A novel signature for predicting prognosis and immune landscape in cutaneous melanoma based on anoikis-related long non-coding RNAs.

Anoikis is a unique form of apoptosis associated with vascularization and distant metastasis in cancer. Eliminating anoikis resistance in tumor cells could be a promising target for improving the prognosis of terminal cancer patients. However, current studies have not elaborated on the prognosis effect of anoikis-related long non-coding RNAs (lncRNAs) in cutaneous melanoma. Pre-processed data, including RNA sequences and clinical information, were retrieved from TCGA and GTEx databases. After a series of statistical analyses, anoikis-related lncRNAs with prognostic significance were identified, and a unique risk signature was constructed. Risk scores were further analyzed in relation to the tumor microenvironment, tumor immune dysfunction and exclusion, immune checkpoint genes, and RNA methylation genes. The indicators were also used to predict the potentially sensitive anti-cancer drugs. An anoikis-related lncRNAs risk signature consisting of LINC01711, POLH-AS1, MIR205HG, and LINC02416 was successfully established in cutaneous melanoma. Overall survival and progression-free survival of patients were strongly linked with the risk score, independently of other clinical factors. The low-risk group exhibited a more beneficial immunological profile, was less affected by RNA methylation, and was more sensitive to the majority of anti-cancer drugs, all of which indicated a better prognostic outcome. The 4 hub lncRNAs may be fundamental to studying the mechanism of anoikis in cutaneous melanoma and provide personalized therapy for salvaging drug resistance.

Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon's up-and-down method: a double-blind, prospective clinical study of drug dose response.

BACKGROUND: Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care unit (ICU), but the incidence of pain during IV infusion can reach 28-90%. Ketamine can attenuate pain associated with IV propofol injection through local and central analgesic effects. Ketamine is gradually being transitioned to its S-enantiomer, esketamine, which has a similar mechanism of action. The purpose of our study is to determine the half effective dose (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) of esketamine for attenuating propofol injection pain using Dixon's up-and-down method to provide a reference for optimal dose selection for surgeries and procedures. METHODS: Thirty gynecological patients undergoing hysteroscopic surgery were enrolled in a sequential method to determine the effective dose of esticketamine for analgesic propofol injection in order of operation. This study was based on the sequential allocation up-and-down rule designed by Dixon, and each patient was induced by esticketamine combined with propofol. During induction, the target dose of esketamine was first given via venous access in the left hand of the patient, and 30 s later, a fixed dose of 2 mg/kg (1 ml/s) of propofol was given. Patient perception of pain was scored with the verbal rating scale (VRS) every 5 s after the start of the propofol infusion, and the evaluation was stopped once the patient became unresponsive. The dosage of esketamine was increased or decreased up or down according to the patient's pain response. The initial dose of esketamine was 0.2 mg/kg, and the gradient of adjacent dose was 0.02 mg/kg. If the pain response assessment of the upper patient was positive (+), the dose of esselketamine in the next patient was increased by 0.02 mg/kg; if the pain response assessment of the upper patient was negative (-), the dose of esselketamine in the next patient was decreased by 0.02 mg/kg. The tests were carried out sequentially, with the pain response changing from positive to negative or from negative to positive, and the tests were stopped after at least 6 crossover points, and the effective dose of esticketamine was calculated using probit probability regression analysis. RESULTS: The ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. The 95% CI was set as the confidence interval of effective dose ED value，and we found esketamine's ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 0.189 mg/kg (0.167, 0.394 mg/kg). The esketamine dose and VRS score during propofol injection were significantly different between the two groups (P < 0.05), whereas surgical duration, emergence time, visual analogue scale (VAS) score of postoperative uterine contraction pain, and Riker sedation/anxiety scale (SAS) score were not significantly different. Bradycardia occurred in only one patient during anesthesia induction, while hemodynamics was stable in the rest of the patients without obvious adverse reactions. CONCLUSION: Small doses of esketamine combined with propofol can be safely and effectively used for hysteroscopic surgery. We recommended a dose of 0.2 mg/kg IV esketamine before induction of anesthesia to reduce the pain of propofol injection. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.

Effect of Lactobacillus casei fermented milk on fracture healing in osteoporotic mice.

