR=0.827, 95%CI (0.723, 0.931), P=0.003], preoperative cardiac tamponade [OR=5.344, 95%CI (1.65, 17.958), P=0.005], preoperative renal hypoperfusion syndrome [OR=12.629, 95%CI (5.003, 35.373), P<0.001], postoperative peak serum creatinine time>3 d [OR=7.566, 95%CI (2.799, 22.731), P<0.001], and AKI grade [grade 1: OR=4.418, 95%CI (1.339, 15.361), P=0.016; grade 2: OR=8.345, 95%CI (1.762, 40.499), P=0.007; grade 3: OR=9.463, 95%CI (2.602, 37.693), P<0.001]. Conclusion AKI related to ATAAD repair can recover in the early postoperative period, but both the duration and severity of AKI will affect long-term renal function. In addition, patients' nutritional status, preoperative cardiac tamponade, and renal hypoperfusion syndrome are also independent risk factors for long-term renal dysfunction.

Objective To compare the differences in clinical features and treatment choices between periph-eral spondyloarthritis(pSpA)and axial spondyloarthritis(axSpA),and better understand the clinical charac-teristics and medication needs of pSpA.Methods Our study is a retrospective cohort study.The patients who first visited the First Medical Center of Chinese PLA General Hospital between January 2016 and December 2022 and were diagnosed with axSpA or pSpA according to the classification criteria established by the Assess-ment of SpondyloArthritis International Society were selected as the study subjects.Demographic data,clinical characteristics,laboratory tests,and treatment information of these patients were obtained through the electronic medical records management system and the intelligent management system for spondyloarthritis.The research compared the distribution of swollen and tender joints between pSpA and axSpA patients,as well as that between pSpA1(excluding patients with psoriatic arthritis)and axSpA patients.Additionally,we analyzed differences in clinical features and treatment options among these groups.Results A total of 1639 pa-tients were included in the study,of which 184 had pSpA(including 97 with psoriatic arthritis),and 1455 had axSpA.Compared to axSpA patients,pSpA patients had fewer male patients(62.5％vs.79.7％,P＜0.001),later onset age(33.8 years vs.22.0 years,P＜0.001),shorter diagnostic delays(6.0 months vs.14.2 months,P=0.004),more associated peripheral arthritis(71.7％vs.9.3％,P＜0.001)and dac-tylitis(6.5％vs.0.3％,P＜0.001),more cases of psoriasis(52.7％vs.1.1％,P＜0.001)and a more common family history of psoriasis(11.4％vs.3.4％,P＜0.001).pSpA patients had higher levels of in-flammatory markers but a lower positive rate of human leukocyte antigen(HLA)-B27(43.5％vs.87.4％,P＜0.001).A positive HLA-B27 was associated with an earlier onset age,fewer cases of psoriasis,and a fami-ly history of ankylosing spondylitis.pSpA patients had a higher proportion of using conventional synthetic dis-ease-modifying antirheumatic drugs(csDMARDs),biologic disease-modifying antirheumatic drugs(bDMARDs),and oral glucocorticoids,and they also more frequently used a combination of bDMARDs and csDMARDs(19.0％vs.12.2％,P=0.009)or multiple csDMARDs(65.8％vs.12.5％,P＜0.001).Compared to axSpA patients,pSpA1 patients(excluding psoriatic arthritis)did not show significant differences in the prevalence of psoriasis,uveitis,family history of psoriasis,or the use of bDMARDs,but the subgroup analysis of other variables was consistent with the results of pSpA patients.Conclusions pSpA patients tend to have a later onset of disease,a lower proportion of male and HLA-B27 positivity,more associ-ated peripheral arthritis,dactylitis,psoriasis,and a more common family history of psoriasis.The disease bur-den in terms of treatment for pSpA is not lower than that for axSpA.Due to the presence of more peripheral symptoms,psoriasis,and higher levels of inflammation,they also require more medication.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective To compare the application effects of different puncture techniques in the autonomous arteriovenous fistula puncture of patients undergoing hemodialysis,providing a reference for nurses in selecting puncture methods.Methods A total of 135 patients undergoing hemodialysis at a tertiary hospital in Changzhou from September 2023 to September 2024 were selected and randomly divided into 3 groups,including a multiple puncture group,a rope ladder puncture group,and a buttonhole puncture group.Follow-up was conducted every 3 months,and the first puncture success rate,puncture pain,diameter of blood scab at the puncture site,hemostasis time,and complications of arteriovenous fistula(infection,embolism,aneurysm,stenosis,intimal hyperplasia)were compared among the 3 groups.Results A total of 114 patients completed the study,with 40 in the multiple puncture group,42 in the rope ladder puncture group,and 32 in the buttonhole puncture group.The single-puncture success rate was higher in the multiple single-puncture group(99.4％)and the buttonhole puncture group(99.6％)than it in the rope-ladder puncture group(93.3％),with all P＜0.001.The scab diameter in the buttonhole puncture group(2 mm)was larger than that in the multiple single-puncture group(1 mm)and the rope-ladder puncture group(l mm),with all P＜0.001.The incidence of intimal hyperplasia in the buttonhole puncture group(34.3％)was higher than that in the multiple single-puncture group(10.0％)and the rope-ladder puncture group(11.9％),with all P＜0.05.Conclusion Each of the 3 arteriovenous fistula puncture techniques has its advantages and disadvantages.The multiple puncture group technique can improve the first puncture success rate,and it does not significantly increase the complications of arteriovenous fistula compared to the rope ladder and buttonhole techniques,making it suitable for widespread use.

