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Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified in various digestive system cancers, including esophageal, gastric, liver, colorectal, and pancreatic cancers. Aberrantly expressed Trp metabolites are associated with diverse clinical features in digestive system tumors. Moreover, the levels of these metabolites can serve as prognostic indicators and predictors of recurrence risk in patients with digestive system tumors. Trp metabolites exert their influence on tumor growth and metastasis through multiple mechanisms, including immune evasion, angiogenesis promotion, and drug resistance enhancement. Suppressing the expression of key enzymes in Trp metabolism can reduce the accumulation of these metabolites, effectively impacting their role in the promotion of tumor progression and metastasis. Strategies targeting Trp metabolism through specific enzyme inhibitors or tailored drugs exhibit considerable promise in enhancing therapeutic outcomes for digestive system tumors. In addition, integrating these approaches with immunotherapy holds the potential to further enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: A single injection of local anaesthetic (LA) in the erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy (MRM) surgery, but the duration of analgesia is affected by the duration of the LA. The aim of this study is to investigate the effect of continuous ESPB on acute and chronic pain and inflammatory response after MRM surgery. Methods: In this prospective, randomised, controlled trial, we will recruit 160 patients, aged 18–80 years, scheduled for elective MRM surgery under general anaesthesia. They will be randomly assigned to two groups: a continuous ESPB group (group E) and a sham block group (group C). Both groups of patients will have a nerve block (group C pretended to puncture) and an indwelling catheter fixed prior to surgery. Electronic pumps containing LA are shielded. The primary outcome is the total consumption of analgesic agents. The secondary outcomes include the levels of inflammation-related cytokines; the occurrence of chronic pain (post-mastectomy pain syndrome, PMPS); static and dynamic pain scores at 2, 6, 12, 24 and 48 h postoperatively; and post-operative and post-puncture adverse reactions. Discussion: Analgesia after MRM surgery is important and chronic pain can develop when acute pain is prolonged, but the analgesic effect of a nerve block with a single injection of LA is limited by the duration of drug action. The aim of this trial is to investigate whether continuous ESPB can reduce acute pain after MRM surgery and reduce the incidence of chronic pain (PMPS), with fewer postoperative analgesic drug-related complications and less inflammatory response. Continuous ESPB and up to 12 months of follow-up are two innovations of this trial. Trial registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/) ChiCTR2200061935. Registered on 11 July 2022. This trial is a prospective registry with the following registry names: Effect of ultrasound-guided continuous erector spinae plane block on postoperative pain and inflammatory response in patients undergoing modified radical mastectomy for breast cancer. [ABSTRACT FROM AUTHOR]

Background: The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC. Methods: A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated. Results: A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18–17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS). Conclusions: The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine (DEX) has been thought to be an effective adjuvant to local anesthetics (LAs) in erector spinae plane block (ESPB), however, this method of use is not recorded in the drug instructions. Hence, our meta-analysis will evaluate its efficacy and safety for the first time. Methods: A systematic search of published articles was conducted in the PubMed, Embase, Web of science, and Cochrane Library databases up to July 17, 2022, using specific keywords related to our aims. The time first to request rescue analgesia, number of patient controlled intravenous analgesia (PCIA) presses, rate of rescue analgesia use, postoperative nausea and vomiting (PONV), arrhythmia, and hypotension were calculated by using random-effect models. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42022345488). Results: Numerous electronic databases were searched and finally 8 studies with a total of 570 patients, 303 in the DEX arm, 267 in the control arm were included. As an adjuvant to LAs, DEX significantly increased the time to first request of rescue analgesia (mean difference [MD] = 8.40, 95% confidence interval [CI] = 4.70–12.10, P < 0.00001), reduced the number of PCIA presses (MD = -4.12, 95% CI = -7.79 to -0.45, P = 0.03) and the rate of rescue analgesia (odds ratio [OR] = 0.33, 95% CI = 0.17–0.65, P = 0.002). Moreover, the combination reduced the risk of PONV (OR = 0.57, 95% CI = 0.36–0.91, P = 0.02). In addition, there was no difference in the incidence of hypotension (OR = 1.01, 95% CI = 0.37–2.74, P = 0.99) and arrhythmia (OR = 0.76, 95% CI = 0.19–3.07, P = 0.70). Conclusion: DEX can reduce analgesic requirements after various surgical procedures when used as an adjuvant to LAs for ESPB. Moreover, there was no significant difference between the two groups in terms of safety indicators (arrhythmia, hypotension). [ABSTRACT FROM AUTHOR]

