[Minimally invasive intelligent innovative technologies in foot and ankle surgery: development status and prospects].

The rapid development of technology has ushered in a new era of minimally invasive and intelligent surgery.Minimally invasive surgeries, such as small incision, percutaneous surgery, arthroscopic surgery, and endoscopic surgery, have contributed to less invasive surgical trauma, better cosmesis, and faster recovery. Furthermore, the recent adoption of artificial intelligence (AI) has introduced new assistances and tools for minimally invasive foot and ankle surgery. By the help of advanced AI algorithms, surgeons can accurately make diagnose and personalized treatment strategies. Applications of computer-assisted navigation systems and robotics have facilitated precise surgical procedures and real-time confirmation of surgical outcomes. Foot and ankle surgery has lagged behind other surgical specialties in adopting these advancements. Currently, the integration of various forms of minimally invasive surgery and AI technology stand as the main trend in the development of foot and ankle surgery. It is believed that in the near future, intelligent minimally invasive surgery will become the mainstream in the domain of foot and ankle.

[The efficiency of total endoscopic surgery with preferential incision of the tendon sheath and traditional open surgery for the treatment of peroneal tendondislocation].

Objective: To compare the outcomes between the patients of peroneal tendon dislocation treated by either total endoscopic surgery with preferential incision of the tendon sheath or traditional open surgery. Methods: This is a retrospective cohort study. The clinical data of 45 patients with peroneal tendon dislocation were operated at the Department of Sports Medicine and Joint Surgery, Nanjing First Hospital from July 2016 to June 2020. There were 26 males and 19 females,aged (31.2±9.3) years (range: 17 to 45 years). Among them,23 patients underwent open peroneal tendon groove deepening followed by tendon sheath repair(traditional open group), and the other 22 patients underwent similar operations but all-endoscopically with preferential incision of peroneal tendon sheath(total endoscopic group). The perioperative data of patients were collected, and pain visual analogue score (VAS) was used to evaluate the pain changes before and after surgery and during the follow-up period, and the American Orthopaedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH), range of motion (ROM), the MOS item short form health survey (SF)-36, and the homemade questionnaire of patient satisfaction were used to evaluate the patients' outcomes after the operation, and CT scan was carried out to observe the deepening of the fibular groove and MRI to observe the status of the peroneal tendon and sheath during the follow-up. Independent sample t test, Wilcoxon rank sum test were used for comparison of quantitative data between groups. Chi-square test,Mann-whitney U or Fisher exact test was used for comparison of classified data, respectively;repeated measure ANOVA and paired sample t test were used for comparison of quantitative data before and after surgery in groups. Results: There was no statistically significant difference between the two groups of patients in terms of gender, age, disease duration, side of injury, and injury typing (all P>0.05). There was no significant difference between the two groups in terms of operation time ((47.9±5.4)minutes vs. (47.2±6.3)minutes;t=0.402, P=0.690), but the incision length ((2.17±0.35)cm vs.(5.97±0.42)cm;t=32.892,P<0.01) and hospitalization time ((4.0±1.7)days vs. (7.6±3.6)days;t=4.249,P<0.01) were significantly shorter in the total endoscopic group than those in the traditional open group. All patients were followed up for more than 12 months, and the follow-up time was (19.2±3.9) months (range: 12 to 24 months). The total endoscopic group showed a significant increase in VAS, AOFAS-AH, SF-36 score and patient satisfaction rate at 3 months postoperatively and the last follow-up (all P<0.05). Three months after surgery, the ROM in the total endoscope group was higher than that in the traditional group ((62.14±1.46) ° vs. (53.13±1.52) °;t=20.315, P<0.01), and there was no significant difference between the two groups at the last follow-up ((63.18±1.10) ° vs. (63.48±2.43) °;t=0.531, P=0.599). The imaging examination results showed that the situation of fibular groove deepening in the total endoscopic group was better than that in the traditional open group. Conclusion: Total endoscopic surgery with preferential incision of the tendon sheath has the advantages of minimally invasivenessas compared with traditional open surgery with faster recovery and better outcome.

[Evaluation of arthroscopic anterior talofibular ligament and calcaneofibular ligament repair separately for chronic lateral ankle instability in conjunction with subtalar instability].

