The impact of enhanced recovery after surgery on inflammatory indicators and prognosis related to complex appendicitis in children.

Objective: To explore the application effect of enhanced recovery after surgery (ERAS) perioperative plan in the treatment of complex appendicitis in children, and further enrich the implementation plan of ERAS in the field of pediatric surgery. Method: This study selected 122 children who underwent laparoscopic complex appendectomy at Inner Mongolia Maternal and Child Health Hospital and Baotou Fourth Hospital from August 2018 to July 2022, and randomly divided them into a traditional surgery group (TS) and an enhanced recovery surgery group (ERAS). The changes of white blood cell (WBC), hypersensitive C-reactive protein (CRP), pro Calcitonin (PCT) and interleukin 6 (IL-6) before and after surgery were compared. The degree of pain, recovery time of intestinal function, length of hospital stay, hospital costs, postoperative complications and parental satisfaction were compared between the two groups. Result: The WBC and CRP levels in the ERAS group at 6 h after surgery, as well as the IL-6 levels on the 3rd day after surgery, were lower than those in the TS group. Meanwhile, the analgesic effect of ERAS group at 3 h and 6 h after surgery was better than that of TS group. And the ERAS group had a shorter postoperative first exhaust time, fewer overall hospital stays, and lower hospitalization costs. In addition, the ERAS group had high parental satisfaction during hospitalization. There was no statistically significant difference in postoperative complications between the two groups of children. Conclusion: ERAS can promote postoperative recovery of children, reduce surgical stress, save family medical expenses, alleviate the pain of children, and improve parental satisfaction. It is a safe and effective method for treating complex appendicitis in children.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Comparative transcriptome analysis of sensory genes from the antenna and abdomen of Quadrastichus mendeli Kim.

Quadrastichus mendeli Kim is one of the most important parasitoids of Leptocybe invasa Fisher et La Salle, which is an invasive gall-making pest in eucalyptus plantations in the world. Gall-inducing insects live within plant tissues and induce tumor-like growths that provide the insects with food, shelter, and protection from natural enemies. Empirical evidences showed that sensory genes play a key role in the host location of parasitoids. So far, what kind of sensory genes regulate parasitoids to locate gall-inducing insects has not been uncovered. In this study, sensory genes in the antenna and abdomen of Q. mendeli were studied using high-throughput sequencing. In total, 181,543 contigs was obtained from the antenna and abdomen transcriptome of Q. mendeli. The major sensory genes (chemosensory proteins, CSPs; gustatory receptors, GRs; ionotropic receptors, IRs; odorant binding proteins, OBPs; odorant receptors, ORs; and sensory neuron membrane proteins, SNMPs) were identified, and phylogenetic analyses were performed with these genes from Q. mendeli and other model insect species. The gene co-expression network constructed by WGCNA method is robust and reliable. There were 10,314 differentially expressed genes (DEGs), and among them, 99 genes were DEGs. A comprehensive sequence resource with desirable quality was built by comparative transcriptome of the antenna and abdomen of Q. mendeli, enriching the genomic platform of Q. mendeli.

Enhancing the Chemical Stability of MXene Through Synergy of Hydrogen Bond and Coordination Bond in Aqueous Solution.

MXenes with unique physicochemical properties have shown substantial potential in electromagnetic interference (EMI) shielding. However, the chemical instability and mechanical fragility of MXenes has become a major hurdle for their application. Abundant strategies have been dedicated to improving the oxidation stability of colloidal solution or mechanical properties of films, which always come at the expense of electrical conductivity and chemical compatibility. Here, hydrogen bond (H-bond) and coordination bond are employed to achieve chemical and colloidal stability of MXenes (0.1 mg mL-1 ) by occupying the reaction sites of Ti3 C2 Tx attacking of water and oxygen molecules. Compared to the Ti3 C2 Tx , the Ti3 C2 Tx modified with alanine via H-bond shows significantly improved oxidation stability (at room temperature over 35 days), while the Ti3 C2 Tx modified with cysteine by synergy of H-bond and coordination bond can be maintained even after 120 days. Simulation and experimental results verify the formation of H-bond and Ti-S bond by a Lewis acid-base interaction between Ti3 C2 Tx and cysteine. Furthermore, the synergy strategy significantly improves the mechanical strength of the assembled film (up to 78.1 ± 7.9 MPa), corresponding the increment of 203% compared to untreated one, almost without compromising the electrical conductivity and EMI shielding performance.