Objective: To explore the association between ovulation induction drugs and ovarian cancer. Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women without ovarian cancer who ever or never underwent ovarian induction. Intervention(s): An extensive electronic search of the following databases was performed: PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library and CNKI, from inception until January 2022. A total of 34 studies fulfilled our inclusion criteria and were included in the final meta-analysis. The odds ratio (OR) and random-effects model were used to estimate the pooled effects. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Funnel plots and Egger tests were used to assess publication bias. Main outcomes: New diagnosed borderline ovarian tumor (BOT) and invasive ovarian cancer (IOC) between ovulation induction (OI) group and control (CT) group considering fertility outcome, OI cycles and specific OI drugs. Results: Primarily, there was no significant difference in the incidence of IOC and BOT between the OI and CT groups. Secondly, OI treatment did not increase the risk of IOC and BOT in the multiparous women, nor did it increase the risk of IOC in the nulliparous women. However, the risk of BOT appeared to be higher in nulliparous women treated with OI treatment. Thirdly, among women exposed to OI, the risk of IOC and BOT was higher in nulliparous women than in multiparous women. Fourthly, the risk of IOC did not increase with increasing OI cycles. Lastly, exposure to specific OI drugs also did not contribute to the risk of IOC and BOT. Conclusion: Overall, OI treatment did not increase the risk of IOC and BOT in most women, regardless of OI drug type and OI cycle. However, nulliparous women treated with OI showed a higher risk of ovarian cancer, necessitating their rigorous monitoring and ongoing follow-up. [ABSTRACT FROM AUTHOR]

Objective: To report Peutz-Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test.Clinical Presentation and Intervention: PJS was suspected in 3 families with tortuous medical courses. Two of them had relatives departed due to polyposis or colon cancer without pathological results, and the other one had been diagnosed as hyperplastic polyposis before. Diagnosis of PJS was confirmed by endoscopy and repeated pathological examinations, and the STK11 mutation test finally confirmed the diagnosis at genetic level, during which 3 novel mutation were detected (536C > A, 373_374insA, 454_455insGGAGAAGCGTTTCCCAGTGTGCC).Conclusion: Early diagnosis of PJS is important and may be based on a family history with selective features among family members, and the pathological information is the key. The novel mutations also expand the STK11 variant spectrum. [ABSTRACT FROM AUTHOR]

Background: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC).Methods: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references.Results: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation.Conclusions: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p. [ABSTRACT FROM AUTHOR]

Background: Enormous clinical and biomedical researches have demonstrated that microbes are crucial to human health. Identifying associations between microbes and diseases can not only reveal potential disease mechanisms, but also facilitate early diagnosis and promote precision medicine. Due to the data perturbation and unsatisfactory latent representation, there is a significant room for improvement. Results: In this work, we proposed a novel framework, Multi-scale Variational Graph AutoEncoder embedding Wasserstein distance (MVGAEW) to predict disease-related microbes, which had the ability to resist data perturbation and effectively generate latent representations for both microbes and diseases from the perspective of distribution. First, we calculated multiple similarities and integrated them through similarity network confusion. Subsequently, we obtained node latent representations by improved variational graph autoencoder. Ultimately, XGBoost classifier was employed to predict potential disease-related microbes. We also introduced multi-order node embedding reconstruction to enhance the representation capacity. We also performed ablation studies to evaluate the contribution of each section of our model. Moreover, we conducted experiments on common drugs and case studies, including Alzheimer's disease, Crohn's disease, and colorectal neoplasms, to validate the effectiveness of our framework. Conclusions: Significantly, our model exceeded other currently state-of-the-art methods, exhibiting a great improvement on the HMDAD database. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E infection is a global disorder that causes substantial morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome (GBS), have occurred in patients with hepatitis E virus (HEV) infection.Case Presentation: We report a 58 year-old non-immunocompromised man who presented with progressive muscle weakness in all extremities during an episode of acute HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in the serum. Both cerebrospinal fluid examination and electrophysiological study were in agreement with the diagnosis of HEV-associated GBS. Following the treatment with intravenous immunoglobulin, the patient's neurological condition improved rapidly.Conclusions: HEV infection should be strongly considered in patients with neurological symptoms, especially those with elevated levels of liver enzymes. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is caused by mutations in the tumor suppressor gene, STK11, and is characterized by gastrointestinal hamartomas, melanin spots on the lips and the extremities, and an increased risk of developing cancer. Case presentation: We reported an isolated PJS patient who died of colon cancer, whose blood sample was collected together with all the available family members'. The entire coding region of the STK11 gene was amplified by PCR and analyzed by Sanger sequencing, through which, a novel mutation, c.962_963delCC in exon 8 was identified in this patient. This mutation causes a frameshift mutation and a premature termination at codon 358. Protein structure prediction by Swiss-Model indicated a dramatic change and partial loss of the C-terminal domain. We did not observe this mutation in both parents of the proband. Therefore, it is considered a novel de-novo mutation. Furthermore, the mutation was not found in 50 unrelated healthy people. Conclusions: The novel mutation we reported here had not been recorded in databases or literature, and the patient who possessed it suffered from PJS and colon cancer. So our results enlarge the spectrum of STK11 variants in PJS patients. This mutation is most likely responsible for development of the PJS phenotype, especially the cancer occurrence. [ABSTRACT FROM AUTHOR]

