ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

Pathologically,hepatocellular carcinoma(HCC)is prone to invade the portal vein and form portal vein tumor thrombus(PVTT).Although great advances in the treatment of HCC have been achieved in recent years,HCC patients with PVTT still have limited therapeutic options and poor prognosis.Hepatic arterial infusion chemotherapy(HAIC)is a therapeutic approach that combines local therapy with systemic antitumor effects,and a lot of studies have shown that HAIC carries certain survival benefit to patients with advanced HCC complicated by PVTT,and it is considered to be an effective local therapy for advanced HCC,especially for patients with type Vp3-4 HCC.Systemic therapy is the main treatment for advanced HCC,but the diversity of HAIC combined with targeted and immunotherapy may become a more effective treatment option for HCC with severe PVTT,and it is possible to achieve a tumor-free state through translational therapy,allowing patients with advanced HCC to survive for a longer time.This article aims to summarize the research progress in HAIC for advanced HCC complicated by PVTT.

Objective To discuss the application of partial antiplatelet drug genotype detection and thromboelastography-platelet mapping(TEG-PM)in guiding the selection of antiplatelet regimens in patients with intracranial aneurysms(IAs)after receiving stenting.Methods A total of 106 patients with IAs in the First Affiliated Hospital of Kunming Medical University,who underwent implantation of stent and received the testings of platelet-endothelial aggregation receptor 1(PEAR 1)and clopidogrel-related gene-cytochrome P450 enzyme 2C19(CYP2C19),and some of whom received TEG-PM testing from January 2019 to August 2022,were collected for this study.The patients were divided into group A(gene detection group,according to the drug-related gene detection results to adjust the medication)and group B(combination group,according to the two testing results to guide the medication).The patient's gender,age,testing data were collected,and the occlusion of IAs,stent intimal hyperplasia,drug-related hemorrhagic and ischemic complications during follow-up period were recorded.Results A total of 123 IAs lesions in 106 patients were treated.The patient's mean age was(53.67±6.66)years,67 patients were female.Group A had 41 patients and group B had 65 patients.No statistically significant differences in the baseline data,IAs features,stent types used,and medication regimen existed between the two groups(all P＞0.05).In Group A,the ischemic complications and hemorrhagic complications occurred in two patients each.In Group B,no ischemic complications occurred and 4 patients developed hemorrhagic complications.The difference in the incidence of related complications between the two groups was not statistically significant(P=0.287 and P=0.782 respectively).There were no statistically significant differences in the postoperative one-month and 3-month intimal hyperplasia grade and the aneurysm occlusion rate between the two groups(all P＞0.05).The postoperative 6-month overall intimal hyperplasia grade in Group A was slightly higher than that in Group B,and the difference was statistically significant(P=0.034).Conclusion In order to improve the precision and individualized treatment of antiplatelet therapy,it is suggested that clinicians should adopt TEG-PM-guided conventional double-antibody therapy first when making selection of testing items.For patients with insufficient inhibition rate indicated by TEG-PM,testing of the genes associated with antiplatelet drugs should be used.Based on the genetic test results it is necessary to determine the reasons for the insufficient inhibition rate as well as to adjust the medication promptly according to the specific situation of the patient,so as to ensure the effectiveness of antiplatelet therapy and achieve the purpose of individualized precision therapy.

