Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

OBJECTIVE: To compare the aesthetic effects of anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy and whole maxilla clockwise rotation on improving paranasal concavity in patients with Class Ⅲ maxillofacial deformity. METHODS: A non-randomized controlled trial was designed, and 21 patients diagnosed with skeletal Class Ⅲ maxillofacial deformity were included. In the study, 11 patients in the test group were treated by segmental Le Fort Ⅰ osteotomy combined with anterior maxilla clockwise rotation, and 10 patients in the control group were treated by whole maxilla clockwise rotation. The CBCT and 3D photography of preoperative (T0), 2 weeks postoperative (T1), and 6 months postoperative (T2) were collected respectively, and the three-dimensional cephalometry was carried out. The differences of specific parameters between the two groups were compared by independent sample t-test, including saggital displacement of the cheek mass point (CK) and subalare point (SA), nasolabial angle, occlusal plane angle and labial inclination angle of the upper incisor. RESULTS: There were no significant differences of the parameters on T0 between the two groups. The average sagittal displacement of the upper incisors of the test group was (-0.71±1.67) mm and smaller than that of control group [(2.26±1.68) mm], t=-4.052, P < 0.05. The average angle of the occlusal plane clockwise rotation of the test group was 1.46°±2.38° and smaller than that of the control group (4.31°±1.83°), t=-3.047, P < 0.05. The angle of anterior maxilla clockwise rotation was 11.73°±2.81° during the surgery. The average saggital displacement of the paranasal soft tissue landmarks of the test group from T0 to T2 was larger than that of the control group [CK point, (4.96±1.18) mm vs. (2.01± 1.50) mm, P < 0.05;SA point, (5.19±1.17) mm vs. (2.69±1.45) mm, P < 0.05]. The labial inclination angle of the upper incisor of the test group was 112.15°±5.40° in T2 and significantly smaller than that of the control group (122.38°±8.83°), t=-3.237, P < 0.05. The nasolabial angle of the test group was 106.54°±12.82° in T2 and significantly larger than that of the control group (93.90°±12.46°), t=2.288, P < 0.05. CONCLUSION Compared with whole maxilla clockwise rotation, anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy can increase the saggital displacement of the paranasal soft tissue, correct labial inclination of the upper incisors and the acute naso-labial angle and better improve the paranasal aesthetic defects in patients with Class Ⅲ maxillofacial deformity with less changing on the saggital orientation of the upper incisors and the occlusal plane angle.
Humans ; Maxilla/surgery* ; Female ; Male ; Osteotomy, Le Fort/methods* ; Malocclusion, Angle Class III/surgery* ; Adult ; Cephalometry ; Young Adult ; Rotation ; Adolescent

Asthe standard for drafting standards,the Rules for Compiling National Standards for Pharmaceutical Excipients was first issued in the 2020 edition and then revised and re-issued in 2025.It has become an important technical specification for the pharmaceutical excipients standards in the Chinese Pharmacopoeia and for the phar-maceutical excipients standards formulated by pharmaceutical companies for associated review and approval.This article focuses on introducing the working background,main framework and main characteristics of the Rules for Compiling National Standards for Pharmaceutical Excipients,aiming to help the drafters,reviewers and implement-ers of pharmaceutical excipients standards better understand and master them,so as to further improve the standard-ization of writing pharmaceutical excipients standards and enhance the level of standards formulation and revision of pharmaceutical excipients.

Objective To explore the characteristics of acupoint selection and the law of acupoint compatibility in the treatment of Guillain-Barré syndrome(GBS)based on data mining.Methods Literature on acupuncture treatment of GBS was searched and screened from China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,SioMed,PubMed,Embase,Web of Science,and Cochrane Library from the establishment of the database to December 1,2024 and to build database.The author information and acupuncture prescriptions were modified and imported according to the data entry requirements of the Traditional Chinese medicine inheritance computing platform V3.5,the relevant data were analyzed and integrated through the"Acupoint Analysis"module of the platform.Results A total of 140 related papers,145 valid prescriptions,involving 237 acupoints.The acupoints with higher frequency were Zusanli,Hegu,Quchi,Yanglingquan and etc.The analysis yielded 42 core acupoints,22 sets of strong association rules for core acupoints,and 5 new core acupuncture prescriptions.Conclusion Acupuncture treatment for GBS follows the principle of"treating impotence by taking Yangming alone",takes"benefiting Qi and draining heat,supporting the correctness and opening up the collaterals"as the main method,and attaches importance to"regulating the spirit and connecting the internal organs".