Effects of linalool on Botrytis cinerea growth and control of tomato gray mold.

We examined the antifungal characteristics of linalool against Botrytis cinerea using plate inhibition assay and spore germination assay, and assessed the capacity of linalool in controlling tomato gray mold disease via tomato pot inoculation assay. The results showed that linalool exhibited strong inhibitive effects on mycelial growth of B. cinerea, with an EC50 value of 0.581 mL·L-1. In the spore germination test, linalool treatment inhibited spore germination in a dose-dependent manner. The electric conductivity and the malondialdehyde (MDA) contents were significantly increased in linalool-treated B. cinerea than that of the control, indicating that linalool induced oxidative damage and destroyed the cell membrane integrity in B. cinerea. The activities of the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the linalool-treated B. cinerea were decreased significantly by 27.4%, 68.9% and 26.0%, respectively, suggesting that linalool inhibited the antioxidant activity of B. cinerea. In the pot experiment, the diameter of lesions in linalool-treated tomatoes was significantly smaller than that of the control. The activities of SOD, POD, CAT, polyphenol oxidase, and phenylalnine ammonialyase in the linalool-treated tomatoes increased, while the MDA content decreased, suggesting that linalool could alleviate the oxidative damage caused by B. cinerea and promote plant disease resistance. In summary, linalool had inhibitory effect on the growth of B. cinerea and could control gray mold disease in tomatoes. These findings could lay the foundation for developing bota-nical antifungal agents for management of tomato gray mold disease.

Molecular basis of JAK2 H608Y and H608N mutations in the pathology of acute myeloid leukemia.

Risk-stratification of acute myeloid leukemia (AML) based on (cyto)genetic aberrations, including hotspot mutations, deletions and point mutations have evolved substantially in recent years. With the development of next-generation sequence technology, more and more novel mutations in the AML were identified. Thus, to unravel roles and mechanism of novel mutations would improve prognostic and predictive abilities. In this study, two novel germline JAK2 His608Tyr (H608Y) and His608Asn (H608N) mutations were identified and the molecular basis of these mutations in the leukemiagenesis of AML was elucidated. Our results indicated that JAK2 H608Y and H608N mutations disrupted the hydrogen bond between Q656 and H608 which reduced the JH2 domain's activity and abolished interactions between JH1 and JH2 domains, forced JAK2 into the active conformation, facilitated the entrance of substrates and thus caused JAK2 hyperactivation. Further studies suggested that JAK2 H608Y and H608N mutations enhanced the cell proliferation and inhibited the differentiation of Ba/F3 and MV4-11 cells via activating the JAK2-STAT5 signaling pathway. Moreover, rescue experiments demonstrated that mutations repaired the hydrogen bond between Q656 and H608 displayed opposite results. Thus, this study revealed the molecular basis of JAK2 H608Y and H608N mutations in the pathology of AML.

Submucosal Tunneling Endoscopic Resection for Submucosal Tumors in the Proximal Esophagus.

