ObjectiveTo explore the potential mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of regulating mitochondrial autophagy via the PTEN-induced kinase 1 （PINK1）/E3 ubiquitin ligase （Parkin） pathway. MethodsMale SD rats were subjected to abdominal aortic constriction to establish the CHF model. Twenty-four successfully modeled rats were randomly divided into the model group， sacubitril/valsartan group， and low- and high-dose Shenqi Jianxin Formula groups， with 6 rats in each group. Six other rats were set as the sham surgery group， which were only separated the abdominal aorta and then closed the abdomen. Rats in the low-dose and high-dose Shenqi Jianxin Formula groups were given intragastric administration of Shenqi Jianxin Formula suspension at doses of 4.41 g/（kg·d） and 17.64 g/（kg·d）， respectively； the sacubitril/valsartan group received intragastric administration of sacubitril/valsartan sodium tablet suspension at 10 mg/（kg·d）； the sham surgery group and the model group were given normal saline at 10 ml/（kg·d） via intragastric gavage. The intervention lasted for 4 consecutive weeks. Cardiac function indices including left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were detected， and serum brain natriuretic peptide （BNP） content was measured. HE staining and Masson staining were used to observe myocardial histopathological changes. Transmission electron microscopy was employed to examine the ultrastructure of cardiac tissues. Quantitative real-time polymerase chain reaction （Rt-qPCR） was performed to determine the mRNA expressions of PINK1/Parkin pathway-related factors and autophagy-associated proteins including Beclin-1， p62， and microtubule-associated protein 1 light chain 3 （LC3） in myocardial tissues. ResultsCompared with the sham surgery group， the model group showed significant decreases in LVEF and LVFS levels， an increase in serum BNP content， down-regulated mRNA and protein expressions of PINK1， Parkin and Beclin-1 in cardiac tissues， up-regulated mRNA and protein expressions of p62， as well as significant reductions in LC3B mRNA expression， phosphorylated PTEN-induced kinase 1 （p-PINK1） and phosphorylated E3 ubiquitin ligase （p-Parkin） protein levels， and the ratio of microtubule-associated protein 1 light chain 3-Ⅱ to microtubule-associated protein 1 light chain 3-Ⅰ （LC3Ⅱ/LC3Ⅰ） （P＜0.05）. Pathological results revealed obvious myocardial cell edema， necrosis and degeneration， increased disorder of myocardial fiber arrangement， extensive inflammatory cell infiltration， moderate to severe mitochondrial swelling， a few mitochondrial vacuolar changes， and no obvious autophagy in the field of vision in the model group. Compared with the model group， all the above indicators were significantly improved in the high-dose Shenqi Jianxin Formula group and the sacubitril/valsartan group （P＜0.05）. Moreover， the improvement of each index in the high-dose Shenqi Jianxin Formula group was superior to that in the low-dose group （P＜0.05）. In the high-dose Shenqi Jianxin Formula group， myocardial myofibrils were arranged regularly with orderly orientation， the striated structure was clear， and necrotic cells significantly reduced. ConclusionShenqi Jianxin Formula can activate the PINK1/Parkin signaling pathway in myocardial tissues， enhance mitochondrial autophagy， and clear dysfunctional mitochondria， thereby improving cardiac function and delaying the progression of CHF.

