[Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency].

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

[Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study].

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

[Preliminary studies on the role of mast cells in the phenotype and immune activation of type 2 inflammatory cytokine release of atopic dermatitis].

Objective: To investigate the role of mast cells in atopic dermatitis (AD) phenotype and the immune activation of type 2 inflammatory cytokine release. Methods: Nine AD skin samples were obtained from the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, and nine healthy skin control samples were obtained from the surgical excision of excess normal skin by orthopedic surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, which were subjected to toluidine blue staining and fluorescence staining to clarify the mast cell degranulation activation status of the AD skin lesions. We investigated whether MC903 could directly activate mast cells in vivo through the toe swelling and exudation assay in wild-type mice; we constructed the MC903-AD model using wild-type and KitW-sh/W-sh mast cell-deficient mice in order to investigate whether mast cells affected the phenotype, histopathology, and the level of type 2 inflammatory factors in AD mice; we extracted mouse peritoneal mast cells and the ability of MC903 to activate mast cells to release inflammatory mediators in vitro was explored by calcium imaging, tryptase and ß-aminohexokinase release assays, and MCP-1 and CXCL-2 release assays. Results: The number of degranulated mast cells in an activated state was increased in skin lesions of AD patients compared to healthy controls, with (5.40±1.14) and (2.20±0.84), respectively (P<0.001). KitW-sh/W-sh mast cell-deficient AD mice had an attenuated phenotype with ADI scores of (5.50±1.05), compared to wild-type AD mice with (10.00±0.89) (P<0.001). The release of type 2 inflammatory factors in wild-type AD mice was higher than those in KitW-sh/W-sh mast cell-deficient AD mice, with IL-4 levels of (29.50±1.87) and (15.33±1.86) pg/mg (P<0.001), IL-13 levels were (6.32±0.25) and (3.93±0.22) pg/mg (P<0.001), IL-31 levels were (9.73±0.38) and (6.89±0.27) pg/mg (P<0.001), and TSLP levels were (206.00±4.43) and (99.00±4.86) pg/mg (P<0.001), respectively. MC903 could cause mast cell activation in wild-type mice, leading to increased swelling and exudation in the toes of mice, and MC903 could activate mast cells in vitro, leading to increased degranulation and release of inflammatory factors such as MCP-1 and CXCL-2. Conclusions: The number of activated mast cells was increased in skin lesions of AD patients than in healthy controls. KitW-sh/W-sh mast cell-deficient AD mice showed significantly reduced phenotype, histopathology, and type 2 inflammatory factor levels compared with wild-type AD mice. MC903 activates mast cells in vivo and in vitro. Mast cells play a key role in AD phenotype and immune activation.

[Temporal trends in disease burden of major human parasitic diseases in China from 1990 to 2019].

OBJECTIVE: To analysize the temporal trends in the disease burden of major human parasitic diseases in China from 1990 to 2019, so as to provide the evidence for improving the parasitic disease control strategy in China. METHODS: The disability-adjusted life years (DALYs) of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis in China from 1990 to 2019 were captured from the Global Burden of Disease Study 2019 (GBD 2019), and age- and gender-specific DALYs of parasitic diseases were estimated. The temporal trends in DALYs of malaria, intestinal nematode infections, schistosomiasis, food-borne trematodiases, cysticercosis and echinococcosis were evaluated in China from 1990 to 2019 using average annual percent change (AAPC) with Joinpoint regression analysis. RESULTS: The DALYs were 643 836.42 person-years due to food-borne trematodiases, 156 853.03 person-years due to cysticercosis, 79 764.62 person-years due to schistosomiasis, 70 989.73 person-years due to intestinal nematode infections, 4 258.61 person-years due to echinococcosis and 264.86 person-years due to malaria in China in 2019, respectively. The overall DALYs of six parasitic diseases were higher among men (546 441.93 person-years) than among women (409 525.33 person-years), and were greater among adults at ages of 14 to 65 years (684 780.84 person-years) than among children at 14 years and lower (35 437.38 person-years) and the elderly at ages of 65 years and older (235 749.04 person-years). During the period from 1990 to 2019, food-borne trematodiases were the leading cause of DALYs among the six parasitic diseases, and cysticercosis shifted from the fourth leading cause in 1990 to the second leading cause of DALYs in China in 2019, while intestinal nematode infections shifted from the second leading cause in 1990 to the fourth leading cause of DALYs in 2019. The DALYs of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with the fastest drop seen in DALYs due to malaria (AAPC = -19.6%, P = 0.003), followed by due to intestinal nematode infections (AAPC = -8.2%, P < 0.001) and schistosomiasis (AAPC = -3.1%, P < 0.001), and a slow decline was seen in the DALYs of food-borne trematodiases (AAPC = -1.0%, P < 0.001), while there were no significant decrease in the DALYs of echinococcosis (AAPC = -0.5%, P = 0.264) and the DALYs of cysticercosis appeared a tendency towards a rise (AAPC = 0.7%, P < 0.001). CONCLUSIONS: The disease burden of major human parasitic diseases appeared an overall tendency towards a decline in China from 1990 to 2019, with a high disease burden seen due to food-borne parasitic diseases, no remarkable reduction seen in echinococcosis, and a tendency towards a rise seen in cysticercosis. It is recommended to focus on echinococcosis control, and continue to consolidate the control achievements of other major human parasitic diseases in China; meanwhile, the surveillance and prevention of food-borne parasitic diseases should be reinforced.

