Objective To study the clinical efficacy of platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA) and evaluate whether the age,body mass index and grade of KOA are associated with the treatment outcomes.Methods Using the prospective,randomized,controlled study,100 KOA patients hospitalized between December 2013 and November 2014 were enrolled.Twentyeight patients were men and 72 were women.Mean age was 58 years (range,35-85 years).Degenerative arthritis occurred in 68 patients and traumatic arthritis in 32 patients.Kellgren-Lawrence (K-L) score was grade Ⅱ in 35 patients,grade Ⅱ in 46 and grade Ⅲ in 19.The patients were assigned to receive hyaluronic acid (HA) (HA group,n =50) and PRP (PRP group,n =50) by an intraarticular route once weekly for 3 weeks,according to the random number table.Between-group differences were insignificant in age,gender,body mass index (BMI) and K-L grade.Western Ontario and McMaster Universities Arthritis Index (WOMAC),visual analog scale (VAS) and cartilage lesions score (CaLs) were used for clinical and MRI evaluations.At follow-up evaluation,the effective rate was defined at least 36％ improvement from the baseline WOMAC score.Results All patients were followed up for 6 months.The effective rate in PRP group was 84％ versus 68％ in HA group after the last treatment (P ＞0.05),and was 60％ versus 36％ in HA group at the final follow-up (P ＜ 0.05).WOMAC score in both groups had significant improvement after operation,while VAS improved only in PRP group (P ＜ 0.01).In PRP group patients with K-L grade I had better VAS and WOMAC scores than those with grade Ⅱ (P ＜0.05),and patients with grade Ⅱ had better WOAMC score than those with grade Ⅲ (P ＜ 0.05).MRI findings showed seven patients in PRP group had similar CaLs before and after operation (P ＞ 0.05),and the area of abnormal signal in subchondral bone and the depth of cartilage lesion gradually decreased in one of them.Follow-up study showed the outcomes had negative correlation with age and K-L grade (P ＜0.05),but no certain correlation with BMI in PRP group (P ＞ 0.05).Clinical effects in both groups were decreased over time.Conclusions Intraarticular injection of PRP benefits to pain relief,decreased inflammation and tissue repair,and has much better outcome in patients with younger age and lower K-L grade.However,BMI is not associated with the outcome.

BACKGROUND: Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC. METHODS: Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo. RESULTS: TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR. CONCLUSION Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

Male ; Humans ; Infant ; Hypospadias/surgery* ; Urologic Surgical Procedures, Male ; Urethra/surgery* ; Penis/surgery* ; Follow-Up Studies

Diverse types of GABAergic interneurons tend to specialize in their inhibitory control of various aspects of cortical circuit operations. Among the most distinctive interneuron types, chandelier cells (i.e., axo-axonic cells) are a bona fide cell type that specifically innervates pyramidal cells at the axon initial segment, the site of action potential initiation. Chandelier cells have been speculated to exert ultimate inhibitory control over pyramidal cell spiking. Thus, chandelier cells appear to share multiple similarities with basket cells, not only in firing pattern (fast spiking) and molecular components, but also in potentially perisomatic inhibitory control. Unlike basket cells, however, synaptic recruitment of chandelier cells is little known yet. Here, we examined the mediodorsal thalamocortical input to both chandelier cells and basket cells in medial prefrontal cortex, through combining mouse genetic, optogenetic and electrophysiological approaches. We demonstrated that this thalamocortical input produced initially weak, but facilitated synaptic responses at chandelier cells, which enabled chandelier cells to spike persistently. In contrast, this thalamocortical input evoked initially strong, but rapidly depressed synaptic responses at basket cells, and basket cells only fired at the initiation of input. Overall, the distinct synaptic recruitment dynamics further underscores the differences between chandelier cells and basket cells, suggesting that these two types of fast spiking interneurons play different roles in cortical circuit processing and physiological operation.
Mice ; Animals ; Neurons/physiology* ; Pyramidal Cells/physiology* ; Interneurons ; Action Potentials/physiology* ; Synaptic Transmission

OBJECTIVETo compare clinical effects of core decompression with stem cell transplantation and tantalum rod implanting in treating stage II non-traumatic osteonecrosis of femoral head.

METHODSFrom March 2012 to September 2012, 45 patients(55 hips)with stage ARCO II non-traumatic osteonecrosis of femoral head were treated and divided into core decompression with stem cell transplantation group(group A) and tantalum rod implanting group(group B) according to number table. In group A, there were 23 cases(28 hips) , including 12 males and 11 females aged from 23 to 51 years old with an average of (36.87±9.52) years, the courses of disease ranged from 2 to 28 months with an average of (17.13±7.74) months, preoperative Harris score was for 35 to 70 with an average of(54.74±11.81), treated with core decompression with stem cell transplantation. In group B, there were 22 cases(27 hips), including 11 males and 11 females aged from 26 to 46 years old with an average of (35.59±7.39) years, the courses of disease ranged from 3 to 26 months with an average of(16.00±7.46) months, preoperative Harris score was for 35 to 76 with an average of (57.18±12.95), treated with core tantalum rod implanting. Operative time, blood loss, hospital stays, hospitalization expenses were observed and compared after treatment between two groups, the clinical effects were evaluated according to Harris criteria.

