Objective To investigate the expression characteristics and clinical diagnostic value of programmed death receptor 1(PD-1)and its corresponding ligand(PD-L1)in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods One hundred and sixty COPD patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from April 2024 to November 2024 were included and divided into an acute exacerbation group of 100 cases and a stable group of 60 cases according to the severity of the disease.Additionally,40 healthy volunteers during the same period were recruited as the control group.The general clinical data of the patients were collected.Chronic Obstructive Pulmonary Disease Assessment Test(CAT)and Modified Medical Research Council Dyspnea Questionnaire(mMRC)Scale were used to test the severity of the disease;respiratory function testing was performed and fasting venous blood was collected for serum PD-1 and PD-L1 testing.Pearson correlation was used to analyze the correlation between serum PD-1,PD-L1,CAT,and mMRC,and multiple logistic regression analysis to identify the influencing factors of AECOPD.Receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic value of serum PD-1 and PD-L1 level for AECOPD.Results Serum PD-1 level in the stable COPD group and AECOPD group was significantly increased compared with that in the control group,while serum PD-L1 level was significantly decreased,showing statistical significance(P<0.05);The level of PD-1 gradually increased with the grading of lung function and the deterioration of AECOPD,with statistical significance(P<0.05);Pearson correlation showed that serum PD-1 level was positively correlated with CAT scores in COPD patients,while negatively with CAT scores,showing statistical significance(P<0.05);Multiple logistic regression analysis showed that elevated levels of serum inter-leukin-6(IL-6),neutrophil to lymphocyte ratio(NLR),and PD-1 were risk factors for AECOPD,while elevated level of PD-L1 was protective factor for AECOPD(P<0.05);ROC curve showed that the levels of PD-1,PD-L1,IL-6,NLR,and the area under the ROC curve(AUC)for their combined prediction of AECOPD diagnosis were 0.884,0.867,0.868,0.802,and 0.995,respectively.Conclusion Serum PD-1 and PD-L1 in AECOPD patients have presented certain expression characteristics,with elevated PD-1 level while decreased PD-L1 level.Both have good clinical diagnostic value for AECOPD.

Objective:To investigate the method and clinical efficacy of simultaneous correction of sunken upper eyelid during double eyelid plasty.Methods:A retrospective analysis was conducted on patients with single eyelids and sunken upper eyelid treated at the Department of Plastic Surgery, the First People’s Hospital of Zhengzhou, from October 2022 to February 2024. All patients underwent incisional double eyelid plasty with individualized correction based on depression severity. For mild depression, a combination of pretarsal orbicularis oculi muscle flap folding and orbital septum fat flap transposition was performed for correction. For moderate depression, additional autologous stromal vascular fraction (SVF)-gel grafting would be performed if residual depression persisted after the aforementioned approach. For severe depression, if the orbital fat was sufficient, the orbicularis oculi muscle flap folding, orbital fat flap repositioning and autologous SVF-gel transplantation were used. If there was insufficient orbital fat, the correction involved the use of a orbicularis oculi muscle flap and SVF-gel transplantation. Postoperative follow-up was conducted regularly, and related complications were statistically analyzed. Six months after the surgery, two blinded plastic surgeons evaluated outcomes via visual analog scale (VAS), including five aspects: symmetry of palpebral folds(including width and curvature of the double eyelid fold), fold contour, depression improvement, scar quality, overall eyelid aesthetics. Each aspect was rated on a scale from 1 to 10, with higher scores indicating better outcomes. Patient satisfaction was scored separately (1-5 per item), with higher scores indicating greater satisfaction.Results:A total of 64 patients were enrolled, including 4 males and 60 females; the age ranged from 19 to 66 years[ (32.0±9.7) years]. The degree of sunken upper eyelid was mild in 33 cases, moderate in 19 cases and severe in 12 cases. All patients underwent double eyelid plasty and orbicularis oculi flap folding. Based on this, 45 cases (33 mild and 12 moderate cases) underwent orbital septum fat flap transposition, 11 severe cases underwent SVF-gel grafting, and 8 cases (7 moderate and 1 severe cases) required combined approaches to correct depression. During the procedure, 19 cases (38 sides) received (1.8±0.8) ml of SVF-gel injection. Among