[Conversion of serum anti-Schistosoma japonicum antibodies detected by immunological tests following treatment with praziquantel: a meta-analysis].

OBJECTIVE: To evaluate the conversion of serum antibodies against Schistosoma japonicum in humans and livestock detected by immunological tests following treatment with praziquantel. METHODS: The studies pertaining to serological tests of schistosomiasis japonica published from 1991 to 2020 were retrieved in electronic databases, including Chinese National Knowledge Infrastructure, WanFang Data, PubMed and ScienceDirect. Data were extracted from included studies. The publication bias was assessed with funnel plots using the software RevMan version 5.3, and the conversion of antibodies against S. japonicum was evaluated through meta-analysis. RESULTS: A total of 40 publications were included in the final meta-analysis, consisting of 33 Chinese publications and 7 English publications, and all immunological tests were performed with indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA). Pooled analysis showed that the negative rates of serum anti-S. japonicum antibody were 45.36% [95% confidential interval (CI): (43.96%, 46.76%)] and 20.83% [95% CI: (19.69%, 21.97%)] detected by ELISA and IHA within 6 months post praziquantel treatment, 62.95% [95% CI: (61.59%, 64.31%)] and 55.61% [95% CI: (54.21%, 57.01%)] within 6 to 12 months after treatment and 85.92% [95% CI: (84.94%, 86.90%)] and 86.90% [95% CI: (85.95%, 87.85%)] over 12 months after treatment, respectively. CONCLUSIONS: The negative rate of the serum anti-S. japonicum antibody by IHA and ELISA increased with the time of post-treatment with praziquantel. The overall negative rates of anti-S. japonicum antibody detected by IHA and ELISA are low within 12 months post praziquantel treatment. However, a high negative rate of anti-S. japonicum antibody is detected if there is no new contact with infested water after 12 months of praziquantel treatment.

Hyperlipidemia Impairs Osseointegration via the ROS/Wnt/ß-Catenin Pathway.

The influence of hyperlipidemia on titanium implant osseointegration and the underlying mechanisms is not well understood. This study investigates the changes in osseointegration and explores the potential mechanisms in hyperlipidemia conditions. In vivo, specialized titanium implants were implanted in the femurs of diet-induced or genetic hyperlipidemia mice. In vitro, primary murine osteoblasts were cultured on the titanium surface in high-fat medium. Results showed that hyperlipidemia led to poor osseointegration in both types of mice in vivo, and high-fat medium impaired the osteogenic differentiation of primary osteoblasts on the titanium surface in vitro. In addition, high-fat medium caused significant overproduction of reactive oxygen species (ROS) and inhibition of the Wnt/ß-catenin pathway in osteoblasts. Both N-acetyl-L-cysteine (NAC, an ROS antagonist) and Wnt3a (an activator of the Wnt/ß-catenin pathway) attenuated the poor osteogenic ability of osteoblasts. In addition, NAC reactivated the Wnt/ß-catenin pathway in osteoblasts under high-fat stimulation. These results demonstrate that hyperlipidemia impairs osseointegration via the ROS/Wnt/ß-catenin pathway and provide support for the ROS or Wnt/ß-catenin pathway as a promising therapeutic target for the development of novel drugs or implant materials to improve the osseointegration of implants in hyperlipidemic patients.

