Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review / 中华儿科杂志

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

Analysis of the effects of national centralized drug volume-based procurement policy in public medical institutions of the Guangxi Zhuang Autonomous Region / 中国药房

OBJECTIVE To investigate the implementation effects of the national centralized drug volume-based procurement policy （abbreviated as “national centralized procurement policy”） in Guangxi Zhuang Autonomous Region prefecture， and to provide a reference for the future centralized drug procurement work of the medical institution. METHODS Drug procurement data before and after policy implementation were included in the study. The six secondary indicators （such as availability， affordability， and drug safety） and eighteen third-level indicators （such as completion rate of agreed purchase volume， affordability level， drug revenue proportion） were introduced， guided by the policy objectives and issues of concern to policy beneficiaries. Descriptive statistics was adopted to analyze the data before and after policy implementation （in 2019 and 2020） in terms of differences and change trends. RESULTS In terms of accessibility， the participation rate of medical institutions in Guangxi Zhuang Autonomous Region was 92.55%， the proportion of diseases involved and median completed procurement rate were 40.16%， and 287.82% respectively， and the total centralized delivery rate was 97.20%. In terms of affordability， the total reduction amplitude in drug price was 74.80% from 2019 to 2022； the charge for medicine per capita in hospitalization， the proportion of medicine used for outpatient service and hospitalization， decreased by 17.61%， 10.22%， and 20.10% in order； the burden levels on medical fares for patients were all below 1 in addition to chronic diseases， and anti-tumor drugs. In terms of the impact on medicine， the ratio of adverse drug reaction event cases in 2022 was 66.00%， an increase of 1.29% compared to the previous； since the implementation of the policy， 12 drugs from local pharmaceutical enterprises from Guangxi Zhuang Autonomous Region had passed the consistency evaluation， and the market concentration rate of the top 8 pharmaceutical companies was less than 20.00%. In terms of the impact on healthcare and medical insurance， the public medical institutions achieved generic substitution for originator drugs mostly until 2022； about 9.12% of drugs that were non- centrally purchased in the same category were used； 63.39% of people under investigation did not show a need for a second dressing change； drug expenditure decreased by 2.459 billion yuan. CONCLUSIONS The national centralized procurement policy achieves a significant effect in Guangxi Zhuang Autonomous Region. On the other hand， attention should be paid to these suggestions as follows: expanding the category of drugs used in clinic， conducting clinically comprehensive evaluation of selected drugs， and improving reasonable allocation strategy， etc.

Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on NPoly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers.

BACKGROUND: For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers. RESULTS: Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone. CONCLUSIONS: This is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.

Clinical implementation of iterative cone-beam computed tomography guided online adaptive radiotherapy for the pelvic malignancies / 中华放射肿瘤学杂志

Objective:To evaluate the clinical application of online adaptive radiotherapy based on iterative cone-beam computed tomography (iCBCT) for the pelvic malignancies.Methods:This was a prospective clinical trial of iCBCT guided online adaptive radiotherapy for pelvic malignancies in Department of Radiation Oncology, Peking Union Medical College Hospital. Clinical data of 13 patients with pelvic malignancies who received online adaptive radiotherapy from August to November, 2022 were preliminarily analyzed (2 cases of cervical cancer, 4 postoperative cervical cancer, 3 postoperative endometrial cancer, 3 bladder cancer and 1 prostate cancer). The feasibility of online adaptive radiotherapy, adaptive radiotherapy time, the frequency and magnitude of edits for organs at risk and target volume, target volume coverage and organs at risk doses were analyzed. Statistical analysis was performed by SPSS software. Data conforming to normal distribution were described by Mean±SD, and data with non-normal distribution were expressed by M ( Q1, Q3). Data with homogeneous variances were analyzed by t-test, and data with non-normal distribution or heterogeneous variances were analyzed by nonparametric test. Results:The average adaptive time was 15 min and 38 s (from acceptance of acquired CBCT scan to completion of the final plan selection). 85.4% (830/972 fractions) of influencer structures (system-defined organs adjacent to and with high impact on the generation of clinical target volume and planning target volume, primarily bladder, rectum and small intestine in pelvic neoplasms) automatically generated by artificial intelligence required no edits or minor editors, and 89.8% (491/547 fractions) of clinical target volume automatically generated by artificial intelligence required no edits or minor editors. The adapted plan was adopted in 98.5% (319/324 fractions) of radiotherapy fractions. Compared with the scheduled plan, the adapted plan showed better target volume coverage and reduced the dose of organs at risk.Conclusions:iCBCT guided online adaptive radiotherapy for the pelvic malignancies can be achieved within clinically acceptable timeslots. In addtion, better dose coverage of target volume shows the advantages of online adaptive radiotherapy.