Background: Jasmonic acid (JA) and methyl jasmonate (MeJA) regulate plant development, resistance to stress, and insect attack by inducing specific gene expression. However, little is known about the mechanism of plant defense against herbivore attack at a protein level. Using a high-resolution 2-D gel, we identified 62 MeJA-responsive proteins and measured protein expression level changes. Results: Among these 62 proteins, 43 proteins levels were increased while 11 proteins were decreased. We also found eight proteins uniquely expressed in response to MeJA treatment. Data are available via ProteomeXchange with identifier PXD001793. The proteins identified in this study have important biological functions including photosynthesis and energy related proteins (38.4%), protein folding, degradation and regulated proteins (15.0%), stress and defense regulated proteins (11.7%), and redox-responsive proteins (8.3%). The expression levels of four important genes were determined by qRT-PCR analysis. The expression levels of these proteins did not correlate well with their translation levels. To test the defense functions of the differentially expressed proteins, expression vectors of four protein coding genes were constructed to express in-fusion proteins in E. coli. The expressed proteins were used to feed Ostrinia furnacalis, the Asian corn borer (ACB). Our results demonstrated that the recombinant proteins of pathogenesis-related protein 1 (PR1) and thioredoxin M-type, chloroplastic precursor (TRXM) showed the significant inhibition on the development of larvae and pupae. Conclusions: We found MeJA could not only induce plant defense mechanisms to insects, it also enhanced toxic protein production that potentially can be used for bio-control of ACB. [ABSTRACT FROM AUTHOR]

Background: We previously identified brain type fatty acid-binding protein (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased expression of FABP7 is associated with reduced survival. To investigate possible molecular mechanisms underlying this association, we compared the expression and subcellular localization of FABP7 in non-tumor brain tissues with different types of glioma, and examined the expression of FABP7 and epidermal growth factor receptor (EGFR) in GBM tumors. Methods: Expression of FABP7 in non-tumor brain and glioma specimens was examined using immunohistochemistry, and its correlation to the clinical behavior of the tumors was analyzed. We also analyzed the association between FABP7 and EGFR expression in different sets of GBM specimens using published DNA microarray datasets and semi-quantitative immunohistochemistry. In vitro migration was examined using SF763 glioma cell line. Results: FABP7 was present in a unique population of glia in normal human brain, and its expression was increased in a subset of reactive astrocytes. FABP7 immunoreactivity in grade I pilocytic astrocytoma was predominantly cytoplasmic, whereas nuclear FABP7 was detected in other types of infiltrative glioma. Nuclear, not cytoplasmic, FABP7 immunoreactivity was associated with EGFR overexpression in GBM (N = 61, p = 0.008). Expression of the FABP7 gene in GBM also correlated with the abundance of EGFR mRNA in our previous microarray analyses (N = 34, p = 0.016) and an independent public microarray dataset (N = 28, p = 0.03). Compared to those negative for both markers, nuclear FABP7-positive/EGFR-positive and nuclear FABP7-positive/EGFR-negative GBM tumors demonstrated shortest survival, whereas those only positive for EGFR had intermediate survival. EGFR activation increased nuclear FABP7 immunoreactivity in a glioma cell line in vitro, and inhibition of FABP7 expression suppressed EGF-induced glioma-cell migration. Our data suggested that in EGFR-positive GBM the presence of nuclear FABP7 immunoreactivity increases the risk of poor prognosis Conclusion: In this study, we identified a possible mechanism as the basis of the association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7 were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7 and EGFR overexpression correlated with short survival in EGFR-positive GBM patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the progression of EGFR-overexpressed GBM. [ABSTRACT FROM AUTHOR]

