ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Feline coronavirus (FCoV) is classified into two biotypes: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV and FECV might evolve and mutate via genetic recombination and mutation, leading to novel subtypes and variants. This study examined the genomic structure and biological subtyping of FCoV, analyzed the infection characteristics of FIPV and FECV, and investigated the mechanisms of FECV transforming into FIPV. The findings revealed that while their genome structures were fundamentally similar, differences in their ability to efficiently infect monocytes/macrophages significantly influenced their pathogenicity and transmission characteristics, with FIPV exhibiting higher virulence. Moreover, the analysis of the open reading frames (ORF)3/7 as well as the N/S sequences of FIPV indicated that its non-structural proteins were associated with modulation of the host immune system. These proteins enabled immune evasion, leading to more severe disease. The genomic variability of FCoV constitutes an important foundation for studying the pathogenicity and epidemiology of FIPV and FECV, and offers references for virus detection and drug development.

Objective To evaluate the predictive performance of the Alberta stroke program early computed tomography score(ASPECTS),the Lausanne stroke scale(ASTRAL),DRAGON,START,and the total healthy risks for patients with vascular events calculated(THRIVE-c)score prediction models for the prognosis of patients with acute ischemic stroke(AIS)in Baoding advanced stroke centers,Hebei Province.Methods Clinical data of 909 patients with AIS who were admitted for intravenous thrombolysis in the department of emergency of the advanced stroke center of the Baoding NO.1 Central Hospital from January 2016 to August 2022 were collected and scored using the ASPECTS,ASTRAL,DRAGON,START,and THRIVE-c scales.The 3-month modified Rankin scale(mRS)score was observed for each score,with a score of 0-2 as a good prognosis and 3-6 as a poor prognosis,and multivariate Logistic regression coefficients for the variables in the 5 scores were compared with the original derivation cohort.The predictive efficacy of each scoring model for 3-month poor prognosis of AIS patients was analyzed by using the receiver operator characteristic curve(ROC curve),and area under the curve(AUC)was calculated;the degree of fit of each model to the actual prognostic results was assessed by using the Hosmer-Lemeshow goodness-of-fit test;at the same time,the calibration curves and Brier scores were used as an evaluation of the model's calibration performance indicators.Results A total of 786 patients were enrolled and 340 had a poor prognosis.Comparison of the validation cohort with the original cohort for model construction showed that the mean age in the validation cohort was 65 years old,with a relatively small proportion of 33.84%females,and a median glycemic value of 8.09 mmol/L.The proportion of poor prognosis was lower in the validation cohort compared to the original ASPECTS and THRIVE-c cohort(43.68%vs.51.90%,43.68%vs.50.30%)and higher in the validation cohort compared to the original cohorts of ASTRAL,DRAGON,and START(43.68%vs.34.00%,43.68%vs.35.20%,43.68%vs.39.10%,all P<0.05).ROC curve analysis showed that ASPECTS,ASTRAL,DRAGON,START and THRIVE-c scores all had predictive value for the prognosis of patients with AIS,with AUC and 95%confidence intervals(95%CI)of 0.848(0.820-0.876),0.825(0.795-0.855),0.833(0.805-0.861),0.838(0.811-0.866),and 0.727(0.691-0.762);in the anterior circulation it was 0.852(0.821-0.883),0.817(0.782-0.853),0.815(0.781-0.849),and 0.833(0.800-0.866),0.710(0.668-0.751);and 0.841(0.781-0.902),0.850(0.792-0.908),0.874(0.816-0.931),0.854(0.800-0.908),and 0.775(0.704-0.846)in the posterior loops,respectively.Hosmer-Lemeshow goodness-of-fit test showed that the DRAGON model curve had a smaller gap from the middle diagonal and was better calibrated(χ2=1.483,P=0.993).The Brier score showed that the ASPECTS scoring model had the smallest Brier score was 0.150 and the best performance.Conclusions The ASPECTS,ASTRAL,DRAGON,START,and THRIVE-c scoring models have been shown to be effective in predicting poor prognosis in patients with AIS treated with intravenous thrombolytic therapy at 3 months,with the ASPECTS model showing the most outstanding predictive performance.For anterior infarcts,the ASPECTS score demonstrated the highest predictive efficacy,whereas for posterior infarcts,the DRAGON score had the best predictive performance.The probability of the ASPECTS score in predicting prognosis in the prediction model was in good agreement with the actual probability.