The interaction between the gut microbiota and the host has been described experimentally by germ-free animals or by antibiotic-disturbed gut microbiota. Studies on germ-free mice have shown that gut microbiota is critical for bone growth and development in mice, emphasizing that microbiota dysbiosis may interfere with normal bone development processes. This study aimed to clarify the effect of antibiotic treatment on disturbed gut microbiota on bone development in mice and to investigate the effect of probiotic treatment on fracture healing in mice with dysbiosis. Our results showed that 4 weeks old female Kunming mice showed significantly lower abundance and diversity of the gut microbiota and significantly lower bone mineral density after 12 weeks of antibiotic treatment and significantly increased levels of RANKL and Ang II in serum (p<0.05). Mice with dysbiosis received 5 mL of Lactobacillus casei fermented milk by daily gavage after internal fixation of femoral fractures, and postoperative fracture healing was evaluated by X-ray, micro-CT scan, and HE staining, which showed faster growth of the broken ends of the femur and the presence of more callus. Serological tests showed decreased levels of RANKL and Ang II (p<0.05). Similarly, immunohistochemical results also showed increased expression of α smooth muscle actin in callus tissue. These results suggest that oral antibiotics can lead to dysbiosis of the gut microbiota in mice, which in turn leads to the development of osteoporosis. In contrast, probiotic treatment promoted fracture healing in osteoporotic mice after dysbiosis, and the probiotic effect on fracture healing may be produced by inhibiting the RAS/RANKL/RANK pathway.

Gut microbiota can affect bone quality by regulating serum estrogen levels.

Germ-free (GF) animals and animal models of the antibiotic disruption of gut microbiota are widely used to explore studies of gut microbiota-host interactions. The role of gut microbiota in bone growth and development has been well explained in studies on GF mice, indicating that changes in the gut microbiota may affect normal bone developmental processes. The mechanisms, however, are yet unclear. This study aims to clarify the effect of antibiotic treatment disrupting the gut microbiota on bone development in mice and investigate the possible causes of this effect. Our results show that long-term antibiotic feeding significantly alters gut microbiota composition in mice, reduces the bone mineral density of the spinal region, and leads to changes in trabecular microstructure. Interestingly, we found a significant decrease in the serum estrogen levels in mice treated with antibiotics, suggesting that gut microbiota may affect bone quality by regulating serum estrogen levels. These results may help understand how gut ecological dysregulation affects sex hormones and provide a new conception for the clinical treatments of osteoporosis.

Adipose-derived mesenchymal stem cells with hypoxic preconditioning improve tenogenic differentiation.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs), as seed cells for tendon tissue engineering, are promising for tendon repair and regeneration. But for ADSCs, diverse oxygen tensions have different stimulatory effects. To explore this issue, we investigated the tenogenic differentiation capability of ADSCs under hypoxia condition (5% O2) and the possible signaling pathways correspondingly. The effects of different oxygen tensions on proliferation, migration, and tenogenic differentiation potential of ADSCs were investigated. METHODS: P4 ADSCs were divided into a hypoxic group and a normoxic group. The hypoxic group was incubated under a reduced O2 pressure (5% O2, 5% CO2, balanced N2). The normoxic group was cultured in 21% O2. Two groups were compared: HIF-1α inhibitor (2-MeOE2) in normoxic culturing conditions and hypoxic culturing conditions. Hypoxia-inducible factor-1α (HIF-1α) and VEGF were measured using RT-qPCR. Specific HIF-1α inhibitor 2-methoxyestradiol (2-MeOE2) was applied to investigate whether HIF-1α involved in ADSCs tenogenesis under hypoxia. RESULTS: Hypoxia significantly reduced proliferation and migration of ADSCs. Continuous treatment of ADSCs at 5% O2 resulted in a remarkable decrease in HIF-1α expression in comparison with 20% O2. Additionally, ADSCs of hypoxia preconditioning exhibited higher mRNA expression levels of the related key tenogenic makers and VEGF than normoxia via RT-qPCR measurement (p ˂ 0.05). Furthermore, the effects of hypoxia on tenogenic differentiation of ADSCs were inhibited by 2-MeOE2. Hypoxia can also stimulate VEGF production in ADSCs. CONCLUSIONS: Our findings demonstrate that hypoxia preconditioning attenuates the proliferation and migration ability of ADSCs, but has positive impact on tenogenic differentiation through HIF-1α signaling pathway.