LncRNA NEAT1 accelerates the occurrence and development of diabetic nephropathy by sponging miR-23c.

OBJECTIVE: LncRNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to play an oncogenic role in the occurrence and development of diabetic nephropathy (DN). The aim of our study was to investigate the potential mechanism by which NEAT1 facilitates the progression of DN. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was carried out to determine the abundance of NEAT1, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), proliferating cell nuclear antigen (PCNA), Cyclin D1, P38, apoptosis signal-regulating kinase 1 (ASK1), Fibronectin, α smooth muscle actin (α-SMA) and miR-23c in the serum of DN patients, normal patients and mouse mesangial cells (MMCs). Cell proliferation was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), qRT-PCR and Western blot assays. Flow cytometry and Western blot were applied to measure apoptosis of MMCs. Cell fibrosis and epithelial-to-mesenchymal transition (EMT) were analyzed by qRT-PCR and Western blot. The binding sites between miR-23c and NEAT1 were predicted by starBase bioinformatics software, and the relationship was verified by dual-luciferase reporter assay. RESULTS: The enrichment of NEAT1 was elevated in the serum of DN patients and MMCs induced by high concentration of glucose. NEAT1 overexpression accelerated proliferation, fibrosis and EMT and restrained apoptosis of MMCs induced by high concentration of glucose. MiR-23c bound to NEAT1, and the inhibition of miR-23c counteracted the suppressive effect of NEAT1 depletion on proliferation, fibrosis and EMT of MMCs induced by high concentration glucose. CONCLUSIONS: LncRNA NEAT1 promoted proliferation, fibrosis and EMT while impeded apoptosis of MMCs through sponging miR-23c. LncRNA NEAT1 and miR-23c might be underlying therapeutic targets for the treatment of DN.

[The prognostic significance of peripheral lymphocyte/monocyte ratio and PET-2 evaluation in adult Hodgkin's lymphoma].

Objective: To evaluate the prognostic value of lymphocyte to monocyte ratio (LMR) and PET scan performed after first two cycles of chemotherapy (PET-2) in Hodgkin's lymphoma (HL) . Methods: The clinical data of 133 patients with HL diagnosed from January 2007 to March 2016 at the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The X-tile software was used to calculate the optimal cut-off value of LMR. Kaplan-Meier method and Cox regression were used for survival analysis. Results: The median age of 133 HL patients was 33 (18-84) years, and the male to female ratio was 1.9∶1. The optimal cut-off value of LMR was 2.5, and progression free survival (PFS) (P<0.001) and overall survival (OS) (P<0.001) were significantly lower in the LMR<2.5 group than that of LMR≥2.5. Multivariate survival analysis showed that LMR<2.5 was an independent predictor of PFS (P=0.002, HR=2.35, 95%CI 1.36-4.07) and OS (P=0.002, HR=10.36, 95%CI 2.35-45.66) in HL patients. The analysis of PET-2 from 56 HL patients showed that PET-2 positive patients had significantly poorer PFS (P=0.022) . After grouping LMR combined with PET-2, significant differences were found in PFS and OS between the three groups (P values were 0.009 and 0.012) . Conclusion: LMR<2.5 is an independent prognostic factor for patients with HL. PET-2 combined with LMR may have better prognostic value.

Inhibition of miR-17-5p promotes mesenchymal stem cells to repair spinal cord injury.

