ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Diabetic retinal neurodegeneration is a serious complication of diabetes mellitus, manifested by apoptosis and gliosis, and its pathogenesis is closely related to the oxidative stress induced by high glucose levels. The increase in blood glucose in the body leads to excessive production of reactive oxygen species and the downregulation of antioxidant defense signaling pathways, which leads to oxidative stress in the body, which in turn induces apoptosis, mitochondrial damage and autophagy, resulting in diabetic retinal neurodegeneration. Antioxidant stress therapy with gene therapy, flavonoids, recombinant Ad-β-catenin carriers, and autophagy inducers to exert neuroprotective effects. In the future, more clinical trials are needed to explore the effective dosage and side effects of drugs, and to develop new drugs and treatment strategies for oxidative stress to prevent and treat diabetic retinal neurodegeneration and protect retinal nerve function.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Cordyceps sinensis(C.sinensis)is a widely used and highly valuable traditional Chinese medicine.Several dipeptides have been detected in C.sinensis,but current scientific knowledge of its chemical makeup remains limited.In this study,an improved approach that integrates offline two-dimensional liquid chromatography(2D LC)separation,precursor ion list,library screening,and diagnostic ion filtering was established to systematically screen and characterize dipeptides in C.sinensis.Offline 2D LC integrating hydrophilic interaction LC and reverse phase separations was established to eliminate interference and identify the target dipeptides.A library containing the potential 400 dipeptides was created,and a precursor ion list with all theoretical precursor ions was adopted to trigger the MS/MS scan with high sensitivity.To identify dipeptides,the type and connection sequence of amino acids were determined according to the product ions.Ile and Leu residues were differentiated for the first time according to the characteristic ion at m/z 69.07.Ultimately,170 dipeptides were identified or tentatively characterized from C.sinensis,and most are reported for the first time in this species herein.In addition,the identified dipeptides were also applied for discrimination among the three Cordyceps species,and 11 markers were identified.The obtained results provide a deeper understanding of the chemical basis of C.sinensis.

Objective:To explore the feasibility and efficacy of subpatellar artery balloon molding in the treatment of diabetic foot ulcer caused by arterial ischemia.Methods:The clinical data of patients with diabetic foot ulcer caused by subpatellar artery disease treated in Xuanwu Hospital of Capital Medical University from December 2020 to April 2022 were retrospectively analyzed. Among them, 29 patients received medical balloon dilatation (drug balloon group) and 30 patients received balloon dilatation alone (simple balloon group). The improvement of lower limb ischemia at 3 and 6 months after surgery was analyzed in the two groups. The observation indicators included case-fatality rate, limb preservation rate, ulcer healing, Rutherford grading and pain score.Results:There was no significant difference in preoperative Rutherford grading between the two groups ( P>0.05). Three and six months after operation, the Rutherford grading in both groups was significantly improved compared with that before surgery (all P<0.05), and there was no statistical significance between the two groups ( P>0.05). There was no significant difference in preoperative pain scores between the two groups ( P>0.05). The pain scores of both groups were significantly decreased 3 and 6 months after surgery ( P<0.05), and there was no statistical significance between the two groups ( P>0.05). Three and six months after surgery, the wound ulcer healing rate in the drug balloon group was higher than that in the simple balloon group [51.7%(15/29) vs 43.3%(13/30), P=0.519; 86.2%(25/29) vs 50.0%(15/30), P=0.002]. There was no death or amputation in the two groups 3 and 6 months after surgery. Conclusions:Balloon dilatation can improve severe limb ischemia of diabetic foot. Compared with balloon dilatation alone, drug balloon dilatation is more beneficial to the healing of ulcer wounds in diabetic limb ischemia patients.