Effects of hypoxia on Achilles tendon repair using adipose tissue-derived mesenchymal stem cells seeded small intestinal submucosa.

BACKGROUND: The study was performed to evaluate the feasibility of utilizing small intestinal submucosa (SIS) scaffolds seeded with adipose-derived mesenchymal stem cells (ADMSCs) for engineered tendon repairing rat Achilles tendon defects and to compare the effects of preconditioning treatments (hypoxic vs. normoxic) on the tendon healing. METHODS: Fifty SD rats were randomized into five groups. Group A received sham operation (blank control). In other groups, the Achilles tendon was resected and filled with the original tendon (Group B, autograft), cell-free SIS (Group C), or SIS seeded with ADMSCs preconditioned under normoxic conditions (Group D) or hypoxic conditions (Group E). Samples were collected 4 weeks after operation and analyzed by histology, immunohistochemistry, and tensile testing. RESULTS: Histologically, compared with Groups C and D, Group E showed a significant improvement in extracellular matrix production and a higher compactness of collagen fibers. Group E also exhibited a significantly higher peak tensile load than Groups D and C. Additionally, Group D had a significantly higher peak load than Group C. Immunohistochemically, Group E exhibited a significantly higher percentage of MKX + cells than Group D. The proportion of ADMSCs simultaneously positive for both MKX and CM-Dil observed from Group E was also greater than that in Group D. CONCLUSIONS: In this animal model, the engineered tendon grafts created by seeding ADMSCs on SIS were superior to cell-free SIS. The hypoxic precondition further improved the expression of tendon-related genes in the seeded cells and increased the rupture load after grafting in the Achilles tendon defects.

Retraction of "Roflumilast Ameliorates Isoflurane-Induced Inflammation in Astrocytes via the CREB/BDNF Signaling Pathway".

[This retracts the article DOI: 10.1021/acsomega.0c04799.].

Propofol regulates activated macrophages metabolism through inhibition of ROS-mediated GLUT1 expression.

OBJECTIVE: Activated macrophages undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, which plays a critical role in inflammation. Increasing evidence suggests the important role of propofol in the regulation of inflammatory response and metabolism, but the effect of propofol on the metabolic shift in macrophage, and the mechanisms involved remain unclear. METHODS: The effect of propofol on the metabolic switch was analyzed by extracellular acidification rate and oxygen consumption rate assays. The effect of propofol on glycolysis was analyzed by lactate and glucose uptake assay. The mRNA, protein, cell surface levels of glucose transporter 1 (GLUT1) and the silencing of GLUT1 were employed to understand the effects of GLUT1-mediated metabolism by propofol. Finally, to understand the antioxidation of propofol on the regulation of metabolism, the reactive oxygen species (ROS) production and NADPH activity were performed. RESULTS: We show that propofol can change the metabolic pathway switch from aerobic glycolysis to OXPHOS in LPS-activated macrophages. Moreover, propofol suppresses aerobic glycolysis via inhibited GLUT1-mediated glucose uptake. Furthermore, we show that propofol reduces ROS overproduction, which in turn inhibits GLUT1 expression. Finally, we find that propofol reduces ROS production via inhibits NADPH activity. CONCLUSION: These findings shed light on the function and mechanism of propofol in the metabolic switch and highlight the importance of targeting metabolism by propofol in the clinical medication of inflammatory diseases.

Roflumilast Ameliorates Isoflurane-Induced Inflammation in Astrocytes via the CREB/BDNF Signaling Pathway.