Objective: To investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI). Methods: This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results: The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2(t=9.482, P<0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1(t=-13.132, P<0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 (t=-12.510, P<0.01). There was no complication such as recurred instability or joint stiffness. Conclusions: Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

[Resveratrol protects dopaminergic neurons in a mouse model of Parkinson's disease by regulating the gut-brain axis via inhibiting the TLR4 signaling pathway].

OBJECTIVE: To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons. METHODS: Fifty-two C57BL/6J mice were randomized into control group (n= 12), MPTP group (n=14), MPTP + resveratrol (30 mg/kg) group (n=13), and MPTP + resveratrol (90 mg/kg) group (n=13), and mouse models were established by intraperitoneal MPTP (30 mg/kg) injection for 7 days in the latter 3 groups. Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice. Western blotting was used to detect the expression of TH, α-syn, ZO-1, Claudin-1, TLR4, MyD88, and NF-κB in the brain tissues of the mice. Immunohistochemistry, immunofluorescence, ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier. RESULTS: Compared with those in the normal control group, the mice in MPTP group showed significant changes in motor function, number of dopaminergic neurons, neuroinflammation, levels of LPS and LBP, and expressions of tight junction proteins in the intestinal barrier. Resveratrol treatment significantly improved motor function of the PD mice (P < 0.01), increased the number of neurons and TH protein expression (P < 0.05), down-regulated the expressions of GFAP, Iba-1, and TLR4, lowered fecal and plasma levels of LPS and LBP (P < 0.05), restored the expression levels of ZO-1 and Claudin-1 (P < 0.01), and down-regulated the expressions of TLR4, MyD88, and NF-κB in the colon tissue (P < 0.05). The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi. CONCLUSION: Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response, thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

Knockdown of Long Noncoding RNA CCAT2 Suppresses Malignant Phenotype in Human Laryngeal Squamous Cell Carcinoma.

This study aimed to explore the biological role and mechanism underlying the effects of colon cancer-associated transcript 2 (CCAT2), a long noncoding RNA (lncRNA) in human laryngeal squamous cell carcinoma (LSCC). CCAT2 expression levels in clinical LSCC samples and TU-212 cell line were evaluated by quantitative real-time PCR. The correlation of CCAT2 expression level with clinical-pathological characteristics of patients and their prognosis was analyzed. The functional role of CCAT2 in human LSCC was assessed by Cell Counting Kit-8, Transwell assay, flow cytometric analysis, and LSCC xenograft experiment in vivo. The expression of potential targeted proteins was detected by Western blotting and immunohistochemistry. We found that expression of CCAT2 was significantly elevated in LSCC tissues and TU-212 cells (p<0.05). Survival analysis showed that LSCC patients with high expression of CCAT2 had a shorter 5-year overall survival rate than those with low expression (p<0.05). In addition, CCAT2 silencing with short hairpin RNA significantly decreased the proliferative and invasive potential of TU-212 cells (p<0.05) and promoted their apoptosis. In Nude mice, CCAT2 knockdown suppressed the growth of tumor and decreased its volume and weight in comparison with the controls (p<0.05). In TU-212 cells, CCAT2 silencing with short hairpin RNA significantly down-regulated the expression of ß-catenin and CDK8 (p<0.05). Thus, knockdown of CCAT2 suppresses proliferation and invasion of the cells and inhibits Wnt/ß-catenin signaling pathway in LSCC, which indicates novel therapeutic targets and prognostic indicators in patients with LSCC.

Passion fruit peel and its zymolyte enhance gut function in Sanhuang broilers by improving antioxidation and short-chain fatty acids and decreasing inflammatory cytokines.

