Application of Modified Kite Flap in Reconstruction of Facial Wounds After Operation and Case Series.

Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.

Menstrual Blood-Derived Endometrial Stem Cell Transplantation Improves Male Reproductive Dysfunction in T1D Mice by Enhancing Antioxidative Capacity.

Diabetes is known to negatively affect male reproduction. Recent clinical results have confirmed that mesenchymal stem cell (MSC)-based therapies are safe and effective for the treatment of diabetes. However, the effect and potential mechanism through which MSC transplantation improves diabetes-derived male reproductive dysfunction are still unknown. In the present study, we first established a male T1D mouse model through intraperitoneal injection of streptozotocin for five consecutive days. Subsequently, we evaluated the blood glucose levels, fertility, and histology and immunology of the pancreas, testes, and penis of T1D mice with or without transplantation of menstrual blood-derived endometrial stem cells (MenSCs) or umbilical cord mesenchymal stem cells (UCMSCs). Glucose was added to the medium in which the Leydig cells were cultured to imitate high glucose-injured cell viability. Subsequently, we evaluated the cellular viability, ROS levels, and mitochondrial membrane potential of Leydig cells treated with or without MenSC-conditioned medium (MenSC-CM) using a CCK8 assay, immunofluorescence, and flow cytometry. The targeted proteins are involved in the potential mechanism underlying MenSC-derived improvements, which was further validated via Western blotting. Collectively, our results indicated that MenSC transplantation significantly ameliorated reproductive dysfunction in male T1D mice by enhancing cellular antioxidative capacity and promoting angiogenesis. This study provides solid evidence and support for the application of MSCs to improve diabetes-induced male reproductive dysfunction.

Treating rosacea with botulism toxin: Protocol for a systematic review and meta-analysis.

BACKGROUND: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta-analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. METHODS: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. RESULTS: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self-limiting. CONCLUSION: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long-term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911).

Traditional Chinese medicine inhibits PD-1/PD-L1 axis to sensitize cancer immunotherapy: a literature review.

The Programmed death-1 (PD-1) and its programmed death-ligand 1 (PD-L1) comprise the PD-1/PD-L1 axis and maintain tumor immune evasion. Cancer immunotherapy based on anti-PD-1/PD-L1 antibodies is the most promising anti-tumor treatment available but is currently facing the thorny problem of unsatisfactory outcomes. Traditional Chinese Medicine (TCM), with its rich heritage of Chinese medicine monomers, herbal formulas, and physical therapies like acupuncture, moxibustion, and catgut implantation, is a multi-component and multi-target system of medicine known for enhancing immunity and preventing the spread of disease. TCM is often used as an adjuvant therapy for cancer in clinical practices, and recent studies have demonstrated the synergistic effects of combining TCM with cancer immunotherapy. In this review, we examined the PD-1/PD-L1 axis and its role in tumor immune escape while exploring how TCM therapies can modulate the PD-1/PD-L1 axis to improve the efficacy of cancer immunotherapy. Our findings suggest that TCM therapy can enhance cancer immunotherapy by reducing the expression of PD-1 and PD-L1, regulating T-cell function, improving the tumor immune microenvironment, and regulating intestinal flora. We hope this review may serve as a valuable resource for future studies on the sensitization of immune checkpoint inhibitors (ICIs) therapy.

MenSCs Transplantation Improve the Viability of Injured Endometrial Cells Through Activating PI3K/Akt Pathway.

Endometrial injury is one of the leading causes of female infertility and is caused by intrauterine surgery, endometrial infection, repeated abortion, or genital tuberculosis. Currently, there is little effective treatment to restore the fertility of patients with severe intrauterine adhesions and thin endometrium. Recent studies have confirmed the promising therapeutic effects of mesenchymal stem cell transplantation on various diseases with definite tissue injury. The aim of this study is to investigate the improvements of menstrual blood-derived endometrial stem cells (MenSCs) transplantation on functional restoration in the endometrium of mouse model. Therefore, ethanol-induced endometrial injury mouse models were randomly divided into two groups: the PBS-treated group, and the MenSCs-treated group. As expected, the endometrial thickness and gland number in the endometrium of MenSCs-treated mice were significantly improved compared to those of PBS-treated mice (P < 0.05), and fibrosis levels were significantly reduced (P < 0.05). Subsequent results revealed that MenSCs treatment significantly promoted angiogenesis in the injured endometrium. Simultaneously, MenSCs enhance the proliferation and antiapoptotic capacity of endometrial cells, which is likely contributed by activating the PI3K/Akt signaling pathway. Further tests also confirmed the chemotaxis of GFP-labeled MenSCs towards the injured uterus. Consequently, MenSCs treatment significantly improved the pregnant mice and the number of embryos in pregnant mice. This study confirmed the superior improvements of MenSCs transplantation on the injured endometrium and uncovered the potential therapeutic mechanism, which provides a promising alternative for patients with serious endometrial injury.

