ObjectiveTo analyse the efficacy and mechanism of Guizhi Fulingwan in regulating sex hormone disorders in rats with benign prostatic hyperplasia （BPH）. MethodsThirty male SD rats were randomly divided into a sham group， a model group， a finasteride group （0.45 mg·kg^-1·d^-1）， and low-dose and high-dose groups of Guizhi Fulingwan （0.135， 0.337 5 g∙kg^-1∙d^-1）， with six in each group. The BPH model was prepared by subcutaneous injection of 3.5 mg∙kg^-1∙d^-1 testosterone propionate after debridement surgery in all groups except the sham group. The rats in the sham group and the model group were administered with an equal volume of saline by gavage， and the rest of the groups were administered with the corresponding medicinal solution by gavage for 35 days. Histopathology in rats was evaluated by prostate wet weight， volume， index， and hematoxylin-eosin （HE） staining. The serum sex hormone levels of testosterone （T）， dihydrotestosterone （DHT）， and estradiol （E₂） were determined by enzyme-linked immunosorbent assay. The protein expression of the androgen receptor （AR） was detected by immunohistochemistry. The serum metabolism profiles of rats in the sham group， the model group， and the high-dose group of Guizhi Fulingwan were compared by ultra-high performance liquid chromatography tandem Fourier transform mass spectrometry （UHPLCQ Exactive） to screen for metabolic markers and to obtain relevant metabolic pathways. ResultsCompared with those in the sham group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the model group were all elevated （P<0.05， P<0.01）， and the histomorphology showed pathological changes. Compared with those in the model group， the wet weight， volume， index， serum sex hormone level， and AR protein expression of the prostate in the intervention groups showed a decreasing trend （P<0.05， P<0.01）， and histopathology was improved. Serum metabolomics analysis obtained a total of 40 metabolic markers related to the intervention effect of Guizhi Fulingwan， such as dehydrosafynol， hyoscyamine， and lumichrome， which were involved in the pathways of autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling. ConclusionGuizhi Fulingwan can effectively regulate sex hormone disorders in BPH rats， and its mechanism may be related to autophagy， riboflavin metabolism， and retrograde endocannabinoid signaling.

This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*

OBJECTIVE: To preliminarily investigate the effects and mechanism of action of Yishen Yangsui Formula (, YSYSF)on the recovery of neurological function in rats with degenerative cervical myelopathy. METHODS: Fifty adult SD female rats were randomly divided into control group, sham group, model group, YSYSF group and positive drug group by using randomized numerical table method. In the model group, YSYSF group and positive drug group, polyvinyl alcohol acrylamide interpenetrating network hydrogel(water-absorbent swelling material) was used to construct a rat spinal cord chronic compression model. The sham group was implanted with the water-absorbent swelling material and then removed without causing spinal cord compression. The control group, the sham group and the model group were given equal amounts of saline by gavage, the group of YSYSF was given Chinese herbal medicine soup by gavage 9.1 g·kg^-1 once a day, and the positive drug group was given tetrahexylsalicylglucoside sodium monosialate ganglioside by intraperitoneal injection 4.2 mg·kg^-1 once a day. The motor function of the rats was assessed by the BBB method after 1, 3, 7, and 14 d of drug administration. The spinal cord tissues were taken from rats executed 14 d after drug administration, and the morphological changes of the spinal cord compression site were observed by HE staining, and the expression levels of Caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 were detected in the area of spinal cord injury by Western blot method. RESULTS: The BBB scores of the control group and the sham group were normal at all time points after modeling, which were higher than the BBB scores of the model group, the YSYSF, and the positive drug group (P<0.05). From the 3rd day after gavage, at all time points, the BBB scores of rats in the YSYSF group and the positive drug group were higher than those of rats in the model group (P<0.05). The staining pattern of HE spinal cord tissue was normal in the control group and the sham group, and the HE spinal cord in the model group was severely damaged with a large number of neuron deaths, whereas the damage to the spinal cord and neuron cells was reduced in the YSYSF group and the positive drug group. The expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β and IL-18 in the spinal cord of the model group were significantly higher than those of the sham group (P<0.0001), and the expression levels of caspase-1, GSDMD, NLRP3, PYCARD, IL-1β, and IL-18 in the YSYSF group and the drug group were significantly lower than those in the model group (P<0.05). CONCLUSION YSYSF can improve the motor function of rats with degenerative cervical spinal cord disease, alleviate the pathological changes, and promote the recovery of spinal cord neurological function. The specific mechanism may be related to the inhibition of the activation of inflammatory vesicles NLRP3 and PYCARD, the reduction of the release of inflammatory factors IL-1β and IL-18, the reduction of the expression of caspase-1 and GSDMD, the reduction of cellular death, and the inhibition of inflammatory response.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Pyroptosis/drug effects* ; Spinal Cord/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Spinal Cord Diseases/drug therapy* ; Interleukin-1beta/metabolism*