Objective To investigate the relationship between intracranial arterial calcification and prognosis after mechanical thrombectomy in patients with acute large vessel occlusion stroke. Methods A total of 147 patients with acute large vessel occlusion stroke who underwent mechanical thrombectomy were enrolled in this study. The length, density, and location of intracranial arterial calcification were evaluated by CT. Based on the intracranial arterial calcification status, patients were divided into three groups: symptomatic intracranial arterial calcification group (n=42), asymptomatic intracranial arterial calcification group (n=24), and no intracranial arterial calcification group (n=81). Multivariate Logistic regression analysis was performed to explore the relationship between intracranial arterial calcification and clinical outcomes after mechanical thrombectomy. Results Compared with patients in the asymptomatic and no intracranial arterial calcification groups, patients in the symptomatic intracranial arterial calcification group, had older age, a higher proportion of hypertension, and required more rescue angioplasty or stenting after mechanical thrombectomy (P < 0.05). There was a statistically significant difference in the location of calcification between the symptomatic and asymptomatic intracranial arterial calcification groups (P < 0.05), but no significant differences in the length and density of calcification between the two groups were observed (P>0.05). Multivariate Logistic regression analysis revealed that symptomatic intracranial arterial calcification was an independent risk factor for failed revascularization (adjusted OR=8.67, 95%CI, 2.39 to 15.68, P < 0.001), the need for rescue interventional therapy (adjusted OR=6.46, 95%CI, 2.26 to 14.29, P < 0.001), and poor neurological recovery (adjusted OR=3.91, 95%CI, 1.38 to 10.16, P=0.023) after adjusting for potential confounding factors. Conclusion Symptomatic intracranial arterial calcification is closely associated with poor clinical outcomes after mechanical thrombectomy in patients with acute large vessel occlusion stroke. Preoperative assessment of intracranial arterial calcification is crucial for selecting revascularization strategies in these patients.

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.
Animals ; Mice ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics* ; Neuralgia ; RNA, Small Interfering ; Thalamus/metabolism* ; Up-Regulation

Objective:To analyze the status of follow-up and its correlation with highly active antiretroviral therapy (HAART) for newly diagnosed HIV/AIDS patients from 2014 to 2016 in Shandong province, then to provide theoretical evidence for the improvement of follow-up and HAART.Methods:Based on retrospective cohort study, logistic regression model was used to identify influencing factors of follow-up for HIV/AIDS, and chi-square test was used to do correlation analysis.Results:There were 6253 newly diagnosed HIV/AIDS cases from 2014 to 2016 in Shandong province, and 6011 cases accepted follow-up service. The cumulative follow-up rate was 96.13%, and timely follow-up rate was 94.51%. Higher prevalence of follow-up was found among those aged 15-24 years at diagnosis, diagnosed by VCT, with education level of college and above, lived in east of Shandong province and infected with homosexual sex behaviors. HIV/AIDS cases who received follow-up service within 1 year of diagnosis were more likely to receive HAART ( OR=5.28, 95% CI: 3.51-7.95) and meet the level of viral load (VL) suppression ( OR=4.30, 95% CI: 2.89-6.40) than those who received follow-up service later. Conclusions:The status of follow-up of HIV/AIDS in Shandong province was influenced by age at diagnosis, sample resource, cultural level, address and transmission route. Timely follow-up can improve the proportion and effect of HIV/AIDS treatment.

