Loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats.

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2 Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes (Tas1r2 and Tas1r3) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat (Myotis ricketti) showed no preference for natural sugars, whereas the frugivorous species (Rousettus leschenaultii) showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.

Variability of functional knee phenotype for coronal alignment in advanced varus knee osteoarthritis in the Japanese population.

PURPOSE: New concept of functional knee phenotypes in Caucasians demonstrated the variability of coronal alignment in knee osteoarthritis (OA), but it remains unclear in Japanese. This study aims to analyze the knee phenotype in advanced varus knee OA for Japanese. In addition, the ethnical difference is discussed. METHODS: This study analyzed 879 knees involving 186 males (74 years) and 693 females (74 years). The knee phenotypes were assessed by the definition in Hirschmann's group. The hip-knee-ankle angle (HKA), femoral mechanical angle (FMA) and tibial mechanical angle (TMA) were assessed in CT data according to the coordinate system. The neutral angle was 180° in HKA, 93° in FMA and 87° in TMA. The smaller angle means larger varus angles. RESULTS: The average angle (males, females) of the HKA (170.9 ± 4.3°, 169.4 ± 5.0°), FMA (91.5 ± 2.7°, 90.6 ± 3.0°), and TMA (82.4 ± 3.6°, 82.7 ± 3.7°) demonstrated varus angles with the sex difference (HKA, p < 0.001; FMA, p = 0.001). The phenotypes were 73 types in males and 150 types in females with a mild correlation between the HKA and the FMA or TMA. In 61.3% of males and 52.2% of females, the TMA was greater than the FMA, while the FMA was greater in 16.7% of males and 23.1% of females. CONCLUSION: There were many functional knee phenotypes with sex differences for advanced varus knee OA in Japanese, showing ethnical differences of larger varus angles compared to those for Caucasians in the previous report. LEVEL OF EVIDENCE: IV.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Trehalase Gene as a Molecular Signature of Dietary Diversification in Mammals.

Diet is a key factor in determining and structuring animal diversity and adaptive radiations. The mammalian fossil record preserves phenotypic evidence of many dietary shifts, whereas genetic changes followed by dietary diversification in mammals remain largely unknown. To test whether living mammals preserve molecular evidence of dietary shifts, we examined the trehalase gene (Treh), which encodes an enzyme capable of digesting trehalose from insect blood, in bats and other mammals with diverse diets. Bats represent the largest dietary radiation among all mammalian orders, with independent origins of frugivory, nectarivory, carnivory, omnivory, and even sanguivory in an otherwise insectivorous clade. We found that Treh has been inactivated in unrelated bat lineages that independently radiated into noninsectivorous niches. Consistently, purifying selection has been markedly relaxed in noninsectivorous bats compared with their insectivorous relatives. Enzymatic assays of intestinal trehalase in bats suggest that trehalase activity tends to be lost or markedly reduced in noninsectivorous bats compared with their insectivorous relatives. Furthermore, our survey of Treh in 119 mammal species, which represent a deeper evolutionary timeframe, additionally identified a number of other independent losses of Treh in noninsectivorous species, recapitulating the evolutionary pattern that we found in bats. These results document a molecular record of dietary diversification in mammals, and suggest that such molecular signatures of dietary shifts would help us understand both historical and modern changes of animal diets.

Clinical and bacteriological features and prognosis of ascitic fluid infection in Chinese patients with cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) and bacterascites (BA) represent frequent and serious complications in cirrhosis patients with ascites. However, few detailed data are available regarding the clinical and bacteriological feature of SBP or BA patients in China. METHODS: We retrospectively analyzed bacteriological and clinical characteristics of patients with SBP and BA at Beijing 302 Hospital in China from January 2012 to December 2015. RESULTS: A total of 600 patients with SBP (n = 408) or BA (n = 192) were enrolled. Patients with BA appeared to have a less severe clinical manifestation and lower mortality rate than patients with SBP. Gram-negative bacteria formed the majority of pathogens in SBP (73.9%) and BA (55.8%) cases. Higher ascitic fluid polymorphonuclear leucocytes (PMN) count and hepatocellular carcinoma were independent risk factors for BA episode progressing to SBP. The concentration of blood urea nitrogen (BUN) was independent risk factor for 30-day mortality of BA patients. For patients with SBP, the independent risk factors for 30-day mortality were age, Model for End-Stage Liver Disease (MELD) score, septic shock and hepatocellular carcinoma. Patients with third-generation cephalosporin or carbapenems resistant infection had a significantly lower survival probability. There were significant differences in clinical characteristics and outcome among the major bacteria. Multivariate analysis showed that patients infected with Klebsiella spp. had higher hazard ratio of 30-day mortality. CONCLUSION: Our study reported the bacteriological and clinical characteristics of patients with SBP and BA. Higher ascitic fluid PMN count and hepatocellular carcinoma were found to be independent risk factors for BA episode progressed to SBP. Outcome of ascitic fluid infection in patients with cirrhosis was influenced by the type of bacteria and antimicrobial susceptibility.