BACKGROUND: Submucosal tunneling endoscopic resection (STER) is widely applied for treatment of gastrointestinal submucosal tumors (SMTs) originating from the muscularis propria layer. However, the tumor location within the proximal esophagus makes STER a challenge for the endoscopists. The aim of this study was to summarize the technique skill and evaluate the outcomes of proximal esophageal STER. STUDY DESIGN: A total of 72 patients with SMTs in the proximal esophagus undergoing STER were included from February 2019 to March 2021. Imaging 3-dimensional reconstruction was used for patients with large SMTs. Clinicopathological, endoscopic, and follow-up data were collected and analyzed. RESULTS: In this study, all the tumors were removed completely and no gross disease was remaining. The en bloc resection was achieved in 90.28% of patients, and the complications rate was 6.95%. Three-dimensional reconstruction was used for 30 patients (41.67%) with large SMTs (transverse diameter >2.0 cm). Based on statistical analysis, tumors with irregular shape and larger size were the significant contributors to piecemeal resection. Larger tumors increase the risk of long operation time, and irregular tumor shapes increase the risk of complications. The median hospitalization time was 4 days. All of the complications were cured by conservative treatment. A median follow-up of 12 months was available, and all patients were free from local recurrence or distant metastasis during the study period. CONCLUSIONS: STER is an effective and safe methodology for the resection of proximal esophageal SMTs. Tumor size and shape mainly impact the piecemeal resection rate, STER-related complications, and procedural difficulty.

Characterization of HPV subtypes not covered by the nine-valent vaccine in patients with CIN 2-3 and cervical squamous cell carcinoma.

BACKGROUND: As the second most common female malignant tumor, cervical cancer is also one of the most preventable and avoidable cancers. The World Health Organization has launched a global plan to accelerate the elimination of cervical cancer. Therefore, in the era of postvaccine, the role of HPV subtypes in cervical precancerous lesions and cervical cancer that are not covered by vaccine should be further discussed. The purpose of this study was to explore the role of HPV subtypes not covered by the nine-valent vaccine in high-grade cervical precancerous lesions and cervical cancer. MATERIALS AND METHODS: A retrospective analysis was performed on the clinical data of 5220 patients with an HPV infection who were diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between October 2016 and February 2020. In addition, the clinical characteristics of the biopsy results of 470 cases of cervical intraepithelial neoplasia (CIN) 2-3 and 205 cases of cervical squamous cell carcinoma were analyzed. RESULTS: Among patients with HPV subtype infection not covered by the nine-valent vaccine, univariate analysis showed that compared with patients with CIN 2-3, age ≥ 50, not using condom and TCT reported as ASC-H were risk factors for cervical squamous cell carcinoma (P < 0.05). The detection rates of HPV subtype not covered by the nine-valent vaccine in CIN 2-3 and cervical squamous cell carcinoma patients were 7.23% and 6.34%, respectively. CONCLUSION: In patients with CIN 2-3 and cervical squamous cell carcinoma, the infection rates of HPV subtype not covered by the nine-valent vaccine were 7.23% and 6.34%, respectively. With the increasing popularity of the vaccine, the infection rates of the corresponding HPV subtype decreased; however, HPV subtype infection not covered by the nine-valent vaccine should not be ignored.

Sensory gene identification in the transcriptome of the ectoparasitoid Quadrastichus mendeli.

Sensory genes play a key role in the host location of parasitoids. To date, the sensory genes that regulate parasitoids to locate gall-inducing insects have not been uncovered. An obligate ectoparasitoid, Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae: Tetrastichinae), is one of the most important parasitoids of Leptocybe invasa, which is a global gall-making pest in eucalyptus plantations. Interestingly, Q. mendeli can precisely locate the larva of L. invasa, which induces tumor-like growth on the eucalyptus leaves and stems. Therefore, Q. mendeli-L. invasa provides an ideal system to study the way that parasitoids use sensory genes in gall-making pests. In this study, we present the transcriptome of Q. mendeli using high-throughput sequencing. In total, 31,820 transcripts were obtained and assembled into 26,925 unigenes in Q. mendeli. Then, the major sensory genes were identified, and phylogenetic analyses were performed with these genes from Q. mendeli and other model insect species. Three chemosensory proteins (CSPs), 10 gustatory receptors (GRs), 21 ionotropic receptors (IRs), 58 odorant binding proteins (OBPs), 30 odorant receptors (ORs) and 2 sensory neuron membrane proteins (SNMPs) were identified in Q. mendeli by bioinformatics analysis. Our report is the first to obtain abundant biological information on the transcriptome of Q. mendeli that provided valuable information regarding the molecular basis of Q. mendeli perception, and it may help to understand the host location of parasitoids of gall-making pests.

