ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

The inheritance, innovation, and development of traditional Chinese medicine(TCM) need to be based on Chinese medicinal materials. The TCM seed industry is the source of TCM production, which is related to the stable supply and quality safety of TCM. This paper summarizes the basic situation of the TCM seed industry and introduces relevant policies and regulations to TCM seeds in the seed industry and the TCM field. At present, the Management Measures of TCM Seeds and Seedlings has not yet promulgated, and TCM seeds are classified as non-major crops in the category of crops for management. This paper also describes the current situation of TCM seed and seedling system construction, which is in the development stage, from six aspects, including the construction of TCM seed industry technical support system; the establishment of TCM seed standard; the construction of germplasm resource preservation system; TCM seed testing, variety registration, and variety protection; production and management of TCM seeds; TCM seed supervision. According to the development status of the TCM seed industry, four problems are put forward, including imperfect systems and standards relevant to TCM seeds, insufficient supervision and law enforcement regarding TCM seeds, insufficient policy measures and capital investment to promote the development of the industry, and the industry's falling into a low-level cycle.Accordingly, four suggestions are provided, including improving laws, regulations, and policies, perfecting standards and norms,strengthening supervision and law enforcement, and promoting support system construction, in order to boost the high-quality development of the TCM seed industry.
Seeds/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/standards* ; Plants, Medicinal/chemistry*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

OBJECTIVE: To investigate the prognostic value of ¹⁸ F-deoxyglucose (FDG) PET/CT metabolic parameters combined with clinicopathological features for newly diagnosed diffuse large B-cell lymphoma (DLBCL) before treatment, and analyze the relationship between tumor metabolic volume (MTV), total lesion glycolysis (TLG) and clinicopathological features. METHODS: The clinical data of 120 patients with pathologically confirmed DLBCL were retrospectively analyzed and ¹⁸F-FDG PET/CT was performed 1 week before treatment. The metabolic parameters including SUVmax, SUVmean, tumor-to-blood standardized uptake value ratio (TBR), tumor-to-liver standardized uptake value ratio (TLR) were obtained. MTV and TLG of the lesions were obtained with 41% of SUVmax as the threshold, and the correlation of MTV and TLG with clinicopathological features were analyzed. Progression-free survival (PFS) was calculated by follow-up for 6-153 months. Receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier test, log-rank test and Cox proportional hazards model were used to analyze the date. RESULTS: The optimum cut-off values of the SUVmax, MTV, TLG, TBR and TLR for predicting tumor progression were 22.25, 256.05, 5 232.67, 12.97 and 10.60, respectively. The patients were divided into two groups according to the above cut-off values, respectively. Kaplan-Meier survival analysis showed that there were statistically significant differences in PFS between the two group (all P <0.05). The MTV and TLG values were correlated with NCCN-IPI score, Ann Arbor stage, serum lactate dehydrogenase level, and C-MYC, BCL-2, BCL-6 gene rearrangement (all P <0.05). Univariate analysis showed that NCCN-IPI score >3, C-MYC, BCL-2, BCL-6 gene rearrangement positive, SUVmax≥22.25, MTV≥256.05 cm³, TLG≥5 232.67 g and TBR≥12.97 were adverse factors for prognosis (HR: 1.949-5.759, all P <0.05). Multivariate Cox regression analysis showed that C-MYC, BCL-2 gene rearrangement positive and TLG≥5 232.67 g were all independent risk factors affecting PFS (HR: 4.660, 3.350, 4.031, all P <0.05). CONCLUSION The ¹⁸F-FDG PET/CT metabolic parameters SUVmax, MTV, TLG, TBR and TLR can be used as important indicators to predict PFS of DLBCL patients, and combining clinicopathological features can better predict the prognosis of patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Adult

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Hypertrophic cardiomyopathy (HCM) is a major contributor to cardiovascular diseases (CVD), the leading cause of death globally. HCM can precipitate heart failure (HF) by causing the cardiac tissue to weaken and stretch, thereby impairing its pumping efficiency. Moreover, HCM increases the risk of atrial fibrillation, which in turn elevates the likelihood of thrombus formation and stroke. Given these significant clinical ramifications, research into the etiology and pathogenesis of HCM is intensifying at multiple levels. In this review, we discuss and synthesize the latest findings on HCM pathogenesis, drawing on key experimental studies conducted both in vitro and in vivo. We also offer our insights and perspectives on these mechanisms, while highlighting the limitations of current research. Advancing fundamental research in this area is essential for developing effective therapeutic interventions and enhancing the clinical management of HCM.
Cardiomyopathy, Hypertrophic/physiopathology* ; Humans ; Animals

