OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

BACKGROUND:A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects,either directly as carriers for loading other small molecules or surface modifications,or by binding to biomaterials to promote the repair and regeneration of bone tissue.OBJECTIVE:To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.METHODS:Chinese search terms"stem cell,exosome,bone,biomaterial,carrier,bioceramic,polymer,metal,hydrogel,engineered exosome"were used to search CNKI.English search terms"stem cell,exosome,bone defect,biomaterial,carrier,bioceramic,ploymer,metal material,hydrogel,engineering exosome"were used to search PubMed database.According to the inclusion and exclusion criteria,77 relevant articles were finally included for summary.RESULTS AND CONCLUSION:Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation,promote angiogenesis,and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization.In addition,many achievements of exosomes in the field of bone defect repair were described from two aspects:biomaterial-assisted exosomes and engineered exosomes.However,the current research on stem cell exosomes in bone tissue engineering is still insufficient,and most of these studies are limited to small animal models,while the treatment of bone defects in large animals,including humans,will be more complex,which will also become a major challenge for the treatment of bone defects.This will also be a great challenge in the dissemination of exosome therapy.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Background Air pollution has widespread adverse health effects on human health, but research on its impact on reproductive health and related physiological mechanisms remains insufficient. Objective To investigate the associations between short-term exposure to particulate matter and nitrogen dioxide (NO₂) and serum levels of anti-Müllerian hormone (AMH) and testosterone in healthy adults. Methods A total of 152 healthy adults were recruited for a panel study, undergoing four follow-up visits from September 2019 to January 2020. Basic demographic information and serum samples were collected. Reproductive hormone levels were measured by enzyme-linked immunosorbent assay kits. Concurrently, environmental data in the study area were monitored, including fine particulate matter (PM_2.5), black carbon (BC), NO₂, particle number concentrations in the 5-560 nm size fraction (PNC_{5_560}), and meteorological variables. Linear mixed-effects models were constructed to estimate the effects of short-term exposure to these particulate matter on serum reproductive hormone levels. Results The participants had an average age of (23.9±2.4) years, with 102 women. For each interquartile range (IQR) increment in pollutant moving average concentrations, PM_2.5, PNC_{5_25}, PNC_{100_560}, BC, and NO₂ were associated with relative decreases in female serum AMH levels by 10.2%-16.9%, 46.2%-58.0%, 16.9%-21.2%, 14.8%-26.5%, and 11.3%-17.6%, respectively. These negative associations were stronger in females with waist-to-hip ratio > 0.76 and physical activity levels ≤ 1217 metabolic equivalents (MET) min per week. Similarly, in males, an IQR increase in the same pollutants was associated with relative decreases in serum free testosterone by 11.1%-17.2%, 35.2%, 10.5%-18.9%, 18.7%-24.2%, and 10.3%-26.0%, respectively. These effects were more pronounce in male with a waist-to-hip ratios > 0.81 and physical activity levels ≤ 1498 MET-min per week. Conclusion Short-term exposure to particulate matter and NO₂ may reduce serum levels of AMH and testosterone in healthy adults. Furthermore, these adverse effects appears to be stronger in adults with higher waist-to-hip ratios.

Jiegeng decoction is a classic prescription composed of two Chinese medicinal herbs： Platycodon grandiflorum and Glycyrrhiza uralensis. It has the efficacy of diffusing lung qi， resolving phlegm， relieving sore throat and discharging pus， and is commonly used in the treatment of respiratory diseases such as cough and pharyngodynia. This article reviews the chemical components， pharmacological mechanisms and clinical applications of Jiegeng decoction. It was found that Jiegeng decoction contains triterpenoid saponins， flavonoids， glycosides， acids， and other components， with platycodin D， platycodin D2， glycyrrhizic acid， glycyrrhetinic acid， liquiritin， etc.， serving as the main active pharmaceutical ingredients. Jiegeng decoction and its chemical constituents exert anti-inflammatory effects by inhibiting signaling pathways such as nuclear factor-κB and mitogen- activated protein kinases， and demonstrate anti-tumor activities through mechanisms like modulating the tumor immune microenvironment and promoting cancer cell apoptosis. Additionally， it exhibits various pharmacological actions including antibacterial， antiviral， and antioxidant effects. Clinically， Jiegeng decoction， its modified prescription and compound combinations are widely used in the treatment of respiratory diseases such as cough， pneumonia， and pharyngitis， as well as digestive system disorders like constipation.