Long non-coding RNA NEAT1 functions as a competing endogenous RNA to regulate S100A9 expression by sponging miR-196a-5p in rosacea.

BACKGROUND: Rosacea is a complex, chronic, and recurrent dermatologic condition that adversely affects quality of life and self-esteem. However, clinical relevance and molecular mechanisms underlying NEAT1 influence in rosacea remain unclear. OBJECTIVE: The present study aims to investigate the dynamics and influences of lncRNAs, miRNAs, and mRNAs in rosacea patients, and to explore the impacts of NEAT1 treatments on miR-196a-5p and S100A9 expression in LL37-treated HaCaT cells. METHODS: RNA-sequencing of skin tissues from rosacea patients and integrative analyses facilitated comprehensive exploration of lncRNA, mRNA, and miRNA networks. We identified differentially expressed lncRNAs in paired rosacea afflicted and non-lesioned tissues by hub lncRNAs in the ceRNA network. The role of NEAT1 in LL37-treated HaCaT cells was identified by in vitro experiments. RESULTS: There were 237 lncRNAs, 38 miRNAs, and 1784 mRNAs in lesioned skin compared to non-lesioned skin in six rosacea patients. NEAT1 was upregulated in rosacea skin and in LL37-treated HaCaT cells. Moreover, inflammatory damage was able to be reduced in vitro after knockdown of NEAT1. Finally, NEAT1 was able to directly interact with miR-196a-5p, and downregulating miR-196a-5p was efficient in reversing the influence of NEAT1 siRNA on S100A9. CONCLUSION: We have completed the first genome-wide lncRNA profiling of paired lesioned and non-lesioned samples from rosacea afflicted patients. The NEAT1/miR-196a-5p/S100A9 axis may have played an important role in the dynamics underlying inflammatory responses of rosacea. NEAT1 may have functioned as a competing endogenous RNA which regulated inflammatory responses in rosacea by sponging miR-196a-5p and upregulating S100A9 expression.

Vertebral Collapse Prevented Following Teriparatide Treatment in Postmenopausal Kümmell's Disease Patients with Severe Osteoporosis.

OBJECTIVE: To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single-level Kümmell's disease (KD). METHODS: From March 2013 to December 2020, the medical records for 53 postmenopausal single-level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. RESULTS: At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P < 0.001). Sagittal CT substantiated the formation of bone bridge in 16 patients in teriparatide group. No bone bridge was detected in alendronate group. The KA was significantly smaller and the ABH, PBH, and SCD was greater in teriparatide group than in alendronate group (all P < 0.001). The KA increments were significantly smaller in teriparatide group (3.98° ± 1.30°) than in alendronate group (11.43° ± 3.73°) (P < 0.001). The ABH and PBH decrement were significantly lower in teriparatide group (11.96% ± 1.93% and 2.80% ± 2.52%) than in alendronate group (37.04% ± 8.00% and 19.50% ± 8.22%) (both P < 0.001). The BTMs and BMD were significantly greater in the teriparatide group than in the alendronate group. In teriparatide group, KA increment was negatively correlated with the change in PINP (r = -0.781, P < 0.001) and the ratio of AIMB to AFVB (r = -0.592, P = 0.002) from baseline to month 12. The ABH decrement was negatively correlated with the change in PINP (r = -0.612, P = 0.001) and the ratio of AIMB to AFVB (r = -0.806, P < 0.001) from baseline to month 12. CONCLUSIONS: In postmenopausal single-level KD patients, conservative treatment with teriparatide was better than alendronate at preventing the progressive vertebral collapse.

