Effect of Platelet-Rich Plasma at Different Initiation Times on Healing of the Bone-Tendon Interface of the Rotator Cuff in a Mouse Model.

Background: Platelet-rich plasma (PRP) has demonstrated beneficial effects on healing of the bone-tendon interface (BTI). Purpose: To determine the optimal initiation time for PRP application after rotator cuff repair in an animal model. Study Design: Controlled laboratory study. Methods: A total of 136 C57BL/6 mice were included; 40 mice were used to prepare PRP, while 96 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly divided into 4 groups: a control group and 3 groups in which PRP was injected into the injury interface immediately after surgery, on the 7th postoperative day (PRP-7d), and on the 14th postoperative day. At 4 and 8 weeks postoperatively, the animals were sacrificed, blood was collected by eyeball removal, and samples of the SST-humerus complex were collected. Histological, imaging, immunological, and biomechanical data were compared among the groups using 1-way analysis of variance with the Bonferroni post hoc test. Results: Histological analysis revealed that the fibrocartilage layer at the BTI was larger in the PRP-7d group compared to the other groups at both 4 and 8 weeks postoperatively. Moreover, the PRP-7d group exhibited improved proteoglycan content and distribution compared to the other groups. Enzyme-linked immunosorbent assay results demonstrated that at 4 weeks postoperatively, higher concentrations of transforming growth factor-ß1 and platelet-derived growth factor-BB (PDGF-BB) were seen in the PRP-7d group versus the PRP-14d and control gruops (P < .05), and at 8 weeks postoperatively, the concentration of PDGF-BB was higher in the PRP-7d group versus the control group (P < .05). Biomechanical testing at 4 weeks postoperatively revealed that the failure load and ultimate strength of the SST-humerus complex were superior in the PRP-7d group compared to the other groups (P < .05), at 8 weeks, PRP-7d group was superior to the control group (P < .05). Additionally, at 8 weeks postoperatively, the PRP-7d group exhibited a greater trabecular number and trabecular thickness at the BTI compared to the PRP-14d and control gruops (P < .05). Conclusion: PRP promoted healing of the BTI after a rotator cuff injury at an early stage. Clinical Relevance: A PRP injection on the 7th postoperative day demonstrated superior therapeutic effects compared with injections at other time points.

Comparison of the effects of platelet-rich plasma and corticosteroid injection in rotator cuff disease treatment: a systematic review and meta-analysis.

HYPOTHESIS: Platelet-rich plasma (PRP) and corticosteroids are used to treat rotator cuff diseases. However, few reviews have compared the effects of these 2 treatments. In this study, we compared the effects of PRP and corticosteroid injection on the prognosis of rotator cuff diseases. MATERIALS AND METHODS: According to the Cochrane Manual of Systematic Review of Interventions, the PubMed, Embase, and Cochrane databases were searched comprehensively. Two independent authors screened suitable studies and performed data extraction and risk of bias assessment. Only randomized controlled trials comparing the effects of PRP and corticosteroid in the treatment of rotator cuff injuries were included, as measured by clinical function and pain during different follow-up periods. RESULTS: Nine studies with 469 patients were included in this review. In short-term treatment, corticosteroids were superior to PRP in the improvement of Constant, Simple Shoulder Test, and American Shoulder and Elbow Surgeons scores (mean difference [MD] -5.08, 95% confidence interval [CI] -10.26, 0.06; P = .05 and MD -0.97, 95% CI -1.68, -0.07; P = .03 and MD -6.67, 95% CI -12.85, -0.49; P = .03, respectively). No statistically significant difference was observed between the 2 groups at midterm (P > .05), and the recovery of the Simple Shoulder Test and American Shoulder and Elbow Surgeons scores in PRP treatment was significantly better than that in corticosteroid treatment in the long term (MD: 1.21, 95% CI: 0.68, 1.74; P < .00001 and MD: 6.96, 95% CI: 3.90, 9.61; P < .00001, respectively). In pain reduction based on visual analog scale score, corticosteroids led to better pain reduction (MD: 0.84, 95% CI: 0.03, 1.64; P = .04), but no significant difference was observed in pain reduction between the 2 groups in the any term (P > .05). However, these differences did not reach the minimum clinically important difference. CONCLUSIONS: Current analysis showed that corticosteroids have better efficacy in short term, whereas PRP is more beneficial for long-term recovery. However, no difference was observed in the mid-term efficacy between the 2 groups. Randomized controlled trials with longer follow-up periods and larger sample sizes are also needed to determine the optimal treatment.

Uncut interposed jejunum pouch versus esophago-gastrostomy and double anastomoses of jejunum to the esophagus and residual stomach: An innovative method of digestive tract reconstruction following proximal gastrectomy.

