ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

Objective:To analyze the application effects and safety of continuous negative pressure drainage devices in postoperative drainage of congenital microtia reconstruction of auricle.Methods:A retrospective study was conducted, including 1 211 patients with congenital microtia treated at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2018 to August 2021. All patients underwent auricular reconstruction surgery and were divided into two groups based on the type of negative pressure drainage device used. The study group consisted of 624 patients [315 males and 309 females, aged 6-24 (15.1±2.2) years], while the control group consisted of 587 patients [286 males and 301 females, aged 5-23 (14.7±2.3) years]. The study group used a novel negative pressure drainage ball, while the control group used a conventional negative pressure syringe for drainage. The preoperative and postoperative 1, 7 days scores of the modified Yale preoperative anxiety scale (mYPAS) and the quality of life scores postoperative 3 days (including functional activity, self-image, psychological health, satisfaction and pain) were compared between the two groups. All patients were followed up at 4, 8, 12, and 16 weeks postoperatively to compare the surgical scar area between the two groups. The incidence of adverse reactions within 12 weeks after surgery in two groups were recorded.Results:There was no significant difference in preoperative mYPAS scores between the two groups ( P=0.897). The mYPAS scores at 1 and 7 days after surgery were lower than the preoperative scores in both groups (all P<0.05), and the study group had significantly lower mYPAS scores at all time points than those of the control group (all P<0.001). The study group had higher scores in functional activity, self-image, psychological health, and satisfaction than those of the control group (all P<0.001), and a lower pain score than that of the control group ( P<0.001). Follow-up at 4, 8, 12, and 16 weeks showed that the surgical scar area was significantly smaller in the study group at all time points than in the control group (all P<0.001). The incidence of adverse reactions within 12 weeks after surgery was 9.0% (56/624) in the study group, which was lower than the 19.4% (114/587) in the control group ( P<0.001). Conclusion:The use of continuous negative pressure drainage devices in congenital microtia reconstruction of auricle is more effective and can reduce the incidence of postoperative adverse reactions.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective:To explore the relationship between depression, perfectionism and self-injurious function in adolescents with self-injury.Methods:A total of 6 149 adolescents from two middle schools were selected by multi-stage random sampling method to conduct a cross-sectional investigation, and 530 cases with self-injurious behaviors were screened out as the self-injury group, while the remaining 5 619 students served as the non-self-injury group.The self-rating depression scale, the Chinese-revised Frost multidimensional perfectionism scale, and the Ottawa self-injury inventory Chinese revised version were used for investigation.SPSS 24.0 software was used for descriptive statistics and Spearman correlation analysis, and the PROCESS 4.1 macro program was used for mediating effect test(model 4)and moderating effect test(model 7).Results:(1)The incidence of self-injury among adolescents was 8.62%(530/6 149), which was significantly different in gender( χ2=50.942, P<0.01) and grade( χ2=37.401, P<0.01). (2)The scores of depression(48(41, 55)) and maladaptive perfectionism(64(53, 76)) in the self-injury group were higher than those in the non-self-injury group(36(29, 43), 49(35, 61)), and the differences were statistically significant( Z=-23.233, -18.599, both P<0.01). (3)Adolescents with self-injury mostly had external emotion regulation(70.38%(373/530)) as the dominant function.(4)The results of Spearman correlation analysis showed that self-injurious function was significantly and positively correlated with depression( r=0.382, P<0.01) and maladaptive perfectionism( r=0.356, P<0.01), and depression was significantly and positively correlated with maladaptive perfectionism( r=0.352, P<0.01). (5)Maladaptive perfectionism partially mediated the relationship between depression and self-injurious function( β=0.086, P<0.001), and the mediating effect accounted for 21.88%(0.086/0.393)of the total effect.(6)Gender moderated the first stage of the mediation pathway(depression→maladaptive perfectionism)( β=0.180, P<0.05), which indicated that depression had a stronger predictive effect on maladaptive perfectionism in women( βsimple=0.105, 95% CI=0.063-0.154, P<0.05). Conclusion:In the prediction of depression on self-injurious function, maladaptive perfectionism plays a partial mediating role, and this mediating effect is moderated by gender.

Objective:To explore immunoregulatory function of long non-coding RNA Gm26688 on macrophages RAW264.7,macrophages stimulated by LPS were treated with Chinese giant salamander(CGS)collagen peptides to explore role of Gm26688 in mechanism of CGS collagen peptides in regulating inflammatory reflection.Methods:Gm26688 sequence was cloned by RT-PCR,Gm26688 localization in macrophage was analyzed by RNA-FISH;qRT-PCR was performed to detect expressions of Gm26688 and inflammatory factors after LPS and CGS bone collagen peptides treatment;expression of Gm26688 was silenced by small interfering RNA(siRNA),and qRT-PCR was used to detect effects of LPS and CGS bone collagen peptides on expression of inflammatory factors after Gm26688 interference;Western blot was used to detect protein expression of NF-κB p65 and its phosphorylation level.Results:LPS significantly promoted expression of Gm26688.RT-PCR amplified Gm26688 sequence,and RNA-FISH showed that Gm26688 was mainly expressed in nucleus.CGS bone collagen peptides inhibited expression of Gm26688 induced by LPS,and<3 kD CGS bone collagen peptides had the most significant inhibitory effect on Gm26688.CGS bone collagen peptides(<3 kD)significantly inhibited LPS-induced expressions of inflammatory factors IL-6,TNF-α and IL-1β.Interference of Gm26688 significantly down-regulated expressions of inflammatory factors IL-6 and TNF-α in LPS or LPS+CGS bone collagen peptides-stimulated RAW264.7 cells.Western blot results showed that CGS bone collagen peptides down-regulated level of NF-κB p65 phosphorylation through Gm26688.Conclu-sion:CGS bone collagen peptides inhibit LPS-induced inflammation in RAW264.7 cells via Gm26688/NF-κB pathway.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Myelodysplastic syndrome (MDS) is a heterogeneous clonal myeloid malignancy with a variable prognosis. Some myeloid-related gene alterations have been found to be associated with the diagnosis and prognosis of MDS. As a result, multiple myeloid-related gene mutations have been added to International Working Group for Prognosis in MDS (IWG-PM) and other MDS prognosis evaluation systems as diagnostic and prognostic indications. Further research using the variable allele frequency (VAF) detection technique demonstrated that myeloid-related genes evolve dynamically during the course of MDS with some regularity. Furthermore, significant relevance have been found between the VAF evolution of particular myeloid-related genes and MDS subtypes, risk classification, and prognosis. This article provides an overview of the application of VAF of myeloid-related gene mutations in MDS research, highlighting the critical role of gene mutation VAF in MDS subtype categorization, risk stratification, and therapy response assessment.