The passion fruit peel (PFP) is the by-product of juice processing and is rich in phenolic compounds and dietary fibers. As the high ADF content in PFP (34.20%), we proceeded to treat PFP with cellulase. The ADF decreased to 16.70% after enzymatic processing, and we supposed that enzymolytic passion fruit peel (EPF) should have a greater growth performance than PFP to broilers. Two trials were conducted to evaluate the effects of dietary PFP or EPF supplementation on growth performance, serum biochemical indices, meat quality, and cecal short-chain fatty acids, microbiota, and metabolites in broilers. In Exp. 1, 180 1-day-old Sanhuang broilers (male, 36.17 ± 2.47 g) were randomly allocated into 3 treatments, with 6 replicates in each treatment. The 3 experimental diets included 1 basal diet (control) and 2 PFP-added diets supplemented with 1 and 2% PFP, respectively. The trial lasted for 42 d. In Exp. 2, 144 Sanhuang broilers (male, 112-day-old, 1.62 ± 0.21 kg) were randomly allocated to 3 treatments. Each treatment was distributed among 6 pens, and each pen contained 8 broilers. The 3 treatment diets included: a control diet, a positive control diet supplementing 75 mg/kg chlortetracycline, and the experimental diet supplementing 3% EPF. The trial lasted for 56 d. Results showed that dietary 1 and 2% PFP addition did not affect growth performance in Exp. 1, and the 3% EPF supplementation had a negative effect on ADFI (P < 0.05) in Exp. 2. A decreased serum triglyceride (P < 0.05) in broilers was observed in Exp. 1. Broilers fed EPF had a higher glutathione peroxidase (GSH-Px) (P < 0.05), and lower levels of tumor necrosis factor-α (TNF-α) (P < 0.05) and glucose (P < 0.05) in Exp. 2. We also found that broilers from PFP or EPF-treated treatments had an increased butyrate content and higher microbial diversity in the cecum. The effects of antioxidation, anti-inflammatory function, and elevated SCFAs were confirmed after the microbe and untargeted metabolomic analysis. Dietary EPF supplementation significantly increased the SCFA-generating bacteria, anti-inflammatory-related bacteria, the antioxidant-related and anti-inflammatory-related metabolites. Moreover, dietary 3% EPF addition positively affects the biosynthesis of phenylpropanoids, which strongly correlate with the antioxidant and anti-inflammatory properties. In conclusion, the proper addition level did not affect the growth performance, and the PFP and EPF could improve the antioxidation state, anti-inflammatory activity, and intestinal functions of Sanhuang broilers to some extent.

FE UPTAKE-INDUCING PEPTIDE1 maintains Fe translocation by controlling Fe deficiency response genes in the vascular tissue of Arabidopsis.

FE UPTAKE-INDUCING PEPTIDE1 (FEP1), also named IRON MAN3 (IMA3) is a short peptide involved in the iron deficiency response in Arabidopsis thaliana. Recent studies uncovered its molecular function, but its physiological function in the systemic Fe response is not fully understood. To explore the physiological function of FEP1 in iron homoeostasis, we performed a transcriptome analysis using the FEP1 loss-of-function mutant fep1-1 and a transgenic line with oestrogen-inducible expression of FEP1. We determined that FEP1 specifically regulates several iron deficiency-responsive genes, indicating that FEP1 participates in iron translocation rather than iron uptake in roots. The iron concentration in xylem sap under iron-deficient conditions was lower in the fep1-1 mutant and higher in FEP1-induced transgenic plants compared with the wild type (WT). Perls staining revealed a greater accumulation of iron in the cortex of fep1-1 roots than in the WT root cortex, although total iron levels in roots were comparable in the two genotypes. Moreover, the fep1-1 mutation partially suppressed the iron overaccumulation phenotype in the leaves of the oligopeptide transporter3-2 (opt3-2) mutant. These data suggest that FEP1 plays a pivotal role in iron movement and in maintaining the iron quota in vascular tissues in Arabidopsis.

[Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study].

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.

Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility.

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

LncRNA AFAP1-AS1 promotes proliferation ability and invasiveness of bladder cancer cells.

