ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

Objective: To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells. METHODS The rats were given Sanchong tongluo sanjie formula powder [0.946 g/（kg·d）]， Sanchong tongluo sanjie formula decoction [2.730 g/（kg·d）]， and normal saline intragastrically， and injected with Cisplatin injection （4.2 mg/kg） intra-peritoneally to prepare powder-containing serum， decoction-containing serum， positive control serum and negative control serum. Lewis lung cancer cells were divided into negative control serum group， positive control serum group， and 5%， 10%， 20% drug-containing serum groups. The cell proliferation inhibition rates at 24， 48， and 72 hours post- intervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum. The cell invasion ability， metastasis ability and apoptotic rate were detected in the negative control serum group， positive control serum group， 20% powder-containing serum group， and 20% decoction-containing serum group. Protein expressions of vascular endothelial growth factor （VEGF）， hypoxia-inducible factor-1α （HIF-1α）， prolyl hydroxylase-2 （PHD2）， matrix metalloproteinase-2 （MMP-2）， extracellular regulated protein kinases （ERK），c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK） were detected. RESULTS The cell proliferation inhibition rates for both the 20% powder-containing serum group and the 20% decoction-containing serum group， when intervened for 48 hours， were not less than 50%. Compared with negative control serum group， the number of invasive Lewis lung cancer cells and migration distance were decreased significantly， while the apoptotic rate was increased significantly （P＜0.05）； the apoptotic rate in the 20% powder- containing serum group was significantly higher than 20% decoction-containing serum group （P＜0.05）. The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20% powder-containing serum group （P＜0.05）， while the protein expression of HIF-1α was decreased significantly in the 20% decoction-containing serum group （P＜0.05）. CONCLUSIONS Sanchong tongluo sanjie formula can inhibit the proliferation， invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore， the powder demonstrates superior efficacy compared to the decoction， suggesting that they may possess different mechanisms of action.

Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.

Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.