Background and purpose: Astrocyte-mediated neuroinflammation plays an important role in anesthetic isoflurane-induced cognitive impairment. Roflumilast, a selective inhibitor of phosphodiesterase-4 (PDE-4) used for the treatment of chronic obstructive pulmonary disease (COPD), has displayed a wide range of anti-inflammatory capacity in different types of cells and tissues. In the current study, we aimed to investigate whether roflumilast possesses a protective effect against isoflurane-induced insults in mouse primary astrocytes. Methods: Primary astrocytes were isolated from the cerebral cortices of immature rats. The production of NO was determined using DAF-FM DA staining assay. QRT-PCR and western blot were used to evaluate the expression levels of iNOS, COX-2, and BDNF in the astrocytes treated with different therapies. The gene expressions and concentrations of IL-6 and MCP-1 released by the astrocytes were detected using qRT-PCR and ELISA, respectively. The expression levels of phosphorylated CREB and PGE2 were determined using western blot and ELISA, respectively. H89 was introduced to evaluate the function of CREB. Recombinant human BDNF and ANA-12 were used to verify the role of BDNF. Results: The upregulated iNOS, excessive production of NO, IL-6, and MCP-1, and activated COX-2/PGE2 signaling pathways in the astrocytes induced by isoflurane were significantly reversed by the introduction of roflumilast, in a dose-dependent manner. Subsequently, we found that BDNF could be upregulated by roflumilast, which was verified to be related to the activation of CREB and blocked by H89 (a CREB inhibitor). In addition, the COX-2/PGE2 signaling pathway activated by isoflurane can be inactivated by recombinant human BDNF. Finally, the regulatory effect of roflumilast against the isoflurane-activated COX-2/PGE2 signaling pathway was significantly blocked by ANA-12, which is a BDNF inhibitor. Conclusion: Roflumilast might ameliorate isoflurane-induced inflammation in astrocytes via the CREB/BDNF signaling pathway.

Wrist tuberculosis-experience from eighteen cases: a retrospective study.

BACKGROUND: Wrist tuberculosis is a rare disease, which is easy to be misdiagnosed, leading to delayed treatment and poor prognosis. In this study, the clinical manifestations, diagnosis, treatment, and prognosis of 18 cases of wrist tuberculosis were analyzed retrospectively. METHODS: A retrospective study was conducted, investigating tuberculosis of the wrist, diagnosed in 18 patients from August 2013 to November 2018. Puncture biopsy confirmed the diagnosis. The study includes 11 males and 7 females, and 8 left and 10 right wrists. The average age was 53.5 ± 18.3 years and ranged from 15 to 81 years. The disease course was 1 to 42 months, with an average of 15.1 ± 11.3 months. Eighteen patients were underwent surgery and chemotherapy, 3 patients with severe bone defects were treated with wrist fusion, and 15 patients were underwent focus removal. The Gartland and Werley score, DASH score, the range of motion (ROM), grip strength, and imaging examinations were used to evaluate the postoperative recovery of the patients. RESULTS: Eighteen patients were followed up for 15 to 77 months, with an average follow up of 39.7 ± 15.3 months. The ESR and CRP levels were normal for all patients after chemotherapy. No recurrence of tuberculosis was observed in any of the patients. Among the 15 focus removals, the Gartland and Werley scores at admission, two weeks of chemotherapy, 1 month after surgery, and the last follow-up were 21.73 ± 4.33, 18.60 ± 3.16,11.27 ± 2.79, and 5.07 ± 2.28, respectively; and the DASH scores were 45.87 ± 5.58, 39.47 ± 4.72, 22.67 ± 6.54, and 6.73 ± 2.94, respectively. The range of motion (ROM) of the wrist and grip strength improved significantly when compared to those at admission. Among the three cases of wrist fusion, 2 were fixed with a steel plate and the fixation position of wrist joint was good. One case was fixed with Kirschner wire and resulted in a slightly deformed wrist joint. CONCLUSION: For patients with wrist tuberculosis, early diagnosis, preoperative and postoperative chemotherapy, thorough focus removal, and appropriate fixation of the affected limb can help restore the function of the affected wrist, reduce the recurrence rate, and improve the quality of life.

LncRNA SOX2-OT is a novel prognostic biomarker for osteosarcoma patients and regulates osteosarcoma cells proliferation and motility through modulating SOX2.