Inhibiting pyroptosis: novel immune evasion strategies for pathogens.

Pyroptosis is a type of programmed cell death mediated by the Gasdermin family. It is triggered in response to pathogen infection or other danger signals. The activation of Gasdermins leads to pyroptosis and the release of large amounts of inflammatory cytokines. Pyroptosis plays a crucial role in combating pathogen infections, as it helps to eliminate infected cells and activate the immune system. However, pathogens have already developed sophisticated strategies to evade or inhibit pyroptosis, allowing them to persist and facilitate infection. This review provides an overview of the discovery of pyroptosis and its importance in anti-infectious immunity. We also discuss several new strategies for inhibiting pyroptosis by pathogens. A thorough learning of the occurrence and regulation of pyroptosis may reveal the pathogenesis of related infectious diseases and contribute to developing effective anti-infective therapeutic strategies.

Schwann Cells Promote Myogenic Differentiation of Myoblasts and Adipogenic Mesenchymal Stromal Cells on Poly-ɛ-Caprolactone-Collagen I-Nanofibers.

For the purpose of skeletal muscle tissue engineering, different cell types have been investigated regarding their myogenic differentiation potential, including co-cultured myoblasts and adipogenic mesenchymal stromal cells (Mb/ADSC). As neural cells enhance synaptic junction formation, the aim of this study was to co-culture Schwann cells (SCs) with Mb/ADSC on biocompatible electrospun aligned poly-ε-polycaprolacton (PCL)-collagen I-nanofibers. It was hypothesized that SCs, as part of the peripheral nervous system, promote the myogenic differentiation of Mb/ADSC co-cultures. Mb/ADSC were compared to Mb/ADSC/SC regarding their capacity for myogenic differentiation via immunofluorescent staining and gene expression of myogenic markers. Mb/ADSC/SC showed more myotubes after 28 days of differentiation (p ≤ 0.05). After 28 days of differentiation on electrospun aligned PCL-collagen I-nanofibers, gene expression of myosin heavy chains (MYH2) and myogenin (MYOG) was upregulated in Mb/ADSC/SC compared to Mb/ADSC (p ≤ 0.01 and p ≤ 0.05, respectively). Immunofluorescent staining for MHC showed highly aligned multinucleated cells as possible myotube formation in Mb/ADSC/SC. In conclusion, SCs promote myogenic differentiation of Mb/ADSC. The co-culture of primary Mb/ADSC/SC on PCL-collagen I-nanofibers serves as a physiological model for skeletal muscle tissue engineering, applicable to future clinical applications.

Comparison of Corneal Biomechanical Properties Based on Data from Uniaxial Tensile Test under Fast and Slow Loading / 医用生物力学

Objective To compare the corneal biomechanical parameters identified from uniaxial tensile test under fast and slow loading. Methods The stress-strain and stress relaxation data were obtained from uniaxial tensile tests on corneal strips from 15 healthy adult rabbits at average loading rate of 0.16 mm/s and 0.02 mm/s, respectively. A visco-hyperelastic model was applied to analyze the loading and unloading data from the fast tensile tests, where the model parameter set was denoted by Gvh. The first-order Ogden model and second-order Prony series model were used to fit stress-strain and stress relaxation data from the slow tensile tests, respectively, in which the model parameter set was denoted by Gvh. Correlation analysis was used to compare the correlation of parameters between Gvh and GOP. Results All the goodness-of-fits to the three data sets were greater than 0.95. There were significant differences in 5 (μ, A1, A2, τ1, τ2,) of the 6 parameters between Gvh and GOP (P<0.05), and the Ogden model parameters was positively correlated between the two groups. Conclusions There are differences in corneal biomechanical parameters identified by data from uniaxial tensile tests under fast and slow loading. The results provide a preliminary research basis for further exploring the use of clinical data to identify corneal biomechanical properties.