Unconventional [2 + 3] Cyclization Involving [1,4]-Sulfonyl Transfer to Construct Polysubstituted Fluorazones as Inhibitors of Indoleamine 2,3-Dioxygenase 1.

An unconventional [2 + 3] cyclization of pyridinium ylides with 2-ylideneoxindoles has been developed for the facile construction of pharmacologically interesting polysubstituted 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones). Mechanistic studies revealed that the reaction, which has a broad substrate scope, proceeds via intermolecular [1,4]-sulfonyl transfer. Moreover, biological evaluation showed that polysubstituted fluorazone 3ak potently inhibits indoleamine 2,3-dioxygenase 1, kynurenine production, and immunotolerance in tumors.

[Effect of Water-Fertilizer-Gas Coupling on Soil N2O Emission and Yield in Greenhouse Tomato].

To reveal the effect of water, fertilizer, and gas coupling on soil N2O emissions in greenhouse tomato soil and suggest appropriate measures for increasing yield and reducing N2O emissions, static chamber-gas chromatography was used to study the effects of soil N2O emissions. The variation laws of soil temperature, water-filled pore space (WFPS), NO3--N content, and O2 content and the influence mechanism of N2O emission under the condition of water-fertilizer-gas coupling were analyzed. Aerated conditions comprised two water levels, 0.6 W and 1.0 W (representing 40% deficit irrigation and full irrigation, W represents when sufficient irrigation water was available), and three nitrogen levels (120 kg·hm-2, 180 kg·hm-2, and 240 kg·hm-2, representing low, medium, and high nitrogen, respectively, with 50% F, 75% F, and F, F is the recommended amount of nitrogen application locally). Three levels of fertilization were used as controlled unaerated full irrigation (O representing aeration, and CK representing conventional drip irrigation). Nine treatments were designed in the experiment. The results showed that the tomato field cumulative emission of N2O under full irrigation (W2F1O, W2F2O, and W2F3O) increased by an average of 55.7% compared with the corresponding treatment at W1 level (P<0.05). The N2O emissions of W1F3O, W2F3O, and W2F3CK fields significantly increased by 13.4% and 43.8% compared with medium nitrogen W1F2O, W2F2O, and W2F2CK and low nitrogen W1F1O, W2F1O, and W2F1CK treatments, respectively (P<0.05).Compared with the corresponding unaerated full irrigation, the emissions (W2F1O, W2F2O, and W2F3O) significantly increased by 11.2% (P<0.05). Aeration, the increase of nitrogen rate, and irrigation amount resulted in the increment of tomato yield and yield-scaled N2O emissions. Compared with medium nitrogen, the yield and yield-scaled N2O emission of high nitrogen treatment increased by 12.5% (P<0.05) and 3.9% (P>0.05), respectively. Compared with low nitrogen treatment, the yield and yield-scaled N2O emission of high nitrogen treatment increased by 30.4% and 9.6% (P<0.05), respectively. The yield and yield-scaled N2O emissions of aerated full irrigation significantly increased by 29.7% and 18.7%, respectively, compared with aerated deficient irrigation. Compared with unaerated irrigation treatment, the yield under aerated treatment increased by 10.4% (P<0.05), and the yield-scaled N2O emission increased by 3.9% (P>0.05). Under the conditions of increasing irrigation water, decreasing fertilizer application, and aeration, partial factor productivity, and irrigation water use efficiency (IWUE) can be significantly increased. After comprehensive consideration of cumulative N2O emissions, tomato production, nitrogen fertilizer utilization efficiency, IWUE, and yield-scaled N2O emission, it can be concluded that aerated low nitrogen full irrigation is an optimal management mode. The results provide reference for increasing yield and reducing emissions of greenhouse tomato.

Nocardia colli sp. nov., a new pathogen isolated from a patient with primary cutaneous nocardiosis.

