OBJECTIVE To investigate the mechanism of Yangfei tongluo formula in delaying airway remodeling in post-infectious bronchiolitis obliterans （PIBO） model rats.METHODS Forty-eight 2-week-old SPF male SD rats were randomly divided into control group （Control group）， PIBO model group （Model group）， Prednisone Acetate tablets+Azithromycin tablets group [positive control group， Prednisone Acetate tablets 0.006 3 g/（kg·d）+Azithromycin tablets 0.031 5 g/（kg·d）]， and high-， medium-， and low-dose Yangfei tongluo formula groups [42.42， 21.21， 10.60 g/（kg·d）]. The PIBO rat model was established by intratracheal instillation of diacetyl. After modeling， rats in each group were administered corresponding drug solution or distilled water by gavage once daily for 21 consecutive days. Hematoxylin-eosin staining was used to evaluate the pathological changes of lung tissue， and Masson staining was used to assess the degree of pulmonary fibrosis. Western blot and real-time quantitative PCR were performed to detect the protein and mRNA expression levels of epithelial-mesenchymal transition （EMT）-related markers [E-cadherin， N-cadherin， α -smooth muscle actin （ α -SMA）， Vimentin] and transcription factors [snail homolog 1（Drosophila）-like 1 protein （Snail1）， zinc finger E-box-binding homeobox protein 1 （ZEB1）， Twist-related protein 1 （Twist1）] in lung tissue. ELISA was used to detect the levels of transforming growth factor-β 1 （TGF-β 1 ） and vascular endothelial growth factor （VEGF） in blood and bronchoalveolar lavage fluid.RESULTS Compared with the Control group， the lung tissues of rats in the Model group showed extensive destruction of alveolar structure and massive inflammatory cell infiltration in the interstitium. The protein and mRNA expression levels of E-cadherin were significantly decreased， while the protein and mRNA expression levels of N-cadherin， Vimentin， α -SMA， Snail1， ZEB1， and Twist1， as well as the collagen-positive area and the levels of TGF-β 1 and VEGF， were significantly increased （ P ＜0.05）. Compared with the Model group， the pathological injury of lung tissue in each administration group was significantly improved， and the above indicators （except collagen-positive area） were significantly reversed （ P ＜0.05）.CONCLUSIONS Yangfei tongluo formula may delay airway remodeling in PIBO by regulating the TGF-β 1 /VEGF-mediated signaling network and inhibiting the activation of EMT-related transcription factors， thereby blocking the EMT process.

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

The prevention and treatment of chronic obstructive pulmonary disease （COPD） pose a major global challenge， with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine （TCM） theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention， offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states， signaling pathways， and targeted interventions across different stages of COPD. At the acute exacerbation stage， the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor （NF）-κB/NOD-like receptor protein 3 （NLRP3） inflammation pathway， and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage， the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 （Nrf2）/Kelch-like ECH-associated protein 1 （Keap1） antioxidative stress pathway， and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage， the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor （TGF）-β/Wnt repair network and depletion of stem/progenitor cells， and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk， constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore， this article points out the current shortcomings in quantitative evidence， objective syndrome standardization， and coverage of syndrome states， and proposes future directions including building multi-omics databases， conducting biomarker-stratified randomized controlled trials， and developing disease-pattern combined animal models， aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.

Osteosarcoma is a kind of mesenchymal tissue tumor, which is highly invasive and metastatic. Pro-angiogenic factors and vascular endothelial cells play key roles in the angiogenesis and metastasis of osteosarcoma, and the interaction between vascular endothelial cells and osteosarcoma cells can affect the growth and metastasis of osteosarcoma. Anti-vascular therapeutics agents for osteosarcoma, including monoclonal antibodies, tyrosine kinase inhibitors and traditional Chinese medicines, can inhibit the progression of osteosarcoma. An in-depth study of the correlation between osteosarcoma and angiogenesis can provide new ideas for the study of vascularization of osteosarcoma and anti-vascular treatment of osteosarcoma.