OBJECTIVE: The aim of this study was to explore the role of microRNA-17-5p (miR-17-5p) in the pathogenesis of spinal cord injury repair by mesenchymal stem cells (MSCs), and to investigate the possible underlying mechanism. MATERIALS AND METHODS: MiR-17-5p mimics and negative controls were transfected into MSCs. Dual-luciferase reporter gene assay was used to verify the functional binding between miR-17-5p and its target mRNA. After overexpression or knockdown of miR-17-5p, the expression level of target genes in MSC cells was analyzed by Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. The proliferation ability of cells was detected by cell counting kit-8 (CCK-8) assay. The effect of miR-17-5p and VEGF-A on angiogenesis was assessed by HUVEC assay. T8 spinal cord injury model was constructed in nude mice. All mice were divided into the negative control group, the SCI group, the miR-17-5p-NC group, the miR-17-5p-inhibitor group, and the miR-17-5p-inhibitor + sh-VEGF-A group. After injection of different treated MSCs at the lesion site, the proportion of intact tissue as well as reduced lumen volume was measured at 28 d. Meanwhile, the motor function of hind limbs was scored based on the Basso Beattie Bresnahan (BBB) standard scale at 7 d, 14 d, 21 d, and 28 d after transplantation, respectively. RESULTS: A binding site of miR-17-5p was found on the mRNA of VEGF-A. The protein expression of VEGF-A was strikingly altered after overexpression or knockdown of miR-17-5p. Knocking down miR-17-5p expression significantly increased the protein level of VEGF-A and GDNF. Meanwhile, miR-17-5p down-regulation significantly enhanced the viability and the angiogenic ability of MSCs. However, simultaneous knockdown of miR-17-5p and VEGF-A showed the opposite results. After spinal cord injury, the proportion of intact spinal cord tissues in mice was significantly reduced, whereas reduced lumen volume was remarkably increased. After injection of MSCs alone, the proportion of intact tissues was significantly increased. After knocking down miR-17-5p, the proportion was further increased. However, no significant effect was found on the amount of intact tissues after knocking out VEGF-A. Moreover, the reduction in cavity volume appeared to present an opposite trend comparable to the proportion of intact tissues. The BBB scores were significantly decreased in the mice model, while remarkably increased after MSC transplantation. Furthermore, the BBB score was the highest in the miR-17-5p knockout group, while VEGF-A knockout had little effect on it. In addition, no significant difference was found in the mRNA expression GFP in the spinal cord of mice in different groups after MSCs treatment. CONCLUSIONS: Inhibition of miR-17-5p up-regulates the expression of VEGF-A and GDNF in MSCs, and promotes the repair of spinal cord injury by MSCs.

MiR-26a protects type II alveolar epithelial cells against mitochondrial apoptosis.

OBJECTIVE: This study aims to investigate the miR-26a effects on H2O2-induced apoptosis of Type II alveolar epithelial cells (AEC-II) and the potential mechanism. MATERIALS AND METHODS: AEC-II cells were treated with 0.5 mmol/L H2O2 to mimic cellular model of acute lung injury. Transmitting electron microscopy (TEM) was employed to observe the change of morphological structures. After infecting with miR-26a mimics, flow cytometry was performed to detect cell apoptosis. Western blot was also done to explore mitochondrial apoptosis-related markers: Caspase-3, B-cell lymphoma-2 (Bcl-2) and Bax. AEC-II cells treated with 0.5 mmol/L H2O2 exhibited significant cell apoptosis. Overexpression using miR-26a mimics partially reversed the effects of H2O2-induced apoptosis in AEC-II cells, evidenced by flow cytometry results. RESULTS: Further Western blot results revealed increased levels of Caspase-3 and Bax, and the decreased Bcl-2 level after infecting with miR-26a mimics, indicating miR-26a has protective effects against mitochondrial apoptosis in AEC-II cells. CONCLUSIONS: MiR-26a protected AEC-II cells against apoptosis via mitochondrial pathway. Thus, miR-26a promises to be a potential therapy in treatment of Acute Respiratory Distress Syndrome (ARDS).

Coexistence of Replica Bands and Superconductivity in FeSe Monolayer Films.