Long noncoding RNA (LncRNA) SOX2 overlapping transcript (SOX2-OT) has been shown to serve an oncogenic role in human lung cancer, hepatocellular carcinoma, and gastric cancer. However, the clinical significance and biological function of lncRNA SOX2-OT in osteosarcoma are still unclear. LncRNA SOX2-OT expression was measured in osteosarcoma tissues and cell lines. Loss-of-function and gain-of-function studies were performed to observe the effects of lncRNA SOX2-OT on osteosarcoma cells proliferation, migration, invasion, and expressions of cancer stem cell biomarker. The relationship between lncRNA SOX2-OT and SOX2 was analyzed in osteosarcoma tissues and cells. Rescued-function studies were conducted to confirm the role of SOX2 in the regulation of lncRNA SOX2-OT in osteosarcoma cells migration, invasion, and expression of cancer stem cell biomarkers. In our results, lncRNA SOX2-OT expression was increased in osteosarcoma tissues and cell lines, and associated with malignant status and overall survival in osteosarcoma patients. LncRNA SOX2-OT regulated osteosarcoma cells proliferation, migration, invasion, and expression of cancer stem cell biomarkers. LncRNA SOX2-OT positively regulated SOX2 expression in osteosarcoma cells and positively associated with SOX2 expression in osteosarcoma tissues. The rescued-function studies suggested that SOX2 is necessary for lncRNA SOX2-OT induced osteosarcoma cells migration, invasion, and expression of cancer stem cell biomarkers. In conclusion, lncRNA SOX2-OT is a prognostic biomarker for osteosarcoma patients and serves an oncogenic role to regulate osteosarcoma cells migration, invasion, and expression of cancer stem cell biomarkers. © 2017 IUBMB Life, 69(11):867-876, 2017.

Development of a new model for acute myocardial infarction in rabbits.

The rabbit left anterior descending coronary artery is not macroscopically apparent; this often leads to failure in creation of an acute myocardial infarction (AMI) model. In order to devise a simple method with good reproducibility and high success rate for use as a rabbit AMI model, a new surgical technique was developed, in which the obtuse marginal (OM) branch of the left circumflex coronary artery was coagulated with an electric knife using a left parasternal approach. Four weeks after OM branch coagulation, an electrocardiogram (ECG), blood biochemistry analysis, echocardiographic measurements and pathologic analysis were performed. The left parasternal approach provided the surgeon clear visualization of the targeted blood vessel to accurately identify the proper site to occlude. The successful development of AMI was confirmed by ST segment elevation on the ECG, by high levels of AMI-related markers in blood samples, by cardiac functional damage reflected on echocardiographic images and by changes in pathological sections. Furthermore, an acceptable success rate and low mortality were achieved. Hence, this surgical technique was suggested to be a highly reliable and reproducible method to induce AMI in rabbits for the assessment of new therapeutic interventions or regenerative approaches.

[Short-term effectiveness of bone cement combined with screws for repairing tibial plateau defect in total knee arthroplasty].

Objective: To summarize the effectiveness of bone cement combined with screws for repairing tibial plateau defect in total knee arthroplasty (TKA). Methods: Between March 2013 and March 2016, 30 patients were treated with TKA and bone cement combined with screws for repairing tibial plateau defect. Of the 30 patients, 8 were male and 22 were female, with an average age of 64.7 years (range, 55-71 years). And 17 cases were involved in left knees and 13 cases in right knees; 22 cases were osteoarthritis and 8 cases were rheumatoid arthritis. The disease duration ranged from 9 to 27 months (mean, 14 months). Knee Society Score (KSS) was 41.63±6.76. Hospital for Special Surgery Knee Score (HSS) was 38.10±7.00. The varus deformity of knee were involved in 19 cases and valgus deformity in 11 cases. According to the Rand classification criteria, tibial plateau defect were rated as type Ⅱb. Results: All incisions healed by first intention, without infection or deep vein thrombosis. All the patients were followed up 27.5 months on average (range, 10-42 months). At last follow-up, HSS score was 90.70±4.18 and KSS score was 93.20±3.75, showing significant differences when compared with preoperative values ( t=-58.014， P=0.000; t=-60.629， P=0.000). Conclusion: It is a simple and safe method to repair tibial plateau defect complicated with varus and valgus deformities with bone cement and srews in TKA.

Grafting of mesenchymal stem cell-seeded small intestinal submucosa to repair the deep partial-thickness burns.

