Chronic obstructive pulmonary disease （COPD） is a common clinical chronic airway disease with high morbidity， high mortality， a heavy disease burden， and complex mechanisms that have not been fully elucidated. Clinical problems promote the continuous progress of basic research. The establishment and evaluation of animal models is an important way to delve into the pathogenesis and treatment strategies of COPD. On the basis of the etiology， pathogenesis， diagnostic criteria， and syndrome differentiation of COPD in traditional Chinese medicine （TCM） and Western medicine， this paper summarizes the establishment methods and characteristics of existing animal models of COPD and analyzes the fitting degree of the models with the disease characteristics in Western medicine and syndrome characteristics in TCM. The results showed that the animal models of COPD in Western medicine were mainly induced by single factors and compound factors， and the model with the highest fitting degree was established by cigarette smoke combined with lipopolysaccharide and hormone. The model showed a fitting degree of 84% with the disease characteristics in Western medicine and 70% with the syndrome characteristics in TCM， being consistent with the clinical characteristics of COPD induced by multiple factors. Most of the animal models of COPD in TCM were established on the basis of disease models and combined with TCM etiology and pathogenesis characteristics， and prepared by syndrome differentiation. Among them， the model of accumulation of cold and water retention in lung had the highest fitting degree of 92% with the TCM diagnostic criteria. The models of phlegm-heat obstructing lung and phlegm-stasis obstructing lung had the fitting degree of 94% with clinical manifestations in Western medicine and the highest fitting degree with the diagnostic criteria in Western medicine. Different animal models of COPD have their own advantages and disadvantages， and most of them simply replicate the manifestations of COPD at a certain stage， failing to reflect the multiple causes and the dynamic changes of TCM etiology and pathogenesis. Moreover， the syndromes of these models fail to match the clinical syndromes in TCM. Therefore， establishing the animal models reflecting clinical characteristics of COPD in TCM and Western medicine and improving the model evaluation criteria are important contents to promote the overall development of integrated traditional Chinese and western medicine for COPD.

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

Objective To understand the residual levels of eugenol in aquatic products sold in 4 cities in Hubei Province and timely discover potential food safety hazards, and to provide a scientific basis for supervision of eugenol in aquaculture and transportation of aquatic products. Methods From 2021 to 2023, 124 samples of aquatic products were randomly collected from supermarkets and farmers’ markets in Yichang, Xiantao, Jingmen, and Ezhou cities in Hubei Province. The ultra-high performance liquid chromatography-mass spectrometry was used to detect the residues of eugenol. Results Eugenol was detected in 51 out of 124 samples, with a detection rate of 41.13%，and a concentration range of N.D. - 2601μg/kg. Among them, 19 out of 40 samples were detected in 2021, with a detection rate of 47.50%; 12 out of 40 samples were detected in 2022, with a detection rate of 30.00%; and 20 out of 44 samples were detected in 2023, with a detection rate of 45.45%. There was no statistically significant difference in the detection rates in different years (P>0.05). The detection rates of eugenol in aquatic products sold in Yichang City, Xiantao City, Jingmen City, and Ezhou City were 22.58%, 35.48%, 41.94%, and 64.52%, respectively, and the differences were statistically significant (P<0.05). The detection rates of samples in supermarkets and farmers' markets were 35.56% and 44.30%, respectively, and the difference was not statistically significant (P>0.05). The detection rate of eugenol in bighead carp was the highest at 66.67%, followed by grass carp with a detection rate of 61.22%, which was significantly higher than other fish (P<0.05). Conclusion At present, the widespread use and arbitrary addition of eugenol should be paid attention to by relevant departments.

