ObjectiveTo explore the mechanism by which Qijia Rougan decoction ameliorates liver fibrosis through amino acid/fatty acid metabolic reprogramming and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway， based on the miRNA-mRNA regulatory network and the interaction between metabolism and signaling pathways. MethodsSprague-Dawley （SD） rats were randomized into four groups （n=8）： control， model， and low-dose and high-dose （7.0， 28.0 g·kg^-1·d^-1， respectively） Qijia Rougan decoction. Liver fibrosis was induced by subcutaneous injection of carbon tetrachloride （CCl₄）. From week 9， drug intervention was implemented for 7 weeks. After the final administration， the pathological changes in the liver were evaluated through hematoxylin-eosin （HE） and picrosirius red （PSR） staining. An automated biochemical analyzer was used to measure the serum levels of biochemical indicators， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， total bile acid （TBA）， albumin （ALB）， and cholesterol （TC）. High-throughput miRNA sequencing was performed to identify differentially expressed miRNAs （DemiRs） during liver fibrosis. A miRNA-mRNA interaction network was constructed to identify key targets， which were then subjected to GO and KEGG enrichment analyses. The expression levels of selected DemiRs were validated by Real-time PCR. ResultsCompared with the control group， the model group showed marked hepatic lobular necrosis， increased collagen deposition， significant fibrosis， elevated serum levels of ALT， AST， ALP， and TBA （P<0.01）， and declined levels of ALB and TC （P<0.01）. Compared with the model group， Qijia Rougan decoction treatment reduced hepatic necrosis， collagen accumulation， and fibrosis， lowered the serum levels of ALT， AST， ALP， and TBA （P<0.01）， and raised the levels of ALB and TC （P<0.01）. Integrated miRNA-seq and RNA-seq analysis identified 31 DemiRs （6 upregulated and 25 downregulated） and 498 targets. The expression trends of four selected DemiRs， including rno-miRNA-376b-3p， were consistent with sequencing results （R²=0.93）. Functional annotation revealed that top 20 upregulated targets were enriched in amino acid and fatty acid metabolism， while top 20 downregulated targets were significantly associated with the PI3K/Akt signaling pathway and cancer progression. ConclusionQijia Rougan decoction alleviates liver fibrosis by reconstructing the miRNA-mRNA regulatory network， promoting metabolic reprogramming， and inhibiting the PI3K/Akt signaling pathway. These findings provide mechanism evidence supporting the multi-targeted antifibrotic effects of traditional Chinese medicine compound formulas.

Objective To investigate the effect of astragaloside Ⅳ (AS-Ⅳ) on renal ischemia-reperfusion injury (RIRI) and its specific mechanism. Methods Forty-eight rats were randomly divided into 6 groups, with 8 rats in each group: sham operation group (Sham group), RIRI group, RIRI + AS-Ⅳ (10 mg/kg) group, RIRI + AS-Ⅳ (20 mg/kg) group, RIRI + AS-Ⅳ (40 mg/kg) group and RIRI + AS-Ⅳ + Brusatol group [Brusatol is a nuclear factor E2-related factor 2 (Nrf2) inhibitor]. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels of rats were detected using an automatic biochemical analyzer; the pathological damage degree of rats kidney tissue was evaluated by hematoxylin-eosin staining and scored; the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in rats serum, and interleukin (IL)-1β and IL-18 in rats kidney tissue were detected by enzyme-linked immunosorbent assay; the degree of cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; real-time fluorescence quantitative polymerase chain reaction and Western blotting were used to determine the messenger RNA (mRNA) and protein levels of Nrf2/heme oxygenase-1 (HO-1) signaling pathway and cell pyroptosis regulatory factors in rats kidney tissue. Results Compared with the Sham group, the BUN and Scr levels in the RIRI group were increased, the renal function and tissue damage were more severe, the degree of cell apoptosis was aggravated, the MDA level was increased, and the SOD activity was decreased, the Nrf2 and HO-1 protein and mRNA levels were downregulated, the NOD-like receptor protein 3 (NLRP3), Cle-Caspase-1 (the activated form of Caspase-1) and gasdermin D (GSDMD)-N protein levels were upregulated, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were increased, and the release of IL-1β and IL-18 was increased. Compared with the RIRI group, the BUN and Scr levels in rats after AS-Ⅳ treatment were decreased, the degree of renal function and tissue damage was reduced, the degree of cell apoptosis was decreased, the MDA level was decreased, and the SOD activity was increased, the Nrf2 and HO-1 protein and mRNA levels were increased, the NLRP3, Cle-Caspase-1 and GSDMD-N protein levels were decreased, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were decreased, and the release of IL-1β and IL-18 was reduced. Compared with the RIRI + AS-Ⅳ (20 mg/kg) group, the MDA level and SOD activity in rats of the RIRI + AS-Ⅳ + Brusatol group were increased, the Nrf2 and HO-1 protein and mRNA levels were decreased, the NLRP3, Cle-Caspase-1 and GSDMD-N protein levels were upregulated, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were increased, and the release of IL-1β and IL-18 was increased. Conclusions AS-Ⅳ may alleviate RIRI in rats by inhibiting oxidative stress response and pyroptosis, and this mechanism is related to the activation of Nrf2/HO-1 signaling pathway.