[Structure and function of class 1 integron in clinical isolates of Klebsiella pneumoniae].

To investigate molecular mechanism of multi-resistance of Klebsiella pneumoniae and its spreading, 179 strains isolated from different clinical samples in the period of 2002-2007 with serious resistance to 14 anti-bacterial agents were examined. Among them, 118 (65.9%) were resistant to at least two anti-bacterial agents; 36.3% (65/179) were found to contain class 1 integrons. There was a significant difference for resistance rate between the integron positive and the negative groups, especially for antimicrobial agents of aminoglycosides, quinolones and sulfonamides (P<0.01). Gene cassette structures of the class 1 integrons in these bacteria were analyzed and their resistance genes were further cloned and tested for antibiotic resistance activities. Fifteen gene cassettes were identified with dfrA17-aadA5 being the most popular form. Three recombinant plasmids pET28a-dhfr17, pET28a-dhfr17-orfF and pET28a-dhfr17-orfF-aadA2 were cloned from a gene cassette of dhfr17-orfF-aadA2. When introduced into a recipient E. coli strain BL21, all of them rendered resistance to co-trimoxazole, with minimum inhibitory concentration (MIC) value up to 256 µg/µL. The E. coli BL21 carrying pET28a- dhfr17 or pET28a-dhfr17-orfF had the same MIC value of 8 µg/µL to streptomycin as the recipient strain without plasmid. However, the E. coli carrying pET28a-dhfr17-orfF-aadA2 was resistant to streptomycin with MIC level up to 256 µg/µL. In conclusion, class 1 integrons were regularly identified in Klebsiella pneumoniae. They mainly carry resistance genes against antimicrobial agents of aminoglycosides and sulfonamide. Transferable plasmid carrying integrons with resistance genes may play an important role in resistance spreading among bacterial species.

Bioinformatic analysis of hippocampal histopathology in Alzheimer's disease and the therapeutic effects of active components of traditional Chinese medicine.

Background and aim: Pathological changes in the central nervous system (CNS) begin before the clinical symptoms of Alzheimer's Disease (AD) manifest, with the hippocampus being one of the first affected structures. Current treatments fail to alter AD progression. Traditional Chinese medicine (TCM) has shown potential in improving AD pathology through multi-target mechanisms. This study investigates pathological changes in AD hippocampal tissue and explores TCM active components that may alleviate these changes. Methods: GSE5281 and GSE173955 datasets were downloaded from GEO and normalized to identify differentially expressed genes (DEGs). Key functional modules and hub genes were analyzed using Cytoscape and R. Active TCM components were identified from literature and the Pharmacopoeia of the People's Republic of China. Enrichment analyses were performed on target genes overlapping with DEGs. Result: From the datasets, 76 upregulated and 363 downregulated genes were identified. Hub genes included SLAMF, CD34, ELN (upregulated) and ATP5F1B, VDAC1, VDAC2, HSPA8, ATP5F1C, PDHA1, UBB, SNCA, YWHAZ, PGK1 (downregulated). Literature review identified 33 active components from 23 herbal medicines. Target gene enrichment and analysis were performed for six components: dihydroartemisinin, berberine, naringenin, calycosin, echinacoside, and icariside II. Conclusion: Mitochondrial to synaptic vesicle dysfunction pathways were enriched in downregulated genes. Despite downregulation, UBB and SNCA proteins accumulate in AD brains. TCM studies suggest curcumin and echinacoside may improve hippocampal pathology and cognitive impairment in AD. Further investigation into their mechanisms is needed.

Differences in environmental microbial community responses under rice-crab co-culture and crab monoculture models under cyanobacterial bloom.