Bruceine a exerts antitumor effect against colon cancer by accumulating ROS and suppressing PI3K/Akt pathway.

Bruceine A (BA), a quassic ester from bruceine javanica, regulates diverse intracellular signal transduction pathways and manifests a variety of biological activities, however, its pharmacological mechanism in treating colon cancer (CC) is unclear. In this study, we investigated the anticancer effects of BA on CC cells and the underlying mechanisms. The network pharmacology research indicated that Akt1 and Jun and PI3K/Akt pathways are the predominant targets and critical signaling pathways, respectively, for BA treatment of CC. Meanwhile, molecular docking results implied that BA could conjugate to pivotal proteins in the PI3K/Akt pathway. BA remarkably suppressed the proliferation of CC cells HCT116 and CT26 with 48-h IC50 of 26.12 and 229.26 nM, respectively, and the expression of p-PI3K/p-Akt was restrained by BA at the molecular level as verified by Western blot assay. Further mechanistic studies revealed BA impacted cell cycle-related proteins by regulating the expression of P27 (a protein bridging the PI3K/Akt signaling pathway with cycle-related proteins), arresting the cell cycle in the G2 phase, inhibiting the proliferation of HCT116 and CT26, and facilitated the apoptosis in CC cells by activating the mitochondria-associated apoptosis protein Bax and accumulating reactive oxygen species, in addition to BA apparently inhibited the migration of CC cells. Taken together, our results demonstrated that BA might be a promising chemotherapy drug in the treatment of CC.

Sustainable Production and Activity Determination of Serum-Free Conditioned Medium from Menstrual Blood-Derived Endometrial Stem Cells.

Mesenchymal stem cells (MSCs) have exhibited great potential as a regenerative medicine, and MSC-derived paracrine effects, mainly including the secretion of various bioactive factors, play critical roles in MSC-based therapies. MSC-derived serum-free conditioned medium (MSC-CM) is defined as the secretome of MSC-derived bioactive factors and is considered a new cell-free therapeutic agent for disease treatment. However, the MSC-CM used in previous studies was prepared by a nearly disposable method that the MSCs were discarded after preparing MSC-CM, and the preparation time was variable; simultaneously, the viability changes of MSCs after MSC-CM preparation are still unknown. Therefore, this study takes MenSCs as a research project and aims to explore the suitable period of sustainable MenSC-CM preparation rather than using a disposable method. As expected, our results confirmed that MenSC-CM improves viability of both naïve targeted cells and H2O2-injured targeted cells, and suggested that 36 h is suitable for sustainable MenSC-CM preparation in which the angiogenic factors almost reach to the peak. Simultaneously, the MenSCs used to prepare the MenSC-CM for 36 h also maintained preferable cell viability and could be sustainably used for further MenSC-CM preparation. Moreover, the in vivo results further confirmed the improvement of MenSC-CM on promoting skin wound healing. Consequently, our results not only provide support for optimizing MSC-CM sustainable preparation based on various MSCs but also promote the comprehensive application of MenSCs in the clinic.

A Case of Giant Basal Cell Carcinoma of the Ear Complicated by Primary Cutaneous Aspergillosis.

A 78-year-old female patient with right ear agenesis presented with a skin manifestation of approximately 7 cm × 8 cm deep-invasive ulcer with well-defined borders and a small amount of yellow purulent discharge visible at the base, surrounded by pearl-like margins in a dyke-like elevation, covered with a small amount of necrotic tissue and black crust. The disease lasted for more than 20 years and was diagnosed as giant basal cell carcinoma complicated by primary cutaneous aspergillosis after two histopathological examinations of the skin lesions. There are similarities in the clinical manifestations of these two diseases, which need to be differentiated, and the simultaneous complications are infrequent. It has not been reported.