PURPOSE: Regenerative medicine provides many treatments for burn wounds, of which cell-seeded substitutes are encouraging for large and deep burns. To assess the feasibility of mesenchymal stem cell (MSC)-seeded small intestinal submucosa (SIS) to repair the deep partial-thickness burns, a rat study was performed. MATERIALS & METHODS: The burn model was created by contacting the dorsal surface directly with boiled water for 10 seconds. MSCs at passage 3 were seeded on the SIS before implantation. Three days after burn injury, the grafts were implanted onto the burn area. At 3, 7, 14 and 21 days post implantation, gross observation and histological assessments were performed. RESULTS: SIS alone and MSC-seeded SIS were able to accelerate the burn wound closure by enhancing granulation tissue formation, increasing wound maturity, improving revascularization, and inducing the proliferation of neo-epidermal cells. Additionally, MSC-seeded SIS was much more effective than SIS alone for the repair of deep partial-thickness burns. CONCLUSION: Both SIS and MSC-seeded SIS were able to repair the large and deep burn wounds and the loaded MSCs possessed positive effects to accelerate the wound closure in a rat model.

[HEMOSTASIS EFFECT OF COMPRESSION DRESSING THERAPY AFTER TOTAL HIP ARTHROPLASTY].

OBJECTIVE: To investigate the hemostasis effect of compression dressing therapy after total hip arthroplasty (THA). METHODS: Thirty-four patients undergding unilateral THA between December 2014 and March 2015 were randomly divided into observation group (compression dressing group, n = 17) and control group (ordinary dressing group, n = 17). There was no significant difference in gender, age, height, weight, lesion hips, pathogeny, disease duration, and preoperative hemoglobin between 2 groups (P > 0.05). The total blood loss theoretical value, the postoperative drainage volume, the visible blood loss, the hidden blood loss, the total blood transfusion volume, the number of patients receiving blood transfusion, and the related complications were compared between 2 groups. RESULTS: No significant difference was found in operation time and hospitalization time between 2 groups (t = 0.337, P = 0.738; t = 0.140, P = 0.889). The incisions healed by first intention in all patients. Six cases had incision subcutaneous hematoma in the control group, no incision subcutaneous hematoma occurred in the observation group (χ² = 7.286, P = 0.018). No postoperative complications of wound superficial infection and venous thrombosis occurred in 2 groups. After operation, blood transfusion was given in 1 case of observation group and 7 cases of control group, showing significant difference (χ² = 5.885, P = 0.039), and the total blood transfusion volume was 600 mL and 3 200 mL, respectively. There was no significant difference in preoperative blood volume and intraoperative blood loss between 2 groups (P>0.05), but the total blood loss theoretical value, the postoperative drainage volume, the visible blood loss, and the hidden blood loss in observation group were significantly less than those in control group (P < 0.05). CONCLUSION: The compression dressing should be performed after THA because it can effectively reduce postoperative blood loss and the incidence of wound hematoma.

The Expression of HMGB1 in Bone Marrow MSCs Is Upregulated by Hypoxia with Regulatory Effects on the Apoptosis and Adhesion.

Background and Aims. Hypoxia regulates the survival of mesenchymal stem cells (MSCs) but the mechanism is unclear. In hypoxia, the level of high mobility group box 1 (HMGB1) was increased in many cells which may be involved in the regulation of cell biology. The aim is to determine whether hypoxia affects the expression of HMGB1 in bone marrow MSCs (BM-MSCs) and to investigate the role of HMGB1 in the apoptosis and adhesion. Methods. BM-MSCs were exposed to hypoxia (1% O2) and normoxia (20% O2) and the expression of HMGB1 was measured by RT-PCR and western blotting. The apoptosis and adhesion of BM-MSCs were evaluated after interfered by different concentrations of HMGB1. Results. Expression of HMGB1 in BM-MSCs showed a significant upregulation in hypoxia when compared to those in normoxia. The adhesion of BM-MSCs was increased by HMGB1 in a concentration-dependent manner; the apoptosis effect of HMGB1 depended on its concentrations: HMGB1 at low concentration (50 ng/mL) promoted the apoptosis of BM-MSCs while HMGB1 at high concentration (≥100 ng/mL) reduced this apoptosis. Conclusions. Hypoxia enhanced the expression of HMGB1 in BM-MSCs with influences on apoptosis and adhesion and this could have a significant effect on the regenerative potential of MSC-based strategies.

