This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

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 explore the effect of accelerated intermittent theta burst stimulation(aiTBS)on post-stroke depression(PSD).Methods From July,2021 to July,2023,48 PSD patients in Beijing Bo'ai Hospital were randomly assigned to control group(n=16),high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)group(n=16)and aiTBS group(n=16).aiTBS group received left-sided aiTBS treatment at dorsolateral prefrontal cortex(DLPFC),HF-rTMS group received left-sided 10 Hz rTMS treatment at DLPFC,and the control group received left-sided sham stimulation treatment,for three weeks.They were evaluated with the Hamilton Depression Rating Scale(HAMD),Hamilton Anxiety Rating Scale(HAMA)and Beck Depression Inventory(BDI)before and after treat-ment,and one month of follow-up.Results One case dropped down in each group.The inter-group effect,intra-group effect and interaction effect of HAMD,HAMA and BDI scores were all significant(F>3.235,P<0.05).The post-hoc test results showed that the scores of HAMD,HMMA and BDI were lower in HF-rTMS group and aiTBS group than in the control group(P<0.05),and no significant difference was found between HF-rTMS group and aiTBS group(P>0.05).There was significant difference in the effective rate of depression improvement among three groups(χ2=7.834,P=0.019),the effective rate was higher in aiTBS group than in the control group(P<0.017),and no significant dif-ference was found between HF-rTMS group and aiTBS group(P>0.017).Conclusion aiTBS can improve the depression and anxiety symptoms of patients with PSD,with shorter treatment time,compared with HF-rTMS.

Objective To study the characterization of surface electromyographic signals of upper limb force-generating muscles operated by rolling manipulation of Tuina doctors.Methods Surface electromyographic signals during rolling manipulation were collected from beginners and proficient operators for comparative analysis,and the patterns,similarities,and differences were summarized.Results The iEMG ratio of the ulnar lateral wrist extensor muscle in the proficient group was significantly higher than that in the beginner group(P＜0.05),while that of the middle deltoid fascicle in the beginner group was significantly higher than that in the proficient group(P＜0.05).There was no statistical difference in the iEMG ratios of other muscle groups(P＞0.05).The proficient group mainly used the ulnar wrist extensors,lateral head of triceps brachii,pectoralis major,and ulnar wrist flexors,while the beginner group mainly used the lateral head of triceps brachii,pectoralis major,and radial wrist flexors.Conclusions The proficient group and the beginner group shared common features in the electromyographic signals of the rolling manipulation.The proficient group increased the angle of ulnar deviation by recruiting more ulnar wrist extensors to increase the angle of palmar flexion and the dorsal contact area of the hand,and the proficient group used the middle and posterior deltoid fasciculus muscles less intensively and mastered the'sinking shoulder'principle better.

Objective To investigate the effect of total paeony glycoside(TPG)on airway remodeling in bronchial asthma mice and its underlying mechanisms.Methods Forty-eight BALB/c mice were randomly divided into control group,model group,ovalbumin+budesonide group(OVA+BUD group),and OVA+TPG group,with 12 mice in each group.Except the control group,mice in other groups were sensitized by intraperitoneal injection of 10%OVA aluminum hydroxide suspension,and then stimulated by atomized inhalation of 1%OVA to establish mouse asthma model.One hour before each inhalation of OVA,mice in OVA+BUD group were atomized with 2 ml BUD suspension,and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration.Lung tissues and bronchoalveolar lavage fluid(BALF)of mice from each group were collected,and the pathological morphology of the lung tissues was detected by hematoxylin-eosin(HE)and periodic acid schiff(PAS)staining.Inflammatory cell counts[white blood cell(WBC),neutrophil(NEU),eosinophils(EOS),and leukomonocyte(LYM)]in BALF were detected by Wright-giemsa staining.The contents of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in BALF were determined by ELISA.Airway remodeling proteins[fibronectin,α-smooth muscle actin(α-SMA),collagen Ⅰ]and NOD-like receptor protein 3(NLRP3)inflammasome-related proteins[NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein(ASC)]levels were detected by Western blotting.Human bronchial smooth muscle cells(HBSMCs)were divided into control group(normal culture),transforming growth factor(TGF)-β1 group(culture medium containing 10 ng/ml TGF-β1),and TGF-β1+TPG group(culture medium containing 10 ng/ml TGF-β1 and 50 μg/ml TPG).Cell proliferation was detected by CCK-8 method,and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins.Results Compared with control group,model group exhibited increased infiltration of inflammatory cell in lung tissues,mucosal epithelium hyperplasia,narrowed bronchial lumen narrowed,tube wall thickened,increased cup cells and mucus secretion,and an elevated pathological score of lung injury(P<0.05);the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF were increased(P<0.05),and the expressions of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were elevated(P<0.05).Compared with model group,BUD or TPG treatment effectively reduced asthma symptoms,improved lung histopathology injury,inhibited bronchial wall thickening,significantly reduced the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the content of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF,and inhibited expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Compared with control group,the proliferation rate of HBSMCs was increased,and the protein expression levels of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were increased in TGF-β1 group(P<0.05).Compared with TGF-β1 group,TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins,inhibiting NLRP3 inflammasome activation,and reducing the inflammatory response.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.