Objective:To investigate the effects of macrophage(Mφ)polarization on the cementogenic differentiation of human perio-dontal ligament stem cells(hPDLSCs)and the underlying mechanism.Methods:Human monocytic THP-1 cells were induced to M0,M1 and M2 Mφ subsets,then RPM1 1640 medium or supernatants of different Mφ phenotypes were mixed with an equal volume of ce-mentoblastic induction medium to generate conditioned mediums(CMs),and termed as CM-Control,CM-M0,CM-M1 and CM-M2,respectively.hPDLSCs were cultured with different CMs,and the hPDLSCs sheets were then wrapped around treated dentin matrix(TDM)to generate cell sheet/dentin complexes.The complexes were subcutaneously implanted into nude mice.The cementum-like tissue formation was evaluated by HE staining,immunofluorescent staining(IMF)and qRT-PCR were used to detect the expression level of cementogenic differentiation-related markers bone sialoprotein(BSP),cementum attachment protein(CAP)and cementum pro-tein-1(CEMP-1),oxidant-antioxidant system-related markers superoxide dismutase 1(SOD1)and nuclear factor erythroid 2-related factor 2(NRF2),mitophagy-related markers PTEN induced putative kinase 1(PINK1)and microtubule asso ciated proteins 1A/1B light chain 3(LC3).Results:In vivo,CM-M2-treated hPDLSCs(CM-M2)group formed more cementum-like tissues and expressed higher protein levels of CAP,CEMP-1,SOD1,PINK1 and LC3 than that in other groups.In vitro tests showed that,compared with CM-Control group,hPDLSCs incubated with CM-M2 increased the levels of BSP(P＜0.01),CAP(P＜0.001),CEMP-1(P＜0.01)and SOD1(P＜0.05),while no statistically significant difference was detected for NRF2(P＞0.05),and increasedthe expression of PINK1(P＜0.05).Conclusion:M2 Mφ regulate the cementogenic differentiation of hPDLSCs possibly via modulating oxidant-antioxidant system and mitophagy.

Objective:To investigate the stateand related factors of mental health literacy in college freshmen.Methods:A total of 8 014 college freshmen in the class of 2022 from a comprehensive university in Henan Province were selected.They were assessed with a self-administered general information questionnaire and the Mental Health Literacy Scale(MHLS).Results:The average total score of freshmen on the MHLS was(111.55±9.84),and the MHLS total scores were higher in female freshmen than in male freshmen(P＜0.001).Multiple linear regression analysis showed that gender was significantly negatively associated with total MHLS scores(β=-0.24,P＜0.001),and whether or not they had taken mental health education courses(β=0.09)and whether or not they had read psychology-related books(β=0.08)were positively associated with total MHLS score(Ps＜0.001).Conclusion:In this study,the mental health literacy in freshmen is at amoderate level,with higher levels of mental health literacy in females,those who have taken mental health education courses,and those who have read books on psychology.

Objective We aimed to explore the clinical efficacy of precise electro-acupuncture stimulation in the pterygopalatine fossa for the treatment of chronic sinusitis.Methods In total,40 patients with chronic sinusitis who visited the Xiyuan Hospital,China Academy of Chinese Medical Sciences between January 2022 and January 2023 were selected.The subjects were randomly divided into two groups:the treatment group(receiving precise electro-acupuncture in the pterygopalatine fossa)and the control group(receiving standard western medical treatment),with 20 cases in each groups.The treatments were administered twice a week for a period of 12 weeks.The effectiveness of the treatments was evaluated through computed tomography(CT)of the sinus changes and the Lund-Mackay scoring system.Results In cases of total opacity and partial opacity,there were significant differences between the two patient groups before and after treatment(P<0.05).Intra-group comparison revealed statistically significant improvements in both groups before and after treatment(P<0.05).The treatment group exhibited significant improvement in various sinus conditions(P<0.05),while in the control group,a significant improvement was only observed in the left maxillary sinus(P<0.05).Inter-group comparison also demonstrated that the treatment group's improvements were superior to those of the control group across multiple indicators(P<0.05).Conclusion The precise electro-acupuncture stimulation technique in the pterygopalatine fossa demonstrated significant therapeutic effects in the treatment of chronic sinusitis,with superior outcomes with respect to radiological changes compared to standard western medicine treatment.

