Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective:To observe and verify the changes of transcriptome in hyperoxia-induced acute lung injury (HALI), and to further clarify the changes of pathways in HALI.Methods:Twelve healthy male C57BL/6J mice were randomly divided into normoxia group and HALI group according to the random number table, with 6 mice in each group. The mice in the normoxia group were fed normally in the room, and the mice in the HALI group was exposed to 95% oxygen to reproduce the HALI animal model. After 72 hours of hyperoxia exposure, the lung tissues were taken for transcriptome sequencing, and then Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway enrichment analysis was performed. The pathological changes of lung tissue were observed under light microscope after hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to verify the key molecules in the signal pathways closely related to HALI identified by transcriptomics analysis.Results:Transcriptomic analysis showed that hyperoxia induced 537 differentially expressed genes in lung tissue of mice as compared with the normoxia group including 239 up-regulated genes and 298 down-regulated genes. Further KEGG pathway enrichment analysis identified 20 most significantly enriched pathway entries, and the top three pathways were ferroptosis signaling pathway, p53 signaling pathway and glutathione (GSH) metabolism signaling pathway. The related genes in the ferroptosis signaling pathway included the up-regulated gene heme oxygenase-1 (HO-1) and the down-regulated gene solute carrier family 7 member 11 (SLC7A11). The related genes in the p53 signaling pathway included the up-regulated gene tumor suppressor gene p53 and the down-regulated gene murine double minute 2 (MDM2). The related gene in the GSH metabolic signaling pathway was up-regulated gene glutaredoxin 1 (Grx1). The light microscope showed that the pulmonary alveolar structure of the normoxia group was normal. In the HALI group, the pulmonary alveolar septum widened and thickened, and the alveolar cavity shrank or disappeared. RT-RCR and Western blotting confirmed that compared with the normoxia group, the mRNA and protein expressions of HO-1 and p53 in lung tissue of the HALI group were significantly increased [HO-1 mRNA (2 -ΔΔCt): 2.16±0.17 vs. 1.00±0.00, HO-1 protein (HO-1/β-actin): 1.05±0.01 vs. 0.79±0.01, p53 mRNA (2 -ΔΔCt): 2.52±0.13 vs. 1.00±0.00, p53 protein (p53/β-actin): 1.12±0.02 vs. 0.58±0.03, all P < 0.05], and the mRNA and protein expressions of Grx1, MDM2, SLC7A11 were significantly decreased [Grx1 mRNA (2 -ΔΔCt): 0.53±0.05 vs. 1.00±0.00, Grx1 protein (Grx1/β-actin): 0.54±0.03 vs. 0.93±0.01, MDM2 mRNA (2 -ΔΔCt): 0.48±0.03 vs. 1.00±0.00, MDM2 protein (MDM2/β-actin): 0.57±0.02 vs. 1.05±0.01, SLC7A11 mRNA (2 -ΔΔCt): 0.50±0.06 vs. 1.00±0.00, SLC7A11 protein (SLC7A11/β-actin): 0.72±0.03 vs. 0.98±0.01, all P < 0.05]. Conclusions:HALI is closely related to ferroptosis, p53 and GSH metabolism signaling pathways. Targeting the key targets in ferroptosis, p53 and GSH metabolism signaling pathways may be an important strategy for the prevention and treatment of HALI.

Objective To study the distribution and function of growth hormone receptor(GHR)positive neurons in neonatal mouse brain.Methods Six GHR-CreERT;mTOMATO/mGFP fluorescent reporter gene mice were selected.All of them were induced with tamoxifen on the 3rd day after birth.On the 10th and 17th day,3 mice were sampled respectively at each time point.The distribution of GHR-positive neurons in the developing brain was observed at different stages.GHR floxed mice were generated.By crossing them with neuron-specific Thy1-CreERT;YFP mice,GHR in neurons was inducingly knocked out.Control mice(GHR fl/fl,4 mice)and conditional knockout mice(Thy1-CreERT;YFP;GHR fl/fl,4 mice)were induced on the 3rd day after birth.Samples were collected on the 10th day for observing the effect of neuronal GHR signaling on brain development.Results The GHR fluorescent reporter gene mice showed that GHR-positive cells were widely expressed in the developing mouse brain.GHR-positive neurons were concentrated in the paraventricular hypothalamic nucleus(PVN).After specifically knocking out GHR in neurons of the developing mouse brain,no significant differences were observed in the areal densities of neurons and various types of glial cells.Conclusion GHR-positive neurons are mainly concentrated in the PVN.Knocking out GHR in neurons of the developing mouse brain can not significantly change the morphology and density of various neural cell types.

