Objective To analyze the clinical features of chronic obstructive pulmonary disease (COPD) patients with heart failure (HF) in Nanjing and explore the influencing factors. Methods A total of 773 COPD inpatients were selected from January 2021 to January 2024 in Nanjing Combined Hospital of Traditional Chinese and Western Medicine, Nanjing Qixia District Hospital, Nanjing Lishui District People's Hospital, Nanjing Pukou District Hospital of Traditional Chinese Medicine and Nanjing First Hospital., and were divided into 2 groups according to the presence or absence of combined HF. The general data and medical records of the two groups were compared, the clinical characteristics of COPD patients with HF were summarized, and the influencing factors of COPD patients with HF were analyzed by multivariate logistic regression. Results Among the 242 patients (31.31%) with COPD had HF, chronic paroxysmal dyspnea was the most common first symptom, 169 patients (69.83%) had left heart failure, 63 patients (30.17%) were diagnosed as right heart failure or global heart failure , 17 patients (7.02%) had myocardial infarction. Multivariate logistic regression analysis showed that the risk of HF was 1.678 times and 1.691times higher in COPD groups ≥ 50 years old and male COPD groups than in < 50 years old and female groups, respectively; the risk of HF was 1.491 times higher in COPD groups engaged in physical work than in physical work groups; the risk of HF was 1.447 times and 1.580 times higher in COPD groups with hypertension and coronary heart disease than in COPD groups without hypertension and coronary heart disease, respectively; the risk of HF was 1.859 times higher in COPD groups smoking>400 vial/year than in COPD groups≤400 vial/ year; the risk of HF was 1.757 times higher in COPD groups with acute exacerbation frequency≥2 times/year than in COPD groups<2 times/year; the above differences were statistically significant (P<0.05). Conclusion Attention should be paid to elderly, male and heavy physical work group of COPD patients. Active treatment of hypertension and coronary heart disease, effective tobacco control and reduction of the frequency of acute exacerbation are effective ways to reduce the risk of HF in COPD patients in Nanjing.

AIM:To investigate the regulatory effects of proanthocyanidins on autophagy and apoptosis in the retinas of guinea pigs with form-deprivation myopia via the AMPK/Wnt/β-catenin pathway.METHODS:Fifty guinea pigs were randomly divided into a normal control group, a myopia model group, and low-dose, medium-dose, and high-dose proanthocyanidins groups(25, 50 and 100 mg/kg). Refractive power and axial length of right eye were measured using a retinoscope and A-scan ultrasound. Retinal pathological changes were observed via HE staining. Immunohistochemistry assessed p-AMPK and p-mTOR expression in the retina. Immunofluorescence detected p62 and LC3 expression. TUNEL staining evaluated retinal cell apoptosis. Western blot examined expression of proteins related to the AMPK/Wnt/β-catenin pathway and autophagy(p62, Beclin1, LC3-II/LC3-I), and apoptosis-related proteins(Bax, Bcl-2, Cleaved-Caspase3, Caspase3)in the retina.RESULTS:Compared with the control group, the myopia model group showed significantly reduced refractive power and significantly increased axial length(both P<0.05); retinal cell arrangement became sparse and retinal thickness thinned. The p-AMPK levels in the retina were significantly reduced, while p-mTOR levels were significantly increased(both P<0.05), indicating suppression of the AMPK-Wnt/β-catenin pathway. The p62 levels were significantly elevated and LC3 levels were significantly reduced(both P<0.05), suggesting inhibition of autophagy. Bax and Cleaved-Caspase3 were significantly increased, while Bcl-2 was significantly decreased, indicating significantly increased apoptosis(both P<0.05). Compared with the myopia model group, all proanthocyanidins dose groups significantly inhibited refractive error reduction and axial length growth(both P<0.05), restored retinal cell alignment and thickness, activated the AMPK/Wnt/β-catenin pathway, significantly increased p-AMPK expression, and suppressed p-mTOR expression(all P<0.05); significantly suppressed p62 expression, increased Beclin1 and LC3-II/LC3-I expression(both P<0.05), and activated retinal autophagy; significantly suppressed Bax and Cleaved-Caspase3 expression, increased Bcl-2 expression(both P<0.05), and inhibited retinal cell apoptosis.CONCLUSION:Proanthocyanidins enhance retinal autophagy by activating the AMPK/Wnt/β-catenin pathway, thereby inhibiting retinal apoptosis and preventing or alleviating the onset of myopia.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

Objective:To analyze the differences in heart size，shape and function between fetuses with tetralogy of Fallot（TOF）and fetuses with malalignment ventricular septal defect（VSD）and pulmonary stenosis（PS）（named as，mild TOF）by fetal heart quantification（fetal HQ）and multi-parameter fetal echocardiography.Methods:From June 2021 to June 2023，50 fetuses with TOF（TOF group）diagnosed by fetal echocardiography at the Department of Diagnostic Ultrasound & Echocardiography Sir Run Run Shaw Hospital，Zhejiang University College of Medicine and 34 fetuses with VSD and PS matched to gestational age（mild TOF group）were retrospectively selected. Cardiovascular parameters were measured by 2D echocardiography，M-mode echocardiography and fetal HQ，including aortic dimension（AO）and its Z-score（AO Z-score），pulmonary artery diameter（PA）and its Z-score（PA Z-score），PA/AO ratio，main pulmonary artery diameter（MPA）and its Z-score（MPA Z-score），left pulmonary artery diameter（LPA）and its Z-score（LPA Z-score），right pulmonary artery diameter（RPA）and its Z-score（RPA Z-score），McGoon index（MGI），tricuspid annular diameter（TV）and its Z-score（TV Z-score），mitral annular diameter（MV）and its Z-score（MV Z-score），and MV/TV ratio. Measurements of global ventricular morphologic parameters included cardiac axis，left and right ventricular transverse diameters（LVW，RVW）and their ratio（LVW/RVW），left and right ventricular long diameters（LVL，RVL）and LVL/RVL ratio，left and right ventricular areas（LVA，RVA）and LVA/RVA ratio，global spherical index（GSI）and its Z-score，four chamber view transverse diameter（4CV-Width-ED），four chamber view end-diastolic longitudinal diameter（4CV-Length-ED），four chamber view end-diastolic area（4CV-Area-ED）. Measurements of left and right global ventricular functional parameters included fractional left ventricular and right ventricular area changes（LVFAC，RVFAC），left ventricular ejection fraction（LVEF），left ventricular and right ventricular global longitudinal strains（LVGLS，RVGLS）；end diastolic width diameter（Width-ED），SI and fractional shortening rate（FS）of 24 segments of left and right ventricles. The differences of the above parameters between the two groups were analyzed and compared，and the relationships between absolute values of GLS in left and right ventricles of TOF fetus and PA Z-score，MPA Z-score and PA/AO were analyzed. Binary Logistic regression model was used to select the best variables，and ROC curve was adopted to analyze the predictive values of ultrasonic parameter variables on TOF.Results:There were statistically significant differences in MV，TV，RVW，RVL，LVL，LVA，RVA，4CV-Length-ED，LVGLS，RVGLS，RVFAC，PA/AO，MPA，RPA，LPA，MGI，PA and PA Z-score between TOF group and mild TOF group（all P<0.05）. The Width-ED values of all segments of left ventricle were statistically different between TOF group and mild TOF group（all P<0.05）. There were statistical differences in SI between LV segments 4~6 and 8~24，and RV segments 1~21（all P<0.05）. The FS values between the 8th and 10th to 18th segments of RV revealed statistical differences（all P<0.05）. There were no statistical differences in the other parameters（all P>0.05）. The absolute value of LVGLS in TOF fetuses was positively correlated with PA Z-score，MPA Z-score and PA/AO（ r = 0.313，0.344，0.304，all P<0.05），and the absolute value of RVGLS was positively correlated with PA Z-score，MPA Z-score，and PA/AO（ r = 0.323，0.334，0.357，all P<0.05）. Binary Logistic regression model analysis confirmed that LVGLS，RVFAC and PA/AO were predictive variables. ROC curve analysis showed that the areas under the curves of LVGLS，RVFAC and PA/AO for predicting TOF were 0.746，0.693 and 0.849 respectively. The combined prediction efficiency was higher，and the area under the curve was 0.906. Conclusions:Fetal HQ combined with multiple fetal echocardiographic quantification indices can evaluate the differences in fetal heart size，shape and function between TOF and mild TOF. It is expected to provide important reference information in prenatal diagnosis and consultation for fetuses with TOF and mild TOF.

Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6％vs 35.7％,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1％vs 86.9％,P=0.001)and having cardiovascular disease(20.1％vs 32.1％,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95％CI:1.89-6.27,P＜0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95％CI:0.626-0.709,P＜0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22％and 27.78％of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.

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 analyze the burden and trends of noncommunicable chronic disease(NCD) attributable to metabolic factors in China from 1990 to 2021.Methods:Data from the Global Burden of Diseases(GBD) 2021 database were utilized to describe changes in mortality and disability-adjusted life years(DALYs) of NCD in China from 1990 to 2021. Stratified analyses were conducted by age, sex, sociodemographic index(SDI), and related risk factors. Statistical analyses and predictions were conducted using the age-period-cohort model and the Nordpred model.Results:In 2021, the age-standardized mortality rate and age-standardized DALYs rate of NCD attributable to metabolic factors in China were 227.56 per 100 000 and 4 829.39 per 100 000, respectively. Their average annual percentage changes were -0.76%( P<0.001) and -0.77%( P<0.001). Overall, the burden decreased progressively with higher SDI levels. Analysis using the age-period-cohort model indicated reduced birth cohort and period effects for metabolic factor-attributable NCD, while age effects rose significantly. The minimum relative risk( RR) value was observed in the 15-19 age group( RR=0.01), and the maximum RR value occurred in the 95-99 age group( RR=996.86). The overall rising mortality trend indicated that age effects are the predominant driver at present. Projections estimate that by 2046, deaths from metabolic factor-attributable NCD in China will reach 8 189 563, with an age-standardized mortality rate of 236.95 per 100 000. Conclusions:China continues to face a substantial burden of NCD linked to metabolic factors, with older adults, males, and individuals with hypertension, diabetes, and prediabetes identified as key populations requiring targeted interventions.

Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods* ; Indoles/administration & dosage* ; Isoindoles ; Photosensitizing Agents/administration & dosage* ; Drug Delivery Systems ; Humans

This article systematically summarized the clinical experience of Professor Han Mingxiang,a national TCM master,in treating chronic obstructive pulmonary disease(COPD)from the perspective of the"qi monism"theory,proposing an innovative"three stages,three strategies"diagnostic and treatment approach.Under the guidance of"qi monism",Professor Han believes that the core pathological mechanisms of COPD progress are through three successive stages:dysfunction in the ascent and descent of qi,deficiency of yang qi,and prolapse of the great qi,all of which stem from the disruption of the dynamic balance of qi.In response to this chain of qi imbalance,Professor Han develops three strategies:"strengthening the foundation","illuminating the central yang",and"lifting and correcting",which aim to regulate qi flow,support yang qi,and coordinate the three energizers in a phased manner.This approach seeks to achieve dynamic restoration and holistic balance of qi,with prescriptions carefully aligned with the dynamic balance and pathological changes of qi,yielding distinctive therapeutic effects.

Time rhythm and the immune system play crucial roles in the pathogenesis of allergic rhinitis.Traditional Chinese medicine(TCM)believes that the circulation of qi and blood in lung meridian follows the principle of"yang during the day,yin at night",which has a defensive function to protect the body from external pathogens.Qi stagnation in lung meridian and impaired qi and blood circulation can lead to the invasion of external pathogens,exacerbating allergic reactions,especially during the active period of the lung meridian,when the immune system is most sensitive to allergens.Based on this,this paper proposes the concept of"bidirectional regulation among meridian,time rhythm,and immune system",and in combination with TCM theory of midnight-noon and ebb-flow doctrine,analyzes the fluctuations of allergic rhinitis symptoms and the temporal changes of meridian qi and blood,and reveals the rhythmic relationship between meridian activity and immune response.This paper combines existing clinical and experimental studies to support this hypothesis,integrating the time dimension into traditional TCM syndrome differentiation and treatment,offering a more individualized treatment approach.This concept not only provides novel scientific evidence for TCM treatment of allergic rhinitis,but also offers theoretical support for optimizing treatment timing and intervention strategies.