Objective:To investigate the clinical significance and correlation of arginase 1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression in hepatocellular carcinoma (HCC).Methods:The expression of Arg-1and iNOS in 146 cases of hepatocellular carcinoma tissues and corresponding adjacent tissues was detected by immunohistochemistry. The clinicopathological characteristics and the correlation between the expressions and prognosis were determined by chi square test, Spearman’s rank correlation, Kaplan-Meier survival analysis and Cox regression analysis.Results:The positive rates of Arg-1 and iNOS were 18.7% (23/123) and 37.0% (54/146), respectively, which was significantly lower than the adjacent tissues [100%(146/146) and 93.8% (137/146)] and the difference was statistically significant ( χ2 = 212.521, P < 0.01, χ2 = 104.276, P < 0.01). There was a positive correlation between the both expression ( r = 0.331, P < 0.01). Arg-1 low expression was correlated with preoperative serum alpha-fetoprotein (AFP) level, tumor size, differentiation degree, histological types and Edmondson’s grade. iNOS low expression was correlated with the differentiation degree and Edmondson’s grade ( P < 0.05). Kaplan Meier survival analysis showed that in patients with recurrence-free survival (RFs), Arg-1 (+) group > Arg-1 (-) group and Arg-1 (+) iNOS (+) group > Arg-1 (+) iNOS (-) group > Arg-1 (-) iNOS (-) group ( P < 0.05). Cox multivariate analysis showed that age, tumor size, Edmondson’s grade, vascular tumor emboli were significantly correlated with RFs ( P < 0.05). Conclusion:There is a positive correlation between Arg-1 and iNOS expressions in HCC, and both may reflect the HCC malignant degree. The reduced/absent expression of both may participate in the occurrence and development of HCC. The combined detection of Arg-1 and iNOS on HCC may have certain significance for the judgment of differentiation degree and prognosis.

Trichoderma spp. is a kind of filamentous fungi with important biocontrol value. Twelve strains of Trichoderma spp. were isolated from the soils of different types of crops in Shaoxing, Zhejiang and Foshan, Guangdong. The antagonistic resistance to Fusarium oxysporum was compared by plate confrontation test. The further analysis of volatile secondary metabolites for two strains were carried out using HS-SPME-GC-MS analysis. The results showed that T. asperellum ZJSX5003 and GDFS1009 had fast growth ability, and the inhibition effects on F. oxysporum were 73% and 74% respectively. Six identical volatile metabolites were detected as follows 2-Methyl-1-propanol, 3-Methyl-1-butanol, 3-Methyl-3-buten-1-ol, Acetyl methyl carbinol, Butane-2,3-diol and 6-n-pentyl-2H-pyran-2-one (6-PAP). Among them, 6-PAP was validated to have a higher inhibitory effect on F. oxysporum in vitro. This study will provide basis for the development of biocontrol agents with metabolites of Trichoderma, such as 6-PAP.
Antibiosis ; Antifungal Agents ; pharmacology ; Fusarium ; drug effects ; physiology ; Gas Chromatography-Mass Spectrometry ; Trichoderma ; chemistry ; metabolism

The oral microbial community is widely regarded as a latent reservoir of antibiotic resistance genes. This study assessed the molecular epidemiology, susceptibility profile, and resistance mechanisms of 35 methicillin-resistant Staphylococcus epidermidis (MRSE) strains isolated from the dental plaque of a healthy human population. Broth microdilution minimum inhibitory concentrations (MICs) revealed that all the isolates were nonsusceptible to oxacillin and penicillin G. Most of them were also resistant to trimethoprim (65.7%) and erythromycin (54.3%). The resistance to multiple antibiotics was found to be largely due to the acquisition of plasmid-borne genes. The mecA and dfrA genes were found in all the isolates, mostly dfrG (80%), aacA-aphD (20%), aadD (28.6%), aphA3 (22.9%), msrA (5.7%), and the ermC gene (14.3%). Classical mutational mechanisms found in these isolates were mainly efflux pumps such as qacA (31.4%), qacC (25.7%), tetK (17.1%), and norA (8.6%). Multilocus sequence type analysis revealed that sequence type 59 (ST59) strains comprised 71.43% of the typed isolates, and the eBURST algorithm clustered STs into the clonal complex 2-II(CC2-II). The staphyloccoccal cassette chromosome mec (SCCmec) type results showed that 25 (71.43%) were assigned to type IV. Moreover, 88.66% of the isolates were found to harbor six or more biofilm-associated genes. The aap, atlE, embp, sdrF, and IS256 genes were detected in all 35 isolates. This research demonstrates that biofilm-positive multiple-antibiotic-resistant ST59-SCCmec IV S. epidermidis strains exist in the dental plaque of healthy people and may be a potential risk for the transmission of antibiotic resistance.
Anti-Bacterial Agents ; therapeutic use ; Dental Plaque ; microbiology ; Female ; Humans ; Methicillin ; Methicillin-Resistant Staphylococcus aureus ; isolation & purification ; Staphylococcal Infections ; diagnosis ; Staphylococcus epidermidis ; isolation & purification