Cyanobacterial blooms (CBs) present significant challenges to Chinese mitten crab (CMC) culture, posing hazards to the aquatic microbial ecology. However, the current focus on the microbial ecological changes within the CMC culture system under the influence of CBs is somewhat insufficient. There's an urgent need to analyze the microbial ecosystem of the CMC culture system under CBs. This study employed 16S rRNA gene amplicon sequencing to investigate the dynamics of the environmental microbial community in both the rice-crab co-culture (RC) and crab monoculture (CM) models. The results revealed that cyanobacteria reached high levels in the CM water in July, while they began to increase in the RC water in August. Notably, OTU147 (uncultured bacterium g_Planktothrix NIVA-CYA 15), identified as the dominant taxon associated with CBs, showed a significant linear relationship with TP, NO2 --N, and the N:P ratio. TP, TN, NO2 --N, and CODMn had a more pronounced impact on the structure of bacterial communities and cyanobacterial taxa in the water. The bacterial community structure involved in carbon metabolism displayed temporal succession in the water. The co-occurrence network of the bacterial community primarily consisted of Chloroflexi, Proteobacteria, and Firnicutes in the sediment, and Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidota in the water. In contrast, the co-occurrence network included different peripheral species in the sediment and water. Keystone species were predominantly represented by OTU22 (uncultured actinobacterium g_ hgcI clade) and OTU12 (uncultured Opitutae bacterium g_ norank) in the RC water, and by OTU25 (uncultured bacterium g_ Limnohabitans) in the CM water. TP, TN, NO2 --N, and CODMn were identified as the primary environmental factors influencing these keystone taxa within the culture water. In conclusion, this study on the microbial ecology of the CMC culture system under the influence of CBs provides valuable insights that can be instrumental in subsequent management efforts.

Prevalence and characteristics of cervical human papillomavirus genotypes and cervical lesions among 58630 women from Guangzhou, China.

BACKGROUND: To assess the prevalence and characteristics of human papillomavirus (HPV) genotypes and its associated cervical lesions in Guangzhou, China, which may be useful for adjusting area-specific cervical cancer prevention and control strategies. METHODS: A total of 58630 women were enrolled. Cervical specimens were collected for HPV DNA testing and/or cervical cytology. Patients with visible cervical lesions or abnormal screening results underwent further cervical biopsies. RESULT: The overall HPV positive rate was 14.07%. The top five genotypes in Guangzhou were HPV 52 (3.06%), HPV 16 (2.28%), HPV 58 (1.80%), HPV 51 (1.32%), and HPV 39 (1.15%). The prevalence of overall HPV and vaccine-targeted HPV genotypes showed a significantly decreasing trend from 2016 to 2019 (P < 0.05). While, the infection rate of HPV 35 increased significantly during this time (P = 0.015). The age-specific prevalence of any HPV genotypes showed a bimodal curve, which peaked firstly among the < 20 y age group, and then peaked secondly among the > 59 y age group. Among HPV-positive women, the proportions of HSIL and cervical cancer increased significantly with age (P < 0.05). Among > 59 y age group, 9.35% HPV-positive cases were diagnosed as cervical cancer. HPV 16/18 was the most common cause of cervical cancer. While, the percentage of non-HPV 16/18 infection among cervical cancer patients increased over time, from 15.21% in 2015 to 26.32% in 2019 (P = 0.010). Besides that, the prevalence of non-HPV 16/18 genotypes among cervical cancer patients significantly increased with age, which peaked at the > 59 y age group (P = 0.014). CONCLUSION: Although the prevalence of any HPV and vaccine-targeted HPV genotypes decreased significantly with time, it is still important to follow the HPV genotypes and their associated cancer risk after the large-scale popularization of HPV vaccine. And age should be taken into consideration in screening strategies and risk-based management of cervical cancer in Guangzhou.

Automatic lumbar spinal MRI image segmentation with a multi-scale attention network.

Lumbar spinal stenosis (LSS) is a lumbar disease with a high incidence in recent years. Accurate segmentation of the vertebral body, lamina and dural sac is a key step in the diagnosis of LSS. This study presents an lumbar spine magnetic resonance imaging image segmentation method based on deep learning. In addition, we define the quantitative evaluation methods of two clinical indicators (that is the anteroposterior diameter of the spinal canal and the cross-sectional area of the dural sac) to assist LSS diagnosis. To improve the segmentation performance, a dual-branch multi-scale attention module is embedded into the network. It contains multi-scale feature extraction based on three 3 × 3 convolution operators and vital information selection based on attention mechanism. In the experiment, we used lumbar datasets from the spine surgery department of Shengjing Hospital of China Medical University to evaluate the effect of the method embedded the dual-branch multi-scale attention module. Compared with other state-of-the-art methods, the average dice similarity coefficient was improved from 0.9008 to 0.9252 and the average surface distance was decreased from 6.40 to 2.71 mm.

