ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

This study aimed to investigate the underlying mechanisms of Duhuo Jisheng Decoction(DJD) in the prevention and treatment of knee osteoarthritis(KOA). Forty SPF New Zealand rabbits were randomly divided using SPSS 26.0 software into five groups: blank group, model group, low-dose DJD group, high-dose DJD group, and high-dose DJD+phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway activator group(high-dose DJD+740Y-P group), with eight rabbits in each group. Except for the blank group, the KOA model was established in the other groups using papain injection into the knee joint cavity combined with forced flexion of the knee joint. The day after modeling, the blank group and model group were given normal saline at 10 mL·kg~(-1) by gavage, the low-dose DJD group received DJD at 8.8 g·kg~(-1) by gavage, the high-dose DJD group received DJD at 35.2 g·kg~(-1) by gavage, and the high-dose DJD+740Y-P group received DJD at 35.2 g·kg~(-1) by gavage along with 740Y-P at 0.15 μmoL·kg~(-1) injected via the auricular vein. All groups received treatment continuously for four weeks. After modeling and intervention, behavioral observations were performed for all groups, and after the intervention, imaging assessments of the knee joints were conducted. Cartilage from the knee joints was collected, and gross morphological changes were observed. Pathological changes in cartilage tissue were examined using hematoxylin-eosin(HE) staining. The results of these observations were quantitatively evaluated using the Lequesne MG score, Kellgren-Lawrence(K-L) grading, Pelletier score, and Mankin score. ELISA was used to measure the levels of interleukin-1β(IL-1β), interleukin-18(IL-18), and matrix metalloproteinase 13(MMP13) in cartilage tissue. Real-time RT-PCR was used to detect the mRNA expression levels of PI3K, Akt, mTOR, Nod-like receptor protein 3(NLRP3), cysteine protease 1(caspase-1), and gasdermin D(GSDMD) in cartilage tissue. Western blot was employed to measure the protein expression levels of PI3K, Akt, mTOR, NLRP3, caspase-1, and GSDMD. The results showed that compared with the blank group, the model group exhibited significant knee joint degeneration, increased Lequesne MG score, K-L grading, Pelletier score, and Mankin score, elevated levels of IL-1β, IL-18, and MMP13 in cartilage tissue, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression levels, and elevated protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. Compared with the model group, these indicators were reversed in both the low-dose and high-dose DJD groups, with the high-dose group showing greater decline degree than the low-dose DJD group. However, compared with the high-dose DJD group, the improvements in knee joint degeneration were less pronounced in the high-dose DJD+740Y-P group, with increased Lequesne MG score, K-L grading, Pelletier score, Mankin score, elevated levels of IL-1β, IL-18, and MMP13, activation of PI3K, Akt, and mTOR phosphorylation along with increased mRNA expression, and increased protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD. In conclusion, DJD is effective and safe in the treatment of KOA, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway-mediated pyroptosis in cartilage tissue, thereby improving knee joint bone structure, reducing the inflammatory response, and preventing cartilage matrix degradation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rabbits ; TOR Serine-Threonine Kinases/genetics* ; Osteoarthritis, Knee/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Signal Transduction/drug effects* ; Male ; Disease Models, Animal ; Pyroptosis/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Humans ; Female

Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Nerve Regeneration/physiology* ; Mitochondria/metabolism* ; Zebrafish Proteins/genetics* ; Axons/metabolism* ; Signal Transduction/physiology* ; Axonal Transport/physiology* ; Nerve Tissue Proteins/genetics*

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.

Objective:To summarize and analyze the diagnostic and therapeutic characteristics of asymptomatic primary hyperparathyroidism (aPHPT).Methods:A retrospective analysis was conducted on the clinical data of 103 patients with aPHPT admitted to the Chinese PLA General Hospital from January 2012 to September 2023. The clinical characteristics, treatment modes, and prognoses of the patients were analyzed. GraphPad Prism 8.0 software was used for statistical analysis.Results:Among the 103 cases, there were 37 males and 66 females, aged from 25 to 78 years, with an average age of (53.81±11.34) years. Ninety-eight cases (95.15%) visited due to abnormal findings during physical examination and 5 cases (4.85%) due to hypertension, diabetes or other diseases. All patients underwent minimally invasive parathyroidectomy with small incision, with 96 cases (93.20%) pathologically diagnosed as adenomas and 7 cases as hyperplasia (6.80%). Postoperative mean serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels were respectively significantly lower than preoperative levels, while postoperative serum phosphorus level was significantly higher than preoperative level ( P<0.05). The mean lesion volume was (3.32±6.72)cm 3 (range 0.05-49.50 cm 3). Patients with different lesion volumes had significant differences in preoperative serum calcium, PTH and ALP levels. Lesion volume was positively correlated to preoperative serum calcium(ρ=0.36, P<0.01), PTH(ρ=0.50, P<0.01) and ALP(ρ=0.39, P<0.01). Among 103 patients, 94 cases were followed up (91.26%), 9 cases were lost (8.74%), and the mean follow-up period was (60.15±29.23) months. The followed-up patients were alive and had no recurrence of lesions or complications, and their blood calcium levels were normal. Conclusion:aPHPT can be preliminarily diagnosed through blood biochemistry and imaging examination, and minimally invasive surgery can offer good prognosis without serious complications.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective:To investigate the effect of different isoforms of RBBP6 on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor SRSF1. Methods:RT-PCR was used to detect the expression levels of RBBP6 mRNA splicing isoforms regulated by SRSF1. The GEO database was used to analyze the changes of RBBP6 isoform 1 in the progression of plasma cell disease,and survival analysis was used to evaluate the value of this gene in the prognosis of MM patients. In vitro loss-of-function and gain-of-function experiments were conducted by transfecting control siRNA,RBBP6 isoform 1 siRNA,empty vector (EV),OE-RBBP6 isoform 3 into MM.1S cells,then the expression levels of RBBP6 isoform 1 and RBBP6 isoform 3 were detected by real-time PCR and Western blot. CCK-8 assay was performed to detect the cell proliferation ability. Results:Knockdown of SRSF1 increased the expression of RBBP6 isoform 3 and decreased the expression of RBBP6 isoform 1. RBBP6 isoform 1 was closely related to the progression of plasma cell disease,and the high expression of RBBP6 isoform 1 was associated with poor prognosis in patients with MM. Downregulation of RBBP6 isoform 1 expression and overexpression of RBBP6 isoform 3 both reduced the proliferation ability of MM cells. And after downregulating the expression of RBBP6 isoform 1,the level of p53 protein in MM cells was significantly increased (P<0.05). Conclusion:In MM,splicing factor SRSF1 can cause alternative splicing abnormalities in RBBP6. The RBBP6 isoform 1 promotes MM cell proliferation,while the RBBP6 isoform 3 inhibits MM cell proliferation,and the mechanism may be related to regulating the p53 pathway.

Objective To explore the acupoint selection rules of acupuncture treatment for cerebellar ataxia using data mining techniques.Methods Taking the related literature of acupuncture treatment of cerebellar ataxia as the retrieval content,the computer retrieval of China National Knowledge Internet(CNKI),China Biomedical Literature Database(SinoMed),Wanfang Data Knowledge Service Platform(Wanfang),China Science and Technology Journal Database(VIP),American Biomedical Information Retrieval System(PubMed)and other major databases.The eligible acupoints in the literature were entered into the Microsoft Excel 2021 software table to establish a database of acupoints frequency,meridian tropism,specific acupoints,distribution sites and other information for acupuncture treatment of cerebellar ataxia.SPSS Modeler 18.0 Apriori algorithm,SPSS Statistics 25.0 and SPSS Modeler 18.0 Web complex network were used to analyze the association rules of the included prescription acupoints,Ward cluster analysis and draw the tree diagram and the Web network diagram of high-frequency acupoints and core prescriptions.Results(1)A total of 93 articles were included,including 117 acupuncture prescriptions and 172 acupoints,with a total frequency of 1 199 times of acupoints.(2)The top 10 acupoints were Fengchi(GB20),Zusanli(ST36),Hegu(LI4),Baihui(DU20),Sanyinjiao(SP6),Taichong(LR3),Quchi(LI11),Yanglingquan(GB34),Wangu(GB12),and Tianzhu(BL10).(3)The top five meridians used frequently were gallbladder meridian of foot shaoyang,governor vessel(GV),stomach meridian of foot yangming,large intestine meridian of hand yangming and bladder meridian of foot taiyang.(4)The selection of acupoints is mainly based on the head,face,neck and lower limbs.(5)The highest frequency of the use of specific points is the intersection point.(6)The high-frequency acupoints for acupuncture treatment of cerebellar ataxia are Fengchi-Wangu,Fengchi-Tianzhu and Fengchi-Tianzhu-Wangu.The top 31 high-frequency acupoints(frequency＞10 times)can be divided into nine effective clusters.Conclusion Acupuncture treatment for cerebellar ataxia has formed a compatibility rule with the main principle of"regulating the mind and constraining the bones,extinguishing wind and stopping the movement",with the far and near acupoints as the main body,and attaches importance to the application of yang meridians with multiple qi and blood,presenting the basic acupoint prescription with Fengchi-Wanggu-Tianzhu as the core.

Objective To investigate the dosimetric difference between volume modulated arc therapy(VMAT)and dynamic multi-leaf collimator intensity modulated radiation therapy(dMLC-IMRT)after breast-conserving surgery for left-sided breast cancer so as to optimize the treatment plan for the patient.Methods The clinical data of 15 patients admitted to the radiothe-rapy department of some hospital after breast-conserving surgery for left-sided breast cancer were selected retrospectively.Three groups of plans were designed for each patient,including continue volume modulated arc therapy(cVMAT),tangent volume modulated arc therapy(tVMAT)and dMLC-IMRT plans,and then compared in terms of the dosimetric parameters of the tumor target areas and organs at risk.SPSS 25.0 software was used for statistical analysis.Results The three groups had the dose distribution of the tumor target areas meet clinical requirements,which had significant differences between the values of D2,Dmean,conformity index(CI)and homogeneity index(HI),while the difference between the numbers of monitor units were not statistically significant.The dMLC-IMRT group had higher D2 value while lowerDmeanthan the cVMAT and tVMAT groups;for CI the cVMAT behaved the best in the three groups,followed by the tVMAT group.In the low-dose region,the cVMAT and tVMAT groups had larger illuminated volumes of the affected lung than the dMLC-IMRT group;the tVMAT group had the smallest illuminated volume of heart in the three groups,and the cVMAT group had the illuminated volume of heart slightly higher than that of the dMLC-IMRT group.In the high-dose region,the cVMAT and tVMAT groups had smaller illuminated volumes of the affected lung than the dMLC-IMRT group,and the illuminated volume of the affected lung of the tVMAT group was larger than that of the cVAMT group;the dMLC-IMAT group had the largest illuminated volume of heart in the three groups,and the differences between the tVMAT and cVMAT groups were not statistically significant.Conclusion In the design of intensity-modulated radiotherapy plans after breast-conserving surgery for left-sided breast cancer,VMAT behaves better than dMLC-IMRT in conformability to the tumor target area and protection of heart and lung at risk.[Chinese Medical Equipment Journal,2023,44(9):59-63]