ObjectiveTo explore the possible mechanism of Qishao Tongbi Capsule （芪芍通痹胶囊， QTC） in the treatment of intervertebral disc degeneration （IDD）. MethodsSeventy-five rats were randomly divided into control group， model group， low-dose QTC group， high-dose QTC group， high-dose QTC +agonist group， with 15 rats in each group. Except for the control group， all other groups were subjected to a fibrous ring puncture to prepare an IDD model. After modeling， rats in low-dose QTC group and high-dose QTC group were given QTC at doses of 0.2 and 0.8 g/（kg·d） by gavage， respectively. Rats in high-dose QTC+ agonist group was given QTC at 0.8 g/（kg·d） and SKL2001 solution at 10 mg/（kg·d） by gavage. The control group and model group were given 10 ml/（kg·d） distilled water by gavage. All treatments were given once a day for 4 consecutive weeks. After treatment， X-ray and magnetic resonance imaging （MRI） were used to detect IDD degree. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were used to observe the morphological changes of the intervertebral disc tissue. Immunohistochemical staining was performed to examine the levels of proteoglycan， type Ⅱ collagen （COL Ⅱ）， and matrix metalloproteinase-3 （MMP-3） in the intervertebral disc tissue. Western blotting was used to detect the extracellular matrix （ECM）-related proteins （proteoglycan， COL Ⅱ， MMP-3， MMP-9， MMP-13）， aging-related proteins （P53， P21， P16）， apoptosis related proteins， including B-cell lymphoma/leukemia 2 （BCL-2）， BCL-2 related X protein （BAX）， Cleaved Caspase-3， and Wnt/β-catenin pathway related proteins such as Wnt3a， glycogen synthase kinase-3β （GSK-3β） and β-catenin in the intervertebral disc nucleus pulposus （NP） tissue. Reverse Transcription Quantitative Polymerase Chain Reaction （RT-qPCR） was used to assess the mRNA expression of Wnt3a， GSK-3β， and β-catenin in intervertebral disc tissue. ResultsCompared with the model group， rats in the low-dose QTC group and high-dose QTC group exhibited improved DHI， decreased Pfirmann grading， and alleviated IDD. The structural integrity of the NP and annulus fibrosus increased， and the number of the NP increased. The levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β increased， while the levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX， Cleaved Caspase-3， Wnt3a and β-catenin protein decreased. The mRNA expression of Wnt3a and β-catenin mRNA decreased， while GSK-3β mRNA expression increased （P＜0.05）. Compared with the low-dose QTC group， the high-dose QTC group showed further improvements in DHI， decrease in Pfirrmann grading （P＜0.05）， and greater alleviation of IDD. The structural integrity of NP and annulus fibrosus was further enhanced， and the number of NP cells further increased. The levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β were higher， while the levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX， Cleaved Caspase-3， Wnt3a and β-catenin were lower. The mRNA expression of Wnt3a and β-catenin decreased， while GSK-3β mRNA expression increased （P＜0.05）. Compared with the high-dose QTC group， the high-dose QTC +agonist group showed a decrease of DHI， an increase of Pfirmann grading （P＜0.05）， significant aggravation of IDD， reduction in structural integrity of the NP and annulus fibrosus， a decrease of NP cell count， lower levels of proteoglycan， COL Ⅱ， BCL-2 and GSK-3β， and higher levels of MMP-3， MMP-9， MMP-13， P53， P21， P16， BAX and Cleaved Caspase-3. Additionally， GSK-3β mRNA expression decreased （P＜0.05）. ConclusionQTC can inhibit NP cell aging， apoptosis， and ECM degradation in IDD rats， and its therapeutic effect may be mediated through the inhibition of the Wnt/β-catenin pathway.