AIM: An innovative method of digestive tract reconstruction following proximal gastrectomy, the uncut interposed jejunum pouch, esophagus and residual stomach double anastomosis(Uncut-D), was established in recent years. In order to fully clarify the superiority of the procedure, this study has conducted a systematic analysis and thorough discussion. METHODS: 118 patients with adenocarcinoma of the esophagogastric junction who underwent proximal gastrectomy were enrolled in this study. According to the methods of digestive tract reconstruction, these patients were divided into three groups: Uncut-D(n = 43), esophagogastrostomy (EG, n = 36), jejunal interposition (JI, n = 39).The preoperative indicators, surgical complications and related indicators of postoperative quality of life were analyzed. RESULTS: There were no significant differences in preoperative data among all groups (P > 0.05); The digestive tract reconstruction time in Uncut-D group was more than that in EG group, and less than that in JI group (P < 0.05). The incidence of esophageal anastomotic stenosis in Uncut-D group was significantly lower than that in EG group (P < 0.05); In Uncut-D group, the incidence of reflux esophagitis, postoperative nutrition index(PNI), weight recovery and Visick classification were significantly better than those in EG group (P < 0.05), furthermore, the incidence of delayed gastric emptying,PNI and weight recovery were better than those in JI group (P < 0.05). CONCLUSIONS: The Uncut-D procedure gave full play to jejunal continuity and the advantages of pouch, and played a valuable role in gastric and cardiac replacement, which significantly reduced long-term complications, improved postoperative nutritional status of patients and long-term quality of life.

Comprehensive Analysis of Genomic Alterations in Hepatoid Adenocarcinoma of the Stomach and Identification of Clinically Actionable Alterations.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignancy with aggressive biological behavior. This study aimed to compare the genetic landscape of HAS with liver hepatocellular carcinoma (LIHC), gastric cancer (GC), and AFP-producing GC (AFPGC) and identify clinically actionable alterations. Thirty-eight cases of HAS were collected for whole-exome sequencing. Significantly mutated genes were identified. TP53 was the most frequently mutated gene (66%). Hypoxia, TNF-α/NFκB, mitotic spindle assembly, DNA repair, and p53 signaling pathways mutated frequently. Mutagenesis mechanisms in HAS were associated with spontaneous or enzymatic deamination of 5-methylcytosine to thymine and defective homologous recombination-related DNA damage repair. However, LIHC was characteristic of exposure to aflatoxin and aristolochic acid. The copy number variants (CNVs) in HAS was significantly different compared to LIHC, GC, and AFPGC. Aggressive behavior-related CNVs were identified, including local vascular invasion, advanced stages, and adverse prognosis. In 55.26% of HAS patients there existed at least one clinically actionable alteration, including ERBB2, FGFR1, CDK4, EGFR, MET, and MDM2 amplifications and BRCA1/2 mutations. MDM2 amplification with functional TP53 was detected in 5% of HAS patients, which was proved sensitive to MDM2 inhibitors. A total of 10.53% of HAS patients harbored TMB > 10 muts/Mb. These findings improve our understanding of the genomic features of HAS and provide potential therapeutic targets.

Effects of leukocyte-rich platelet-rich plasma and leukocyte-poor platelet-rich plasma on the healing of bone-tendon interface of rotator cuff in a mice model.

Platelet-rich plasma (PRP) is widely used clinically to treat tendon injuries, and often contains leukocytes. However, the debate regarding the concentration of leukocytes in PRP is still ongoing. This study aimed to evaluate the therapeutic effects of leukocyte-rich platelet-rich plasma (LR-PRP) and leukocyte-poor platelet-rich plasma (LP-PRP) on the healing of the bone-tendon interface (BTI) of the rotator cuff. A total of 102 C57BL/6 mice were used. Thirty mice were used to prepare the PRP, while 72 underwent acute supraspinatus tendon injury repair. The animals were then randomly assigned to three groups: LR-PRP, LP-PRP and control groups. The mice were euthanized at 4 and 8 weeks postoperatively, and histological, immunological and biomechanical analyses were performed. The histological results showed that the fusion effect at the bone-tendon interface at 4 and 8 weeks after surgery was greater in the PRP groups and significantly increased at 4 weeks; however, at 8 weeks, the area of the fibrocartilage layer in the LP-PRP group increased significantly. M2 macrophages were observed at the repaired insertion for all the groups at 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the control group, but some M2 macrophages were retained at the repaired site in the LR-PRP and LP-PRP groups. Enzyme-linked immunoassay results showed that the concentrations of IL-1ß and TNF-α in the LR-PRP group were significantly higher than those in the other groups at 4 and 8 weeks, while the concentrations of IL-1ß and TNF-α in the LP-PRP group were significantly lower than those in the control group. The biomechanical properties of the BTI were significantly improved in the PRP group. Significantly higher failure load and ultimate strength were seen in the LR-PRP and LP-PRP groups than in the control group at 4 and 8 weeks postoperatively. Thus, LR-RPR can effectively enhance the early stage of bone-tendon interface healing after rotator cuff repair, and LP-PRP could enhance the later stages of healing after rotator cuff injury.