To elucidate the mechanisms behind the enhanced T_{c} in monolayer (1 ML) FeSe on SrTiO_{3} (STO), we grew highly strained 1 ML FeSe on the rectangular (100) face of rutile TiO_{2}, and observed the coexistence of replica bands and superconductivity with a T_{c} of 63 K. From the similar T_{c} between this system and 1ML FeSe on STO (001), we conclude that strain and dielectric constant are likely unimportant to the enhanced T_{c} in these systems. A systematic comparison of 1 ML FeSe on TiO_{2} with other systems in the FeSe family shows that while charge transfer alone can enhance T_{c}, it is only with the addition of interfacial electron-phonon coupling that T_{c} can be increased to the level seen in 1 ML FeSe on STO.

[Acute suppurative otitis media caused by pasteurella multocida :a case report].

The pasteurella multocida (PM) is widely gastrointestinal parasitic on dogs, cats and other animals. The PM human infections is caused by animal bites orits close contact. Clinically foundin focal wound infection after bite, and acute suppurative otitis media reportshave not been caused by PM. A 45 years old nasopharyngeal cancer who sudden stabbing painof the left ear for 5h. Physical examination found that the left earexisted a lot of yellowish white purulent secretion. Distribution and drug sensitivity test of bacteria showed PM and it was sensitive to many antibiotics. nasopharygo fiberscope revealed that eustachian tube and theleft ear had a large number of purulentsecretion. The main diagnosis was: ①Recurrent nasopharyngealcarcinoma; ② Acute suppurative otitis media. TREATMENT: according to the results of drug sensitive test and skin test inpatients with selection of levofloxacin (0.2 g/12 h), clindamycin (0.6 g/12 h) anti-infection treatment, the patient get better in the end.

Association between the ERCC2 rs13181 polymorphism and the risk of glioma: a meta-analysis.

Several studies have focused on the association between the ERCC2 rs13181 polymorphism and glioma risk, but the results were inconclusive. We aimed to conduct a meta-analysis to investigate the role of ERCC2 rs13181 on the risk of glioma. We searched and collated the relevant studies in both Chinese and English through the PubMed, Web of Science, Cochrane Library, and EMBASE databases published through June 1, 2014. A total of 11 studies for ERCC2 rs13181 were selected; these included 3456 glioma cases and 4957 controls. Using fixed-effects model analysis, we found that no significant difference could be identified between the ERCC2 rs13181 polymorphism and the risk of glioma. Subgroup analysis showed that the ERCC2 rs13181 GT and TT genotypes were significantly associated with an increased risk of glioma in the Chinese population [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.17-1.85; and OR = 1.50, 95%CI = 1.02-2.22, respectively], but no significant increased risk of glioma was detected with these genotypes in the Caucasian populations. No publication bias was identified in this meta-analysis. Our meta-analysis strongly suggested that ERCC2 rs13181 was associated with a higher susceptibility to glioma in the Chinese population.

Computed tomography navigation combined with endoscope guidance for the removal of projectiles in the maxillofacial area: a study of 24 patients.

The aim of this study was to review recent records on the removal of projectiles in the maxillofacial area from patients with firearm wounds, and to summarize our experience in the use of computed tomography (CT) navigation combined with an endoscope in the treatment of these patients. Twenty-four patients injured by firearms and with projectile retention were identified. For surgical planning and intraoperative navigation, an iCT system integrating navigation with intraoperative CT scanning (iPlan) and an electronic endoscope were used. The records of the 24 patients were reviewed retrospectively. All projectiles in these cases were accessed and removed with CT navigation combined with endoscope guidance; no major complications occurred and the surgery time was reduced compared to conventional procedures. Additional incisions were used in 10 patients; removal of the retained projectile through the original wound is not appropriate in certain cases. There was no excessive intraoperative bleeding except in one case, and no patient experienced postoperative bleeding. In 29.2% of cases, the foreign projectiles involved occupied more than one space. CT navigation combined with endoscope guidance is a useful method for removing most projectiles retained in the maxillofacial and neck area.

Minimally invasive treatment of oral ranula with a mucosal tunnel.