Menstrual blood-derived endometrial stem cells ameliorate the viability of ovarian granulosa cells injured by cisplatin through activating autophagy.

Although the cancer incidence showed a yearly increasing trend, the long-term survival rate of cancer patients significantly increased with the continuous improvements in cancer diagnosis and treatment. Therefore, recent strategies for cancer treatment not only focus on improving the survival rate of patients but also simultaneously consider the life quality of cancer patients, especially for those with fertility requirements. Stem cell-based therapies have exhibited promising improvement in various disease treatments, and provide hope for diseases without effective treatment. Menstrual blood-derived endometrial stem cells (MenSCs) can be noninvasively and periodically obtained from discarded menstrual blood samples and exhibit high proliferative capacity, low immunogenicity and autologous transplantation. As expected, MenSCs treatment effectively improved the viability of cisplatin-injured ovarian granulosa cells (GCs) and significantly upregulated their antiapoptotic capacity. Further results demonstrated that MenSCs treatment significantly upregulated autophagy activity in cisplatin-injured ovarian GCs, and the degree of autophagy activation was positively correlated with the viability improvement of ovarian GCs, while autophagy inhibitors significantly impaired MenSC-promoted viability improvement of cisplatin-injured ovarian GCs. Additionally, MenSCs treatment can also significantly promote the proliferation of normal GCs by activating the PI3K/Akt signaling pathway. Conclusively, MenSCs treatment not only enhanced the antiapoptotic capacity and survival of cisplatin-injured ovarian GCs by upregulating autophagy activity but also improved the viability of normal ovarian GCs by activating the PI3K/Akt signal pathway. These results provide a theoretical and experimental foundation for the clinical application of MenSCs in improving chemotherapy-induced ovarian injury and delaying ovarian senescence.

Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity. AIM: To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment. METHODS: A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot. RESULTS: MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice. CONCLUSION: MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors.

Although the evidence based on current human, animal, or molecular biology can explain some of the relationships between CDK4 and cancer, there is no pan-cancer analysis of the gene CDK4 in human skin tumors. Therefore, the potential carcinogenic effects of CDK4 in 33 tumors were initially explored in the datasets of the GEO (Gene Expression Omnibus) and the CGA (Cancer Genome Atlas). We found that CDK4 was highly expressed in most cancers and that CDK4 performance levels significantly correlated with the prognosis of cancer patients. These were found in our preliminary exploration. In addition, we used the dataset in tumors such as cutaneous melanoma or lung adenocarcinoma and found increased levels of phosphorylation of r24 l/C/h/s. In addition, fibroblast infiltration associated with CDK4 cancer was observed in head and neck, sarcoma, and melanoma skin. Using this pan-cancer study, our group has provided a comprehensive preliminary demonstration of the oncogenic effects of the CDK4 gene on different human skin tumors.

Matrine induces apoptosis and autophagy in human lung adenocarcinoma cells via upregulation of Cavin3 and suppression of PI3K/AKT pathway.

PURPOSE: Lung adenocarcinoma is one of the leading causes of mortality and its treatment is limited by the unavailability of effective chemotherapeutic agents. This study was therefore undertaken to evaluate the anticancer effects of Matrine against the human lung adenocarcinoma cells. METHODS: CCK-8 assay was used to determine cell viability. Acridine orange (AO)/ ethidium bromide (EB) staining was used for the assessment of apoptosis. Transmission electron microscopy (TEM) analysis was employed for the detection of autophagy. Western blotting was used for the determination of protein expression. RESULTS: The results showed Matrine inhibited the proliferation of the human A549 adenocarcinoma cell line with little effects on the normal MRC5 cells. Investigation of the underlying mechanisms showed that Matrine induced apoptosis in A549 cells. Matrine-induced apoptosis was linked with upregulation of Bax and suppression of Bcl-2. TEM analysis showed that matrine led to development of autophagosomes in A549 cells, suggestive of autophagy. The autophagy induced by Matrine was also accompanied by upregulation of LC3-II and Beclin-1 and suppression of p62. The assessment of the effects of Cavin3 protein showed that Matrine suppressed the Cavin3 in a concentration-dependent manner. Additionally, matrine also blocked the phosphorylation of PI3K and AKT dose-dependently. CONCLUSION: Taken together, Matrine may be employed for the treatment of lung adenocarcinoma.