Objective To construct nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)knockout mice in order to investigate the effects of NLRP3 knockout on radiation-induced acute pneumonitis and pulmonary fibrosis.Methods Nlrp3+/+and Nlrp3-/-mice were randomly divided into the control group and irradiation group.To induce radiation-caused acute pneumonitis,the control group was exposed to sham irradiation while the irradiation group was exposed to 60Co γ-rays at a dose of 22 Gy at a dose rate of 184.30 R/min.At 14 days post-irradiation,the body weight of each mouse and the wet weight of its lung tissue were measured separately using an analytical balance to calculate the lung coefficient.Quantitative real-time PCR(qPCR)and cytometric bead array(CBA)were used to detect inflammatory responses in lung tissues and serum.Hematoxylin-eosin(HE)staining and F4/80 immunohistochemical staining were used to assess pathological changes and inflammatory cell infiltration in lung tissues.Cysteinyl aspartate specific proteinase-1(caspase-1)activation was analyzed by Western blotting.To establish a model of radiation-induced pulmonary fibrosis,mice were irradiated with 60Co γ-rays at a dose of 18 Gy at a dose rate of 174.67 R/min.At 24 weeks post-irradiation,HE staining and Masson staining were performed to evaluate pulmonary fibrosis.Results NLRP3 knockout inhibited caspase-1 activation,reduced inflammatory responses in lung tissues and serum,suppressed macrophage infiltration,alleviated pulmonary edema,and thereby protected against acute radiation-induced lung injury.Additionally,NLRP3 knockout significantly ameliorated late-stage radiation-induced pulmonary fibrosis.Conclusion NLRP3 knockout can mitigate both early radiation-induced pneumonia and lateradiation-induced pulmonary fibrosis.

Objective To explore the role of dapansutrile(OLT1177)in radiation-induced intestinal injury and the mechanism.Methods C57BL/6J mice were locally irradiated in the abdomen with 60Co to induce a model of radiation-induced intestinal injury.OLT1177 was intraperitoneally injected at a dose of 100 mg/kg 2 hours before irradiation and 6 hours after irradiation before the drug was administered once a day.At 12 hours after irradiation,intestinal tissues were taken for terminal deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining to detect apoptosis in intestinal tissues.At 4 days after irradiation,mouse serum was collected to detect the levels of inflammatory factors in the serum.Hematoxylin-eosin(HE)stainingwas used for the evaluation of the damage to the intestinal villus structure.Immunohistochemical staining was adopted to detect the changes in crypt proliferation in intestinal tissues.Finally,proteins were isolated from intestinal tissues,and Western blotting was employed to evaluate the activation of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome.Results After irradiation,the intestinal villi in mice were shortened.Meanwhile,there was a notable declinein the number of cells that were proliferating in the crypts,a surge in the number of apoptotic cells,and a significant spike in the overall inflammatory level.However,administration of OLT1177 inhibited the activation of the NLRP3 inflammasome,reduced apoptosis and pyroptosis,decreased the inflammatory level,and thus improved radiation-induced intestinal injury.Conclusion Administration of OLT1177 can significantly mitigate radiation-induced intestinal injury.

Objective To study the root canal morphology of permanent mandibular anterior teeth and explore its correlation with the occurrence of three-rooted mandibular molars using cone beam computed tomographic(CBCT)imaging.Methods CBCT image data of 200 subjects were randomly collected from dental clinics.The root canal morphology of the mandibular anterior teeth was identified and classified by Vertucci's classification,and the root length and labio-lingual dimension at the tooth neck level were measured.The occurrence of three-rooted mandibular first molars was examined as well.The concurrence rates of double-canaled anterior teeth and three-rooted mandibular first molars at each side,and concurrence rates of bilateral double-canaled anterior teeth and three-rooted man-dibular first molars were calculated.Spearman correlation tests were applied to analyze the correlation between the double-canaled ante-rior teeth and three-rooted mandibular first molars,as well as the bilateral antimetric teeth.Results The incidence of double-canaled system was 10.4％,18.6％and 6.5％in mandibular central incisors,lateral incisors and canines,respectively;the bilateral concur-rence rates were 5.7％,11.1％and 3.0％,respectively,and Spearman correlation coefficients(rho)were 0.487,0.505 and 0.440(P＜0.01),respectively;gender difference and side difference were not detected(P＞0.05).The frequency of three-rooted mandibular first molars was 24.6％;gender difference was not detected(P＞0.05),while the incidence was significantly higher at the right side(29.0％)than the left side(20.3％)(P＜0.05).The bilateral concurrence rate was 17.4％,and a moderate correlation was detected(rho=0.666,P＜0.01).The concurrence rates between the double-canaled anterior teeth and three-rooted mandibular first molars at each side were very low(2.6％-7.6％),and Spearman correlation tests demonstrated that no correlation(P＞0.05)could be detected between them.Conclusion The lateral incisors exhibited the highest incidence of two root canals among the mandibular anterior teeth.Ad-ditionally,there was no significant corr-elation between three-rooted mandibular first molars and double-canaled mandibular anterior teeth.

Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.