Background: Oligodendroglioma (ODG) and oligoastrocytoma (OAC) are diffusely infiltrating primary brain tumors whose pathogenesis remains unclear. We previously identified a group of genes whose expression was inversely correlated with survival in a cohort of patients with glioblastoma (GBM), and some of these genes are also reportedly expressed in ODG and OAC. We examined the expression patterns and localization of these survival-associated genes in ODG and OAC in order to analyze their possible roles in the oncogenesis of these two tumor types. Methods: We used UniGene libraries derived from GBM and ODG specimens to examine the expression levels of the transcripts for each of the 50 GBM survival-associated genes. We used immunohistochemistry and cDNA microarrays to examine expression of selected survival-associated genes and Id4, a gene believed to control the timing of oligodendrocyte development. The expression of FABP7 and Id4 and the survival of patients with ODG and OAC were also analyzed. Results: Transcripts of most survival-associated genes as well as Id4 were present in both GBM and ODG tumors, whereas protein expression of Id4 and one of the survival-associated genes, brain-type fatty acid-binding protein (FABP7), was present in cells with astrocytic features, including reactive and neoplastic astrocytes, but not in neoplastic oligodendrocytes. Id4 was co-expressed with FABP7 in microgemistocytes in ODG and in neoplastic astrocytes in OAC. Id4 and FABP7 expression, however, did not correlate with the clinical outcome of patients with ODG or OAC tumors. Conclusion: Expression of Id4 and some of our previously identified GBM survival-associated genes is present in developing or mature oligodendrocytes. However, protein expression of Id4 and FABP7 in GBM, ODG, and OAC suggests that this group of functionally important genes might demonstrate two patterns of expression in these glioma subtypes: one group is universally expressed in glioma cells, and the other group of genes is expressed primarily in neoplastic astrocytes but not in neoplastic oligodendrocytes. Differential protein expression of these two groups of genes in ODG and OAC may be related to the cellular origins and the histological features of the neoplastic cells. [ABSTRACT FROM AUTHOR]

Plasmodiophora brassicae is one of the biggest threats to cruciferous plants and one of the most economically significant diseases worldwide. However, our current understanding of its pathogenic mechanisms remains limited. In this study, we have identified an effector, Pb257, which plays a crucial role in the virulence of P. brassicae. The expression pattern analysis revealed continuous induction of Pb257 during both primary and secondary infections. Ectopic expression of Pb257 strongly triggered cell death in Nicotiana benthamiana and several other plants, which was dependent on SOBIR1 and the salicylic acid pathway but not BAK1, a central molecular regulator, to mediate classical defense pathways. Overexpression of Pb257 increased susceptibility of Brassica rapa to P. brassicae. Silencing of the Pb257-encoding gene led to reduce root swelling. Further investigation showed that the conserved GOLD domain within Pb257 was essential for inducing root enlargement, which is similar to the mild symptoms of clubroot, indicating that it is an important effector for promoting root cell enlargement. GOLD domain-containing family proteins were widely present in the kingdoms of protozoa, fungi, and animalia, and Pb257 was clustered into a clade of protozoa, suggesting the encoding gene as a potential marker gene for classification of P. brassicae. The GOLD domain-containing proteins are known regulators involved in human cell proliferation and immune system disruption, however, no previous reports have described a pathogen-derived GOLD domain protein with elicitor activity. Our findings demonstrate that Pb257 functions as a crucial effector contributing to the virulence of P. brassicae and could be used as a potential molecular target for controlling clubroot disease. [ABSTRACT FROM AUTHOR]