Clinical effect of transcatheter arterial chemoembolization combined with microwave ablation versus repeat resection in treatment of recurrent hepatocellular carcinoma / 临床肝胆病杂志

Objective To investigate the clinical effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation (MWA) (TACE-MWA) versus repeat resection (RR) in the treatment of recurrent hepatocellular carcinoma (RHCC). Methods A total of 178 patients with RHCC who were admitted to The Second People's Hospital of Neijiang from June 2015 to September 2020 were enrolled, and according to the treatment modality, they were divided into RR group with 64 patients and TACE-MWA group with 114 patients. Baseline demographic data, liver function, and tumor conditions before treatment were recorded, and the patients were followed up to October 2021 to compare postoperative overall survival (OS) time and recurrence-free survival (RFS) time between the two groups. Subgroup analysis based on recurrence pattern (recurrence time and tumor size) was performed, and the influencing factors for prognosis were analyzed. The independent samples t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data; the Kaplan-Meier method was used for postoperative survival rate, the Log-rank test was used for survival difference analysis, and a multivariate Cox regression analysis was used to investigate independent risk factors for survival. Results The multivariate analysis showed that tumor diameter, alpha-fetoprotein (AFP) level, alanine aminotransferase, albumin, and time to recurrence were independent prognostic factors for OS (all P 2 years), there were significant differences between the two groups in median OS (54.0 months vs 36.0 months, χ 2 =6.171, P =0.013) and median RFS (28.0 months vs 21.0 months, χ 2 = 5.211, P =0.022). For RHCC with a tumor diameter of ≤5 cm, there was a significant difference in median OS between the two groups (33.0 months vs 27.0 months, χ 2 =6.447, P =0.011). Conclusion RR has a similar clinical effect to TACE-MWA in RHCC with early recurrence or a tumor diameter of > 5 cm, but RR should be the first choice for RHCC with late recurrence or a tumor diameter of ≤5 cm.

Comparison of the application value of X-ray and MRI in the diagnosis of subacromial impingement syndrome / 中国医师进修杂志

Objective:To compare and analyze the value of X-ray examination and MRI in the diagnosis of subacromial impingement syndrome.Methods:Sixty patients with shoulder pain and weakness in Beijing Tiantan Hospital, Capital Medical University from January 2019 to May 2021 were selected. All patients underwent X-ray and MRI. Taking clinical diagnosis as the gold standard, the diagnostic efficacy of X-ray and MRI in subacromial impact syndrome was compared and analyzed.Results:The consistency between MRI and gold standard was good ( Kappa = 0.769, P<0.01), and the consistency between X-ray and gold standard was general ( Kappa = 0.464, P<0.01); there was no significant difference between X-ray examination and MRI examination of acromion morphological classification, subacromial space classification ( P>0.05); The sensitivity of MRI was higher than that of X-ray, and the difference was statistically significant ( χ2 = 4.00, P<0.05). There was no difference between MRI and X-ray, and the difference was not statistically significant ( χ2 = 0.25, P>0.05). Conclusions:X-ray and MRI are complementary to each other in the diagnosis of subacromial impingement syndrome. X-ray examination should be carried out first, and MRI should be carried out when necessary.

Efficacy of mycophenolate mofetil for AQP4 antibody positive optic neuritis immunotherapy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the efficacy of mycophenolate mofetil(MMF)on the prevention of relapse and visual prognosis of patients in neuromyelitis optica spectrum disorders(NMOSD)with AQP4 antibody positive optic neuritis. <p>METHODS: We retrospectively reviewed 11 patients with initial diagnosis of NMOSD and AQP4 antibody positive optic neuritis from January 2017 to December 2019. Among the 11 patients, 3 were male and 8 were female. The unique core clinical manifestation of NMOSD was optic neuritis. The onset age was 36.3±6.0(27-47)years old. Duration of the disease was 3.4±1.4(2.2-6.8)a. MMF was added in the relieving period of NMOSD for 1a or over 1a. Annualized relapsing rate(ARR), best corrected vision activity(BCVA)and adverse reactions of MMF were recorded.<p>RESULTS: The median time of MMF treatment was 18(12, 36)mo. The ARR was 0.66/a at baseline and 0.16/a after the treatment. There were 91% of the patients had decreased ARR and 82% of them had no clinical relapse. The patients had significant improvement on ARR after MMF treatment(<i>P</i><0.05 ). In total, there was no significant difference between the mean BCVA after treatment and that at baseline(<i>P</i>>0.05). Of the 11 patients, 3 patients had side effects(27%), including 1 patient with elevated liver transaminase(9%), and 2 patients with mild gastrointestinal reaction(18%)during follow-up period. None of them discontinued MMF due to adverse events.<p>CONCLUSION: MMF treatment for AQP4 antibody positive NMOSD can reduce the ARR of optic neuritis to a certain extent and protect the visual function of patients.