[CLINGING LESSER TROCHANTER OSTEOTOMY WITH WAGNER CONE IN TREATMENT OF CROWE TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP IN ADULT].

OBJECTIVE: To investigate the effectivness of the clinging lesser trochanter osteotomy with the Wagner cone in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH) in adult. METHODS: Between November 2009 and September 2012, 7 female patients (9 hips) with Crowe type IV DDH were treated by THA procedures of clinging lesser trochanter osteotomy with Wagner cone, aged 24-62 years (mean, 42 years). All patients experienced severe pain and claudication. The left hip was involved in 2 cases, the right hip in 3 cases, and bilateral hips in 2 cases. The Harris score of involved hip was 50.00?7.04. The both limps were discrepancy with an average length difference of 3.4 cm (range, 3-4 cm). The results of Trendelenburg sign were positive. X-ray films showed high complete dislocation of the involved hips. RESULTS: The incisions healed by first intention. There was no complication such as infection, dislocation, prosthesis loosening, neurovascular injury. The average follow-up was 36.4 months (range, 25-48 months). Pain and claudication were improved and all patients could restore to work. The Harris score was improved to 83.42 +/- 6.47, showing significant difference when compared with preoperative score (t=8.90, P=0.00). The results of Trendelenburg sign were negative. X-ray films showed that all patients got a bony union at osteotomy site of greater trochanter at 3-6 months after operation. And the interface between prosthesis and bone was stable. There was no prosthesis loosening or sinking during the follow-up. CONCLUSION: Clinging lesser trochanter osteotomy with Wagner cone could be an option to shorten the femur in THA for patients with Crowe type IV DDH. It is effective in decreasing the risk of neurovascular injury.

[COMPARISON OF BIOLOGICAL DIFFERENCE BETWEEN BONE MARROW AND PLACENTA-DERIVED MESENCHIMAL STEM CELLS IN HYPOXIA].

OBJECTIVE: To comprehensively analyze and compare the biological difference between bone marrow mesenchymal stem cells (BMSCs) and placenta-derived MSCs (PMSCs) in hypoxia and to extend the knowledge for seed cells selection. METHODS: The domestic and foreign related literature about the effects of hypoxia microenvironment on proliferation, apoptosis, differentiation, paracrine secretion, migration, and homing ability of BMSCs and PMSCs were summarized and analysed. RESULTS: PMSCs proliferated much faster and more sensitive to the hypoxia than BMSCs; in addition, PMSCs showed stronger survivability. Similar to BMSCs, PMSCs can home to hypoxic-ischemic tissues efficiently, secrete a lot of growth factors and differentiate into tissue-specific cells to stimulate tissue regeneration. CONCLUSION: PMSCs as the seed cells will have broad application prospects in the regenerative medicine.

Regulation of high mobility group box 1 and hypoxia in the migration of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have been increasingly offered for tissue regeneration with the premise that they can survive and thrive amidst the microenvironment of injured or degenerate tissues. The role of high mobility group box 1 (HMGB1) and hypoxia in the proliferation and migration of rat bone marrow MSCs (rBM-MSCs) has been investigated. First, the effect of HMGB1 on the proliferation of rBM-MSCs was determined. Second, to evaluate the regulation of hypoxia and HMGB1 in the migration of rBM-MSCs, cells in the wound healing model were exposed to four conditions: normoxia (20% O2) and complete medium, normoxia and HMGB1, hypoxia (1% O2) and complete medium, hypoxia and HMGB1. RT-PCR and Western blotting were used to measure the expression of migration-related genes and proteins. HMGB1 inhibited the proliferation of rBM-MSCs; HMGB1 alone or together with hypoxia and promoted the migration of MSCs and upregulated the expression of HIF-1α and SDF-1. These results demonstrated that HMGB1 arrested the proliferation of rBM-MSCs, but enhanced the migration of rBM-MSCs which could be further improved by hypoxia. This study strengthens current understanding of the interaction between MSCs and the microenvironment of damaged tissues.