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that according to the expression levels of achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3), small cell lung cancer (SCLC) can be divided into four subtypes: SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant), SCLC-P (POU2F3-dominant), and SCLC-I (triple negative or SCLC-inflamed). However, there are limited data on the clinical characteristics and prognosis of molecular subtypes of SCLC. Methods: Immunohistochemistry (IHC) was used to detect the expression levels of ASCL1, NEUROD1, and POU2F3 in 53 patient samples of resectable SCLC. The subtype was defined by the differential expression of the transcription factors for ASCL1, NEUROD1, and POU2F3 or the low expression of all three factors with an inflamed gene signature (SCLC-A, SCLC-N, SCLC-P, and SCLC-I, respectively). The clinicopathological characteristics, immunological features (programmed death ligand 1 [PD-L1] expression and CD8+ tumor infiltrating lymphocyte [TIL] density), and patient outcomes of the four subtypes of SCLC were analyzed. Results: Positive ASCL1, NEUROD1, and POU2F3 staining was detected in 43 (79.2%), 27 (51.0%), and 17 (32.1%) SCLC specimens by IHC. According to the results of IHC analysis, SCLC was divided into four subtypes: SCLC-A (39.6%), SCLC-N (28.3%), SCLC-P (17.0%), and SCLC-I (15.1%). The 5-year overall survival (OS) rates of these four subtypes were 61.9%, 69.3%, 41.7%, and 85.7%, respectively (P=0.251). There were significant differences in smoking status among different subtypes of SCLC (P= 0.031). However, we did not confirm the correlation between subtypes of SCLC and other clinicopathological factors or immune profiles. Cox multivariate analysis showed that N stage (P=0.025), CD8+ TILs (P=0.024), Ki-67 level (P=0.040), and SCLC-P (P=0.023) were independent prognostic factors for resectable SCLC. Conclusions: Our IHC-based study validated the proposed classification of SCLC using the expression patterns of key transcriptional regulatory factors. We found that SCLC-P was associated with smokers and was one of the poor prognostic factors of limited-stage SCLC. In addition, no correlation was found between PD-L1 expression or CD8+ TIL density and SCLC subtypes. [ABSTRACT FROM AUTHOR]