We have developed a new method for minimally-invasive treatment of uncomplicated oral ranulas using a mucosal tunnel, and we report the clinical outcome. We constructed a mucosal tunnel for each of 35 patients who presented with an oral ranula, by making 2 parallel incisions across the top of the protruding ranula 2-3mm apart, and dissected the soft tissue along the incisions to its wall. The fluid was removed and the cavity irrigated with normal saline. The wall of the ranula was not treated. The first mucosal tunnel was made by suturing the base of the mucosal strip to the deepest part of the wall of the ranula. The mucosal base of the tunnel and the deepest part of the base of the ranula were fixed with absorbable sutures. The two external edges of the incisions were sutured together to form the second mucosal tunnel, and apposing sutures were inserted between the two parallel incisions to form two natural mucosal tunnels. The duration of follow-up ranged from 1 to 5 years. One patient was lost to follow-up and 34 patients were cured. Outcomes were satisfactory without relapse during the follow-up period and the patients were satisfied with the outcome. The mucosal tunnel is a safe, effective, simple, and minimally-invasive treatment for oral ranula.

Selecting key genes associated with osteosarcoma based on a differential expression network.

Despite recent advances in osteosarcoma diagnosis and therapy, much remains unclear about the molecular mechanisms involved in the disorder, and the discovery of novel drug-targeted genes is essential. We explored the potential molecular mechanisms and target genes involved in the development and progression of osteosarcoma. First, we identified the differentially expressed genes in osteosarcoma patients and matching normal controls. We then constructed a differential expression network based on differential and non-differential interactions. Pathway-enrichment analysis was performed based on the nodes contained in the main differential expression network. Centrality analysis was used to select hub genes that may play vital roles in the progression of human osteosarcoma. Our research revealed a total of 176 differentially expressed genes including 82 upregulated and 94 downregulated genes. A differential expression network was constructed that included 992 gene pairs (1043 nodes). Pathway-enrichment analysis indicated that the nodes in the differential expression network were mainly enriched in several pathways such as those involved in cancer, cell cycle, ubiquitin-mediated proteolysis, DNA replication, ribosomes, T-cell receptor signaling, spliceosomes, neurotrophin signaling, oxidative phosphorylation, and tight junctions. Six hub genes (APP, UBC, CAND1, RPA, YWHAG, and NEDD8) were discovered; of these, two genes (UBC and RPA) were also found to be disease genes. Our study predicted that UBC and RPA had potential as target genes for the diagnosis and treatment of osteosarcoma.

Dietary acid load, kidney function, osteoporosis, and risk of fractures in elderly men and women.

SUMMARY: Because kidney dysfunction reduces the ability to excrete dietary acid excess, we hypothesized that underlying kidney function may have confounded the mixed studies linking dietary acid load with the risk of osteoporosis and fractures in the community. In a relatively large survey of elderly men and women, we report that dietary acid load did neither associate with DEXA-estimated bone mineral density nor with fracture risk. Underlying kidney function did not modify these null findings. Our results do not support the dietary acid-base hypothesis of bone loss. INTRODUCTION: Impaired renal function reduces the ability to excrete dietary acid excess. We here investigate the association between dietary acid load and bone mineral density (BMD), osteoporosis, and fracture risk by renal function status. METHODS: An observational study was conducted in 861 community-dwelling 70-year-old men and women (49% men) with complete dietary data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The exposure was dietary acid load as estimated from 7-day food records by the net endogenous acid production (NEAP) and potential renal acid load (PRAL) algorithms. Renal function assessed by cystatin C estimated glomerular filtration rate was reduced in 21% of the individuals. Study outcomes were BMD and osteoporosis state (assessed by DEXA) and time to fracture (median follow-up of 9.2 years). RESULTS: In cross-section, dietary acid load had no significant associations with BMD or with the diagnosis of osteoporosis. During follow-up, 131 fractures were validated. Neither NEAP (adjusted hazard ratios (HR) (95% confidence interval (CI)), 1.01 (0.85-1.21), per 1 SD increment) nor PRAL (adjusted HR (95% CI), 1.07 (0.88-1.30), per 1 SD increment) associated with fracture risk. Further multivariate adjustment for kidney function or stratification by the presence of kidney disease did not modify these null associations. CONCLUSIONS: The hypothesis that dietary acid load associates with reduced BMD or increased fracture risk was not supported by this study in community-dwelling elderly individuals. Renal function did not influence on this null finding.

