Acupotomy therapy demonstrates the definite clinical efficacy on knee osteoarthritis (KOA). After reviewing systematically the mechanism studies on acupotomy for KOA over the past 5 years, It is revealed that acupotomy synergistically intervenes in the pathological progression of KOA through multi-target approaches, such as regulating cartilage homeostasis, restoring skeletal muscle function, alleviating synovial inflammatory responses, remodeling subchondral bone, and neuromodulation. But the current research still limits to single-tissue phenotypic observation, and is insufficiency in the in-depth exploration of multi-tissue synergistic interactions and molecular upstream-downstream regulatory mechanisms. Future studies should focus on the inheritance and innovation of acupotomy theory, and integrating multi-omics analytical technologies, artificial intelligence, and novel biochemical detection methods. The mechanism research targets on the interaction mechanisms among tissues, direct effects of acupotomy, immune-inflammatory regulatory mechanisms, and analgesic mechanisms, so as to comprehensively elucidate the therapeutic mechanism of acupotomy for KOA.
Humans ; Acupuncture Therapy ; Osteoarthritis, Knee/genetics* ; Animals

Objective To explore the epidemiological and etiological characteristics of hand, foot and mouth disease(HFMD)in the surrounding areas of Shijiazhuang from 2014 to 2023, so as to provide a basis for timely detection of changes in pathogen spectrum, further optimization of treatment plans, and taking targeted prevention and control measures in advance.Methods A retrospective analysis was conducted on the clinical data of children with HFMD who visited Hebei Children's Hospital from January 1, 2014 to December 31, 2023. PCR was used to classify and identify enterovirus 71(EV71), Coxsackievirus A group 16 strain(CA16), and enterovirus undefined(EVU). Descriptive epidemiological statistics and pathogen characteristics analysis were performed on age, gender, season, and other data.Results A total of 26 563 specimens were tested, with a positive rate of 48. 95%(13 003/26 563) and a male to female ratio of 1. 50∶1(15 950 vs.10 613), there was a statistically significant difference in gender ratios between different years(χ~2= 19. 61, P < 0. 05), and the male positive detection rate was higher than that of females(50. 69% vs. 46. 34%), with a statistically significant difference(χ~2= 48. 26,P < 0. 05). The positive rate was highest in 2016(69. 84%) and lowest in 2020(10. 64%). There was a statistically significantly difference in the positive rate of enterovirus detection between different years(χ~2= 2 648. 40, P < 0. 05).Overall, EVU type was the dominant strain of infection in this region, accounting for 75. 37% of cases, followed by EV71 type(18. 42%). After 2018, EVU type has become the absolute dominant strain with a composition rate exceeding 89%. There was a statistically significant difference in the composition of enteroviruses among different years(χ~2= 2 217. 44, P < 0. 05).HFMD occurred throughout the year, with a single peak concentrated in June to August, with a statistically significant difference in the positive detection rate among different months(χ~2= 4 050. 78, P < 0. 05). The composition of enteroviruses in different months was as follows: with CA16 having a higher composition from May to July(7. 11% to 7. 96%), EV71 having a higher composition from March to May(32. 02% to 52. 16%), and EVU having a higher composition from June to December(71. 75% to 82. 96%), with a statistically significant difference(χ~2= 541. 67, P < 0. 05). Among different age groups, the highest positive detection rate(55. 53%) was in the age group of 3-6 years and the lowest rate(33. 42%) was in the age group of older than 6 years, with a statistically significant difference(χ~2= 842. 33, P < 0. 05). The composition of different enteroviruses in different age groups was as follows: with CA16 and EV71 having the highest composition in the age group of1-3 years(8. 33%, 23. 77%), and EVU having the highest composition in the age group of older than 6 years(91. 99%), also with a statistically significant difference(χ~2= 449. 69, P < 0. 05).Conclusion EVU is a common infectious pathogen in the surrounding areas of Shijiazhuang, with a high incidence in children under 3 years old from June to August. This suggests that the epidemic trend of HFMD should be closely monitored, vaccination should be strengthened, and prevention and control measures should be strengthened for key populations.

Objective To clarify the anti-inflammatory quality markers(Q-markers)of Salvia plebeia and determine their contents,so as to provide a reference for the quality control of Salvia plebeia.Methods The main components of Salvia plebeia were characterized by high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS).According to the fragmentation information of the secondary mass spectrometry and the literature data,the analysis and identification were carried out.Further,the active components with high oral bioavailability(OB)and in line with the five principles of drug-like(DL)were screened from the identified chemical components through the SwissADME platform.The SwissTargetPrediction database was used to find and predict the component targets of Salvia plebeia.Disease targets were screened through online Mendelian Inheritance in Man(OMIM),GeneCards database,etc.String11.5 database and Cytoscape3.7.2 software were used to construct the PPI network and screen core targets.Gene Ontology(GO)annotation and KEGG pathway enrichment analysis were performed using DAVID6.8,and the enriched pathways were verified by experiments to clarify their mechanism of action.Reverse traceability was used to analyze the potential pharmacodynamic material basis of key pathways,experimental verification was carried out,and high-performance liquid chromatography(HPLC)content determination method was established.Results 36 main components were identified,including flavonoids and terpenoids.Further screening of 190 active ingredients and disease intersection targets;through network topology screening,18 core targets were obtained;enrichment analysis showed that the primary pathways involved in the anti-inflammatory effect of Salvia plebeia include:NF-κB signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway.Four related components including homoplantaginin,hispidulin,luteolin and isorhamnetin were obtained by reverse traceability of the NF-κB signaling pathway.Molecular docking demonstrated excellent docking activities of the 4 components to PTGS2 with the binding energies of-9.5,-9.7,-9.4,and-9.4 kcal·mol-1,respectively.According to the measurability of quality markers,it was determined that homoplantaginin and hispidulin could be used as anti-inflammatory quality markers of Salvia plebeia.Western Blot results showed that homoplantaginin and hispidulin could significantly reduce the expression of COX-2 and NF-κB p-p65(P<0.05,P<0.01).Conclusion The anti-inflammatory quality markers of Salvia plebeia are homoplantaginin and hispidulin,which can exert anti-inflammatory effects through the NF-κB pathway.

