ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

Objective:To explore the influencing factors related to olfactory dysfunction secondary to different types of chronic rhinosinusitis（CRS）. Methods:A retrospective analysis was conducted on 185 CRS patients treated at the Department of Otolaryngology-Head and Neck Surgery of Shanxi Provincial People's Hospital from July 2023 to July 2024. Based on the presence or absence of nasal polyps, CRS was divided into two groups: chronic rhinosinusitis with nasal polyps（CRSwNP） and chronic rhinosinusitis without nasal polyps（CRSsNP）. Further, based on whether olfactory dysfunction was present, the CRSwNP and CRSsNP groups were divided into subgroups with olfactory dysfunction and normal olfaction. General data, laboratory tests, and modified sinus CT scores were compared between the subgroups. Logistic regression analysis was conducted to identify independent influencing factors based on the results of univariate analysis combined with clinical significance, and two nomogram models were established. The area under the curve of the receiver operating characteristic（ROC） curve, calibration curves, and decision curve analysis were used to assess the diagnostic performance, calibration, and clinical utility of the predictive model. Results:The proportion of blood eosinophils, blood urea nitrogen, and total modified CT scores of the bilateral olfactory region were identified as independent influencing factors in the CRSwNP group; the proportion of blood monocytes and modified CT scores of the bilateral posterior region were independent influencing factors in the CRSsNP group. The nomogram prediction model showed good diagnostic performance, calibration, and clinical utility in both the CRSwNP and CRSsNP groups. Conclusion:Olfactory dysfunction in CRSwNP patients is closely related to the proportion of blood eosinophils, blood urea nitrogen, and total modified CT scores of the bilateral olfactory region, while olfactory dysfunction in CRSsNP patients is closely related to the proportion of blood monocytes and modified CT scores of the bilateral posterior region. Moreover, the predictive model established in this study demonstrates good clinical performance and can be used for early identification and risk prediction of olfactory dysfunction secondary to CRS.
Humans ; Sinusitis/complications* ; Chronic Disease ; Retrospective Studies ; Olfaction Disorders/etiology* ; Nasal Polyps/complications* ; Rhinitis/complications* ; Female ; Male ; Logistic Models ; Middle Aged ; Smell ; Adult ; ROC Curve ; Nomograms ; Eosinophils ; Tomography, X-Ray Computed

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Background China is a major coal producer and consumer country in the world. Coal workers' pneumoconiosis (CWP) is a primary factor endangering the occupational health of coal miners. Research on the disease burden of CWP and its changing trend is significant for disease prevention & control and associated policies. Objective To analyze the disease burden of CWP in China from 1990 to 2021 and its changing trend, and predict the disease burden from 2022 to 2035. Methods Using the Global Burden of Disease Study (GBD) database of 2021, numbers ofincident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs) as well as crude and age-standardized rates of CWP in China were retrieved. Linear regression model was used to calculate the estimated annual percentage change (EAPC) of the age-standardized rates. Joinpoint regression model was used to analyze the temporal trend of disease burden and the disease burden of different sexes and age groups, and Bayesian age-period-cohort (BAPC) model was used to forecast the trend of CWP disease burden. Results In 1990, the incident, prevalent, and deaths cases of CWP in China were 3266, 18872, and 1561, respectively, and the DALYs of CWP were 44614.718 person-years. In 2021, the incident, prevalent, and deaths cases of CWP were 3446, 23975, and 1229, respectively, and the DALYs of CWP were 29610.754 person-years. From 1990 to 2021, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP in China all showed a downward trend, with the EAPCs of −3.121%, −2.532%, −4.018%, and −4.268%, respectively. The disease burden of CWP in China was mainly concentrated in the male population. The annual average percent change analysis indicated that each standardized rate showed a fluctuating downward trend in different periods. The BAPC model showed that from 2022 to 2035, the age-standardized rates of CWP in China would continue to decline steadily. In 2035, the age-standardized incidence, prevalence, mortality, and DALYs rates of CWP would be reduced to 0.10 per 100000, 0.74 per 100000, 0.03 per 100000, and 0.74 per 100000, respectively. Conclusion The disease burden contributed by CWP in China generally show a downward trend from 1990 to 2021, and it is expected that the age-standardized rates will continue to decline steadily from 2022 to 2035.

Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Objective To analyze the prevalence and risk factors of underscreening among cervical cancer screening participants in Wuxiang County,Shanxi Province in 2019,providing evidence-based support for optimizing mobilization strategies.Methods Data from cervical cancer screening programs conducted between 2019 and 2024 in Wuxiang County were retrospectively collected.The follow-up screening behaviors of women screened in 2019 were analyzed,and factors associated with underscreening were identified.Results A total of 3759 women underwent cervical cancer screening in 2019.Among them,492 women(13.09％)with abnormal primary screening results requiring follow-up in 12 months,yet only 43(8.74％)completed;2154 women(57.30％)with negative liquid-based cytology testing(LCT)results needed re-screening after 3 years,701(32.54％)completed;1113 women(29.61％)with negative HPV/combined results needed re-screening after 5 years,734(65.95％)completed.Overall,2299 women(60.69％)exhibited underscreening.Multivariate analysis showed that underscreening was more likely among community residents than rural residents(OR=2.309,P=0.018),older women(OR=1.065,P＜0.001),those in organized screening compared to opportunistic screening(OR=3.789,P＜0.001),those undergoing LCT(OR=4.607,P＜0.001)or combined screening instead of human papillomavirus testing(OR=3.624,P＜0.001),and those with abnormal screening results(OR=6.859,P＜0.001).Conclusion Substantial proportions of cervical cancer screening participants demonstrate poor adherence to guideline-recommended screening intervals,and particularly need to focus on older women and those with abnormal screening results.Implementation of electronic screening record systems and emphasizing knowledge of periodical screening in health education could enhance compliance with"70％screening coverage"target for cervical cancer prevention.