[Clinicopathological Features of Intrathyroid Thymic Carcinoma].

Objective To investigate the clinicopathological features,immunohistochemical characteristics,diagnosis,treatment and prognosis of intrathyroid thymic carcinoma.Methods Clinical data of 7 patients with intrathyroid thymic carcinoma were retrospectively reviewed.Histological examination and immunohistochemical staining were performed on the surgically resected tumors.The infection of Epstein-Barr virus(EBV)was detected by EBER in situ hybridization.Results The 7 patients included 5 males and 2 females.The age ranged from 40 to 71 years,with a median of 54 years.The tumors were located in the thyroid gland,with the maximum diameter ranging from 2.2 cm to 6.0 cm and the average maximum diameter of(4.0±1.2)cm.All the patients underwent thyroid gland resection and local lymph node dissection.After operation,all the cases were treated with radiotherapy and five of them additionally received chemotherapy.Six patients were followed up for 10-163 months,all of whom were still alive,including 2 patients with recurrence in situ,1 patient with homolateral cervical lymph node metastasis and the rest with no recurrence or metastasis.CK-pan,P63,CD5 and CD117 were expressed in all the cases,while TTF-1,TG,CT and PAX8 were negative.One case of them expressed SYN and CgA.Ki-67 proliferation index ranged from 10% to 90%.EBER in situ hybridization showed negative results in all 7 cases.Conclusions Intrathyroid thymic carcinoma is a relatively low-grade malignant tumor.The combination of immunohistochemical CD5,CD117 and monoclonal PAX8 is helpful in the diagnosis and differential diagnosis of intrathyroid thymic carcinoma.EBV may not be involved in the development of intrathyroid thymic carcinoma.Thyroid gland resection plus central lymph node dissection is an important treatment measure for intrathyroid thymic carcinoma.For patients with regional lymph node metastasis and obvious peripheral tissue invasion,postoperative radiotherapy with/without chemotherapy can effectively delay the disease progression.

Budd-Chiari Syndrome: The "inferior vena cava reverse-flow" sign and "jet-blood" sign on CT and MRI.

OBJECTIVE: To investigate the CT and MR features of "inferior vena cava(IVC) reverse-flow" sign and "jet-blood" sign in Budd-Chiari Syndrome (BCS). METHODS: The liver CT and/or MRI plain scan and dynamic enhancement of 107 cases of BCS diagnosed by DSA and/or clinic were collected, including 17 patients with hepatic vein obstruction type, 79 patients with IVC obstruction type, and 11 patients with mixed type. The manifestations of IVC reverse-flow sign and jet-blood sign in the latter two type BCS (90cases) imaging were analyzed. RESULTS: 1) The incidence of IVC reverse-flow sign in the IVC obstruction type and mixed type was 93.3 %(83/90), which was manifested as: The contrast agent was shown below the level of renal veins in the hepatic arterial phase enhancement, while no contrast agent was shown above it at the same time. 2) The incidence of jet-blood sign in membrane-perforated subtype was 100 %(15/15) or 16.7 %(15/90), which was manifested as: The low density/signal dots appeared within full of contrast agent at the superior liver segment IVC on axial slices in arterial phase of CT/MRI enhancement, or the low signal line within agent presented above the IVC membrane on coronal image in equilibrium phase of MR enhancement. 3) Other imaging findings: 75 cases of membrane, 18 cases of membrane calcification, 27 cases of abnormal hepatic vein, 76 cases of abnormal structure of IVC, 18 cases of thrombus/cancer embolus in hepatic vein and/or IVC. There were 65 cases of abnormal liver appearance; 71 cases of abnormal liver enhancement; 21 cases of hepatic vein unsynchronous enhancement. Anastomotic branches among the hepatic veins open with comma sign in 54 cases; dilatation of intraspinal and paravertebral veins, azygos and hemiazygos veins in 90 cases(100 %, 90/90) or 96 cases(89.7 %, 96/107). CONCLUSIONS: The "IVC reverse-flow" sign is a specific CT and MR sign of IVC type and mixed type BCS, and the "jet-blood" sign is a characteristic CT and MR sign of membrane-perforated subtype BCS.