Objectives: The chemokine CXCL1, known as growth-related oncogene α (GRO-α), is a potent chemoattractant and regulator of neutrophils. The purpose of our study was to evaluate the regulatory response of CXCL1 in the serum of patients with systemic lupus erythematosus (SLE) in the active stage of disease and to assess whether it was implicated in the pathogenesis/inflammatory process in lupus. Methods: CXCL1 serum concentrations were examined in 90 SLE patients, 56 other autoimmune diseases (OADs) patients and 100 healthy controls using enzyme-linked immunosorbent methodology. Results: SLE patients exhibited significant increases in serum CXCL1 concentrations [1492.86 (735.47–2887.34) pg/ml] compared with OADs patients [155.88 (10.77–366.78) pg/ml] and healthy controls [13.58 (8.46–37.22) pg/ml] (p < 0.001). Moreover, the level of CXCL1 decreased as the level of anti-dsDNA IgG decreased after treatment between the anti-dsDNA-positive SLE patients and the anti-dsDNA-negative SLE patients. Additionly, serum CXCL1 concentrations were related to different disease activity levels in SLE and lupus nephritis (LN) and high avidity of IgG ANAs (HA IgG ANAs) (p < 0.05). Furthermore, CXCL1 serum concentrations were significantly correlated with the SLE Disease Activity Index(SLEDAI) score, relative avidity index (RAI) of HA IgG ANAs and the levels of anti-dsDNA IgG, CRP, ESR, albumin, C3 and C4.Additionally, Statistical analysis revealed that positivity for IgG ANA (p < 0.001), the presence of HA IgG ANAs (p = 0.001) and the logarithmic level of anti-dsDNA IgG (p = 0.021) were significantly associated with the logarithmic level of CXCL1 with standard partial regression coefficients (95% CI) of 2.371 (1.734–3.009), 1.231 (0.52–1.937) and 0.409 (0.062–0.755), respectively. Finally, using cutoff points of 1182.17 pg/mL and 1500.31 pg/mL, serum CXCL1 levels had a similar sensitivity of 76% and specificity of 100% and 75% for the diagnosis of active SLE and LN, respectively. Conclusions: Serum CXCL13 concentrations might represent a potential marker of disease activity in systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Soft materials have been developed very rapidly in the biomedical field over the past 10 years because of advances in medical devices, cell therapy, and 3D printing for precision medicine. Smart polymers are one category of soft materials that respond to environmental changes. One typical example is the thermally-responsive polymers, which are widely used as cell carriers and in 3D printing. Self-healing polymers are one type of smart polymers that have the capacity to recover the structure after repeated damages and are often injectable through needles. Shape memory polymers are another type with the ability to memorize their original shape. These smart polymers can be used as cell/drug/protein carriers. Their injectability and shape memory performance allow them to be applied in bioprinting, minimally invasive surgery, and precision medicine. This review will describe the general materials design, characterization, as well as the current progresses and challenges of these smart polymers. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the feasibility of the anterior transpedicular root screw (ATPRS) intervertebral fusion system for the cervical spine and provide a basis for the design of the ATPRS intervertebral fusion system. Methods: A total of 60 healthy adult cervical spine CT images examined from our hospital were selected, including 30 males and 30 females, with an average age of 39.6 ± 4.8 years. The image data was imported into Mimics 21.0 software in DICOM format for 3D model reconstruction. Simulated screw insertion was performed on both sides of the midline of the intervertebral space. The entry point (P1) was determined when the upper and lower screw paths did not overlap. When the screw was tangent to the medial edge of the Luschka joint, the insertion point was determined as the entry point (P2). Measurements were taken and recorded for the following parameters: distance from the screw entry point to the midline of the intervertebral space (DPM), the simulated screw length, inclination angle, cranial/caudal tilted angle, the anterior–posterior (AP) and mediolateral (ML) diameters of the cervical intervertebral space, the heights of the anterior, middle, and posterior edges of the cervical intervertebral space, and the curvature diameter of the lower end plate of the cervical vertebral body. Statistical analysis was performed on the measurement results. Results: The screw entry area (P1P2) showed an increasing trend from C3-C7 in both male (2.92–6.08 mm) and female (2.32–5.12 mm) groups. There were statistical differences between men and women at the same level (P < 0.05). The average screw length of men and women was greater than 20 mm, and the upper and lower screw lengths showed an increasing trend from C3 to C7. In the area where screws could be inserted, the range of screw inclination was as follows: male group upper screw (47.73–66.76°), lower screw (48.05–65.35°); female group upper screw (49.15–65.66°) and lower screw (49.42–63.29°); The range of cranial/caudal tilted angle of the screw was as follows: male group upper screw (32.06–39.56°), lower screw (29.12–36.95°); female group upper screw (30.97–38.92°) and lower screw (27.29–37.20°). The anterior–posterior diameter and mediolateral diameter of the cervical intervertebral space showed an increasing trend from C3 to C7 in both male and female groups. The middle height (MH) of the cervical intervertebral space was greater than the anterior edge height (AH) and posterior edge height (PD), with statistical differences (P < 0.05). Conclusions: Through the study of CT images of the cervical spine, it was determined that the ATPRS intervertebral fusion system has a feasible area for screw insertion in the cervical intervertebral space. [ABSTRACT FROM AUTHOR]

Background: Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs. Methods: All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels. Results: Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD. Conclusions: We identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease. [ABSTRACT FROM AUTHOR]

