OBJECTIVE To explore the mechanism of Qiangxin decoction in the treatment of chronic heart failure （CHF） by regulating the inhibitor of nuclear factor-κB alpha/nuclear factor-κB p65 subunit （IκBα/NF-κB p65） signaling pathway-mediated M1 macrophage polarization. METHODS In animal experiments， mice were used as research subjects， and the CHF model was established via coronary artery ligation. Model mice were treated with Qiangxin decoction （21.69 g/kg） for 28 days. After intervention， pathological morphological changes of myocardial tissues and cardiomyocyte apoptosis were observed. Serum levels of inflammatory factors including tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）， myocardial injury marker troponin I3 （TNNI3）， and macrophage-related markers F4/80 and cluster of differentiation 80 （CD80） were detected. In cell experiments， monocyte-macrophage leukemia RAW264.7 cells were induced to undergo M1 polarization by 10 ng/mL lipopolysaccharide combined with 10 ng/mL interferon-γ， followed by 48 h intervention with 10% drug-containing serum of Qiangxin decoction. After intervention， the nuclear translocation of NF-κB p65 and NF-κB p50 was observed. The positive rate of CD80 in cells was measured. The mRNA expression of inflammatory factors including IL-1β， IL-6， IL-8， IL-18， TNF-α， inducible nitric oxide synthase （iNOS）， cyclooxygenase-2 （COX2）， C-C motif chemokine receptor 7 isoform 2 （CCR7-2）， as well as the expression levels of proteins related to the IκBα/NF-κB p65 signaling pathway were detected. RESULTS Animal experimental results showed that Qiangxin decoction alleviated myocardial fibrosis in mice， and significantly reduced the cardiomyocyte apoptosis rate， serum levels of TNF-α and IL-6， as well as the protein expression of TNNI3， F4/80 and CD80 in myocardial tissues （P＜0.05）. Cell experimental results indicated that Qiangxin decoction significantly suppressed the nuclear translocation of NF-κB p65 and NF-κB p50 （P＜0.05）. It significantly decreased the CD80 positive rate， mRNA levels of IL-1β， IL-6， IL-8， IL-18， TNF-α， iNOS， COX2 and CCR7-2， total and nuclear expression of NF-κB p65， total， nuclear and cytoplasmic expression of phosphorylated NF-κB p65， total expression of phosphorylated IκBα （P＜0.05）. Meanwhile， it significantly elevated the total expression of IκBα and cytoplasmic expression of NF-κB p65 （P＜0.05）. CONCLUSIONS Qiangxin decoction can inhibit the activity of the IκBα/NF-κB p65 signaling pathway， reduce the release of pro-inflammatory factors， thereby restraining M1 macrophage polarization， mitigating myocardial fibrosis， and ultimately exerting therapeutic effects against CHF.

ObjectiveTo explore the diagnostic-therapeutic course and epidemiological characteristics of the first imported kala-azar case reported in Changning District of Shanghai, so as to provide references for early detection, timely diagnosis, and effective management of the kala-azar cases in non-epidemic areas. MethodsIn 2025, a comprehensive epidemiological investigation and a complete collection of clinical records of one kala-azar patient imported from other provinces reported by a medical institution in this city were conducted. The source of infection, process of diagnosis and treatment, and clinical outcome of the case were systematically analyzed. ResultsThe case was a male migrant worker from Shanxi Province currently residing in Shanghai. In June 2023, the patient had a history of exposure to mosquito bites during his stay in a kala-azar endemic area. The initial onset occurred in December 2023, with clinical manifestations including unexplained fever accompanied by leukopenia, and subsequently gradually developed night sweats and fatigue during the following months. In June 2024, the patient self-perceived significant weight loss, and physical examination revealed hepatomegaly and splenomegaly, leading to a diagnosis of hemophagocytic syndrome (HPS). Throughout the whole course of the illness, the patient sought treatment at hematology departments of several hospitals multiple times, where he was managed as a case of HPS. In January 2025, a large number of Leishmania donovani were detected in the patient's bone marrow smear, confirming kala-azar. After 2 weeks of standardized treatment with amphotericin B liposomal, there was significant improvement. Combined with the epidemiological investigation, it was speculated that the incubation period of this case was about 6 months, whereas the interval from initial onset to definite diagnosis was approximately 14 months. ConclusionKala-azar has atypical early clinical symptoms, which are prone to confusion with HPS. For patients with recurrent unexplained fever accompanied by peripheral cytopenias, hepatomegaly and splenomegaly, medical institutions should consider the possibility of infectious diseases. Close collaboration between medical institutions and centers for disease control and prevention is essential to conduct a detailed epidemiological investigation and laboratory screening, ensuring confirmed cases receive standardized treatment.

Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

Objective To reveal the effects of sulforaphane(SFN)on the ferroptosis pathway and iron homeostasis in rats with diabetic retinopathy(DR).Methods A DR rat model was established by a single intraperitoneal injection of streptozotocin at 65 mg·kg-1.After modeling,the rats were randomly divided into six groups(n=12 per group):Group C(control group),DR group,0.5SFN group,1.0SFN group,2.0SFN group,and 2.0SFN+Erastin group.Group C con-sisted of non-intervention control rats,while the other groups were DR model rats.Groups C and DR were orally adminis-tered 0.5 g·L-1 sodium carboxymethyl cellulose(CMC-Na).The 0.5SFN,1.0SFN,and 2.0SFN groups were orally ad-ministered SFN at 0.5,1.0,and 2.0 mg·kg-1,respectively.The 2.0SFN+Erastin group was orally administered 2.0 mg·kg-1 SFN and simultaneously received a tail intravenous injection of the ferroptosis inducer Erastin at 10.0 mg·kg-1.The intervention lasted for 4 weeks.Fasting blood glucose(FPG)was measured with a glucometer,glycosylated hemoglo-bin(GHb)was detected by visible spectrophotometry,and fasting insulin(FINS)was measured by ELISA.Retinal tissues were subjected to hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.The level of reactive oxygen species(ROS)in the retina was detected using the DCFH-DA probe,malondialdehyde(MDA)was measured by the TBA method,and reduced glutathione(GSH)was assessed by spectrophotometry.Retinal Fe2+content was determined by spectrophotometry.The mRNA expression levels of ferritin heavy chain 1(FTH1),ferroportin 1(FPN1),transferrin re-ceptor(TFRC),glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),thioredoxin 1(Trx1),and thioredoxin-interacting protein(TXNIP)in the retina were detected by qRT-PCR.GPX4 protein expression in the retina was detected by Western blot.Results Compared with the DR group,the 0.5SFN,1.0SFN,and 2.0SFN groups showed decreased FPG and GHb,increased FINS,improved retinal morphology with reduced neovascular capillaries,decreased levels of ROS and MDA,increased GSH levels,decreased retinal Fe2+content,increased FTH1 and FPN1 mRNA levels,de-creased TFRC mRNA levels,increased retinal GPX4,SLC7A11,and Trx1 mRNA levels,decreased TXNIP mRNA levels,and increased retinal GPX4 protein levels(all P＜0.05).Compared with the 2.0SFN group,the 2.0SFN+Erastin group showed increased FPG and GHb,decreased FINS,aggravated retinal damage with increased neovascular capillaries,elevat-ed levels of ROS and MDA,decreased GSH levels,increased retinal Fe2+content,decreased FTH1 and FPN1 mRNA levels,increased TFRC mRNA levels,decreased retinal GPX4,SLC7A11,and Trx1 mRNA levels,increased TXNIP mRNA levels,and decreased retinal GPX4 protein levels(all P＜0.05).Conclusion SFN alleviates DR in rats by inhibiting the ferrop-tosis pathway and maintaining iron homeostasis.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure(CHF).METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery.Modeled rats were divided into model group,Qiangxin decoction low-dose and high-dose groups(12.25,24.50 g/kg,calculated by crude drug),and chemical medicine group(Sacubitril valsartan sodium tablets,10.42 mg/kg),with 10 rats in each group;control group was set up without treatment.Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days.After the last medication,the contents of N-terminal pro-brain natriuretic peptide(NT-proBNP)and adenosine triphosphate(ATP)in serum and phosphatidic acid(PA)and cardiolipin(CL)in myocardial tissue were all detected;the pathological damage and collagen fibrosis of rat myocardial tissue were observed;the apoptosis of myocardial cells was determined;the ultrastructure of myocardial tissue was observed;the protein expressions of mitofusin 1(Mfn1),Mfn2,optic atrophy protein 1(OPA1)and dynamin-related protein 1(Drp1)were all detected in myocardial tissue.RESULTS Compared with control group,the serum content of NT-proBNP,apoptotic rate of myocardial cells,and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly;serum content of ATP,contents of PA and CL,and relative expressions of Mfn1,Mfn2 and L-OPA1 proteins were all significantly reduced(P＜0.05).There were abnormal membrane tissue structure in various layers of myocardial tissue,degeneration and necrosis of myocardial cells,and severe fibrosis;the mitochondria were swollen,with reduced or absent cristae,and uneven matrix density.After intervention with Qiangxin decoction,the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats(excluding CL content in the Qiangxin decoction low-dose group)were significantly reversed(P＜0.05);the pathological damage of myocardial tissue had significantly improved,fibrosis had significantly reduced,mitochondrial morphology tended to be normal,cristae had increased,and matrix density was uniform.CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats,thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis,the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.