Objective: To explore the relationship of self-injurious behavior with peer discrimination and depression among AIDS orphans, so as to provide the basis for promoting the mental health of AIDS orphans. Methods: From March 2021 to March 2022, 626 AIDS orphans from 5 counties in Henan Province were selected by stratified cluster random sampling methods. Non suicidal Self-injury assessment Tool, Discrimination Experience Scale, and Zung Self-rating Depression Scale were used to investigate AIDS orphans self-injurious behavior, peer discrimination and depression. Multivariate Logistic regression model was used to analyze the relationship between self-injurious behavior and peer discrimination of AIDS orphans. Multivariate linear regression analysis was used to explore the moderating effect of depression between self-injurious behavior and peer discrimination of AIDS orphans. Results: The detection rates of self-injurious behavior, peer discrimination and depression of AIDS orphans were 80.0%, 73.3% and 67.6 % respectively. The detection rates of the three items mentioned above were 86.9%, 81.5%, and 77.5% for double orphaned children, respectively, which were higher than 74.6%, 67.0%, and 59.8% for single orphaned children, and the differences were statistically significant ( χ 2=21.29, 23.78, 14.23, P <0.01). The score of self-injurious behavior of AIDS orphans was positively correlated with peer discrimination and depression ( r=0.55, 0.40, P <0.01). Depression played a moderating role in the relationship between self-injurious behavior and peer discrimination of AIDS orphans ( β= 0.03, P <0.05). Conclusions AIDS orphans are more likely to engage in self-injurious behaviors after experiencing peer discrimination and psychological depression. The society and schools should adopt targeted intervention strategies to promote the mental health among AIDS orphans.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Objective:To explore the risk factors for recurrence of intussusception in children after successful ultrasound-guided saline enema reduction.Methods:The clinical and follow up data of 355 hospitalized children with intussusception at the First Affiliated Hospital of Zhengzhou University from Feb 2018 to Feb 2023 were reviewed.Patients were divided into two groups by recurrence develped and the differences were compared, Data with significant differences were incorporated into multi-factor logistic analysis.Results:The overall recurrence rate was 15.8% (56/355). By univariate variable analysis model, there were statistically significant differences between the two groups in age, previous intussusception history, vomiting, maximum diameter of concentric circles shown by ultrasound, and concurrent bowel organic diseases (lead points) (all P<0.05). In multivariate Logistic regression model, age, previous intussusception history, maximum diameter of concentric circles, and lead points were independent risk factors for recurrent intussusception after saline enema.The optimal cut-off values for age and maximum diameter of concentric circles were 2 years and 33.5 mm, respectively, according to ROC curve analysis. Conclusion:Age older than 2 years, previous intussusception history, maximum diameter of concentric circles longer than 33.5 mm, and lead points are independent risk factors for recurrence after saline enema.

Objective:To compare the effects of treatment with Hybrid-Hyrax-Facemask(FM)versus miniscrews in the anterior pal-ate combined with Hybrid-Hyrax-Facemask(MSI/FM)for patients with early Class Ⅲ malocclusion and maxillary deficiency.Methods:18 patients aged with early Class Ⅲ malocclusion and maxillary deficiency were randomly divided into 2 groups(n=9)and treated with FM and MSI/FM respectively.Alternating rapid maxillary expansion and constriction(Alt-RAMEC)protocol combined with a maxillary protraction force of 3.92 N was applied on each side of all patients from elastics connected to the facemask in a down-ward and forward direction of 30° to the occlusal plane.Iortho cephalometric software was used to analyze the data of lateral cephalo-grams of the patients before(T0)and after(T1)treatment.Results:Improvement was verified in the facial profile and occlusion of all patients.In MSI/FM group the average treatment time was shorter.There were significant differences(P＜0.05)between T0 and T1 in the following measurements in FM group:SNA,ANB,Co-A,Co-Gn,Wits,S-Go,Na-Me,MP,U1-SN,UADH,LADH,Overjet,UL-EP increased,U1-L1 decreased.There were significant differences(P＜0.05)between T0 and T1 in the following measurements in the MSI/FM group:SNA,ANB,Co-A,Wits,Na-Me,MP,Y-axis,U1-SN,Overjet,UL-EP increased,SNB,Co-Gn-Co-A,S-Go/N-Me,U1-L1,L1-MP decreased.Conclusion:Both FM and MSI/FM combined with Alt-RAMEC protocol and a maxillary protraction force are effective in the treatment for Class Ⅲ patients with maxillary deficiency.MSI/FM may produce more significant bone effect and re-duce dental compensation,promote more forward growth of midface and more improvement in the growth direction of mandible and re-duce compensatory lip inclination of anterior teeth in shorter treatment time.