OBJECTIVE To evaluate the application effect of implementation strategies in the prevention and control of sur-gical site infection(SSI),and to review its research progress.METHODS A scoping review method was employed,invol-ving systematic searches across databases such as Web of Science,PubMed,Cochrane,CNKI and Wanfang.After screening based on the inclusion and exclusion criteria,the included literature was analyzed and reported in a standard-ized manner.RESULTS A total of 47 articles were included.Most studies adopted comprehensive evidence-based practices(EBP)(≥2 types)and employed multimodal implementation strategies(≥3 items)to facilitate the implementation of SSI prevention and control EBP.Within the framework of the WHO multimodal strategy,42,39,39 and 24 studies re-spectively applied the four implementation strategies of system change,education and training,monitoring and feedback and reminder and communication,while only 9 studies applied the strategy of creating a safety culture.The highest pro-portion of studies(31.91％,15/47)employed a combination of four implementation strategies,with the common combi-nation being"system change+education and training+monitoring and feedback+reminder and communication"(29.79％,14/47),and this combination of four implementation strategies demonstrated outstanding performance in en-hancing EBP compliance.Totally 26(55.32％)showed decrease in the incidence of SSI after intervention(P＜0.05).CONCLUSIONS Implementation strategies are crucial for the successful implementation of SSI prevention and con-trol EBP.Multimodal implementation strategies are common approaches to facilitate the implementation of EBP.In the future,it is necessary to further standardize the application of scientific methods and improve the effect evaluation of im-plementation strategies,providing a reference for the sustained and widespread application of EBP in clinical practice.

This article elucidates therapeutic approaches for KRAS G12C-mutant advanced non-small cell lung cancer, with focus on global advancements in inhibitor research. It also summarizes clinical evidence on the efficacy of targeted agents in monotherapy and combination therapies, analyzes their clinical advantages and challenges, and explores future directions for novel treatment modalities.

Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Objective:To investigate the anti-inflammatory activity of alcohol extract of Polyrhachis dives(PDAEs)against rheumatoid arthritis(RA)in vitro and in vivo.Methods:In vivo and in vitro anti-RA inflammatory response of PDAEs was investigated using a rat model of collagenous arthritis induced by bovine type Ⅱ collagen and an LPS-induced RAW264.7 cell inflammatory model.Results:PDAEs inhibited the polarization of M1 type macrophages in vivo and in vitro,reduced expressions of TNF-α,IL-1β,IL-6,iNOS,and promoted polarization of M2 type macrophages,enhanced expressions of anti-inflammatory cytokines,such as IL-10 and TGF-β,so as to achieve the anti-inflammatory effect.The experiments in vivo also showed that PDAEs had the immunomodulatory effect,the potential mechanism may be the regulation of Th17/Treg balance by regulating the expression of PD-1 and TGF-β,thus correcting the over-strong autoimmune response.Conclusion:PDAEs may reduce the inflammatory reaction of RA through anti-inflam-matory and immunomodulatory effects.