ObjectiveTo evaluate the clinical efficacy and safety of Xiaozhen Formula （消疹方） in preventing skin toxicity induced by epidermal growth factor receptor inhibitors （EGFRIs） in patients with EGFR-mutant non-small cell lung cancer （NSCLC）. MethodsA randomized， double-blind， placebo-controlled， multicenter clinical study was conducted. A total of 120 patients with EGFR-mutant NSCLC from seven centers were enrolled and randomly assigned to a treatment group （60 cases） or a control group （60 cases）. On the basis of EGFRI-targeted therapy， patients in the treatment group received Xiaozhen Formula granules， whereas those in the control group received Xiaozhen Formula placebo granules， both at 10 g twice daily for 4 consecutive weeks. The primary outcomes were the grading of skin toxicity evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events （NCI-CTCAE） version 5.0 and the incidence of rash. Secondary outcomes included the time to onset and time to resolution of the highest-grade rash， the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 （EORTC QLQ-C30） scores， the Hospital Anxiety and Depression Scale （HADS） scores， and disease control rate， together with safety assessments. ResultsBased on the full analysis set （FAS）， the incidence of skin toxicity in the treatment group was 18.33% （11/60）， significantly lower than 45.00% （27/60） in the control group （P＜0.01）， with the highest severity of skin toxicity in both groups was grade 2. Among patients who developed rash， the resolution rate in the treatment group was 90.91% （10/11）， higher than that 33.33% （9/27） in the control group. The median time to resolution was 15 days （95%CI： 8-17 days） in the treatment group and it was not reached in the control group； the distribution of time to resolution differed significantly between groups （P＜0.001）. After treatment， the treatment group had higher EORTC QLQ-C30 functional scale and global health status/quality-of-life scores， and lower symptom scale， single-item scores， as well as HADS-A， and HADS-D scores than the control group （P＜0.05）. In the FAS analysis， the disease control rate （DCR） was 85.0% （51/60） in the treatment group， lower than 100.0% （60/60） in the control group （P=0.003）， whereas no significant between-group difference was observed in the per-protocol set （PPS） analysis （P=0.464）. The incidence of adverse events did not differ significantly between the two groups （P＞0.05）， and no definite safety signals related to the investigational drug were observed. ConclusionXiaozhen Formula can reduce the incidence of EGFRI-induced skin toxicity， and improve the outcome of rash regression， the patients' quality of life and psychological status in EGFR-mutant NSCLC patients.

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

Objective This study aims to achieve high-yield functional expression of the human voltage-gated potassium channel K_V3.1 using an Escherichia coli cell-free protein synthesis system, thereby providing a novel synthetic approach for drug screening, structural analysis and functional characterization of K_V3.1. Methods K_V3.1 was expressed in an Escherichia coli cell-free protein synthesis system for 10 hours in the presence of peptide surfactant A₆K. The secondary structure of K_V3.1 was analyzed by circular dichroism spectroscopy. The potassium channel activity of the recombinant protein liposome K_V3.1-A₆K was investigated using fluorescent dyes Oxonol VI as indicators, which are capable of reflecting alterations in membrane potential. Results Soluble K_V3.1 protein was successfully synthesized, achieving a purified yield of up to 1.2 mg/mL via an Escherichia coli cell-free protein synthesis system. Circular dichroism spectroscopy revealed that K_V3.1 exhibited characteristic α-helical secondary structures. Membrane potential fluorescence assays demonstrated that the K_V3.1-A₆K proteoliposomes, which were reconstructed with surfactant peptide A₆K, exhibited remarkable potassium ion permeability. Conclusion This study successfully achieved high-yield expression of human K_V3.1 with activity using an Escherichia coli-based cell-free protein synthesis system. This innovative method not only significantly enhances the expression yield of K_V3.1, but also maintains its functional activity, thereby establishing a novel and efficient synthetic platform for drug screening and advancing our understanding of structure-function relationships in K_V3.1 research.
Humans ; Escherichia coli/metabolism* ; Shaw Potassium Channels/biosynthesis* ; Cell-Free System ; Circular Dichroism ; Protein Biosynthesis ; Recombinant Proteins/metabolism* ; Membrane Potentials ; Shab Potassium Channels

Objective In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.

Objective To investigate the value of quantitative parameters of diffusion weighted imaging(DWI)based on mono-expo-nential model(MEM),diffusion kurtosis imaging(DKI)model,and stretched-exponential model(SEM)in predicting the efficacy of neoadjuvant therapy in locally advanced gastric cancer(LAGC).Methods Forty LAGC patients who underwent MRI examinations before neoadjuvant therapy and before radical surgery were prospectively enrolled.A radiologist delineated lesions on DWI images and acquired quantitative parameters before and after treatment,including lesion volume,apparent diffusion coefficient(ADC)of MEM,mean diffusivity(MD)and mean kurtosis(MK)of DKI model,distribution diffusion coefficient(DDC),and α of SEM.According to pathological tumor regression grade(TRG),the patients were stratified into good response group(TRG 0-1)and poor response group(TRG 2-3).The pre-treatment parameters and Δ of pre-and post-treatment parameters were compared between the two groups with Mann-Whitney U test;multivariate analysis was performed with binary logistic regression.Multiple DWI models and the combined model were established,and the prediction efficiency of each model was calculated.Results There was no significant differ-ence in each parameter before neoadjuvant therapy between the two groups(P>0.05).The delta of volume,ΔADC,ΔMD,and ΔDDC pre-and post-treatment were all statistically different between the two groups(P<0.05).The area under the curve(AUC)of ΔADC,ΔMD,and ΔDDC in predicting good response for LAGC were 0.900,0.806,and 0.762,respectively.The AUC of the combined model was 0.946.Conclusion Quantitative parameters of MEM,DKI model,and SEM can help predict the efficacy of neoadju-vant-treated LAGC patients.