Objective To compare the epidemiological characteristics of adult single fractures of the cuneiform between the east and west areas in China from 2010 through 2011.Methods Thirty-five hospitals in the east coast area (group A) and 28 hospitals in the west inland area (group B) were selected for this investigation. The data of adult single fracture of the cuneiform treated between January 2010 and De-cember 2011 at the 63 hospitals were collected through the PACS system and medical records inquiry system. The epidemiological characteristics concerning age, gender and fracture classification were compared between the 2 groups. Results A total of 457 adult single fractures of the cuneiform were collected, involving 384 cases in group A and 73 cases in group B. They accounted respectively for 4.38% (384/8,772) and 3.53% (73/2, 068) of the adult tarsal bone fractures in the same period, showing no significant difference (P >0.05), accounted respectively for 1.71% (384/22, 455) and 1.15% (73/6, 354) of the adult foot frac-tures, showing a significant difference (P <0.05), and accounted respectively for 0.20% (384/192,991) and 0.09% (73/81, 143) of all the adult fractures, showing a significant difference (P <0.05). The median age was 39 years in group A (29, 50) and 36 years in group B (25, 45), showing a significant difference (P <0.05). The male to female ratio was 1.61:1 (237/147) for group A and 1.52:1 (44/29) for group B. The peak age range of the fracture for males was from 21 to 30 years old in both groups, and its proportion was 28.69% (68/237) in group A and 38.64% (17/44) in group B. The peak age range of the fracture for females was from 41 to 50 years old in both groups, and its proportion was 26.53% (39/147)in group A and 27.59% (8/29) in group B. All the above comparisons were statistically insignificant (P> 0.05). The proportion of the age group of≥61 years was significantly larger in group A than in group B (P <0.05). The high risk type of the fracture was type 85-A1 in both groups, and its proportion was 61.98% (238/384) in group A and 52.05% (38/73) in group B. The proportion of type 85-B1 was significantly larger in group B than in group A (P <0.05). Conclusions Adult single fractures of the cuneiform were more common in young and male patients. The proportion of elderly patients (≥61 years old) was significantly larger in the east area. The high risk type of the fracture was simple fracture involving the medial cuneiform bone (type 85-A) in both areas. The proportion of the comminuted fracture of the medial cuneiform (type 85-B1) was significantly larger in the west area.

Objective To analyze the epidemiological features of Galeazzi fractures from 2003 through 2012 in The Third Affiliated Hospital to Hebei Medical University. Methods We retrospectively analyzed the data of Galeazzi fractures between January 2003 and December 2012 in the Third Affiliated Hospital to Hebei Medical University. The data from 2003 through 2008 were defined as group A and those from 2008 through 2012 as group B. The general information was compared between the 2 groups. The epi-demiological characteristics and trends during the 10 years were analyzed concerning gender, age and fracture type of the patients. Results A total of 153 Galeazzi fractures were recorded, accounting for 0. 81％ of ulnoradial fractures and 0. 12％ of all fractures. There were 109 males and 44 females, with a male/female ratio of 2. 48:1. The age range from 11 to 20 years had the highest constituent ratio ( 22. 22％) and type Ⅱthe highest proportion ( 76. 47％) . There were 74 cases in group A, with a male/female ratio of 2. 22:1. There were 79 cases in group B, with a male/female ratio of 2. 76:1. There was no significant difference between the 2 groups concerning the male/female ratio ( P > 0. 05 ) . The median age for group A was 29 years, significantly younger than that for group B ( 34 years ) ( P <0. 05 ) . The high risk age was from 11 to 20 years in group A (32. 43％) and from 21 to 50 years (22. 78％) in group B. Compared with group A, the constituent ratio of age range from 11 to 20 years in group B was significantly lower and the constituent ratio of age range from 41 to 50 years significantly higher ( P <0. 05 ) . There were no significantly differences between the 2 groups concerning the constituent ratio of each fracture type ( P> 0. 05 ) . Conclusions Galeazzi fractures accounted for 0. 81％ of ulnoradial fractures and 0. 12％ of all fractures. There were more male patients than female ones. The age range from 11 to 20 years and typeⅡhad the highest constituent ratios. Compared with the first 5 years, the latter 5 years witnessed increased mean age.

Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1⁺ acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1⁺ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test. Results: Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1⁺ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome. Conclusion The clone evolution was detected in pediatric ETV6-RUNX1⁺ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

OBJECTIVETo evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.

METHODTotally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.

RESULTAmong the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).

CONCLUSIONThe CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.

Adolescent ; Child ; Core Binding Factor Alpha 2 Subunit ; DNA Copy Number Variations ; Disease-Free Survival ; Humans ; Multiplex Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Proto-Oncogene Proteins c-ets ; Repressor Proteins ; Survival Rate