Multiple Injections of Autologous Adipose-Derived Stem Cells Accelerate the Burn Wound Healing Process and Promote Blood Vessel Regeneration in a Rat Model.

Stem cell-based therapies have the potential to heal burn wounds, but thus far have had limited success in clinical practice. This study aimed to test and improve the therapeutic effects of adipose-derived stem cells (ASCs) on burn wound healing in a rat model. We also explored the role of ASCs in burn wound healing We first isolated the autologous ASCs of each Sprague-Dawley rat used in this experiment and expanded them in vitro. Then, a 2-cm2 burn wound was made on the dorsal skin of each rat using a specialized heating iron. The treated rats received either one or three injections of 2 × 106 green fluorescent protein-labeled autologous ASCs, and the control rats received injections of the same volume of phosphate-buffered saline. A digital camera was employed to capture images of the wound area. We explored the role of ASCs in burn wound healing by cell tracing, evaluation of blood vessel number, analysis of a rat cytokine array panel, and cell proliferation in vivo. Multiple injections of autologous ASCs accelerated the wound healing process more efficiently compared with that observed in the control treatment. A rat cytokine array test showed that transplanting ASCs led to significantly elevated expression of VEGF. Therefore, angiogenesis was significantly improved in ASC-treated rats, as more microvessels were observed in the wound skin of the experimental rats than in that of the control rats. Transplanted ASCs not only survived in the wound bed but also participated in the blood vessel regeneration process. ASCs also accelerated the wound healing process by increasing the rate of cell proliferation in the wound skin. Our data suggest that autologous ASCs transplantation accelerated the burn wound healing process and promoted blood vessel regeneration. ASCs could potentially be used in burn wound healing treatment.

A Multicentered Randomized Study on Early versus Rescue Calsurf Administration for the Treatment of Respiratory Distress Syndrome in Preterm Infants.

OBJECTIVE: Surfactant and noninvasive ventilation are two major strategies for the treatment of neonates with respiratory distress syndrome (RDS). However, the optimal time for surfactant administering is yet controversial. This study compared the early and rescue Calsurf administration in preterm infants with RDS. STUDY DESIGN: Preterm infants born between 260/7 and 326/7 weeks of gestation and needed nasal continuous positive airway pressure (nCPAP) immediately after birth were randomly assigned to the early or rescue Calsurf treatment group. In the early treatment group, neonates were intubated, administered surfactant with bag-mask ventilation, and extubated to nCPAP (INSURE [intubation-surfactant-extubation]). In the rescue treatment group, InSurE was given until the clinical manifestation and chest X-ray displayed RDS. The primary outcome was to compare the reintubation rate within 72 hour age between the two groups. RESULTS: Among 305 neonates randomized to the early (n = 154) and rescue (n = 151) groups, the reintubation rate within 72 hours of age in these two groups did not differ significantly (p > 0.05). The incidence of oxygen dependence until 36 weeks' corrected age was similar in both groups. CONCLUSION: No differences were observed between early and rescue Calsurf treatment groups with respect to the reintubation rate within 72 hours of age and the incidence of bronchopulmonary dysplasia.

Comparative analysis of curative effect of bone marrow mesenchymal stem cell and bone marrow mononuclear cell transplantation for spastic cerebral palsy.

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. METHODS: A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were used to evaluate the therapeutic efficacy before transplantation and 3, 6, and 12 months after transplantation. RESULTS: Three months after cell transplantation, scores in the A dimension of GMFM and the A and C dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). Six months after cell transplantation, scores in the A, B dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are higher than those of the BMMNC and the control groups (P < 0.05). Twelve months after cell transplantation, scores in the A, B, and C dimensions of GMFM and the A, B, C, D, and E dimensions of FMFM scores in the BMMSC group are all higher than those of the BMMNC and the control groups (P < 0.05). No obvious adverse effects were investigated during follow-up. CONCLUSIONS: BMMSC transplantation for the treatment of cerebral palsy is safe and feasible, and can improve gross motor and fine motor function significantly. In addition, compared with BMMNC, the motor function of children improved significantly in terms of gross motor and fine motor functions.