Objective To compare the differences in efficacy and safety between transarterial chemoembolization(TACE)com-bined with lenvatinib and camrelizumab(triple therapy)and TACE combined with lenvatinib(double therapy)in intermediate or advanced stage hepatocellular carcinoma(HCC).Methods The clinical data of 145 patients who were diagnosed with HCC and received triple therapy or double therapy were retrospectively collected.The differences of objective response rate(ORR),disease control rate(DCR),median progression-free survival(mPFS),median overall survival(mOS),and adverse events were compared between the two groups.Results The ORR and DCR in 1,3 and 6 months of the triple therapy group were higher than those of the double therapy group,and the differences were statistically significant in 3 and 6 months.The mPFS and mOS of the triple therapy group were higher than those of the double therapy group,and the differences were statistically significant.The Cox proportional hazards model results showed that the therapy methods,maximum tumor diameter and alpha-fetoprotein(AFP)were independent risk factors of progres-sion-free survival(PFS)and overall survival(OS).Besides,Barcelona Clinic Liver Cancer(BCLC)staging was independent risk fac-tor of OS.In terms of adverse events,the incidence of reactive cutaneous capillary endothelial proliferation(RCCEP)and hypothy-roidism in the triple therapy group were higher than those in the double therapy group,and the differences were statistically signifi-cant.Conclusion Compared with double therapy,triple therapy can significantly improve the efficacy of intermediate or advanced stage HCC,prolong patients'PFS and OS,and its safety can be well controlled.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Femtosecond laser small incision lenticule extraction (SMILE) with different residual stromal thicknesses (RST) is set to investigate its effect on corneal biomechanical properties of rabbits in vivo. In this study, 24 healthy adult Japanese rabbits were randomly divided into group A and B. The RST of group A was set 30% of the corneal central thickness (CCT), and the RST of group B was 50% of the CCT. The thickness of the corneal cap in both groups was set one third of CCT. Corneal visualization Scheimpflug technology (Corvis ST) and Pentacam three-dimensional anterior segment analyzer were used to determine corneal biomechanical and morphological parameters before surgery, and 1 week, 1 month and 3 months after surgery. Pearson correlation analysis was used to analyze factors affecting corneal biomechanical parameters after SMILE. The results showed that the corneal stiffness of group A was significantly higher than that of group B at 1 week and 1 month after surgery, and most biomechanical parameters returned to preoperative levels at 3 months postoperatively. The results of correlation analysis showed that postoperative CCT and RST were the main factors affecting corneal biomechanical parameters after SMILE. There was no significant difference in corneal posterior surface height (PE) between 3 months after surgery and before surgery in both two groups. It indicates that although the ability to resist deformation of cornea decreases in SMILE with thicker corneal cap and less RST, there is no tendency to keratoconus, which may be related to the preservation of more anterior stromal layer.
Animals ; Biomechanical Phenomena ; Cornea/surgery* ; Postoperative Period ; Rabbits

OBJECTIVE: To analyze the clinical and genetic features of a patient with mevalonate kinase deficiency (MKD). METHODS: Whole exome sequencing was carried out for the proband. Candidate variant was verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the MVK gene, including a c.248C>T (p.Phe83Cys) variant derived from his father and a c.971C>T (p.Ala324Val) variant from his mother. Based on the guidelines of the American College of Medical Genetics and Genomics, both variations were predicted to be likely pathogenic (PM1 + PM2 + PM3 + PP3). CONCLUSION The compound heterozygous variants of the MVK gene probably underlay the MKD in the proband. Above findings have enriched the mutational spectrum of the MVK gene.
Child ; Genomics ; Humans ; Immunoglobulin D/genetics* ; Mevalonate Kinase Deficiency/genetics* ; Mutation ; Whole Exome Sequencing

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

Objective:To develop nursing quality evaluation indicator system for perioperative patients with Da Vinci robotic under enhanced recovery after surgery(ERAS), in order to provide references for clinical evaluation of nursing quality for lobectomy patients.Methods:Based on the theory of structure-process-outcome quality model and ERAS, literature review, semi-structured interviews were adopted to determine nursing quality indicator system for perioperative patients. Delphi method was used in two rounds of consultation among 21 experts.Results:The positive coefficient was 100%, authority coefficient was 0.839,0.901, and the coefficients of concordance were 0.317,0.335. The final indicator system consisted of 3 first-level indicators, 14 second-level indicators, and 52 third-level indicators.Conclusion:The nursing quality evaluation indicator system for lobectomy patients with Da Vinci robotic was scientific and reliable, which can provide scientific references for evaluating nursing quality for perioperative patients with Da Vinci robotic under ERAS.

Objective To study the prevalence trends and etiology of hand,foot,and mouth disease (HFMD) in hospitalized children.Methods The clinical data of 11 510 cases of children hospitalized with HFMD from 2008 to 2017 in Department of Infection Diseases of Kunming Children's Hospital were collected,and to retrospectively analyze the characteristics,time distribution and pathogen distribution of the cases.Results Of the 11 510 children with HFMD,6 100 were male and 5 410 were female.There were 9 814 cases under 3 years old,1 696 over 3 years old.HFMD occurred throughout the year.The peak months of the disease were April to July,with the time distribution of single peak.There were 4 690 severe cases and 3 452 critical cases,accounting for 70.34％.The main pathogens detected were enteroviruses A71 (EV-A71),coxsackievirus A16 (CV-A16) and other enteroviruses (EV),with 3 803 cases (36.02％),1 122 cases (10.63％) and 3 401 cases (32.21％) respectively.EV-A71 and CV-A16 infections dominated from 2008 to 2013,while EV-A71 and other EV infection dominated from 2014 to 2017.Conclusions EV-A71,CV-A16 and other EV are the main pathogens of HFMD in Kunming.Critical HFMD cases are mainly caused by EV-A71 infection.