Objective To explore the effects of probiotic-assisted conventional treatment on in-testinal flora,blood glucose homeostasis and neurological function in patients with type 2 diabetes mellitus complicated with stroke.Methods A total of 93 patients with type 2 diabetes mellitus com-plicated by stroke were selected as the study subjects and randomly divided into control group(n=46)and experimental group(n=47)using random number table method.The control group received conventional therapy,while the experimental group received probiotics(oral Bifidobacterium,Lacto-bacillus,and Enterococcus triple viable tablets,4 tablets/time,twice daily)in addition to convention-al therapy.Both groups were treated continuously for 7 days.The intestinal flora(counts of Bifidobacterium,Lactobacillus and Bacteroides),inflammatory markers[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and high-sensitivity C-reactive protein(hs-CRP)],glycemic pa-rameters[fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),largest amplitude of glycemic excursions(LAGE),average blood glucose(BGL-ave),standard deviation of mean blood glucose(BGL-sd),and coefficient of variation of blood glucose(BG-cv)],and neurological function[National Institutes of Health Stroke Scale(NIHSS)score,improvement rate of neurological func-tion,proportion of patients with modified Rankin Scale(mRS)score ≤ 3,and Loewenstein Occupa-tional Therapy Cognitive Assessment(LOTCA)score]were compared between the two groups after treatment.Results After treatment,the counts of intestinal flora(Bifidobacterium,Lactobacillus,and Bacteroides)in both groups were higher than those before treatment,and the counts in the ex-perimental group were higher than those in the control group,with statistically significant differences(P＜0.05).The levels of TNF-α,IL-6 and hs-CRP in both groups were lower than those before treatment,and the levels in the experimental group were lower than those in the control group,with statistically significant differences(P＜0.05).The levels of FBG and HbA1c in both groups were lower than those before treatment.The FBG level,LAGE,BGL-sd,and BG-cv in the experimental group were lower than those in the control group,with statistically significant differences(P＜0.05),but there were no statistically significant differences in HbA1c and BGL-ave between the two groups(P＞0.05).After treatment,the NIHSS score in the experimental group was lower than that in the control group,while the LOTCA score and improvement rate of neurological function were higher than those in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the proportion of patients with an mRS score ≤3 between the two groups(P＞0.05).Conclusion Probiotic-assisted conventional treatment can regulate the number of intestinal flora in patients with type 2 diabetes mellitus complicated with stroke,relieve inflammatory responses,stabilize blood sugar levels,and improve neurological function.

Dyskeratosis congenita is a hereditary short telomere disease caused by mutations in telomerase-related genes.The classic clinical manifestations are oral leukoplakia,nail dystrophy,and skin pigmentation.This article reported a 7-year-old male child diag-nosed with dyskeratosis congenita but with dorsal tongue erosion as the first manifestation.Genetic testing results confirmed DKC1 gene mutations and a literature review was performed.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

Objective To exploring the effect of inflammatory indicators on the outcome of assisted conception of in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)in patients with ovarian endometriosis(OEM).Methods The study subjects were selected as the patients with OEM who received IVF/ICSI treatment at the Third Affiliated Hospital of Zhengzhou University from January 2019 to February 2024.Based on whether previous surgery for uterine endometriosis cyst removal had been performed,they were divided into non-surgery group(n=73)and surgery group(n=112).To explore the differences in inflammatory markers between two groups and to determine whether they have an impact on the outcome of assisted reproduction.Results The lymphocytes(L)and blastocyst formation rates of patients in surgery group were significantly higher than those in non-surgery group,platelet to lymphocyte ratio(PLR)and carbohydrate antigen 125(CA125)were significantly lower than those in non-surgery group(P＜0.05).There were no statistically significant differences in the clinical pregnancy rate and live birth rate between two groups of patients(P＞0.05).After adjusting for confounding factors,the results of multivariate Logistic regression analysis showed that L,PLR,and CA125 had no statistically significant impact on the clinical pregnancy rate and live birth rate(P＞0.05).Both maternal age and the number of embryos transferred exerted a certain influence on clinical pregnancy rates and live birth rates(P＜0.05),furthermore,the type of embryo transferred had a significant effect on clinical pregnancy rates(P＜0.05).Conclusion Compared with non-surgery group,surgery group had higher L level and lower PRL and CA125 levels,but these changes did not significantly affect clinical pregnancy or live birth outcomes in OEM patients undergoing IVF/ICSI assisted reproduction.

[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome