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 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.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

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 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.

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.

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.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

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.