Effect of Mechanical Stimulation Combined With Platelet-Rich Plasma on Healing of the Rotator Cuff in a Murine Model.

BACKGROUND: Mechanical stimulation and platelet-rich plasma (PRP) have been shown to be beneficial for healing of the bone-tendon interface (BTI), but few studies have explored the efficacy of a combination of these applications. We investigated the effect of mechanical stimulation combined with PRP on rotator cuff repair in mice. HYPOTHESIS: Mechanical stimulation combined with PRP can enhance BTI healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice were used. Overall, 40 mice were used to prepare PRP, while 120 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly assigned to 4 groups: control group, mechanical stimulation group, PRP group, and mechanical stimulation combined with PRP group (combination group). At 4 and 8 weeks postoperatively, animals were sacrificed, the eyeballs were removed to collect blood, and the SST-humeral complexes were collected. Histological, biomechanical, immunological, and bone morphometric tests were performed. RESULTS: Histologically, at 4 and 8 weeks after surgery, the area of the fibrocartilage layer at the BTI in the combination group was larger than in the other groups. The content and distribution of proteoglycans in this layer in the combination group were significantly greater than in the other groups. At 8 weeks postoperatively, trabecular number, and trabecular bone thickness of the subchondral bone area of interest at the BTI of the combination group were greater than those of the other groups, bone volume fraction of the combination group was greater than the control group. On biomechanical testing at 4 and 8 weeks after surgery, the failure load and ultimate strength of the SST-humeral complex in the combination group were higher than in the other groups. Enzyme-linked immunosorbent assay results showed that, at 4 weeks postoperatively, the serum concentrations of transforming growth factor beta 1 and platelet-derived growth factor (PDGF) in the combination group were significantly higher than in the other groups; at 8 weeks, the PDGF-AB concentration in the combination group was higher than in the control and mechanical stimulation groups. CONCLUSION: Mechanical stimulation combined with PRP can effectively promote the early stage of healing after a rotator cuff injury. CLINICAL RELEVANCE: These findings imply that mechanical stimulation combined with PRP can serve as a potential therapeutic strategy for rotator cuff healing.

Repeated lumps and infections: A case report on breast augmentation complications.

BACKGROUND: Polyacrylamide hydrogel (PAAG) injections were once common in breast augmentation and have been prohibited for augmentation mammaplasty in China since a large number of patients who underwent breast augmentation with PAAG injections have continued to seek medical advice as a result of related complications. Among all these complications, distant migration is relatively rare. CASE SUMMARY: A 49-year-old female presented at the hospital with a one-year history of a vulvar lump. The sonography of the lump showed several subcutaneous fluid-filled regions from the left vulva to the pubic symphysis, which suggested possible fat liquefaction. An enhanced magnetic resonance imaging (MRI) revealed a cystic area, which was considered a benign lesion. Intraoperative observations showed that the mass did not have an obvious capsule, the subcutaneous tissue presented as a cavity, and some yellow material came out of this cavity. A culture of the drainage did not show bacterial contamination. Histopathology revealed a foreign body granuloma. After resection and closed drainage, lumps were successively observed in the left lower abdomen and the bilateral hypochondriac region with infections. Sonography found that the hypoechoic areas in the bilateral hypochondriac region seemed continuous with deep in the breasts. The patient reported that she had undergone surgery with PAAG injections 20 years ago after she was repeatedly asked about her past history. Finally, a diagnosis of distant migration of PAAG was made. CONCLUSION: PAAG gel can migrate after long periods of time. A diagnosis should not be limited to the area where the symptom develops.

MicroRNA-186 affects the proliferation of tumor cells via yes-associated protein 1 in the occurrence and development of pancreatic cancer.