Objective To investigate the molecular mechanism of Brusatol(BRU)regulating apoptosis of Hela cells through TLR9-MyD88 signaling pathway.Methods Hela cells preserved in our laboratory were treated with Brucea javanica at different concentrations(0,5.0,10.0,20.0,40.0,80.0 nmol·L-1).Hela cells were divided into Control group(normal cultured Hela cells),BRU-L group(treated with 10.0 nmol·L-1 Brucea javanica)and BRU group-H(treated with 20.0 nmol·L-1 Brucea javanica)Cells were treated with nmol·L-1 of Brucea javanica),BRU+pcDNA-NC group(transfected with pcDNA-NC+20.0 nmol·L-1 of Brucea javanica),BRU-H+pcDNA-TLR9 group(transfected with pcDNA-TLR9+20.0 nmol·L-1 of Brucea javanica).Cell proliferation was detected by CCK-8 and EdU methods.Apoptosis was detected by TUNNEL staining and flow cytometry.The protein expression levels of TLR9,MyD88,Bax,Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were detected by Western blot.Cell apoptosis and mitochondrial membrane potential detection kit(JC-1)were detected by flow cytometry,and the contents of adenosine triphosphate(ATP)and reactive oxygen species(ROS)were detected by ELISA.Results Compared with 0 nmol·L-1 group,the survival rate and IC50 value of 10 nmol·L-1 group were significantly decreased(P<0.05).After stimulation of BRU with different concentrations,the proliferation ability of cells was significantly decreased in a dose-dependent manner(P<0.05).Compared with control group,the 5-ethynyl-2'-deoxyuracil(EDU)positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein of cells in BRU-L,BRU-H and pcDNA-NC groups were significantly decreased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly increased(P<0.05).In control group,BRU-L,BRU-H group/BRU-H+pcDNA-NC,there was a continuous decreasing trend(P<0.05).Compared with the BRU-H+pcDNA-NC group,the EDU positive cell rate,TUNEL positive cell rate,apoptosis rate and Bcl-2 protein in the BRU-H+pcDNA-TLR9 group were significantly increased.The protein levels of TLR9 and MyD88,Bax,Bax/Bcl-2,Cleaved Caspase-3 and Cleaved Caspase-9 were significantly decreased(P<0.05).Compared with Control group,JC-1 level and ATP content in BRU-L,BRU-H and BRU-H+pcDNA-NC groups were significantly decreased,while ROC content and mitotracker positive cell level were significantly increased(P<0.05).Compared with BRU-L group,JC-1 level and ATP content in BRU-H group and BRU-H+pcDNA-NC group were further decreased,while ROC content and mitotracker positive cell level were further increased(P<0.05).Compared with the BRU-H+pcDNA-NC group,the levels of JC-1 and ATP in the BRU-H+pcDNA-TLR9 group were increased,while the levels of ROC,mitotracker staining positive cells were decreased(P<0.05).Conclusion Brucea javanica can produce Hela cell proliferation by regulating TLR9-MyD88 signaling pathway.

Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P＜0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P＜0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P＜0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P＜0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63％,65.12％and 65.12％,respectively;the sensitivity was 88.00％,96.00％and 100.00％,respectively;the specificity was 50.82％,52.46％and 50.82％,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Trib. Lorantheae used as traditional Chinese materia medica has a long history. There are 41 genera of Trib. Lorantheae， of which 6 belong to China， all have medicinal value， mainly distributed in Southwest， Southern， and Central and Southern China， with abundant resources. Twenty-two species of Trib. Lorantheae are used as medicinal materials or herbs in China. It mainly includes Taxillus. chinensis， T. sutchuenensis， Scurrula parasitica， Loranthus tanakae， Dendrophthoe pentandra， S. ferruginea， etc.， of which T. chinensis is the most widely used. The main chemical components of Trib. Lorantheae include flavonoids， terpenoids， sterols， phenylpropanoids， curcumins， phenolic acids， violate oils， sugars， and other compounds. Modern studies show that the extracts and monomer compounds of Trib. Lorantheae have various pharmacological effects such as anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， bacteriostasis， anti-virus， and lowering blood sugar， blood pressure， and lipid. It is believe that most active components related to their pharmacological effects are flavonoids， most of which are the main pharmacodynamic substances of the parasitic plants of Trib. Lorantheae， playing an important role in anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， and other pharmacological effect. This paper systematically summarized the literature and data on plants of Trib. Lorantheae and reviewed their chemical components and pharmacological effects， which provided references for the research， development， and utilization of Trib. Lorantheae.