these cases, one case with severe sunken upper eyelid who did not receive orbital fat transfer was injected with high density fat (left side: 0.6 ml, right side: 0.8 ml) due to insufficient SVF-gel volume. Two cases with severe sunken upper eyelid who only had autologous SVF-gel transplantation did not fully correct the depression within 3 months post-surgery received a second SVF-gel injection[(1.0±0.1) ml]. Follow-up was conducted for 6 to 12 months after surgery. All patients experienced varying degrees of eyelid edema, which typically lasted 2 to 3 months. Ecchymosis (34 sides), conjunctival congestion (3 sides), and temporary ptosis (5 sides) all resolved within 2 weeks. Pigmentation (14 sides) and scar hyperplasia (3 sides) disappeared or stabilized within 6 months. No patients developed complications such as incision infection, hematoma, fat liquefaction, local skin unevenness, or induration. The surgeons’ VAS scores of the above five indicators were all > 8 points, and the satisfaction scores of patients for the five indicators were all > 4 points. In both scoring, the improvement of sunken upper eyelid scored the highest, which were (9.2 ± 0.9) points and (4.8 ± 0.6) points respectively.Conclusion:For patients with single eyelids and varying degrees of sunken upper eyelid, performing double eyelid plasty and orbicularis oculi muscle flap folding, individualized correction is achieved through autologous fat redistribution techniques, based on the severity of the sunken upper eyelid and the amount of orbital fat. This single procedure can restore upper eyelid volume and rejuvenate the appearance, resulting in a natural and aesthetically pleasing double eyelid with minimal complications and high patient satisfaction.

Objective·To explore the potential role of SUMO-specific protease 1(SENP1)in ferroptosis.Methods·The Cancer Genome Atlas(TCGA)database was used to analyze the correlation between the expression levels of SENP1 and the ferroptosis-related genes,acyl-CoA synthetase long chain family member 4(ACSL4)and glutathione peroxidase 4(GPX4).Ferroptosis in human fibrosarcoma HT1080 cells,murine fibrosarcoma MCA-205 cells,and human embryonic kidney 293T cells was induced by RAS-selective lethal 3(RSL3).Quantitative real-time PCR(RT-qPCR)and Western blotting were used to detect the expression of SENP1.In 293T cells,immunoprecipitation-mass spectrometry was used to investigate the interacting proteins of SENP1 in the process of ferroptosis.The Flag-SENP1 plasmid was transiently transfected into 293T cells,and the overexpression efficiency of SENP1,along with the expression levels of ferroptosis-related genes ACSL4 and GPX4,was assessed by RT-qPCR and Western blotting.Results·TCGA database analysis showed that the expression of SENP1 was positively correlated with ACSL4 and negatively correlated with GPX4 in most tumor tissues.RT-qPCR and Western blotting showed that the expression level of SENP1 was significantly down-regulated in RSL3-treated HT1080,MCA-205,and 293T cells.Immunoprecipitation-mass spectrometry showed that SENP1 enriched SUMO molecules in the process of ferroptosis.Western blotting showed that the level of ACSL4 protein increased after SENP1 overexpression,and there was no significant change in the level of GPX4 protein.RT-qPCR showed that after SENP1 overexpression,there was no significant change in the mRNA levels of ACSL4 and GPX4.Conclusion·SENP1 gene expression is downregulated during ferroptosis,and may regulate the stability of ferroptosis-related protein ACSL4.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To identify candidate strains of Nontoxigenic Clostridioides difficile (NTCD) with potential for intervention in Clostridioides difficile infection (CDI) and analyze their phenotypic characteristics. Methods:A total of 713 Clostridioides difficile strains from various sources were systematically collected nationwide between 2015 and 2023. This included 649 strains isolated from human fecal samples and 64 strains isolated from the fecal samples of farmed animals. NTCD strains were preliminarily screened through toxin gene detection and antibiotic sensitivity test, and then NTCD candidate strains with potential for intervention in CDI were screened by a series of in vitro experiments, including MLST, sporulation, germination, adhesion, motility, and biofilm formation ability. Ultimately, the virulence genes and antimicrobial resistance genes of the candidate strains were comprehensively analyzed to rigorously assess their safety profiles. Results:Among 713 strains of C. difficile from different sources, 10 strains were initially screened out, which were non-toxin-producing and sensitive to antibiotics. MLST showed that seven strains were from the Clade1 branch and three strains were of a novel type. The results of sporulation and germination showed that SD59, SD178, SJZ17, and WZ142 had stronger sporulation and germination abilities. The adhesion of 10 strains was high, and the adhesion rate was between 72.93% and 99.32%. The motility of all strains was different, and the motility of SD178, SD59 and SJZ17 was stronger. The biofilm-forming ability of all strains was weak. SD59, SD178 and SJZ17 carried a limited number of virulence and resistance genes, thereby posing a relatively low safety risk. Conclusion:Three NTCD strains are successfully selected as potential effective NTCD strains to interfere with CDI.