OBJECTIVE: It was the aim of this study to explore the role and mechanism of long non-coding RNA (lncRNA) AFAP1-AS1 in the progression of bladder cancer (BCa) by in vitro experiments. PATIENTS AND METHODS: AFAP1-AS1 levels in 40 pairs of clinical BCa tissue samples and normal ones collected from BCa patients were determined, and paired sample t-test was applied to compare the differences between groups. The prognosis data of patients with BCa were collected, and survival analysis and t-test were performed to specify the interplay between AFAP1-AS1 and the prognosis of BCa patients. Subsequently, AFAP1-AS1 expression level in BCa and normal cells were further confirmed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), and transwell assays were performed to figure out the influence of this lncRNA on the proliferation ability and invasiveness of BCa cells. Meanwhile, the interaction between AFAP1-AS1 and its sense mRNA was analyzed. We used co-transfection technology to simultaneously transfect si-AFAP1-AS1 and pcDNA3.1-AFAP1 or their corresponding negative controls into BCa cells, and cell proliferation and invasion ability in different subgroups were determined to explore the underlying mechanism through which AFAP1-AS1 plays a role in BCa progression. RESULTS: No matter in BCa tissues or in cell samples, compared to the corresponding normal controls, AFAP1-AS1 was found highly expressed; at the same time, in invasive bladder cancer tissues, the expression level of AFAP1-AS1 was also higher than that in non-invasive tissues. Meanwhile, survival analysis revealed that patients with BCa with high expression of AFAP1-AS1 owned a shorter overall survival rate than those with low expression, indicating a negative interplay between AFAP1-AS1 expression and patients' prognosis. In addition, in BCa cell lines, according to the results of CCK-8, EDU, and transwell assays, the proliferative capacity, as well as the invasive ability of BCa cells, were found weakened after downregulation of AFAP1-AS1. Meanwhile, a negative interplay was discovered between AFAP1-AS1 and its sense mRNA. Finally, the results of cell reversal experiment using co-transfection technique revealed that overexpression of AFAP1 can reverse the inhibitory impact of lncRNAAFAP1-AS1 on the malignant ability of BCa cells. CONCLUSIONS: AFAP1-AS1 may enhance the proliferation ability as well as the invasiveness of BCa cells so as to aggravate the degree of BCa malignancy.

[Interpretation of 2019 edition of Wilderness Medical Society practice guidelines for prevention and treatment of frostbite].

The Wilderness Medical Society updated and published the Wilderness Medical Society practice guidelines for the prevention and treatment of frostbite in July 2019. The guidelines provide evidence-based recommendations for the prevention and treatment of frostbite, mainly including pathophysiology, classification, prevention, and treatment of frostbite. This paper focuses on the interpretation of the guidelines, aiming at making clinical medical staff understand the new progress of frostbite treatment and providing reference for clinical practice.

Parkia speciosa empty pod extract exerts anti-inflammatory properties by modulating NFκB and MAPK pathways in cardiomyocytes exposed to tumor necrosis factor-α.

Parkia speciosa Hassk is a plant found abundantly in the Southeast Asia region. Its seeds, with or without pods, have been used in traditional medicine locally to treat cardiovascular problems. The pathogenesis of cardiovascular diseases involves inflammation and oxidative stress. Based on this information, we sought to investigate the potential protective effects of Parkia speciosa empty pod extract (PSE) on inflammation in cardiomyocytes exposed to tumor necrosis factor-α (TNF-α). H9c2 cardiomyocytes were divided into four groups; negative control, TNF-α, PSE + TNF-α and quercetin + TNF-α. Groups 3 and 4 were pretreated with PSE ethyl acetate fraction of ethanol extract (500 µg/mL) or quercetin (1000 µM, positive control) for 1 h before inflammatory induction with TNF-α (12 ng/mL) for 24 h. TNF-α increased protein expression of nuclear factor kappa B cell (NFκB) p65, p38 mitogen-activated protein kinase (p38 MAPK), inducible nitric oxide synthase, cyclooxygenase-2 and vascular cell adhesion molecule-1 when compared to the negative control (p < 0.05). It also elevated iNOS activity, nitric oxide and reactive oxygen species levels. These increases were significantly reduced with PSE and quercetin pretreatments. The effects of PSE were comparable to that of quercetin. PSE exhibited anti-inflammatory properties against TNF-α-induced inflammation in H9c2 cardiomyocytes by modulating the NFκB and p38 MAPK pathways.

Post-zygotic genomic changes in glutamate and dopamine pathway genes may explain discordance of monozygotic twins for schizophrenia.

BACKGROUND: Monozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia. METHODS: We sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient. RESULTS: We found multiple twin specific sequence differences between co-twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families. CONCLUSIONS: We have identified genome-wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins.

Dexmedetomidine increases acetylation level of histone through ERK1/2 pathway in dopamine neuron.

Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg ( n = 6), 10 mg/kg ( n = 6), and 100 mg/kg ( n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via α2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine.

Integration of DNA sequence and DNA methylation changes in monozygotic twin pairs discordant for schizophrenia.