A novel nocardioform strain, CICC 11023T, was isolated from a tissue biopsy of neck lesions of a patient with primary cutaneous nocardiosis and characterized to establish its taxonomic position. The morphological, biochemical, physiological and chemotaxonomic properties of strain CICC 11023T were consistent with classification in the genus Nocardia. Whole-cell hydrolysates were rich in meso-diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were present. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and two unidentified lipids, and the predominant menaquinone was cyclo MK-8 (H4, ω-cyclo). The main fatty acids (>5 %) were C18 : 0 10-methyl (TBSA), C16 : 0, summed feature 4 (C16 : 1 trans 9/C15 : 0 iso 2OH), C15 : 0 and C17 : 0 10-methyl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is most closely related (>98 % similarity) to the type strains Nocardia ninae OFN 02.72T, Nocardia iowensis UI 122540T and Nocardia alba YIM 30243T, and phylogenetic analysis of gyrB gene sequences showed similarity (89.1-92.2 %) to Nocardia vulneris NBRC 108936T, Nocardia brasiliensis IFM 0236T and Nocardia exalbida IFM 0803T. DNA-DNA hybridization results for strain CICC 11023T compared to Nocardia type strains ranged from 20.4 to 35.4 %. The genome of strain CICC 11023T was 8.78 Mbp with a G+C content of 67.4 mol% overall. The average nucleotide identity (ANI) values between strain CICC 11023T and N. alba YIM 30243T were low (OrthoANIu=77.47 %), and the ANI values between strain CICC 11023T and N. vulneris NBRC 108936 T were low (OrthoANIu=83.75 %). Consequently, strain CICC 11023T represents a novel Nocardia species on the basis of this polyphasic study, for which the name Nocardia colli sp. nov. is proposed. The type strain is CICC 11023T (=KCTC 39837T).

Ablation of Mature miR-183 Leads to Retinal Dysfunction in Mice.

Purpose: The microRNA cluster miR-183C, which includes miR-183 and two other genes, is critical for multiple sensory systems. In mouse retina, removal of this cluster results in photoreceptor defects in polarization, phototransduction, and outer segment elongation. However, the individual roles of the three components of this cluster are not clearly known. We studied the separate role of mouse miR-183 in in vivo. Methods: miR-183 knockout mice were generated using the CRISPR/Cas9 genome-editing system. Electroretinography were carried out to investigate the changes of retinal structures and function. miR-183 was overexpressed by subretinal adeno-associated virus (AAV) injection in vivo. Rnf217, a target of miR-183 was overexpressed by cell transfection of the photoreceptor-derived cell line 661W in vitro. RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to compare the gene expression changes in AAV-injected mice and transfected cells. Results: The miR-183 knockout mice showed progressively attenuated electroretinogram responses. Over- or under-expression of Rnf217, a direct target of miR-183, misregulated expression of cilia-related BBSome genes. Rnf217 overexpression also led to compromised electroretinography responses in WT mice, indicating that it may contribute to functional abnormalities in miR-183 knockout mice. Conclusions: miR-183 is essential for mouse retinal function mediated directly and indirectly through Rnf217 and cilia-related genes. Our findings provide valuable insights into the explanation and analysis of the regulatory role of the individual miR-183 in miR-183C.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) improving pregnancy outcomes after surgery for endometriosis-associated infertility. METHODS: A multicenter, randomized, double-blind placebo parallel controlled clinical trial was designed. A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017, 101 patients in each group. The two groups received continuous intervention at 1-5 days after surgery, for 6 menstrual cycles. Before ovulation, the CM group was treated Huoxue Xiaoyi Granule (); after ovulation, Bushen Zhuyun Granule ( was involved. The control group was treated with placebo. Transvaginal ultrasonography was performed every menstrual cycle during the treatment, and female hormone levels in the follicular and luteal phases were measured during the 1st, 3rd and 6th menstrual cycles. The analysis was continued until pregnancy. The primary outcomes were clinical pregnancy rate and pregnancy outcome, and the secondary outcomes were follicular development and endometrial receptivity. Safety evaluations were performed before and after treatment. RESULTS: (1) Clinical pregnancy and live birth rates: the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group [44.6% (45/101) vs. 29.7% (30/101), 34.7% (35/101) vs. 20.8% (21/101), both P<0.05]. (2) Follicle development: the incidence of dominant follicles, rate of cumulative cycle ovulation, and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group [93.8% (350/373) vs. 89.5% (341/381), 80.4% (275/342) vs. 69.1% (253/366), 65.8% (181/275) vs 56.1% (142/253), P<0.05 or P<0.01]). The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group [11.7% (40/342) vs. 17.8% (65/366), P<0.05). (3) Endometrial receptivity: after treatment, both endometrial types and endometrial blood flow types in the CM group were mainly types A and B, while those in the placebo group were mainly types B and C, with a significant difference between the two groups (both P<0.05). (4) Adverse events: the incidence of adverse events between the two groups was not significantly different (P>0.05). CONCLUSION: Strategies for activating blood circulation-regulating Gan (Liver)-tonifying Shen (Kidney) sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy, improve follicular development, promote ovulation, improve endometrial receptivity, while being a safe treatment option. (Trial registration No. NCT02676713).