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSCScx) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSCScx derived exosomes (BMMSCScx-exos). Local injection of BMMSCScx-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSCScx-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.

Tripterygium wilfordii Hook F Treatment for Stage IV Diabetic Nephropathy: Protocol for a Prospective, Randomized Controlled Trial.

BACKGROUND: Diabetic nephropathy (DN) is a major cause of chronic kidney disease (CKD). There are no effective treatments to prevent or reverse the progression of DN. A preliminary study showed that Tripterygium glycosides from Tripterygium wilfordii Hook F (TwHF) with valsartan decrease proteinuria in patients with DN. OBJECTIVES: The objective of the present study is to investigate the efficacy and safety of Tripterygium glycosides from TwHF, a traditional Chinese medicine, for the treatment of DN. Methods and Analysis. This is a prospective, single-center randomized controlled trial. Seventy participants diagnosed with DN were recruited and randomized 1 : 1 to two groups: (1) angiotensin receptor blocker (ARB) combined with TwHF and (2) ARB-only. The treatment period is 48 weeks. The primary endpoint is 24 h proteinuria decreased level (reduction of 30% vs. baseline) after 48 weeks of treatment. The secondary endpoints are (1) all-cause and cardiovascular-related mortality, (2) development of ESRD (serum creatinine > 530.4 µmol/L or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2), (3) the need for renal replacement therapy, and (4) increased serum creatinine (2-fold higher than the baseline value or ≥442 µmol/L, with confirmation of the initial results after 4 weeks). A health economics analysis will be carried out. Discussion. A meta-analysis of RCTs carried out in patients with stage 4 (Mogensen classification) diabetic CKD showed that TwHF combined with an ARB was more effective than an ARB alone when considering 24 h proteinuria and serum albumin, but with an increase in adverse event (AE) frequency of 8%. This is a prospective clinical trial that may provide information on a safe and effective novel method for the treatment of DN, especially for patients with macroproteinuria. Ethics and Dissemination. The protocol is approved by the ethics committee of Beijing Hospital (2016BJYYEC-059-02). The results will be disseminated through peer-reviewed publications and international conferences. This trial is registered with ChiCTR-IOR-17010623.

Self-debriefing Model Based on an Integrated Video-Capture System: An Efficient Solution to Skill Degradation.

OBJECTIVE: Video-based teaching is considered highly effective in debriefing, especially in minimally invasive surgeries. In this study, the benefits of using a new integrated video recording system, were investigated and compared to those of the standard basic skills robotic training procedure. DESIGN: Fifty residents from the 2nd and 3rd year medical faculty without any experience of robot usage or laparoscopy were randomized into 2 groups: group A--a natural self-training group without a trainer, and group B--a self-training group assisted by an integrated video recording system during training. The training was divided into four 2-hour sessions, with a 72-hour delay between each session. Two tasks were selected for testing on the dV-Trainer, a virtual reality based robotic simulator: Match board 2 and Thread the Rings 1. After each session, the practice video recorded by the system of group B was transferred to the residents' smartphones for self-debriefing. At the end of each session, the performance score was evaluated automatically by using the simulator to plot learning curves A and B. RESULTS: Group A showed a significant drop in performance score due to skill decay caused by the 72-hour delay. Group B exhibited a regular stepwise rising learning curve. At the end of the training, group B showed a significantly higher performance score both in Match board 2 and Thread the Rings 1. The autoanalysis and capture function, which selects only the critical errors and most valuable parts, could facilitate time saving. CONCLUSIONS: The use of an integrated video recording system makes the self-manipulated protocol with own smartphone feasible to improve training efficiency and overcome the skill decay during robotic surgical training.

Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway.