Objective To observe the value of self-made improved cone-beam CT(CBCT)fixation components for maxillofacial scanning.Methods CBCT fixation components(chin rest,temporal clamp)equipped by Planmeca ProMax 3D Mid dental panoramic X-ray system were modified to obtain improved CBCT fixation components,including improved chin rest,temporal clamp and occipital retention band.Totally 571 patients who underwent maxillofacial CBCT examinations for dental-related diseases were retrospectively enrolled,including 288 cases(group A)underwent scanning by a junior technician using original chin rest+original temporal clamp(component 1,n=78,A1 subgroup),modified chin rest+original temporal clamp(component 2,n=74,A2 subgroup),original chin rest+original temporal clamp+occipital retention band(component 3,n=68,A3 subgroup)or modified chin rest+original temporal clamp+occipital retention band(component 4,n=68,A4 subgroup),while the rest 283 cases(group B)underwent scanning by a senior using the above components,respectively,and were taken as B1(n=72),B2(n=69),B3(n=73)and B4(n=69)subgroups.The incidence of motion artifacts were compared among A2/B2,A3/B3,A4/B4 subgroups and A1/B1 subgroups.Results Compared with A1+B1 subgroups,the overall motion artifacts rate in A4+B4 subgroups decreased from 17.33％(26/150)to 8.03％(11/137)(P=0.019),while in A2+B2 subgroups(13.29％[19/143])and A3+B3 subgroups(9.93％[14/141])did not significantly decrease(P=0.337,0.067).In group A,no statistical difference of motion artifacts rate was found between A 2(17.57％[13/74])or A3(13.24％[9/68])subgroups and A1 subgroup(23.08％[18/78])(P=0.399,0.127),while the motion artifacts rate in A4 subgroup(10.29％[7/68])was lower than that in A1 subgroup(23.08％[18/78])(P=0.041).In group B,no significant difference of motion artifacts rates was found between B2,B3 or B4 subgroups(8.70％[6/69],6.85％[5/73],5.80％[4/69])and B1 subgroup(11.11％[8/72])(P=0.632,0.369,0.258).Conclusion Self-made improved CBCT fixation components could effectively secure patients' head and reduce motion artifacts in maxillofacial CBCT.

Objective To investigate the value of quantitative parameters of diffusion weighted imaging(DWI)based on mono-expo-nential model(MEM),diffusion kurtosis imaging(DKI)model,and stretched-exponential model(SEM)in predicting the efficacy of neoadjuvant therapy in locally advanced gastric cancer(LAGC).Methods Forty LAGC patients who underwent MRI examinations before neoadjuvant therapy and before radical surgery were prospectively enrolled.A radiologist delineated lesions on DWI images and acquired quantitative parameters before and after treatment,including lesion volume,apparent diffusion coefficient(ADC)of MEM,mean diffusivity(MD)and mean kurtosis(MK)of DKI model,distribution diffusion coefficient(DDC),and α of SEM.According to pathological tumor regression grade(TRG),the patients were stratified into good response group(TRG 0-1)and poor response group(TRG 2-3).The pre-treatment parameters and Δ of pre-and post-treatment parameters were compared between the two groups with Mann-Whitney U test;multivariate analysis was performed with binary logistic regression.Multiple DWI models and the combined model were established,and the prediction efficiency of each model was calculated.Results There was no significant differ-ence in each parameter before neoadjuvant therapy between the two groups(P>0.05).The delta of volume,ΔADC,ΔMD,and ΔDDC pre-and post-treatment were all statistically different between the two groups(P<0.05).The area under the curve(AUC)of ΔADC,ΔMD,and ΔDDC in predicting good response for LAGC were 0.900,0.806,and 0.762,respectively.The AUC of the combined model was 0.946.Conclusion Quantitative parameters of MEM,DKI model,and SEM can help predict the efficacy of neoadju-vant-treated LAGC patients.