The oncogenic roles of 27-hydroxycholesterol in glioblastoma.

Glioblastoma is the most frequent primary malignant brain tumor in adults. Oxysterols are oxidation products of cholesterol generated by enzymatic reactions. 27-hydroxycholesterol (27-HC), an oxysterol, is an abundant metabolite of cholesterol. 27-HC significantly accelerates mammary cancer growth, proliferation and progression in experimental models. However, to the best of our knowledge, the effect of 27-HC on glioblastoma has not been studied. Therefore, the present study aimed to determine the exact role of 27-HC in glioblastoma. The present study demonstrated that 27-HC promoted proliferation, epithelial to mesenchymal transition, colony formation, migration and invasion of U251 and U118 MG glioblastoma cells. Treatment with 27-HC was also associated with an increase in the formation of glioblastoma-initiating cells in U251 and U118 MG cell lines. Additionally, it was observed that high levels of 27-HC in glioblastoma tissues were associated with poor outcome in patients. In conclusion, 27-HC, a primary metabolite of cholesterol, may serve an important role in the progression of glioblastoma.

Roles of T875N somatic mutation in the activity, structural stability of JAK2 and the transformation of OCI-AML3 cells.

Activating mutations in JAK2 have been described in patients with various hematologic malignancies including acute myeloid leukemia (AML) and myeloproliferative neoplasms. However, mechanism of these mutations in JAK2's activity, structural stability and pathology of AML remains poorly understood. The JAK2 T875N somatic mutation has been detected in about 5.2% of AML patients. But the structural basis and mechanism of JAK2 T875N mutation in the pathology of AML is still unclear. Our results suggested that JAK2 T875N mutation disrupted the T875 and D873 interaction which destroyed the compact structure of JH1 domain, forced it into the active conformation, facilitated the entrance of substrate and thus led to JAK2 hyperactivation. Mutations (T875N, T875A, D873A and D873G) disrupted the T875 and D873 interaction enhanced JAK2's activity, decreased its structural stability and JH2 domain's activity which further enhanced JAK2's activity, while mutations (T875R, D873E, T875R/D873E) repaired this interaction displayed opposite results. Moreover, JAK2 T875N mutation enhanced the activity of JAK2-STAT5 pathway, promoted the proliferation and transformation of OCI-AML3 cells. This study provides clues in understanding structural basis of T875N mutation caused JAK2 hyperactivation and its roles in the pathology of AML.

Disruption of R867 and Y613 interaction plays key roles in JAK2 R867Q mutation caused acute leukemia.

Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations were important for the leukemogenesis of acute leukemia (AL). The JAK2 R867Q somatic mutation is detected in a subset of AL patients. However, roles of JAK2 R867Q mutation in the pathogenesis of AL remain unclear. In this study, homology modeling analysis showed that loss of interaction between R867 and Y613 disrupted the JAK2 JH1/JH2 domain's interactions was responsible for its activation. JAK2 R867Q and mutations (R867A and R867G) abolished this interaction caused JAK2 constitutive activation. While, mutations (R867K, Y613E, R867K/Y613E) repairing this interaction reduced JAK2 R867Q mutation's activity. Furthermore, our studies showed that abolished R867 and Y613 interaction disrupted JH1/JH2 domains' interactions and led to JAK2 constitutive activation. More importantly, mutations (R867Q, R867A and R867G) disrupted this interaction enhanced the activity of JAK2-STAT5 pathway and the proliferation of Ba/F3 and MV4-11 cells. Further study showed that JAK2 R867Q mutation promoted the expression of proliferation marker and inhibited the differentiation marker of Ba/F3 and MV4-11 cells. Thus our studies provide clues in understanding the pathogenesis of JAK2 R867Q mutation in AL.

Xin-Ji-Er-Kang ameliorates kidney injury following myocardial infarction by inhibiting oxidative stress via Nrf2/HO-1 pathway in rats.

AIM: Cardiovascular diseases, such as coronary heart disease and myocardial infarction (MI) are currently considered as the leading causes of death and disability. The aim of the present study is to investigate the effects of Xin-Ji-Er-Kang (XJEK) on kidney injury and renal oxidative stress. In addition, the associated mechanism involved in these processes was examined in an MI model, and particularly focused on the nuclear factor erythroid 2-related factor (NRF2)/heme oxygenase-1 (HO-1) pathway. MATERIALS AND METHODS: A total of 138 Sprague-Dawley rats were used in the present study. The control group was designated as 0 wk (n = 8). A total of 3 phases (2, 4, 6 wk) of administration were used in the sham-operated groups (sham, n = 10), MI groups (MI, n = 10), MI + XJEK groups (XJEK, n = 10) and MI + fosinopril groups (fosinopril, n = 10). Additional 10 rats were used to evaluate the infarct area. At 2, 4 or 6 wk post-MI, the hemodynamic parameters were monitored, the rats were sacrificed, then blood, heart and renal tissues were collected for furtherly analysis. RESULTS: The results indicated that XJEK administration continuously ameliorated renal hypertrophy index, blood urea nitrogen and cystatin C concentrations. XJEK further improved post-MI cardiac function by limiting scar formation and caused a downregulation in the hemodynamic parameters at the end of 2 and 4 wk. The hemodynamic parameters were upregulated after 6 wk treatment with XJEKcompared with those noted in the MI groups. Similarly, XJEK treatment for 2 wk potentiated Nrf2 nuclear translocation and HO-1 expression and inhibited the deficiency of nuclear Nrf2 and HO-1 at 6 wk post-MI compared with that of the MI groups, indicating the attenuation of the renal oxidative stress condition. The levels of malondialdehyde and angiotensin II (Ang II) in plasma and renal tissues, as well as the levels of aldosterone, 8-hydroxydeoxyguanosine, angiotensin II type 1 receptor and NADPH Oxidase-4 in the kidney tissue significantly decreased following XJEK treatment for 6 wk. In addition, the XJEK treatment groups revealed a significant upregulation in the activity of superoxide dismutase and in the total antioxidant capacity activity compared with those noted in the corresponding MI groups. CONCLUSION: These results demonstrated that progressive nephropathy in MI rats was associated with intrarenal activation of the renin-angiotensin-aldosterone system. Concomitantly, this process was associated with oxidative stress and impaired Nrf2 activation. The improvement in the severity of nephropathy by XJEK in this model may be associated with the reversal of these abnormalities.