The present study was to evaluate the effect of ergosterol (ER) on CS (cigarette smoke)-induced chronic obstructive pulmonary disease (COPD) in mice. Fifty male ICR mice were randomly assigned to five groups: control group, CS group, CS + dexamethasone (Dex, 2 mg/kg) group, CS + ER (ER, 25 mg/kg) group, CS + ER (ER, 50 mg/kg). H&E staining demonstrated that ER inhibited CS-induced pathological injury in lung tissue. Besides, ER could restore the activities of superoxide dismutase (SOD) in serum and in the lung, catalase (CAT) in serum and reduce the content of malondialdehyde (MDA) in serum and in the lung. ER also inhibited pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in serum and the lung. Furthermore, ER significantly inhibited the protein expression of JAK3/STAT3/NF-κB pathway in CS-induced mice. Our findings suggested that ER might effectively ameliorate the progression of COPD via JAK3/STAT3/NF-κB pathway in mice.

[Changes of liver fibrosis-related miRNAs induced by soluble egg antigen of Schistosoma japonicum].

OBJECTIVE: To investigate the expression of miRNA associated with hepatic fibrosis induced by Schistosoma japonicum soluble egg antigen stimulation in mouse hepatocytes (AML12), so as to lay the foundation for clarifying the mechanism of schistosome infection leading to hepatic fibrosis. METHODS: The expressions of miR-122, miR-182, miR-23b, miR27b and KSRP in AML12 cells treated with SEA were measured by q-PCR. KSRP protein in cell lyses was measured by Western blotting. AML12 cells were transfected with miR-27b precursor or anti-miR-27b for 24 h, then q-PCR was adopted to determine KSRP mRNA, and KSRP protein was detected by Western blotting. RESULTS: The expressions of miR-182, miR-23b and miR27b were decreased and miR-122 was increased in AML12 cells following SEA treatment (all P < 0.05). An increase of mRNA and protein of KSRP expression was also observed in AML12 cells after SEA stimulation (both P < 0.05). In addition, KSRP mRNA expression was not changed significantly in AML12 cells transfected with anti-miR-27b or miR-27b precursor, and miR27b precursor reduced KSRP protein expression as compared with the control. In contrast, the expression of KSRP protein was increased in the anti-miR-27b group and decreased in the miR-27b precursor group. CONCLUSIONS: After the stimulation of SEA, the expressions of a variety of liver fibrosis-related miRNAs and KSRP change in murine hepatocytes, including miR-27b. And miR-27b can regulate the expression of KSRP. These findings might lay a foundation for further study on the molecular mechanism of fibrosis induced by schistosome infection.

Radiosynthesis and in-vivo evaluation of [125I]IBT: a single-photon emission computed tomography radiotracer for α7-nicotinic acetylcholine receptor imaging.

AIM: The aim of this study was to develop several novel α7-nicotinic acetylcholine receptor (nAChR) radioligands for the early diagnosis and treatment of Alzheimer's disease. PATIENTS AND METHODS: The study reported six compounds and studied the in-vitro receptor binding affinity, and selected the I-labeled IBT with good characteristics as a novel radioligand suitable for studying α7-nAChRs. After verifying the stability of the radiotracer [I]IBT, the biodistribution in vivo and regional brain biodistribution studies were carried out in mice. Blocking studies with methyllycaconitine citrate and nicotine were carried out under control and blocking conditions, and the metabolic stability was assessed in vivo in the plasma, brain, and liver. RESULTS AND CONCLUSION: The results of our study suggested that [I]IBT had affinity for α7-nAChRs. The in-vivo evaluation in mice of [I]IBT showed a high brain/blood ratio and excellent metabolic stability. The regional brain distribution studies and the blocking studies showed that it had favorable selectivity and specificity and was a potential α7-nAChRs radioligand.

Unilateral C-1 posterior arch screws and C-2 laminar screws combined with a 1-side C1-2 pedicle screw system as salvage fixation for atlantoaxial instability.