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

OBJECTIVE: To explore the current status and changing trends of the disease burden of traumatic brain injury (TBI) in China from 1990 to 2023, and to quantitatively assess the impact of different influencing factors on this disease burden, thereby providing references for the prevention of TBI. METHODS: Based on the 2023 Global Burden of Disease Study (GBD), indicators including incidence and years lived with disability (YLDs) were used to analyze the status and changing trends of TBI disease burden in China from 1990 to 2023. Additionally, the decomposition method established by Gupta was adopted to quantify the effects of population growth, population aging, age-specific incidence rate, and disease severity on YLDs. RESULTS: From 1990 to 2023, the age-standardized incidence rate and YLDs rate of TBI in China showed an overall upward trend, with a significant downward trend between 2015 and 2020, followed by a resumption of upward trend after 2020. The disease burden of TBI in males was higher than that in females, with a larger increase amplitude. The elderly population had higher TBI incidence rate and YLDs rate, also with a larger upward amplitude. Falls were the main cause of TBI in China, and the changing trend of the disease burden caused by falls was consistent with the overall trend of TBI disease burden; meanwhile, the elderly population bore a relatively high disease burden from falls. Taking 1990 as the baseline, the growth rates of YLDs in males and females in 2023 were 101.54% and 101.40%, respectively. For males, the proportions of YLDs growth attributed to population growth, population aging, age-specific incidence rate, and disease severity were 26.91%, 49.62%, 37.74%, and -12.73%, respectively; for females, the corresponding proportions were 28.85%, 57.69%, 27.65%, and -12.79%. CONCLUSION From 1990 to 2023, population aging had a significant impact on the disease burden of TBI in China. Strengthening the prevention and control of falls and paying close attention to males and the elderly population should be the key focuses of TBI prevention and control work in China in the future.
Humans ; Brain Injuries, Traumatic/epidemiology* ; China/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Aged ; Adult ; Cost of Illness ; Adolescent ; Young Adult ; Persons with Disabilities/statistics & numerical data* ; Child ; Global Burden of Disease ; Disability-Adjusted Life Years ; Child, Preschool ; Infant ; Aged, 80 and over

Tissue-resident memory T cells(TRM)are a key immune memory cell type responsible for the recurrence of many skin diseases.TRM cells remain in the skin tissue following infection or injury and maintain immune memory by forming a memory reservoir.When the same or similar external stimuli are encountered again,TRM cells can be rapidly activated,releasing inflammatory cytokines and cytotoxic substances,leading to local tissue damage and/or disease recurrence.The formation and function of TRM cells are regulated by various factors,such as T cell receptor signals,cytokines,co-stimulatory molecules,etc.Furthermore,TRM cells may exhibit different phenotypes and functions in different types of skin diseases.Therefore,understanding the characteristics and regulatory mechanisms of TRM cells is of great significance for studying the mechanisms of skin disease recurrence as well as for developing therapeutic strategies targeting TRM cells.