Objective To explore the effect of Huangqi Yanghe Decoction on wound healing of diabetic foot ulcer(DFU)rats based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-κB(NF-κB)signal pathway.Methods DFU rat model was constructed,and 48 rats successfully modeled were randomly divided into the model group,the Huangqi Yanghe Decoction low(8.5 g/kg)group,the Huangqi Yanghe Decoction high(17 g/kg)dose group and the Huangqi Yanghe Decoction high dose(17 g/kg)+LY294002(PI3K/AKT pathway inhibitor,0.3 mg/kg)group.There were 12 rats in each group.Another 12 rats were selected as the control group.Rats in each group were given corresponding drug intervention for 4 weeks.After the 14th and 28th day-administration,the general state and wound changes of rats were observed,and the wound healing rate was calculated.The fasting blood glucose(FBG)level of rats was measured,and the percutaneous partial pressure of oxygen(TcpO2)of tissue around the wound was detected.Serum levels of vascular endothelial growth factor(VEGF),hypoxia inducible factor-1α(HIF-1α),C-reactive protein(CRP)and interleukin(IL)-6 were determined by enzyme linked immunosorbent assay.Histopathological changes of the wound were observed by hematoxylin-eosin staining.Immunohistochemical staining was used to measure the microvascular density of rat wound tissue.The protein expression levels of PI3K,phosphorylated PI3K(p-PI3K),AKT,phosphorylated AKT(p-AKT),NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65)and NF-κB inhibitory protein α(IκB-α)in rat wound tissue were determined by Western blot assay.Results Rats in the control group had smooth hair color,normal diet,drinking water and excretion,more active,wound healing fast,less inflammatory reaction in wound tissue,and there were more new blood vessels.Fibroblasts and collagen matrix were abundant in granulation tissue.In the model group,the fur color of rats was dull and matte,and the activity was reduced.The symptoms of polydipsia,polyphagia and polyuria were appeared in the model group,the wound color was dark,and edema and ulcer appeared in the surrounding tissue,a large number of inflammatory cells infiltrated in the wound tissue,accompanied by tissue necrosis and exudation,fewer neovascularization and fibroblasts were observed.Wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were decreased,and FBG,serum CRP,IL-6,p-NF-κB p65 protein expression in wound tissue were increased(P＜0.05).Compared with the model group,the state of rats was gradually improved in the Huangqi Yanghe Decoction low and high dose groups,and the lesion degree of wound tissue was reduced successively,wound healing rate,TcpO2 in wound surrounding tissue,serum VEGF,HIF-1α,microvascular density,p-PI3K,p-AKT and IκB-α protein expression levels in wound tissue were increased in turn(P＜0.05).The FBG,serum CRP,IL-6 and p-NF-κB p65 protein expression in wound tissue were decreased in turn(P＜0.05).LY294002 could partially reverse the therapeutic effect of high-dose Huangqi Yanghe Decoction on DFU rats(P＜0.05).Conclusion Huangqi Yanghe Decoction can regulate PI3K/AKT/NF-κB pathway,inhibit inflammatory response in DFU rats,promote angiogenesis and thus promote wound healing.

Objective To explore the effect of barretinib on mice with acute lung injury(ALI)by regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods The male C57BL/6 mice were randomly divided into control group,model group and experimental-L,-M-H groups.Except for the control group,the other four groups were constructed ALI models by intraperitoneal injection of lipopolysaccharide.The control and model groups were given equal volume 0.9％NaCl by gavage.The experimental-H,-M,-L groups were administered with 1.00,0.50 and 0.25 mg·mL-1 barretinib solution 200 μL by gavage.Five groups were treated for 48 hours with once every 12 hours.The levels of inflammatory cytokine in bronchoalveolar lavage fluid were measured by enzyme linked immunosorbent assay.The expression levels of Occludin,JAK2 and STAT3 in mouse lung tissue were detected by Western blot.Results The levels of tumor necrosis factor-α in bronchoalveolar lavage fluid for experimental-M,-H groups,model group and control group were(228.48±25.41),(198.53±23.11),(317.32±32.85)and(48.93±2.59)ng·L-1;the levels of interleukin-6 were(118.81±14.85),(98.58±13.82),(172.23±25.94)and(49.47±3.06)ng·L-1;the relative expression levels of Occludin were 0.48±0.13,0.49±0.11,0.28±0.09 and 0.69±0.21;the phospho-JAK2/JAK2 ratios were 0.51±0.13,0.32±0.09,0.75±0.21 and 0.16±0.05;the phospho-STAT3/STAT3 ratios were 0.43±0.11,0.27±0.08,0.78±0.21 and 0.17±0.05,respectively.The differences of above indicators were statistically significant between the experimental-M,-H groups,control group and model group(all P＜0.05).Conclusion Barretinib can reduce the lung inflammatory response and improves the level of tight junction protein in lung tissue to protect ALI mice by inhibiting the JAK2/STAT3 signaling pathway.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.