OBJECT Atlantoaxial instability often requires surgery, and the current methods for fixation pose some risk to vascular and neurological tissues. Thus, new effective and safer methods are needed for salvage operations. This study sought to assess unilateral C-1 posterior arch screws (PASs) and C-2 laminar screws (LSs) combined with 1-side C1-2 pedicle screws (PSs) for posterior C1-2 fixation using biomechanical testing with bilateral C1-2 PSs in a cadaveric model. METHODS Six fresh ligamentous human cervical spines were evaluated for their biomechanics. The cadaveric specimens were tested in their intact condition, stabilization after injury, and after injury at 1.5 Nm of pure moment in 6 directions. The 3 groups tested were bilateral C1-2 PSs (Group A); left side C1-2 PSs with an ipsilateral C-1 PAS + C-2 laminar screw (Group B); and left side C1-2 PSs with a contralateral C-1 PAS + C-2 LS (Group C). During the testing, angular motion was measured using a motion capture platform. Data were recorded, and statistical analyses were performed. RESULTS Biomechanical testing showed that there was no significant difference among the stabilities of these fixation systems in flexion-extension and rotation control. In left lateral bending, the bilateral C1-2 PS group decreased flexibility by 71.9% compared with the intact condition, the unilateral C1-2 PS and ipsilateral PAS+LS group decreased flexibility by 77.6%, and the unilateral C1-2 PS and contralateral PAS+LS group by 70.0%. Each method significantly decreased C1-2 movements in right lateral bending compared with the intact condition, and the bilateral C1-2 PS system was more stable than the C1-2 PS and contralateral PAS+LS system (p = 0.036). CONCLUSIONS A unilateral C-1 PAS + C-2 LS combined with 1-side C-1 PSs provided the same acute stability as the PS, and no statistically significant difference in acute stability was found between the 2 screw techniques. These methods may constitute an alternative method for posterior atlantoaxial fixation.

[Investigation on epidemic foci of paragonimiasis in eastern part of Zhenghe County, Fujian Province].

OBJECTIVE: To investigate the species and hosts of Paragonimus and its infection rate in eastern part of Zhenghe County, Fujian Province, so as to determine the local foci of Paragonimus. METHODS: The snails, crabs and stools of wild cats were collected for the examinations of cercariae, metacercariae and eggs of Paragonimus. The geographical and environmental conditions of the areas were also investigated. RESULTS: A total of 4 890 Pseudobythinella jianouensis snails and 1 035 Semisulcospira liberlina snails were examined, and the cercariae of Paragonimus were only found in P. jianouensis, with an infection rate of 0.10% (5/4 890). Bottapotamon zhengheensis sp. nov. as the second intermediate host of P. skrjabini, were examined, and the infection rate was 85.29% (29/34) and the average numbers of metacercariae per crab and per gram of crab tissues were 3.85 and 0.62, respectively. Thirty-six Sinopotamun fujianensis crabs, as the second intermediate host of P. westermani, were examined, and the infection rate was 38.89% (14/36) and the average numbers of metacercariae per crab and per gram of crab tissues were 6.43 and 0.03, respectively. The eggs of Paragonimus were detected in 1 of 2 muck specimens of wild cats. CONCLUSIONS: The data suggest that there is a focus of middle-to-high level of infection caused by P. westermani and P. skrjabini in the eastern part of Zhenghe County.

Effect of gradient decompression on the occurrence of intraoperative hypotension and prognosis in traumatic brain injury.

AIM: To investigate the effect of gradient decompression on the occurrence of intraoperative hypotension and prognosis in traumatic brain injury. MATERIAL AND METHODS: A retrospective analysis was performed in 186 hospitalized patients from January, 2008 to January, 2012 in the Affiliated Hospital of Jiangsu University. Demographic data, the abnormality of pupils, and Glasgow Coma Scale (GCS) before operation, and gradient decompression measures, and intraoperative hypotension during operation, and mortality after operation were recorded. Gradient decompression measures were mannitol, hyperventilation, graded craniotomy, and Chi-square test was conducted to evaluate the association of gradient decompression with intraoperative hypotension and prognosis. RESULTS: All the gradient decompression measures were shown non-significantly associated with the occurrence of intraoperative hypotension and prognosis, including mannitol (p=0.852, p=0.328), hyperventilation (p=0.484, p=0.619) and graded craniotomy (p=0.326, p=0.605). Mannitol with hyperventilation (p=0.733, p=0.758), mannitol with graded craniotomy (p=0.319, p=1.000), hyperventilation with graded craniotomy (p=0.269, p=0.685) and all the three measures (p=0.135, p=0.589) were also non-significantly associated with the occurrence of intraoperative hypotension and prognosis. The abnormality of pupils (p=0.006), GCS (p<0.001) and hypotension (p=0.006) were closely associated with the prognosis. CONCLUSION: Gradient decompression is not effective in avoiding the occurrence of intraoperative hypotension and improving the prognosis. It provides a new insight into clinical measures for curing patients with severe traumatic brain injury (sTBI).

Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone.