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.

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

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 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.

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.

Cervical cancer is one of the most common gynecological malignant tumors in China. Given their lack of obviously early symptoms, more than half of patients with cervical cancer are diagnosed in the middle and late stages of this malignancy, resulting in poor prognosis. Finding new therapeutic targets is the current research direction. Metabolomics, as a new omics technology, is expected to provide new targets for tumor precision diagnosis and treatment through the analysis of the changes and potential mechanisms of metabolites in tumor occurrence and development by chromatography, mass spectrometry, and other technologies. Herein, we review the research methods of metabolomics; metabolic characteristics of cervical cancer; and progress of the research on metabolomics in cervical cancer diagnosis, curative effect prediction, and prognosis evaluation to provide new ideas for the precise diagnosis and treatment of cervical cancer.

Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings， it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia （PSD）. In clinical practice， treatment is tailored according to the location of PSD. During the oral stage， when the pathogen invades the face and mouth， resulting in excessive salivation， acupoints are primarily selected from the foot shaoyin （少阴） kidney channel， in combination with ren mai （任脉） ， du mai （督脉）， chong mai （冲脉） and the spleen channel， to replenish essence and fill the marrow， dispel dampness and unblock the channels. In the pharyngeal stage， as the pathogen obstructs the throat， disrupting normal swallowing， the therapy emphasizes dredging the shaoyang （少阳） channel and warming and tonifying the jueyin （厥阴） channel， by taking acupoints mainly from the hand and foot shaoyang channels， along with the jueyin channels， so as to soothe the liver and promote bile secretion， regulate and harmonize qi and blood. During the esophageal stage， where the pathogen damages the esophagus， impeding food passage， the treatment emphasizes activating the yangming （阳明） channels and regulating taiyin （太阴） channels； acupoints are mainly selected from the foot yangming stomach channel， along with the taiyin channels， aiming to warm yang， unblock the channels and dispel stasis.

The cost economics of early-stage lung cancer treatments is a key focus in the field of lung cancer. The primary treatment modalities for early-stage lung cancer include radiotherapy and thoracic surgery, each offering distinct advantages in therapeutic outcomes and costs. To better understand the cost-effectiveness of radiotherapy versus thoracic surgery for early-stage lung cancer, this paper reviews the progress of recent research on economic evaluations of these two treatment approaches.