Objective:To analyze the effect of PAK4 interruption by microRNA-199a/b-3p (miR-199a/b-3p) on migration and invasion of hepatocellular carcinoma (HCC).Methods: To test targeting of PAK4 by miR-199a/b-3p,we used luciferase assay in HEK293T cells cotransfected miR-199a/b-3p mimcs and pmirGLO-PAK4 3′UTR.The expression of PAK4 in SMMC-7721 transfected with miR-199a/b-3p was detected by Western blot.The biology behaviors of SMMC-7721 cells transfected with miR-199a/b-3p or PAK4 Si were analysed by cell migration assay and invasion assay.Results:MiR-199a/b-3p could suppress the mRNA and protein ex-pression of PAK4 by targeting PAK4 3′UTR,and the downregulating PAK 4 expression suppress the migration and invasion of SMMC-7721 cells.Conclusion: MiR-199a/b-3p could suppress the expression of PAK 4, which are considered key HCC suppressors and inhibit the migration and invasion of HCC cells.

Objective:To analyze the inhibiting mechanism of microRNA-199a/b-3p ( miR-199a/b-3p) on cell motility of breast cancer cells.Methods:The expression of PAK4 in MDA-MB-231 cells transfected with miR-199a/b-3p was detected by Western blot.The biology behaviors of MDA-MB-231 cells transfected with miR-199a/b-3p or PAK4 SiRNA were analysed by cell migration assay,invasion assay and protrusion dynamics.Results: MiR-199a/b-3p could suppress the expression of PAK 4 in MDA-MB-231 cells.Comparing with normal control ,miR-199a/b-3p or PAK4 SiRNA could suppress the migration ,invasion and membrane protrusion of MDA-MB-231 cells.Conclusion:miR-199a/b-3p could suppress the expression of PAK4,which are considered key breast cancer suppressors and inhibit the cell motility of breast cancer cells.

Objective:To analyze the inhibiting mechanism of microRNA-199a/b-3p(miR-199)on cell proliferation of triple negative breast cancer(TNBC)cells.Methods:Expression of miR199 in BT549 and MDA-MB-231 cells transfected with miR-199a/b-3p was detected by qRT-PCR.The proliferation of BT549 and MDA-MB-231 cells transfected with miR-199 were analysed by MTT as-say.Cell cycle of TNBC cells transfected with miR-199 was detected by Flow Cytometry assay.Results:MiR-199a/b-3p could suppress the proliferation of BT549 and MDA-MB-231 cells.Comparing with normal control,the proliferation rate were up to(41.02±2.34)%and(28.42 ±6.70 )%,and the cell cycle were arrest at G 1 phase.Conclusion: MiR-199a/b-3p could suppress the proliferation of TNBC,and may be a promising anti-cancer drug for TNBC.

Objective To summarize the complications and their incidences following Anterior Subcutaneous Internal Pelvic Fixation(ASIPF).Methods A comprehensive search was conducted of PubMed Library,Cochrane Library,Web of Science,SinoMed,Wanfang Data and China National Knowledge Internet for all articles addressing the postoperative complications of ASIPF published in English and Chinese from January 2009 to November 2018.A proportion Meta-analysis across the studies was performed for the complications after ASIPF (lateral femoral cutaneous nerve irritation,femoral nerve palsy,heterotopic ossification,infection and implant failure) using R software.Results This meta-analysis included 29 clinical studies involving a total of 825 patients.The complications following ASIPF were lateral femoral cutaneous nerve irritation,femoral nerve palsy,heterotopic ossification,infection and implant failure;their incidences were respectively 12％ (95％ CI:from 7％ to 19％),3％ (95％ CI:from 2％ to 4％),30％ (95％ CI:from 22％ to 39％),4％ (95％ CI:from 3％ to 6％) and 4％ (95％ CI:from 3％ to 6％).Conclusions Lateral femoral cutaneous nerve irritation and heterotopic ossification are common complications following minimally invasive internal fixation for anterior pelvic ring injury.High-quality clinical research is needed into the factors leading to the complications and into their preventive countermeasures.