Neonatal mortality and morbidity among infants between 24 to 31 complete weeks: a multicenter survey in China from 2013 to 2014.

BACKGROUND: The outcome of preterm infants has been varied in different hospitals and regions in developing countries. Regular clinical monitor are needed to know the effects of health care. This study aimed to describe the survival and morbidity rates of extreme to very preterm infants in 15 neonatal-intensive care hospitals in China. METHODS: Data were collected from January 1, 2013 to December 31, 2014 for preterm neonates with gestational age (GA) between 24 and 31 complete weeks born in hospitals from our collaborative study group. The primary outcomes were survival and major morbidities prior to hospital discharge. Major morbidities included bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis. Mutivariate logistic regression was used to analyze the risk factor influencing on the outcomes. RESULTS: The preterm birth rate was 9.9 % (13 701/138 240). The proportion of extreme to very preterm infants was 1.1 % and 11.8 % respectively. The survival rate prior to discharge was increased with increasing GA (0, 24 weeks; 28 %, 25 weeks; 84.8 %, 26 weeks; 83.5 %, 27 weeks; 87.4 %, 28 weeks; 90.7 %, 29 weeks; 93.9 %, 30 weeks; 96 %, 31 weeks). Rate of survival and without severe morbidity according to GA were 0 at 24 weeks, 8 % at 25 weeks, 60.6 % at 26 weeks; 53.2 % at 27 weeks; 62.3 % at 28 weeks; 67.9 % at 29 weeks; 79.1 % at 30 weeks, 85.8 % at 31 weeks respectively. Rate of antenatal steroid use was 56 %. The antenatal steroid use was lower in GA < 28 weeks infants than that in GA between 28 and 32 weeks (28-44.3 % vs 49.7-60.1 %, P < 0.05). Infants at the lowest GAs had a highest incidence of morbidities. Overall, 58.5 % had respiratory distress syndrome, 12.5 % bronchopulmonary dysplasia, 3.9 % necrotizing enterocolitis, 15.4 % intraventricular hemorrhage, 5.4 % retinopathy of prematurity, 28.4 % patent ductus arteriosus, and 9.7 % sepsis. Mortality and morbidity were influenced by gestational age (OR = 0.891, 95 % CI: 0.796-0.999, p = 0.0047 and OR = 0.666, 95 % CI: 0.645-0.688, p = 0.000 respectively), birth weight (OR = 0.520, 95 % CI: 0.420-0.643, p = 0.000 and OR = 0.921, 95 % CI: 0.851-0.997, p = 0.041 respectively), SGA (OR = 1.861, 95 % CI: 1.148-3.017, p = 0.012 and OR = 1.511, 95 % CI: 1.300-1.755, p = 0.000 respectively), Apgar score <7 at 5 min (OR = 1.947, 95 % CI: 1.269-2.987, p = 0.002 and OR = 2.262, 95 % CI: 1.950-2.624, p = 0.000 respectively). The survival rate was increased with more prenatal steroid use (OR = 1.615, 95 % CI: 1.233-1.901, p = 0.033). CONCLUSION: Although most of the preterm infants with GAs ≥26 weeks survived, a high complication in survivors still can be observed. Rate of survival of GAs less than 26 weeks was still low, and quality improvement methods should be used to look into increasing the use of antenatal steroids in the very preterm births.

Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors.

BACKGROUND AIMS: The objective of this study was to compare the impact of umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to analyze the correlation between the efficacy and hereditary factors. METHODS: Eight pairs (16 individuals) of identical twins with CP were recruited and received allogenic UCMSC transplantation by means of subarachnoid injection. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were performed before and 1 and 6 months after the treatment to analyze the results of individuals before and after the therapy, between two individuals of an identical twin and among twin pairs. Repeated-measured data variance was used to analyze the GMFM and FMFM scores of patients before and 1 and 6 months after the therapy. RESULTS: Eight pairs (16 individuals) of children with CP had significant improvement in the GMFM at the end of the 1st and 6th months after the therapy compared with that before the therapy, whereas the amelioration of the FMFM was not statistically significant. The improvements in motor functions between two individuals of an identical twin but not among twin pairs were correlated. CONCLUSIONS: UCMSC transplantation significantly improves GMFM in children with CP; motor function improvements in the GMFM between two individuals of an identical twin were closely correlated, but improvements among twin pairs were not correlated. We hypothesize that hereditary factors contribute to the mechanisms of UCMSC transplantation in motor function improvement in children with CP.

Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury.

BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSCs) have a considerable advantage and potential in treating for central nervous system diseases and have become a novel alternative treatment for spinal cord injury. This study aims to compare the neurological function outcome of stem cell transplantation, rehabilitation therapy, and self-healing for sequelae of spinal cord injury. METHODS: Thirty-four cases of thoracolumbar spinal cord injury were randomly divided into three groups: the stem cell transplantation group was given CT-guided UCMSC transplantation twice; the rehabilitation group received rehabilitation therapy; and the blank control group did not receive any specific treatment. AIS grading, ASIA scoring, the manual muscle strength and muscle tension scale, and the Barthel index were used to evaluate the clinical outcome. Urodynamic examination was also performed for patients in the UCMSC group and the rehabilitation therapy group. RESULTS: Seven of the ten patients in the UCMSC group had significant and stable improvement in movement, self-care ability, and muscular tension; five of the forteen patients (36%) in the rehabilitation group also had certain improvement in these aspects. Urodynamic examination demonstrated that patients in the UCMSC group exhibited an increase in maximum urinary flow rate and maximum bladder capacity, as well as a decrease in residue urine volume and maximum detrusor pressure. The rehabilitation group exhibited decreased maximum bladder capacity, but no perceptible change in maximum urinary flow rate, residue urine volume or maximum detrusor pressure. CONCLUSIONS: UCMSC transplantation can effectively improve neurological functional recovery after spinal cord injury, and its efficacy is superior to that of rehabilitation therapy and self-healing. TRIAL REGISTRATION: The present clinical study was registered at chictr.org (registration number: NCT01393977).

A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus.

INTRODUCTION: Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus (T2DM). However, no data are available on the efficacy and safety of allogeneic Wharton's Jelly-derived mesenchymal stem cell (WJ-MSC) transplantation in patients with T2DM. Here we performed a non-placebo controlled prospective phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM. METHODS: Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection (catheterization). They were followed up for 12 months after transplantation. The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage, fasting blood glucose (FBG), post-meal blood glucose (PBG), inflammatory markers and T lymphocyte counts. RESULTS: WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function, and reduced markers of systemic inflammation and T lymphocyte counts. No major WJ-MSC transplantation-related adverse events occurred, but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment, possibly related to intrapancreatic endovascular injection. CONCLUSIONS: Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM. The therapeutic mechanism may involve improvements in systemic inflammation and/or immunological regulation. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-ONC-10000985. Registered 23 September 2010.

RAD18 mediates resistance to ionizing radiation in human glioma cells.

Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). RAD18 a central regulator of translesion DNA synthesis (TLS), has been shown to play an important role in regulating genomic stability and DNA damage response. In the present study, we investigate the relationship between RAD18 and resistance to ionizing radiation (IR) and examined the expression levels of RAD18 in primary and recurrent GBM specimens. Our results showed that RAD18 is an important mediator of the IR-induced resistance in GBM. The expression level of RAD18 in glioma cells correlates with their resistance to IR. Ectopic expression of RAD18 in RAD18-low A172 glioma cells confers significant resistance to IR treatment. Conversely, depletion of endogenous RAD18 in RAD18-high glioma cells sensitized these cells to IR treatment. Moreover, RAD18 overexpression confers resistance to IR-mediated apoptosis in RAD18-low A172 glioma cells, whereas cells deficient in RAD18 exhibit increased apoptosis induced by IR. Furthermore, knockdown of RAD18 in RAD18-high glioma cells disrupts HR-mediated repair, resulting in increased accumulation of DSB. In addition, clinical data indicated that RAD18 was significantly higher in recurrent GBM samples that were exposed to IR compared with the corresponding primary GBM samples. Collectively, our findings reveal that RAD18 may serve as a key mediator of the IR response and may function as a potential target for circumventing IR resistance in human GBM.