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective"Lie flat"has recently become a buzz word describing a specific psychological state in some individuals.However,its psychological meaning and mechanisms remain unclear.Lack of motivation under certain conditions may be one of the key psychological characteristics of this condition.Methods Sixteen male SD rats were randomly assigned to two food-restriction levels(90%and 80%of baseline weight,respectively),and subjected to a sucrose-pellet self-administration task.The establishment of the model is divided into three stages.The rats were trained to self-administer sucrose pellets in a high-reward learning stage and in a low-reward learning stage.We then assessed"lie flat"behavior in a preference-test stage,in which rats could choose between high-reward-and low-reward-paired nose-pokes in a discrete choice procedure.Results Combining self-feeding training with Western blot,the results showed that:(1)rats showed significantly decreased nose-poke behavior for low-reward,i.e."lie flat"behavior,but not for high-reward,when≥90%of the maximal reward was obtained in the high-reward task and the effort(X)in the low-reward task increased to the breaking point.(2)Dopamine D1R expression in the NAc was significantly higher in the"lie flat"group compared with the"not lie flat"rats,while D2R expression was similar in both groups.Conclusions Rats can show"lie flat"behavior,and up-regulation of D1R expression in the NAc may be a key part of the molecular basis responsible for this motivation deficiency in"lie flat"behavior.These results extend our understanding of"lie flat"behavior,and provide a new paradigm for the study of its mechanism.

Objective To analyze the correlations between the thoracic electrical impedance tomography(EIT)-derived parameters global inhomogeneity(GI),center of ventilation(COV),regional ventilation delay(RVD),and atelectasis in hospitalized patients,and to explore their effectiveness in evaluating atelectasis.Methods The clinical data of 140 hospitalized patients monitored by thoracic EIT between Sep.2024 and Jan.2025 were retrospectively analyzed.Patients were assigned to 2 groups based on chest computed tomography confirmation of atelectasis within the preceding short-term period during EIT monitoring:non-atelectasis group or atelectasis group.The algorithm software designed with MATLAB was used to acquire GI and COV.RVD was obtained through analysis with the Dr?ger EIT Data Analysis Tool 6.3 software,and patients'general data were concurrently documented.Comparative analysis of EIT-derived parameters between groups was conducted.Multivariate logistic regression analysis was employed to investigate the correlations of GI,COV,and RVD with atelectasis,while receiver operating characteristic curve analysis was performed to assess the efficacy of EIT-derived parameters in evaluating atelectasis.Results A total of 140 patients were enrolled,with 19(13.6%)cases presenting atelectasis.Compared to the non-atelectasis group,the atelectasis group demonstrated significantly higher proportions of male patients and cardiovascular disease and thoracic surgery(non-pulmonary)histories,lower body mass index(BMI),and alongside elevated GI and RVD values with reduced COV(all P＜0.05).Multivariate logistic regression analysis revealed that GI,COV,and RVD maintained independent associations with atelectasis after adjusting for age,gender,BMI,pleural effusion,and emphysema(odds ratio[OR]=1.39,95%confidence interval[CI]1.20-1.67;OR=0.85,95%CI 0.75-0.96;OR=1.22,95%CI 1.09-1.39;all P＜0.05).The area under curve(AUC)values of GI,COV,and RVD for evaluating atelectasis in hospitalized patients were 0.82,0.80,and 0.82,respectively(while RVD demonstrated a higher AUC,its clinical applicability was influenced by respiratory patterns).Conclusion Thoracic EIT-derived parameters GI and COV demonstrate significant correlations with atelectasis and may serve as valuable indicators for evaluating atelectasis in hospitalized 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

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*