Objective To investigate the correlation between serum homeodomain interacting protein ki-nase 2(HIPK2),annexin A5(ANXA5)and coronary stenosis and prognosis in patients with acute myocardial infarction(AMI).Methods A total of 277 AMI patients who received interventional treatment in this hospi-tal from January 2021 to July 2023 were selected as the AMI group,and another 140 cases with normal or very mild stenosis in coronary angiography during the same period were selected as the control group.According to the degree of coronary artery stenosis(Gensini score),the AMI patients were divided into mild coronary arter-y stenosis group(86 cases),moderate coronary artery disease group(111 cases)and severe coronary artery disease group(80 cases).According to the prognosis,they were divided into poor prognosis group(80 cases)and good prognosis group(197 cases).Enzyme-linked immunosorbent assay was used to detect the serum HIPK2 and ANXA5 levels.Spearman correlation analysis was used to analyze the correlation between serum HIPK2 and ANXA5 levels and Gensini score in patients with AMI.Multivariate unconditional Logistic regres-sion was used to determine the relationship between serum HIPK2 and ANXA5 levels and prognosis of AMI patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive efficiency of serum HIPK2 and ANXA5 levels on prognosis of AMI patients.Results Compared with the control group,the ser-um HIPK2 level in the AMI group increased and the ANXA5 level decreased,and the differences were statisti-cally significant(P＜0.05).The serum HIPK2 levels in the mild coronary artery stenosis group,moderate coronary artery stenosis group and severe coronary artery stenosis group increased successively,while the ANXA5 levels decreased successively,and the differences were statistically significant(P＜0.05).Gensini score was positively correlated with serum HIPK2 level and negatively correlated with serum ANXA5 level in AMI patients(P＜0.05).The Gensini score of AMI patients was positively correlated with the serum HIPK2 level(r=0.785,P＜0.05),and negatively correlated with the serum ANXA5 level(r=-0.798,P＜0.05).Compared with the good prognosis group,the serum HIPK2 level in the poor prognosis group increased(P＜0.05),and the ANXA5 level decreased(P＜0.05).After adjusting for confounding factors,high HIPK2 was an independent risk factor for poor prognosis in AMI patients(P＜0.05),and high ANXA5 was an independ-ent protective factor(P＜0.05).The area under the curve of the combined prediction of serum HIPK2 and ANXA5 levels for the prognosis of AMI patients was 0.875,which was greater than 0.778 and 0.784 predic-ted by serum HIPK2 and ANXA5 levels alone(P＜0.05).Conclusion The serum HIPK2 level is increased and the ANXA5 level is decreased in patients with AMI,which is related to the aggravation of coronary steno-sis and the poor prognosis.The combination of serum HIPK2 and ANXA5 levels is more effective in predic-ting the prognosis of patients with AMI.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.

Objective To investigate the role of the prefrontal cortex in the generation and adaptation of chro-nic subjective tinnitus using resting-state functional magnetic resonance imaging(rs-fMRI).Methods Resting-state functional magnetic resonance imaging scan were acquired from 20 patients with chronic subjective tinnitus and 20 healthy controls.Fractional amplitude of low-frequency fluctuations(fALFF)and seed-based whole-brain functional connectivity(FC)methods were used to detect abnormal prefrontal cortex activity in tinnitus patients and to investi-gate interactions between prefrontal cortex activity and brain regions associated tinnitus perception.The analysis aimed to assess the relationship between prefrontal cortex spontaneous neural activity,atypical functional connectivi-ty across various brain regions,and clinical characteristics of tinnitus.Results Compared with healthy controls,pa-tients with chronic tinnitus showed a significant reduction in fALFF values in some specific brain areas of prefrontal cortex,including the left/right medial superior frontal gyrus and the left/right middle frontal gyrus.Functional con-nectivity values were notably enhanced between the left medial superior frontal gyrus and the left anterior insula,as well as between the right medial superior frontal gyrus and the left superior temporal gyrus.Furthermore,increased functional connectivity was observed between the left middle frontal gyrus and the right middle temporal gyrus,as well as between the right middle frontal gyrus and the left parahippocampal gyrus,left superior parietal lobule,and left supplementary motor area.Importantly,the functional connectivity between the left middle frontal gyrus and the right superior temporal gyrus exhibited a negative correlation with tinnitus handicap inventory scores(r=-0.627,P=0.003)and visual analogue scale scores(r=-0.596,P=0.005).Conclusion There are abnormal brain function changes in medial prefrontal cortex and dorsolateral prefrontal cortex in patients with chronic subjec-tive tinnitus,accompanied by changes in the intensity of functional connections with the salience and auditory net-works.These abnormalities are highly related to the severity of tinnitus.The prefrontal cortex may play an impor-tant role in the sensory prediction and auditory regulation of tinnitus.