Prp5-Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription.

Transcription and pre-mRNA splicing are coupled to promote gene expression and regulation. However, mechanisms by which transcription and splicing influence each other are still under investigation. The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the branch-point region. From an open UV mutagenesis screen for genetic suppressors of prp5 defects and subsequent targeted testing, we identify components of the TBP-binding module of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex, Spt8p and Spt3p. Spt8Δ and spt3Δ rescue the cold-sensitivity of prp5-GAR allele, and prp5 mutants restore growth of spt8Δ and spt3Δ strains on 6-azauracil. By chromatin immunoprecipitation (ChIP), we find that prp5 alleles decrease recruitment of RNA polymerase II (Pol II) to an intron-containing gene, which is rescued by spt8Δ. Further ChIP-seq reveals that global effects on Pol II-binding are mutually rescued by prp5-GAR and spt8Δ. Inhibited splicing caused by prp5-GAR is also restored by spt8Δ. In vitro assays indicate that Prp5p directly interacts with Spt8p, but not Spt3p. We demonstrate that Prp5p's splicing proofreading is modulated by Spt8p and Spt3p. Therefore, this study reveals that interactions between the TBP-binding module of SAGA and the spliceosomal ATPase Prp5p mediate a balance between transcription initiation/elongation and pre-spliceosome assembly.

Alternative splicing regulation of doublesex gene by RNA-binding proteins in the silkworm Bombyx mori.

Doublesex is highly conserved and sex-specifically spliced in insect sex-determination pathways, and its alternative splicing (AS) is regulated by Transformer, an exonic splicing activator, in the model system of Drosophila melanogaster. However, due to the lack of a transformer gene, AS regulation of doublesex remains unclear in Lepidoptera, which contain the economically important silkworm Bombyx mori and thousands of agricultural pests. Here, we use yeast three-hybrid system to screen for RNA-binding proteins that recognize sex-specific exons 3 and 4 of silkworm doublesex (Bm-dsx); this approach identified BxRBP1/Lark binding to the exon 3, and BxRBP2/TBPH and BxRBP3/Aret binding to the exon 4. Investigation of tissues shows that BxRBP1 and BxRBP2 have no sex specificity, but BxRBP3 has - three of its four isoforms are expressed with a sex-bias. Using novel sex-specific silkworm cell lines, we find that BxRBP1 and BxRBP3 directly interact with each other, and cooperatively function as splicing repressors. Over-expression of BxRBP1 and BxRBP3 isoforms efficiently inhibits splicing of the exons 3 and 4 in the female-specific cells and generates the male-specific isoform of Bm-dsx. We also demonstrate that the sex-determination upstream gene Masc regulates alternatively transcribed BxRBP3 isoforms. Thus, we identify a new regulatory mechanism of doublesex AS in the silkworm, revealing an evolutionary divergence in insect sex-determination.

Influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma in patients with chronic hepatitis B: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo investigate the influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection. MethodsPubMed, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for articles on the influence of dual positivity of HBsAg and anti-HBs on the risk of HCC published from July 1, 1975 to March 27, 2019. RevMan5.3 and Stata11.2 were used for statistical analysis of data. A heterogeneity analysis was performed for the studies included; a random effects model was used in case of significant heterogeneity, and a fixed effects model was used in case of non-significant heterogeneity. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to investigate the association of dual positivity of HBsAg and anti-HBs with the development of HCC. Begg funnel plots were used to investigate publication bias. By removing one article each time, the sensitivity analysis was used to assess the quality and reliability of the Meta-analysis. ResultsA total of 4 articles were included, with 2 studies in the Korean population and 2 in the Chinese population, and there were 3042 patients in total. The meta-analysis showed that there was no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC (OR=1.46, 95%CI: 0.76-2.80, P=0.25). A country-based subgroup analysis showed significant association between dual positivity of HBsAg and anti-HBs and the development of HCC in the Korean population (OR=2.67, 95%CI: 1.61-4.43, P=0.000 1), while no significant association was found in the Chinese population (OR=0.89, 95%CI: 0.48-1.64, P=0.70). ConclusionThere is no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC, and further studies are needed in future.