Fragile X-associated tremor/ataxia syndrome(FXTAS)is a neurodegenerative disorder caused by a pre-mutationof the fragile X mental retardation protein 1(FMR1)gene on the X chromosome,and its low incidence rate and complex clinical manifestations often lead to misdiagnosis and missed diagnosis,which requires improving the awareness of this disease among clinicians.This article reviews the recent research advances in the pathogenesis,clinical manifesta-tions,pathological features,and diagnostic criteria of FXTAS.

Objective To identify epidemiological characteristics and pathogen distribution of hand,foot,and mouth disease(HFMD)in Hebei Children's Hospital in order to support prevention and treatment of HFMD.Methods A total of 1 698 cases throat swab samples from children diagnosed as HFMD from 2016 to 2023 were collected.Real-time PCR was used to detect the specific classification of HFMD.Statistical analysis was performed according to the year,season,age,and sex and enterovirus type of HFMD in the children.Results From 2016 to 2023,the ratio of male to female patients among the 1 698 children admitted to Hebei Children's Hospital was 1.72∶1.Among them,the highest incidence rate in summer was 778 cases,accounting for 45.8%of all cases,followed by autumn,with a total of 614 cases,accounting for 36.2%of cases.The highest incidence was recorded in age group of 1-3 years,with a total of 1 032 cases(60.8%).The lowest incidence was 38 cases in age group＞6 years old(2.2%);There were 988 cases of HFM(58.2%)caused by different strains of enterovirus undefined(EVU)except enterovirus 71(EV71)and coxsackievirus A16(CA16).Conclusions HFMD found in Hebei Children's Hospital from 2016 to 2023 are mainly caused by enteroviruses except EV 71 and coxsackievirus A16.High morbid-ity is found in children aged 1-3 years,and summer and autumn are the main epidemic seasons.This result may facilitate and support decision making and strategy development in disease prevention and control as well as to strengthen public health resources.

Purpose: Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)–positive breast cancer patients under different genotypes. Materials and Methods: CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. Results: A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Conclusion Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Primary liver cancer is a major global public health issue and currently the second leading cause of cancer death worldwide. The continuous changes in early cancer detection and treatment strategies have improved the overall survival rate of patients. Emerging organoid technologies have had a dramatic impact on cancer research in recent years, and tumor organoids are widely used in basic and translational cancer research. Tumor organoid culture technology will bridge the gap among molecular genetics, biology and clinical treatment. In this review, we discussed the recent different applications of liver organoids in liver cancer biology and clinical translation, involving liver cancer molecular studies, microenvironment and metastasis studies and drug screening trials, in order to provide a reference for clinical practice.

Objective:High-throughput screening to obtain small molecular compounds against Gram-negative bacilli by targeting BamA outer membrane protein.Methods:The sybyl-X2.1 software was used to perform high-throughput virtual screening of small molecular compounds in Chemdiv compound library based on the molecular docking. The top 150 hits by high-throughput screening were re-screened through in vitro biological experiments. The top 4 small molecules with obvious antibacterial activity were selected for in-depth molecular docking analysis, and the small molecule 8308-0401 with the highest docking score was selected for further experiments. The antibacterial effect of 8308-0401 combined with rifampicin was tested by checkerboard assay. Finally, the affinity between 8308-0401 and BamA was tested by plasma surface resonance assay. Results:The docking score of the top 150 hits calculated by high-throughput virtual screening had a mean value of 5.63. In vitro biological experiments showed that small molecules 8308-0401, 8365-1335, C066-2507 and L582-0346 exhibited strong antibacterial activity. Among those molecules, 8308-0401 showed the highest molecular docking score, and synergistic antibacterial activity against both types of strains and clinical isolates when combined with rifampicin. 8308-0401 has a strong affinity to BamA with binding a constant of 182 μmol/L. Conclusion:The small molecule 8308-0401 exerts antibacterial activity against Gram negative bacilli by targeting the outer membrane protein BamA.

With the changes of lifestyle, type 2 diabetes mellitus(T2DM) is spreading among the adolescents. T2DM in adolescents is distinct from type 1 diabetes mellitus and T2DM in adults. T2DM in adolescent progresses more rapidly and is more difficult to treat than that in adults. The prevention and therapy of T2DM in youth is facing severe challenges. This article reviews the epidemiology, pathophysiology, risk factors, comorbidities and complications of T2DM in adolescents as well as evidence-based clinical trials for the management of this disease based on the related hot spots of the 81 st annual meeting of the American Diabetes Association and the results from the latest clinical trials, so as to provide enough reference for the formulation of clinical strategies of T2DM in adolescents.