Objective To investigate the role of the prefrontal cortex in the generation and adaptation of chro-nic subjective tinnitus using resting-state functional magnetic resonance imaging(rs-fMRI).Methods Resting-state functional magnetic resonance imaging scan were acquired from 20 patients with chronic subjective tinnitus and 20 healthy controls.Fractional amplitude of low-frequency fluctuations(fALFF)and seed-based whole-brain functional connectivity(FC)methods were used to detect abnormal prefrontal cortex activity in tinnitus patients and to investi-gate interactions between prefrontal cortex activity and brain regions associated tinnitus perception.The analysis aimed to assess the relationship between prefrontal cortex spontaneous neural activity,atypical functional connectivi-ty across various brain regions,and clinical characteristics of tinnitus.Results Compared with healthy controls,pa-tients with chronic tinnitus showed a significant reduction in fALFF values in some specific brain areas of prefrontal cortex,including the left/right medial superior frontal gyrus and the left/right middle frontal gyrus.Functional con-nectivity values were notably enhanced between the left medial superior frontal gyrus and the left anterior insula,as well as between the right medial superior frontal gyrus and the left superior temporal gyrus.Furthermore,increased functional connectivity was observed between the left middle frontal gyrus and the right middle temporal gyrus,as well as between the right middle frontal gyrus and the left parahippocampal gyrus,left superior parietal lobule,and left supplementary motor area.Importantly,the functional connectivity between the left middle frontal gyrus and the right superior temporal gyrus exhibited a negative correlation with tinnitus handicap inventory scores(r=-0.627,P=0.003)and visual analogue scale scores(r=-0.596,P=0.005).Conclusion There are abnormal brain function changes in medial prefrontal cortex and dorsolateral prefrontal cortex in patients with chronic subjec-tive tinnitus,accompanied by changes in the intensity of functional connections with the salience and auditory net-works.These abnormalities are highly related to the severity of tinnitus.The prefrontal cortex may play an impor-tant role in the sensory prediction and auditory regulation of tinnitus.

Objective To explore the characteristics of acupoint selection and the law of acupoint compatibility in the treatment of Guillain-Barré syndrome(GBS)based on data mining.Methods Literature on acupuncture treatment of GBS was searched and screened from China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP,SioMed,PubMed,Embase,Web of Science,and Cochrane Library from the establishment of the database to December 1,2024 and to build database.The author information and acupuncture prescriptions were modified and imported according to the data entry requirements of the Traditional Chinese medicine inheritance computing platform V3.5,the relevant data were analyzed and integrated through the"Acupoint Analysis"module of the platform.Results A total of 140 related papers,145 valid prescriptions,involving 237 acupoints.The acupoints with higher frequency were Zusanli,Hegu,Quchi,Yanglingquan and etc.The analysis yielded 42 core acupoints,22 sets of strong association rules for core acupoints,and 5 new core acupuncture prescriptions.Conclusion Acupuncture treatment for GBS follows the principle of"treating impotence by taking Yangming alone",takes"benefiting Qi and draining heat,supporting the correctness and opening up the collaterals"as the main method,and attaches importance to"regulating the spirit and connecting the internal organs".

Asthe standard for drafting standards,the Rules for Compiling National Standards for Pharmaceutical Excipients was first issued in the 2020 edition and then revised and re-issued in 2025.It has become an important technical specification for the pharmaceutical excipients standards in the Chinese Pharmacopoeia and for the phar-maceutical excipients standards formulated by pharmaceutical companies for associated review and approval.This article focuses on introducing the working background,main framework and main characteristics of the Rules for Compiling National Standards for Pharmaceutical Excipients,aiming to help the drafters,reviewers and implement-ers of pharmaceutical excipients standards better understand and master them,so as to further improve the standard-ization of writing pharmaceutical excipients standards and enhance the level of standards formulation and revision of pharmaceutical excipients.