Objective:To assess the safety and efficacy of fenestrated endovascular aortic repair for the treatment of diseases involving in the aortic arch.Methods:The clinical data of 52 patients with aortic arch diseases treated with fenestrated endovascular aortic repair technique at Beijing Anzhen Hospital, Capital Medical University from Nov 2021 to Jan 2024 was retrospectively analyzed.Results:Fenestration technique was used to reconstruct the branches of the arch for all 52 patients, with a success rate of 100%. A total of 56 stent grafts in the thoracic aorta and 56 bridging stents in the branch artery were implanted. The follow-up time ranged from 3 to 24 months, with an average of 11.3 months. One patient with type B aortic dissection underwent secondary intervention treatment after six months due to the distal reentry tear, and none of the patients experienced branch vessel ischemia, spinal cord ischemia, renal dysfunction, or aortic disease-related deaths during the following-up period.Conclusion:Fenestrated technique in endovascular aortic repair is safe and effective for treating aortic arch diseases.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Objective:To analyze the long-term trends in cause-specific mortality across different sexes and age groups in China from 1990 to 2021, and quantitatively assess the impact of population aging on cause-specific deaths by sex.Methods:Based on data from the Global Burden of Disease Study 2021, this study extracted the number of deaths, crude mortality rates and age-standardized mortality rates (ASMRs) for all causes, Level 1 causes (communicable, maternal, neonatal, and nutritional diseases; non-communicable diseases; injuries) and Level 3 causes in China from 1990 to 2021, stratified by sex and age group. This study analyzed the current situation and long-term trends in mortality in China, applying decomposition analysis to quantify the impact of population aging on the number of deaths.Results:In 2021, the ASMRs of all-cause death and the three primary causes of death in Level 1 in China were 644.68, 26.59, 575.55, and 41.82 per 100 000, respectively. The ASMRs of the three primary causes continued to decline, with the smallest decrease observed in non-communicable diseases [EAPC=-1.79%, 95% CI (-1.92%, -1.66%)] and the largest in communicable, maternal, neonatal, and nutritional diseases (CMNND) [EAPC=-5.86%, 95% CI (-6.06%, -5.65%)]. The ASMRs were higher in males than females, with a smaller decline. Mortality was higher in the elderly. CMNND deaths mainly occurred in children under 5 and the elderly; non-communicable disease deaths were concentrated in the elderly; injury deaths were relatively evenly distributed across age groups. The proportion of CMNND deaths decreased annually, while the proportion of non-communicable disease deaths increased. From 1990 to 2021, population aging contributed to an increase of 8.11 million all-cause deaths, 167 464.42 CMNND deaths, 7.74 million non-communicable diseases deaths, and 196 287.78 injury deaths. The impact of population aging differed by sex and disease, with male and female aging-related deaths increasing by 4.47 million and 3.70 million, respectively. Compared to 1990, the age-specific mortality rate contributions in 2021 were -72.82% for males and -93.87% for females, with variations by sex and disease. Conclusion:The composition of disease-related deaths in China has changed notably. Population aging is linked to the sharp rise in deaths, with varying impacts across sexes and diseases. Reducing disease mortality can help lessen the negative effects of population aging.

Tissue-resident memory T cells(TRM)are a key immune memory cell type responsible for the recurrence of many skin diseases.TRM cells remain in the skin tissue following infection or injury and maintain immune memory by forming a memory reservoir.When the same or similar external stimuli are encountered again,TRM cells can be rapidly activated,releasing inflammatory cytokines and cytotoxic substances,leading to local tissue damage and/or disease recurrence.The formation and function of TRM cells are regulated by various factors,such as T cell receptor signals,cytokines,co-stimulatory molecules,etc.Furthermore,TRM cells may exhibit different phenotypes and functions in different types of skin diseases.Therefore,understanding the characteristics and regulatory mechanisms of TRM cells is of great significance for studying the mechanisms of skin disease recurrence as well as for developing therapeutic strategies targeting TRM cells.