The epidemic spectrum of acetabular fractures is changing with the changing population structure in China which has resulted in an increased proportion of the elderly patients. As acetabular fractures are intra-articular in nature, their management should follow the principles for intra-articular ones. However, it is still a great challenge for orthopedists to choose an appropriate treatment to deal with the fracture because of the pathophysiological changes in the elderly patients and the particular characteristics of acetabular fractures. Technical advances may offer a diversity of treatment options for geriatric acetabular fractures and demands for individualized management are increasing. In order to deepen the knowledge of geriatric acetabular fractures for orthopedists, this review expounds on the current achievements in the management and research concerning the fractures.

Objective:To investigate the clinical efficacy of robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation in the treatment of pelvic fracture.Methods:A retrospective analysis was conducted on 28 cases with pelvic fractures treated with robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation from May 2018 to November 2022. There were 19 males and 9 females, with an average age of 43.4±16.9 years (range, 14-74 years). There was 1 case of B1 type, 1 case of B2 type, 4 cases of B3 type, 10 cases of C1 type, 9 cases of C2 type and 3 cases of C3 type by Tile classification. All the cases were treated with closed reduction, LC-II external fixation for the anterior lesions and robot-assisted minimally invasive sacroiliac screw fixation for the posterior lesions. The operation time, fluoroscopy time and excellent rate of screw placement were recorded. The quality of fracture reduction was evaluated by Matta's criteria, and the clinical effect was evaluated by Majeed score.Results:All the 28 cases successfully underwent the surgery. In 11 cases the fractures were reduced by the pelvic unlocking closed reduction device while in the other 17 cases manual reduction was applied. In this cohort, 43 screws were implanted. All the screw positions reached level I by Gras grading. The average fluoroscopy time was 16.3±5.2 s (range, 9-31 s) per screw. The average operation time was 154.9±54.7 min (range, 55-226 min). According to the Matta's criteria, the reduction was rated as excellent in 19 cases, good in 7 cases, fair in 2 cases, yielding an excellent or good rate of 93% (26/28). No iatrogenic neurovascular injury was found in all the 28 patients. The average follow-up was 18.3±7.3 months (range, 4-31 months). The fractures healed at 3.6±1.1 months (range, 2-6 months) after the surgeries. At the final follow-up, the results of the Majeed scores were rated as excellent in 13 cases, good in 11 cases, fair in 3 cases and poor in 1 case, with an excellent or good rate of 86% (24/28).Conclusion:The technique of robot-assisted minimally invasive sacroiliac screw fixation combined with LC-II external fixation used in the treatment of pelvic fracture showed good clinical results.

Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

The present study aims to explore the genetic diversity of germplasm resources of Chrysanthemum×morifolium (hereinafter, C.×morifolium) at the molecular level and to establish a fingerprint database of C.×morifolium varieties. We employed 12 pairs of primers with high levels of polymorphism, clear bands, and high degrees of reproducibility to analyze the SSR molecular markers and genetic diversity of 91 C.×morifolium materials and 14 chrysanthemum- related materials. With regard to constructing the fingerprints of the tested materials, we chose 9 pairs of core primers. The findings revealed that 12 primer pairs detected 104 alleles in 105 samples, ranging from 2 to 26. The average number of observed alleles (N_a) per site was 9.25. The average number of effective alleles (N_e) per site was 2.745 6, with its range being 1.276 0 to 4.742 5. Shannon genetic diversity index (I) values ranged between 0.513 3 and 2.239 9 (M=1.209 0). Nei's gene diversity index (H) ranged between 0.216 3 and 0.789 1 (M=0.578 0). The observed heterozygosity (H_o) ranged between 0.223 3 and 0.895 2 (M=0.557 5). The expected heterozygosity (H_e) ranged between 0.217 4 and 0.793 3 (M=0.580 8). The polymorphism information content (PIC) ranged between 0.211 5 and 0.774 0 (M=0.532 9). The genetic similarity (GS) ranged between 0.228 5 and 1.000 0 (M=0.608 3). Cluster analysis revealed that when the genetic distance (GD) equals to 0.30, the tested materials can be classified into 2 groups. When the GD equals to 0.27, the first group can be divided into 6 subgroups; accordingly, 105 tested materials can be divided into 7 subgroups. The cophenetic correlation test was carried out based on the cluster analysis, and the corresponding results showed that the cluster map correlated with the genetic similarity coefficient (r=0.952 73). According to the results of Structure population analysis, we obtained the optimal population number, with the true number of populations (K) being 3 and the population being divided concerning Q≥0.5. Three subgroups, i.e., Q1, Q2 and Q3, included 34, 33 and 28 germplasms, respectively, and the remaining 10 germplasms were identified as the mixed population. During the experiment, 9 pairs of core primers were screened among the total of 12 for a complete differentiation regarding 105 tested materials, and the fingerprints of 91 C.×morifolium materials and 14 chrysanthemum-related materials were further constructed. Overall, there were significant genetic differences and rich genetic diversity among C.×morifolium materials, which would shed light on the garden application and variety selection fields of C.×morifolium. The fingerprint database of 105 C.×morifolium varieties and chrysanthemum-related species may provide technical support for future research regarding the identification and screening system of C.×morifolium varieties.
Genetic Variation ; Chrysanthemum/genetics* ; Reproducibility of Results ; Microsatellite Repeats/genetics* ; Polymorphism, Genetic ; Biomarkers ; Phylogeny

OBJECTIVE: Immunotherapy has brought significant clinical benefits to a subset of patients, but has thus far been disappointing in the treatment of immunologically "cold" tumors. Existing biomarkers that can precisely identify these populations are insufficient. In this context, a potential cold tumor microenvironment (TME) marker FARSB was investigated to reveal its impact on TME and patients' response to immunotherapy across pan-cancer. METHODS: The expression levels and mutational landscape of FARSB in pan-cancer were investigated. Kaplan-Meier and univariate Cox regression analyses were applied to analyze the prognostic significance of FARSB. Pathways affected by FARSB were investigated by gene set enrichment and variation analysis. The relationship between FARSB expression and immune infiltration was examined using the TIMER2 and R packages. Single-cell RNA sequencing (scRNA-seq) data of several cancer types from GSE72056, GSE131907, GSE132465, GSE125449 and PMID32561858 were analyzed to validate the impact of FARSB on the TME. The predictive effect of FARSB on immunotherapy efficacy was explored in 3 immune checkpoint inhibitors (ICIs)- treated cohorts (PMID32472114, GSE176307, and Riaz2017). RESULTS: FARSB expression was significantly higher in 25 tumor tissues than in normal tissues and was associated with poor prognosis in almost all tumor types. FARSB expression exhibited a strong association with several DNA damage repair pathways and was significantly associated with TP53 mutation in lung adenocarcinoma (P < 0.0001, OR=2.25). FARSB characterized a typical immune desert TME and correlated with impaired expression of chemokines and chemokines receptors. Large-scale scRNA-seq analysis confirmed the immunosuppressive role of FARSB and revealed that FARSB potentially shapes the cold TME by impeding intercellular interactions. In 3 ICI-treated cohorts, FARSB demonstrated predictive value for immunotherapy. CONCLUSION This study provides a pan-cancer landscape of the FARSB gene by integrated single-cell and bulk DNA sequencing analysis and elucidates its biological function to promote DNA damage repair and construct the immune desert TME, suggesting the potential value of FARSB as a novel marker for stratifying patients with poor immunotherapeutic benefits and "cold" TME.
Humans ; Tumor Microenvironment ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Sequence Analysis, RNA