ObjectiveThis study aims to systematically analyze the blood-absorbed components and metabolic profiles of Xiebaisan（XBS） in normal and chronic bronchitis （CB） mice using ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， while comparing differences between the two states. MethodsThirty female BABL/c mice were randomly divided into the normal group， the normal drug administration group， the CB group， the CB drug administration group and the dexamethasone group， with 6 mice in each group. The CB mouse model was established by inducing with ovalbumin （OVA）. The mice in the normal drug administration group and the CB drug administration group started to be gavaged with XBS（13.2 g·kg^-1） from the 21^st day， and the dexamethasone group mice were simultaneously gavaged with dexamethasone （0.5 mg·kg^-1） until the end of the 35^th day of the experiment. Subsequently， serum samples were collected and evaluated for their efficacy， based on the pharmacological evaluation indicators， to determine the efficacy of XBS in treating CB. Then the UPLC-Q-Exactive Orbitrap MS was employed to identify and analyze the chemical constituents， blood-absorbed components， and metabolites of XBS. Chemometric analysis was conducted to reveal metabolic profile differences under "dual states". Concurrently， Real-time PCR technology was utilized to detect the expression levels of key liver metabolic enzymes CYP2E1， CYP3A1， UGT1A1， and UGT1A6. ResultsA total of 28 prototype components and 158 metabolites （including 48 phase Ⅰ metabolites and 110 phase Ⅱ metabolites） of XBS were unambiguously identified in the serum of normal mice. Additionally， a comprehensive characterization was performed on a total of 32 prototype components and 178 metabolites （including 50 phase Ⅰ metabolites and 128 phase Ⅱ metabolites） of XBS in the serum of CB mice. Among them， 27 prototype components were detected in both states， including 12 flavonoids， 2 alkaloids， 3 triterpenes， 4 organic acids， 3 amides， 1 stilbene and 2 other compounds. The chemometrics analysis revealed no significant difference in the prototype components and metabolites of XBS between normal and CB mice； however， there was a significant increase in the in-vivo exposure of XBS in CB mice. Compared to normal mice， the levels of phase Ⅰ metabolites such as oxidation， reduction and methylation of blood components of XBS as well as phase Ⅱ metabolites of glucuronidation showed significant changes in CB mice. Real-time PCR further confirmed that these alterations were attributed to the upregulation of CYP2E1 （P<0.05）， CYP3A1 （P>0.05）， UGT1A1 （P<0.01） and UGT1A6 （P<0.01） enzymes expression in the liver of CB mice. ConclusionThis study elucidated the disparities in the levels of the blood-absorbed components and metabolic profiles of XBS in normal and CB mice， especially in oxidation， reduction， methylation in phase Ⅰ metabolism and glucoaldehyde acidification in phase Ⅱ metabolism. And there are related to the differences in the expression levels of phase Ⅰ and phase Ⅱ metabolic enzymes CYP2E1， CYP3A1， UGT1A1 and UGT1A6 in the liver.

Objective: To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC. Results The expression level of CCDC97 was elevated in HCC patients and HCC cells, closely associated with pathological features and prognosis. CCDC97 was identified as a novel prognostic biomarker. It is linked to the spliceosome pathway, which is significantly active in tumors and potentially promotes carcinogenesis. CCDC97 is also highly expressed in various immune cells and is associated with microenvironment. Furthermore, knocking down CCDC97 in vitro suppressed cell migration, invasion, and proliferation. Conclusion CCDC97 plays a critical role in HCC progression and the immune microenvironment, making it a potential target for prognosis and therapeutic intervention.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Tumor Microenvironment/genetics* ; Cell Movement/genetics* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics* ; Male

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the tumors.Therefore,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned.As carbonic anhydrase Ⅸ(CA Ⅸ)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfo-namide(ABS)as a CA Ⅸ inhibitor has inherent inhibitory activity and good targeting effect.In this study,Ag2S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bio-probe(Ag2S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation reaction.Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor im-aging by the near infrared-Ⅱ(NIR-Ⅱ)fluorescence characteristics of Ag2S QDs.PEG modification of Ag2S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal sta-bility and high photothermal conversion efficiency(PCE)of 45.17％.Under laser irradiation,Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in vitro.It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility.Therefore,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.

Atypical sensory responsivity is widely reported in autistic individuals and is related to elevated functional difficulties. Dynamically, altered initial responses and/or habituation rates could underlie their atypical averaged responses to repeated sensory stimuli. In this study we aimed to measure the arousal level in response to different types of auditory stimuli and the dynamic change of atypical arousal level using pupillometry in autistic children. In Experiment 1, 43 autistic children and 49 neurotypical (NT) children were asked to passively listen to a mild sound and an aversive sound repeatedly. In Experiment 2, 39 autistic children and 44 NT children who went through Experiment 1 listened to a gradually emerging non-startling sound and a suddenly emerging startling sound in a random order. We found that the autistic group showed hyper-arousal in response to the aversive sound and the startling sound as reflected by their larger change in pupil area. In comparison, these autistic children demonstrated normal arousal in response to the mild sound and the non-startling sound. Dynamically, the autistic group had a larger peak pupil area change than the NT group in the first trial and a normal habituation rate to the aversive sound. In summary, our results suggest hyper-arousal to aversive and startling stimuli and the role of larger initial responses in hyper-arousal in autism. Minimizing aversive and startling sensory stimuli or gradually increasing the volume of aversive auditory stimuli to allow autistic children to adapt using the principle of habituation is recommended to reduce the arousal level and problematic behaviors of autistic children.
Humans ; Male ; Child ; Female ; Acoustic Stimulation ; Autistic Disorder/physiopathology* ; Arousal/physiology* ; Pupil/physiology* ; Habituation, Psychophysiologic/physiology* ; Auditory Perception ; Child, Preschool

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Malignant tumors， with the increasing crude morbidity and mortality year by year， have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions， which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth， improve the quality of life of patients， and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years， they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis， inhibition of tumor cell migration and invasion， suppression of proliferation， induction of autophagy of tumor cells， cell cycle arrest， inhibition of tumor angiogenesis， regulation of microRNA， and modulation of immunity. In addition， Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， c-Jun N-terminal kinase （JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， mammalian target of rapamycin （mTOR）， Notch， Hedgehog， Wnt/β-catenin， and other signaling pathways to participate in the processes of tumor proliferation， invasion and metastasis， autophagy and apoptosis， and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility， utilization， and anti-tumor activity of alkaloids， bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids， their representative derivatives， and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.