The present study aimed to determine the expression of microRNA (miRNA or miR)-186 in tumor tissues and peripheral blood of patients with pancreatic cancer (PC), as well as its mechanism of regulation. A total of 65 patients with PC who underwent surgery between June 2013 and October 2015 were included. In addition, 59 healthy subjects were recruited as controls. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of mRNA and miRNA. Western blotting and enzyme-linked immunosorbent assay were used to determine protein expression. Bioinformatics was employed for the prediction of the target gene of miR-186, whereas dual luciferase reporter assay was performed to identify whether miR-186 directly bound to YAP1 mRNA. Human pulmonary aortic endothelial cells (HPACs) were transfected with ago-miR-186. YAP1 expression in HPACs was silenced by siRNA. MTT assay was used to evaluate the viability of HPACs. YAP1 mRNA and protein expression levels were elevated in PC. In addition, expression levels of miR-186 in PC were downregulated. miR-186 regulated the expression of YAP1 by binding with the 3'-untranslated region of YAP1. Elevated expression of miR-186 inhibited the proliferation of HPACs by downregulating the expression of YAP1. Decreased expression of YAP1 by siRNA reduced the viability of HPACs. The present study demonstrates that YAP1 is upregulated in the tumor tissues and blood of PC patients, and this may be associated with the downregulation of miR-186. In addition, miR-186 may affect the occurrence and development of PC by controlling the proliferation of PC cells via YAP1.

Primary hepatic malignant fibrous histiocytoma combined with invasion of inferior vena cava: A case report and literature review.

RATIONALE: Malignant fibrous histiocytoma (MFH), primary presented in liver, was very rare and displayed a poor prognosis because of high aggression. As a few of cases had been reported merely, we shared the case of primary hepatic MFH combined with invasion of inferior vena cava (IVC). PATIENTS CONCERNS: A 69-year-old women presented with abdominal pain. DIAGNOSES: Abdominal computed tomography and magnetic resonance imaging indicated a soft mass about 5.4 × 4.2 cm in the caudate lobe, accompanied with IVC invaded. INTERVENTIONS: After the multidisciplinary consultation, laparotomy was performed, followed by chemotherapy and radiotherapy. Primary hepatic MFH was demonstrated pathologically. Till now, the patient was alive for >22 months after surgery and no evidence of recurrence or distant metastasis was suspected. OUTCOMES: We discussed the integrated procedure of diagnosis and treatment, combined with data from literature review. LESSONS: To our knowledge, the primary hepatic MFH combined with invasion of IVC was hardly reported. Despite the poor prognosis, the comprehensive treatment integrating the surgery, chemotherapy, and radiotherapy showed the satisfactory disease-free and overall survival. However, further investigations are definitely warranted.

[Inhibition of malignant phenotype of HeLa cells by RNA interference of the telomerase activity].

OBJECTIVE: To investigate the biology of HeLa cells upon inhibition of human telomerase catalytic subunit (hTERT) gene by RNA interference in vitro. METHODS: Four shRNAs (A, B, C and D) targeting hTERT gene were designed and prepared by in-vitro transcription. The expression of hTERT gene was evaluated by immunofluorescent staining and telomeric repeat amplification protocol (TRAP) ELISA (TRAP-ELISA), after transient transfection of shRNAs by lipid formulation. Through the initial selection, shRNA (B) was noticed as the most efficient one in down-regulating hTERT gene and therefore was chosen as the ultimate shRNA used in the experimental groups. Those transfected by non-silencing RNAi were chosen as the control groups. Cell spreading and migration were studied by microscopy and cell adhesion to fibronectin (FN) was assayed by cell counting kit-8 (CCK-8). Cell invasion was assessed by Boyden chamber assay. RESULTS: Cell spreading study revealed that the rates of spreading cells in the experimental groups were (5.6 +/- 2.3)% at 30 min, and (26.3 +/- 6.1)% 2 h after the inoculation, respectively, whereas the rates of spreading cells in the control groups were (31.3 +/- 7.9)% and (79.4 +/- 4.8)%, respectively. There were significant differences between the two groups (P < 0.01). However, most of the cells in both groups became spreading after 24 h. Cell adhesion assay demonstrated that the rate of adhesion cells on FN in experimental groups was (67.2 +/- 2.8)%, less than that in control groups (83.7 +/- 5.4)% (P < 0.05). The relative migration distance was (27.1 +/- 6.2)% in the experimental group, lower than that of the control group (58.7 +/- 15.0)%. The invasion assay revealed that the invading cells were 75.7 +/- 14.5 in the experimental group, in contrast to 165.1 +/- 11.0 in the control group after 4 h incubation on matrigel. The difference between these two groups was significant (P < 0.05). CONCLUSION: In vitro shRNA silencing of hTERT gene can down-regulate the telomerase activity, leading to an inhibition of the malignant phenotype of HeLa cells, including decreased ability of cell spreading and adhesion, reduction of cell migration, and declined invasive ability through Matrige assay.