RESULTSAll patients were followed up from 6 to 12 months with an average of 10.8 months. There were significant difference in hospitalization expenses between two groups(<0.05), while there was no significant statistical difference in blood loss and hospital stay (>0.05). At the final following-up, Harris score in group A was(83.04±8.97), 6 cases obtained excellent results, 14 good, 2 good and 1 poor;while Harris score in group A was(84.41±9.94), and 9 cases obtained excellent results, 9 good, 3 good and 1 poor; there was no statistical meaning differences between two groups(>0.05).

CONCLUSIONSCore decompression with stem cell transplantation and tantalum rod implanting could both improve function of hip joint, while core decompression with stem cell transplantation had advantages of shorter operation time, less cost, and higher potency ratio. It is suitable for stage ARCO II non-traumatic femoral head necrosis.

OBJECTIVE: To explore the genetic basis for a child with clinically suspected nephronophthisis (NPHP). METHODS: Peripheral blood samples of the patient and her parents were collected subjected to high-throughput sequencing. Sanger sequencing was used to verify the gene variants. RESULTS: The patient, a 7-year-old girl with congenital blindness, was admitted to a local hospital due to repeated vomiting for 7-8 days and then transferred to author's hospital due to renal failure. Her urine occult bloods (3+) and urine protein (1+) were abnormal. Her blood urea nitrogen and creatinine showed a significant progressive increase. Renal ultrasound showed a mild enlargement in bilateral renal, increased echogenicity, loss of corticomedullary differentiation, and the presence of cysts in both kidneys. No familial genetic history was found in the family of patient and the child was clinically diagnosed with nephronophthisis. The proband was found to harbor compound heterozygous variants of the CEP290 gene, namely c.2587-2A>T and c.2251C>T, which were inherited from her mother and father, respectively. Based on the ACMG guidelines, both variants were predicted to be pathogenic. CONCLUSION The patient was diagnosed with NPHP type 6 due to variants of the CEP290 gene. Above finding has provided new evidence for the genotype-phenotype correlation of this disease.

Objective To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer(CRC)based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids(CRC-PDOs).Methods NMF(non-negative Matrix Factorization)algorithm,Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis,and disulfidptosis-related risk scoring formula was constructed.The differential genes and enrichment pathways among different clusters were analyzed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes).The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs.Results The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes.COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients(P=0.047,0.033).Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival(OS)(P=0.004,0.003).Based on LASSO regression analysis,the mortality risk scoring formula for disulfidptosis was as follows:Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2,and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly.There were 125 differentially expressed genes(DEGs)between the two clusters.According to the GO and KEGG results,the up-regulated genes in high-risk cluster were mainly enriched in immune regulation,such as leukocyte chemotaxis,granulocyte migration and toll-like receptor binding.Low-risk cluster was characterized by pathways associated with sulfide metabolism,such as sulfur compound transmembrane transporter activity.Based on the GDSC database,the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity.As a representative,the efficacy of chemotherapy drug(irinotecan)on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients(P=0.007,0.040).Conclusion According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs,disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients,with potential clinical application prospect.

Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.

We aim to design a new glanuloplasty procedure combined with spongiosum to reduce the incidence of glans dehiscence and coronal fistula after proximal hypospadias repair. Patients who underwent urethroplasty by dorsal preputial island flap for proximal hypospadias between January 2014 and December 2016 were reviewed in this retrospective cohort study. Those who underwent spongiosum-combined glanuloplasty comprised the new-maneuver group, whereas those who underwent conventional glanuloplasty comprised the control group. The incidence of complications was then compared. In the new-maneuver group, dysplastic corpus spongiosum alongside lateral Buck's fascia (0.3-0.4 cm wide) on both sides of the urethral plate was separated from the proximal normal spongy tissue, joining into the glans wings to increase tissue volume and covering the neourethra in the glans penis. In the control group, the neourethra was covered with superficial fascia under the coronal sulcus. As a result, the new-maneuver and control groups comprised 47 and 28 patients, respectively. In the new-maneuver group, no glans dehiscence was detected; however, two (4.3%) patients had coronal fistula, two (4.3%) had urethral stricture, and four (8.5%) had diverticulum. In the control group, two (7.1%) patients had glans dehiscence, eight (28.6%) had coronal fistula, four (14.3%) had urethral stricture, one (3.6%) had diverticulum, and one (3.6%) had penile curvature recurrence. The new-maneuver group had less incidences of coronal fistula (P < 0.001), glans dehiscence (P = 0.033), and urethral stricture (P = 0.008) but had a higher incidence of diverticulum than the control group (P = 0.040). It clearly demonstrates that spongiosum-combined glanuloplasty can significantly reduce the incidences of coronal fistula and glans dehisce.