Objective:To investigate the role and mechanism of molecular hydrogen in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Balb/c male mice were randomly(random number) divided into control group, control+H 2, LPS and LPS+H 2 group with 6 mice in each group. The levels of malondialdehyde (MDA) and Fe 2+ in lung tissue were detected by kits. The lung tissue morphology was observed. The infiltration levels of F4/80 positive macrophages in lung tissue were detected by immunofluorescence staining. A549 cells were divided into control, control+H 2, erastin and erastin+H 2 group. The reactive oxygen species (ROS), malondialdehyde, (MDA), lactate dehydrogenase (GSH), number of cell death and lactate dehydrogenase (LDH) release in each group were detected by kits. Nrf2, GPX4, and HO-1mRNA were quantified by real-time PCR, the protein expression level of Nrf2 was detected by western blot, and the nuclear translocation level of Nrf2 was observed by immunofluorescence. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups. Results:Compared with the control group, the histopathological damage was aggravated, and the levels of MDA, Fe 2+ significantly increased in the LPS group, and F4/80 positive immune cells infiltration significantly increased (all P<0.05). Compared with LPS group, the degree of lung injury in LPS+H 2 group significantly reduced (all P<0.05). In vitro experiments, compared with the control group, the ROS, MDA levels, number of cell death and LDH release significantly increased in erastin group (all P<0.05), while GSH, and GPX4 mRNA levels decreased (all P<0.05). HO-1mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Compared with erastin group, ROS, MDA levels, cell death number and LDH release decreased in earstin+H 2 group (all P<0.05). The levels of GSH, GPX4 mRNA, Nrf2 mRNA, HO-1 mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Conclusions:Molecular hydrogen attenuates LPS-induced ALI by promoting Nrf2 nuclear translocation to inhibit ferroptosis of alveolar epithelial cells.

Heart failure is the leading cause of mortality in cardiovascular diseases and represents the ultimate common manifestation of most cardiovascular conditions,impacting over 60 million individuals globally.Currently,heart transplantation remains the standard treatment for heart failure patients.Adherence to fundamental pharmacotherapy can improve quality of life and extend survival time for heart failure patients.However,due to the complex mechanism of heart failure and numerous complications,the limitations of conventional heart failure treatment strategies in clinical work are gradually magnified.In recent years,interventional therapy has emerged as an innovative approach for managing heart failure,attracting significant attention and achieving substantial breakthroughs that offer new hope for affected individuals.Injectable hydrogel has garnered considerable interest in biomedicine due to its minimally invasive nature and capacity for efficient therapeutic drug delivery.In the context of chronic heart failure,injectable hydrogel finds application primarily in tissue regeneration,drug delivery,and immunotherapy.This review mainly describes the application and research progress of injectable hydrogel in the treatment of heart failure.

Objective:To establish a highly sensitive and quantitative detection method for ABL1 kinase region mutations,provide strong support for the early diagnosis and treatment of chronic myeloid leukemia(CML).Methods:Sampele from 35 CML patients who were initially tested negative for ABL1 kinase region mutations by Sanger sequencing were collected.The ABL1 kinase region mutation was detected by the fluorescence quantitative detection kit of Shanghai Yuanqi Biopharmaceutical Technology Co.,Ltd.The mutation rate was analyzed byΔΔCt value method.The relative mutation rate of the final ABL1 kinase region was determined by dividing the mutation rate by the expression level of the fusion gene.Results:Among the 35 CML patients initially tested negative for ABL1 mutations by the Sanger sequencing method,7 cases of T315I mutation,2 cases of T315A mutation,2 cases of Y253H mutation,and 1 cases of E255K mutation after detection of the new method.The relative mutation rates range from 0.1％to 19.42％,which could not be detected by Sanger sequencing method.Subsequently,this method was used to detect the ABL1 mutation in 126 CML patients,and the positive rate exceeded that of the Sanger sequencing method.The BCR-ABL1 gene expression significantly reduced or negative after adjusting treatment strategy based on the mutation situation.Conclusion:Compared with Sanger sequencing,fluorescence quantitative PCR has higher sensitivity and can screen for low-frequency ABL1 kinase mutations in the early stage.Moreover,it can also perform relative quantitative analysis,so the method has good clinical application prospects for detecting ABL1 mutation.

Objective:To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.Methods:A total of 210 RhD-samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population.Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene.Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene,and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.Results:Among 210 RhD-specimens,128 cases(60.38％)had RHD gene deletion.27 cases had partial exons of RHD,including 2 cases with RHD*DVI.3/RHD*01N.01,24 cases with RHD*01N.04/RHD*01N.01,and 1 case with RHD-CE(2-10)/RHD*01N.01.55 cases had retained all of 10 exons,including 4 cases with RHD*01/RHD*01N.01,6 cases with RHD*15/RHD*01N.01,1 case with RHD*01W.72/RHD*01N.01,1 case with RHD*15/RHD*01EL.01,39 cases with RHD*01EL.01/RHD*01N.01,and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G＞A mutation loci.Conclusion:There is polymorphism in the molecular mechanism of RhD-D gene in Wuhu blood donor population,among which RHD*01EL.01 and RHD*15 are the main variants in this region.The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.