Combination gene therapy targeting on interleukin-1ß and RANKL for wear debris-induced aseptic loosening.

This study investigated the efficacy of a combination gene therapy to repress interleukin-1 (IL-1) and receptor activator of nuclear factor NF-kappa B ligand (RANKL) for the treatment of particulate debris-induced aseptic loosening, and tried to explore the molecular mechanism of the exogenous gene modifications on osteoclastogenesis. RAW cells activated by titanium particles were transduced with DFG-IL-1Ra (retroviral vector encoding IL-1 receptor antagonist) and AAV-OPG (adeno-associated viral vectors-osteoprotegerin) individually or in combination for 4 weeks. Pro-inflammatory cytokines in culture media were determined by enzyme-linked immunosorbent assay, and gene expressions of RANK, IL-1ß, c-Fos, TRAF6, JNK1 and CPK were examined using real-time PCR. An established knee-implant-failure mouse model was employed to evaluate the efficacy of the in vivo double-gene therapy. The surgical implantation of a titanium alloy pin into the proximal tibia was followed by monthly challenge with titanium debris. Peri-implant gene transfers of IL-1Ra and OPG (respectively or in combination) were given 3 weeks after surgery. The combination of OPG and IL-1Ra gene transfer exhibited strong synergetic effects in blockage of inflammation and osteoclastogenesis at 8 weeks after gene modification. The combination therapy reversed peri-implant bone resorption and restored implant stability when compared with either single gene transduction. Real-time PCR data indicated that the action of IL-1Ra gene therapy may be mediated via the JNK1 pathway, while the reduction of osteoclastogenesis by OPG gene modification may be regulated by c-Fos expression. In addition, both gene modifications resulted in significant diminishment of TRAF6 expression.

Urodynamic study of bladder function for patients with lumbar spinal stenosis treated by surgical decompression.

Lumbar spinal stenosis usually leads to different degrees of nerve damage, presenting with back and leg pain, and/or neurogenic bladder symptoms. To determine whether lumbar decompression improved urological function, bladder dysfunction was evaluated in this retrospective study of 26 patients with lumbar spinal stenosis who had undergone lumbar decompression surgery. Urodynamic study procedures were performed pre-operatively and 6 months post-operatively. The Japanese Orthopaedic Association score rating system and Oswestry Disability Index were employed for clinical evaluation. Following surgery, post-voiding residual urine, maximum cystometric capacity and maximum flow rate improved significantly. There was no statistically significant improvement in voided volume, bladder compliance, maximum detrusor pressure or upper urinary tract damage. Urodynamic study was important in the diagnosis of neurogenic bladder dysfunction, prevention of renal deterioration and assessment of post-operative effects after surgical decompression for patients with lumbar spinal stenosis.

Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model.

Exogenous osteoprotegerin (OPG) gene modification appears a therapeutic strategy for osteolytic aseptic loosening. The feasibility and efficacy of a cell-based OPG gene delivery approach were investigated using a murine model of knee prosthesis failure. A titanium pin was implanted into mouse proximal tibia to mimic a weight-bearing knee arthroplasty, followed by titanium particles challenge to induce periprosthetic osteolysis. Mouse fibroblast-like synoviocytes were transduced in vitro with either AAV-OPG or AAV-LacZ before transfused into the osteolytic prosthetic joint 3 weeks post surgery. Successful transgene expression at the local site was confirmed 4 weeks later after killing. Biomechanical pullout test indicated a significant restoration of implant stability after the cell-based OPG gene therapy. Histology revealed that inflammatory pseudo-membranes existed ubiquitously at bone-implant interface in control groups, whereas only observed sporadically in OPG gene-modified groups. Tartrate-resistant acid phosphatase+osteoclasts and tumor necrosis factor α, interleukin-1ß, CD68+ expressing cells were significantly reduced in periprosthetic tissues of OPG gene-modified mice. No transgene dissemination or tumorigenesis was detected in remote organs and tissues. Data suggest that cell-based ex vivo OPG gene therapy was comparable in efficacy with in vivo local gene transfer technique to deliver functional therapeutic OPG activities, effectively halted the debris-induced osteolysis and regained the implant stability in this model.