Schizophrenia is a complex mental disorder with high heritability (80%), extensive genetic heterogeneity, environmental contributions and only 50% concordance in discordant monozygotic (MZ) twins. Discordant MZ twins provide an exceptional opportunity to assess patient specific genome-wide genetic and epigenetic changes that may account for the disease phenotype. A combined analysis of genetic and epigenetic changes on the same twin pairs is expected to provide a more effective approach for two reasons. First, it is now possible to generate relatively reliable complete genome sequences as well as promoter methylation states on an individual level and second, the unaffected twin that originated from the same zygote provides a near perfect genetic match for contrast and comparison. This report deals with the combined analysis of DNA sequence data and methylation data on two pairs of discordant MZ twins that have been clinically followed for over 20 years. Results on Family 1 show that 58 genes differ in DNA sequence as well as promoter methylation in a schizophrenia-affected twin as compared to her healthy co-twin. The corresponding number for family 2 was 13. The two lists are over represented by neuronal genes and include a number of known schizophrenia candidate genes and drug targets. The results argue that changes in multiple genes via co-localized genetic and epigenetic alteration contribute to a liability threshold that is necessary for development of schizophrenia. This novel hypothesis, although logical, remains to be validated.

A novel mutation links to von Hippel-Lindau syndrome in a Chinese family with hemangioblastoma.

Hemangioblastoma of the central nervous system occurs as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by a germline mutation in the VHL tumor suppressor gene. We screened a Chinese family with VHL for mutations in the VHL gene and evaluated a genetic test for diagnosing VHL disease and clinical screening of family members. DNA extracted from the peripheral blood of all live members and from tissue of deceased family members with VHL disease was amplified by polymerase chain reaction to 3 VHL gene exons. Mutations in the amplification products were compared against the Human Gene Mutation Database. The involvement of multiple organs among the kindred with VHL disease was confirmed by medical history and radiography. Of the 12 members of the 4-generation family, 5 were diagnosed with VHL disease. Patient age at the initial diagnosis was 26-36 years (mean = 31 years). The mean time was 15 (11-19 months) from symptom appearance to the first patient visit to the hospital. Sequence analysis revealed that the frameshift mutation 327del C (p.Gly39Alafs*26) in exon 1 affected all family members, but not the healthy individuals or 16 unrelated controls. Members without gene mutation showed no clinical manifestation of VHL disease. We detected a conserved novel frameshift mutation in the VHL gene of the family members that contributes to VHL. DNA analysis of VHL is advantageous for VHL diagnosis. We developed a quick and reliable method for VHL diagnosis.

Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes.

INTRODUCTION: Gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. We explored whether fetal exposure to a diabetic environment is associated with fetal endothelial progenitor cell dysfunction, and whether vitamin D can reverse the impairment. METHODS: Nineteen women with uncomplicated pregnancies and 18 women with GDM were recruited before delivery. Time to first appearance of endothelial colony forming cell (ECFC) colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined. Angiogenesis-related functions of ECFCs in vitro were tested in the presence or absence of vitamin D. RESULTS: Fetal ECFCs from GDM pregnancies formed fewer colonies in culture (P = 0.04) and displayed reduced proliferation (P = 0.02), migration (P = 0.04) and tubule formation (P = 0.03) compared to uncomplicated pregnancies. Fetal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P < 0.05) and less tubule formation (P < 0.05) than normoglycemic control. Vitamin D significantly improved the dysfunction of fetal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia. DISCUSSION: Fetal ECFCs from GDM pregnancies or ECFCs exposed to hyperglycemia in vitro exhibit reduced quantity and impaired angiogenesis-related functions. Vitamin D significantly rescues these functions. These findings may have implications for vascular function of infants exposed to a diabetic intrauterine environment.

Disease outbreaks caused by steppe-type rabies viruses in China.

While rabies is a significant public health concern in China, the epidemiology of animal rabies in the north and northwest border provinces remains unknown. From February 2013 to March 2014, seven outbreaks of domestic animal rabies caused by wild carnivores in Xinjiang (XJ) and Inner Mongolia (IM) Autonomous Regions, China were reported and diagnosed in brain samples of infected animals by the fluorescent antibody test (FAT) and RT-PCR. Ten field rabies viruses were obtained. Sequence comparison and phylogenetic analysis based on the complete N gene (1353 bp) amplified directly from the original brain tissues showed that these ten strains were steppe-type viruses, closely related to strains reported in Russia and Mongolia. None had been identified previously in China. The viruses from XJ and IM clustered separately into two lineages showing their different geographical distribution. This study emphasizes the importance of wildlife surveillance and of cross-departmental cooperation in the control of transboundary rabies transmission.