Analysis of TCR β chain CDR3 clonetype in HBV-infected patients with coexistence of HBsAg and HBsAb / 临床检验杂志

Objective@#To compare T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) in the patients with coexistence of HBsAg and HBsAb and other HBV infected patients. @*Methods@#The clonotype and diversity of CDR3 in blood of group cases (positive HBsAg and HBsAb) (n=11), control 1 (negative HBsAg and positive HBsAb) (n=10) and control 2 (positive HBsAg and negative HBsAb) (n=10) were analyzed by high-throughput TCR sequencing with Illumina HiseqX10. @*Results@#In the case group, the overlap rate of 6.28% (0.25%, 13.10%) was detected between any two samples, which was significantly lower than the overlap rate of 10.49% (6.20%，17.30%) seen in control 1 group (P=0.008). In control 2 group, the overlap rate of 2.60% (0.13%，13.69%) was significantly lower than control 1 group (P=0.001). There was no difference between case group and control 2 group. After pairwise comparison between the three groups, the frequency of clonotype TRBV7-2/TRBD1/TRBJ2-1 in case group was higher than that of control 1 group (P=0.029), the frequency of TRBV7-3/TRBD1/TRBJ2-7 in case group was lower than that of control 1 group (P=0.031). The difference of TRBV5-8 was significant in comparing case group with control 1 group (P=0.047). There were 14 clonotypes which had differences between case group and control 2 group in frequency. TRBV28was significant in comparing case group with control 2 group (P=0.028). For diversity, there was no difference among the three groups. @*Conclusion@#Clonotype TRBV7-2/TRBD1/TRBJ2-1, TRBV7-3/TRBD1/TRBJ2-7 and TRBV5-8 were associated with coexistence of HBsAg and HBsAb, but the diversity was not associated with TCR β chain CDR3.

A Novel Knotless Barbed Suture Technique for Traumatic Thoracolumbar Fracture in Posterior Surgery.

BACKGROUND: Surgical wound closure directly influences spinal surgical efficiency and several postoperative complications. The traditional suture technique is time-consuming and associated with greater rates of complications. Bidirectional absorbable barbed sutures seem to compensate for some of the limitations of traditional suture; however, they rarely are reported in spinal surgery. We designed a novel suture technique for use in thoracolumbar spinal surgery. METHODS: The data of 189 patients with traumatic thoracolumbar fractures were analyzed between bidirectional barbed suture closure and traditional interrupted suture closure. Data of operative time, wound closure time, length of incision, intraoperative blood loss, complications of wound dehiscence and postoperative hematoma, cost, and neurologic status were collected. RESULTS: No significant differences were observed in the baseline demographics of included patients. Compared with the traditional suturing group, the barbed sutures decreased the mean operative time (P = 0.037), suture time (P < 0.01), and mean suturing time (P < 0.01) significantly, although no statistically significant differences were found in blood loss (P = 0.724) and neurologic functional scores (preoperative: P = 0.901; 3 months after surgery: P = 0.208; final follow-up assessments: P = 0.163), and no statistically significant differences were found in rates of postoperative infection, hematoma, and wound dehiscence. CONCLUSIONS: Our findings suggest that the novel knotless barbed suture has comparable strength to traditional sutures, with the advantage of less suturing time. It is an efficient, safe technique, and alternative choice for patients with thoracolumbar fracture after posterior surgery.

Robust recursive absolute value inequalities discriminant analysis with sparseness.

In this paper, we propose a novel absolute value inequalities discriminant analysis (AVIDA) criterion for supervised dimensionality reduction. Compared with the conventional linear discriminant analysis (LDA), the main characteristics of our AVIDA are robustness and sparseness. By reformulating the generalized eigenvalue problem in LDA to a related SVM-type "concave-convex" problem based on absolute value inequalities loss, our AVIDA is not only more robust to outliers and noises, but also avoids the SSS problem. Moreover, the additional L1-norm regularization term in the objective makes sure sparse discriminant vectors are obtained. A successive linear algorithm is employed to solve the proposed optimization problem, where a series of linear programs are solved. The superiority of our AVIDA is supported by experimental results on artificial examples as well as benchmark image databases.

Celastrol reduces IL-1ß induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo.

Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1ß treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1ß in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB pathway was inhibited by celastrol in nucleus pulposus cells. In vivo study showed that celastrol treated rats had stronger T2-weighted signal than vehicle-treated rats at 2 weeks and 6 weeks' time point, suggesting celastrol could attenuate intervertebral disc degeneration in vivo. Together, our study demonstrates that celastrol could reduce IL-1ß induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo, which shows its potential to be a therapeutic drug for IDD.