Objective:To investigate the intention to stay on among primary health care workers (PHWs) during the COVID-19 epidemics and its influencing factors.Methods:An online questionnaire survey was conducted among PHWs from 62 primary health institutions in 31 provinces, autonomous regions and municipalities across China selected by multi-stage whole cluster random sampling method between May and October 2022. According to the job position, the PHWs were divided into 5 categories: general practitioners (GPs), nurses, public health doctors, managers and support staff. Intention to stay was measured using the Chinese version of the Intention to Stay Questionnaire. Multiple linear regression model was used to analyze the influencing factors of the intention to stay in PHWs of different occupational categories, including personal factors, work factors, factors related to the COVID-19 and psychological reactions.Results:A total of 3 769 PHWs from 44 community health service centers, 18 township hospitals of 27 provinces/autonomous regions and 4 municipalities participated in this survey. The mean age of participants was (37.4±9.2) years, including 2 971(78.8%) women. The mean score of intention to stay of participants was 21.7±4.1. Compared with GPs, managers had lower intention to stay ( P=0.004). Age, female, in marriage, monthly income, years of primary care service, self-evaluation of unit support function, MSQ-SF score, and PA score were positively correlated with the score of intention to stay (all P<0.05), while PHQ-9 score, EE score, and DP score were negatively correlated with the score of intention to stay (all P<0.05). The MSQ-SF scores of all occupational categories were positively correlated with the scores of intention to stay (all P<0.01). In addition, among GPs, monthly income, years of service in primary care, self-evaluation of unit support function, and PA scores were positively correlated with the score of intention to stay (all P<0.05), while PHQ-9 scores and EE scores were negatively correlated with the score of intention to stay (all P<0.05). Among nurses, age, female gender, monthly income, self-evaluation of unit support function, and PA score were positively correlated with the score of intention to stay (all P<0.05), while EE scores and retention will score were negatively associated with ( P<0.001). Among public health doctors, in marriage was positively correlated with the score of intention to stay ( P=0.018). Among managers, DP score was negatively correlated with the score of intention to stay ( P=0.001). Among support staff, female gender, monthly income, years of primary care service, self-evaluation of unit support function, and PA scores were positively correlated with the score of intention to stay (all P<0.05), while EE score and DP score were negatively correlated with intention to stay (all P<0.05). Conclusions:The intention to stay of PHWs in China during the COVID-19 was at an intermediate level, which was affected by many factors. Among them, job satisfaction was positively correlated with the intention to stay of all occupational categories, and the influencing factors of different occupational categories have some variations.

OBJECTIVE: To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR). METHODS: Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4⁺T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-β in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-β in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis. RESULTS: Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4⁺T cells at 6 weeks of age (P < 0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-β in the mesentery were significantly higher than those in control group (P < 0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P < 0.05). The plasma levels of IL-17A and TGF-β were significantly increased in SHRs since 6 weeks of age (P < 0.05) with progressive worsening of mesenteric vascular sclerosis (P < 0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α-SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P < 0.05) and a negative correlation with VE-cad expression level at 10 weeks (P < 0.05). CONCLUSION ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.
Rats ; Animals ; Rats, Inbred SHR ; Rats, Inbred WKY ; Hypertension ; Interleukin-17 ; Sclerosis/pathology* ; Transforming Growth Factor beta ; Mesentery/pathology* ; RNA, Messenger/metabolism* ; Blood Pressure

Excessive application of chemical fertilizer has caused many problems in Angelica dahurica var. formosana planting, such as yield decline and quality degradation. In order to promote the green cultivation mode of A. dahurica var. formosana and explore rhizosphere fungus resources, the rhizosphere fungi with nitrogen fixation, phosphorus solubilization, potassium solubilization, iron-producing carrier, and IAA-producing properties were isolated and screened in the rhizosphere of A. dahurica var. formosana from the genuine and non-genuine areas, respectively. The strains were identified comprehensively in light of the morphological characteristics and ITS rDNA sequences, and the growth-promoting effect of the screened strains was verified by pot experiment. The results showed that 37 strains of growth-promoting fungi were isolated and screened from the rhizosphere of A. dahurica var. formosana, mostly belonging to Fusarium. The cultured rhizosphere growth-promoting fungi of A. dahurica var. formosana were more abundant and diverse in the genuine producing areas than in the non-genuine producing areas. Among all strains, Aspergillus niger ZJ-17 had the strongest growth promotion potential. Under the condition of no fertilization outdoors, ZJ-17 inoculation significantly promoted the growth, yield, and accumulation of effective components of A. dahurica var. formosana planted in the soil of genuine and non-genuine producing areas, with yield increases of 73.59% and 37.84%, respectively. To a certain extent, it alleviated the restriction without additional fertilization on the growth of A. dahurica var. formosana. Therefore, A. niger ZJ-17 has great application prospects in increasing yield and quality of A. dahurica var. formosana and reducing fertilizer application and can be actually applied in promoting the growth of A. dahurica var. formosana and producing biofertilizer.
Fertilizers ; Rhizosphere ; Angelica/chemistry* ; Fungi/genetics* ; Phosphorus

Objective:To investigate the status and influencing factors of activities of daily living (ADL), anxiety and depression of the community-dwelling elderly, and to explore the mediating effect of social support and social participation on ADL, anxiety and depression.Methods:A questionnaire survey was conducted from July to October 2022, among 637 residents over 60 years old registered in the Community Health Service Center of Taiyuan Economic and Technological Development Zone selected by simple random sampling method. The general information questionnaire, Activities of Daily Living (ADL) scale, Anxiety Self-assessment Scale, Depression Self-assessment Scale, Social Support Scale, and Social Participation Scale were used in the survey. The dichotomous logistic regression model was used to analyze the influencing factors of disability, anxiety, and depression of the elderly. Structural equation modeling was used to verify the mediating effects of social participation and social support on the ADL and mental health status in the elderly.Results:The disability rate of the elderly in the community was 42.9%(258/602). Age( OR=2.87-4.91), acute disease attack in the last three months( OR=2.03),poor economic status( OR=2.39), impaired social participation ability( OR=4.07, 11.75) and low level of social support( OR=2.37) were risk factors for disability of the elderly in the community. The incidence of anxiety symptoms was 22.7%(137/602). The risk factors of anxiety were having more than one chronic disease ( OR=2.24), poor economic status ( OR=2.27), mild and intermediate impairment of social participation ability( OR=6.97, 180.43)and low level of social support( OR=2.04). The incidence of depressive symptoms was 19.4%(117/602). The risk factors of depression were acute disease attack in the past three months ( OR=1.90), loneliness in the past three months ( OR=2.17), impaired social participation ( OR=4.17) and low level of social support ( OR=3.90). The direct effect of ADL on mental health was 0.204 (Bootstrap 95% CI:0.081-0.330), accounting for 34.58% of the total effect. The mediating effects of social participation and social support on ADL and mental health were 0.343 (Bootstrap 95% CI:0.274-0.418) and 0.042 (Bootstrap 95% CI:0.015-0.075) respectively, accounting for 58.13% and 7.12% of the total effect. Conclusions:Social support and social participation are not only the common influencing factors of ADL, anxiety and depression of the community-dwelling elderly, but also have a mediating effect on ADL and mental health. Promoting the social participation of the community-dwelling elderly and increasing social support can improve both ADL and mental health for them.

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.