Background: To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life.Methods: Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects.Results: A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC).Conclusion: Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17-20 years ago was demonstrated, there is currently no urgent need for booster immunization. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is a Mendelian disease, whose causative gene is STK11, mainly characterized by gastrointestinal polyposis and increased cancer risk. Clinical observation reveals intussusception in childhood are more frequent and severe than in adults, and it is difficult to prevent this knotty complication.Case Presentation: A boy without a positive family history grew oral MP after birth and developed abdominal pain and bloody stood at 7 years old. Endoscopy revealed multiple polyps within the colon and the ileum, and endoscopic polypectomy and regular surveillance protected him from severe complications and open surgeries. A heterozygous deletion in STK11, c.243delG, was detected in the proband but not in his parents. This mutation has not been documented in databases.Conclusions: We suspect a child of PJS may need a more thorough endoscopic examination including enteroscopy or capsule endoscopy to take care of small bowel when PJS related symptoms comes up. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is caused by mutations in serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been connected to P53 pathway. Methods: PJS probands with STK11 mutation were included in the function analysis. P53 activity elevated by STK11 mutants was investigated using dual-luciferase reporter assay in vitro after constructing expression vectors of STK11 wild type and mutants generated by site-directed substitution. The association between the P53 activity and clinicopathological factors was analysis, especially the cancer history. Results: Thirteen probands with STK11 mutations were involved, and within the mutations, c.G924A was novel. P53 activity elevation caused by 6 truncating mutations were significantly lower than that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5 families. Within them, P53 activity was reduced and cancer occurred before 40 in 2 families, while it was not significantly changed and cancers happened after 45 in the other 3 families. Conclusions: The affected P53 activity caused by STK11 mutations in PJS patients is significantly associated with protein truncation, while cancer risk in PJS can be elevated through pathways rather than P53 pathway. P53 activity test is probably a useful supporting method to predict cancer risk in PJS, which could be helpful in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Identification of promising targeted antigens that exhibited cancer-specific expression is a crucial step in the development of novel antibody-targeted therapies. We here aimed to investigate the anti-tumor activity of a novel monoclonal antibody (mAb) 11C9 and identify the antibody tractable target in the hepatocellular cancer stem cells (HCSCs). Methods: The identification of the targeted antigen was conducted using SDS-PAGE, western blot, mass spectrometry, and co-immunoprecipitation. Silence of HSP90 was induced by siRNA interference. Positive cells were sorted by fluorescence-activated cell sorting. Double-immunofluorescent (IF) staining and two-color flow cytometry detected the co-expression. Self-renewal, invasion, and drug resistance were assessed by sphere formation, matrigel-coated Transwell assay, and CCK-8 assay, respectively. Tumorigenicity was evaluated in mouse xenograft models. RNA-seq and bioinformatics analysis were performed to explore the mechanism of mAb 11C9 and potential targets. Results: MAb 11C9 inhibited invasion and self-renewal abilities of HCC cell lines and reversed the cisplatin resistance. HSP90 (~ 95 kDa) was identified as a targeted antigen of mAb 11C9. Tissue microarrays and online databases revealed that HSP90 was overexpressed in HCC and associated with a poor prognosis. FACS and double-IF staining showed the co-expression of HSP90 and CSCs markers (CD90 and ESA). In vitro and in vivo demonstrated the tumorigenic potentials of HSP90. The inhibition of HSP90 by siRNA interference or 17-AAG inhibitor both decreased the number of invasion, sphere cells, and CD90+ or ESA+ cells, as well as reversed the resistance. Bioinformatics analysis and western blot verified that HSP90 activated Wnt/β-catenin signaling. Conclusions: The study preliminarily revealed the anti-tumor activity of mAb 11C9. More importantly, we identified HSP90 as a targeted antigen of mAb 11C9, which functions as an oncogene in phenotype shaping, stemness maintenance, and therapeutic resistance by activating Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Background: RGB photographs are a powerful tool for dynamically estimating crop growth. Leaves are related to crop photosynthesis, transpiration, and nutrient uptake. Traditional blade parameter measurements were labor-intensive and time-consuming. Therefore, based on the phenotypic features extracted from RGB images, it is essential to choose the best model for soybean leaf parameter estimation. This research was carried out to speed up the breeding procedure and provide a novel technique for precisely estimating soybean leaf parameters. Results: The findings demonstrate that using an Unet neural network, the IOU, PA, and Recall values for soybean image segmentation can achieve 0.98, 0.99, and 0.98, respectively. Overall, the average testing prediction accuracy (ATPA) of the three regression models is Random forest > Cat Boost > Simple nonlinear regression. The Random forest ATPAs for leaf number (LN), leaf fresh weight (LFW), and leaf area index (LAI) reached 73.45%, 74.96%, and 85.09%, respectively, which were 6.93%, 3.98%, and 8.01%, respectively, higher than those of the optimal Cat Boost model and 18.78%, 19.08%, and 10.88%, respectively, higher than those of the optimal SNR model. Conclusion: The results show that the Unet neural network can separate soybeans accurately from an RGB image. The Random forest model has a strong ability for generalization and high accuracy for the estimation of leaf parameters. Combining cutting-edge machine learning methods with digital images improves the estimation of soybean leaf characteristics. [ABSTRACT FROM AUTHOR]

Background: RNA 5-methyluridine (m5U) modifications are obtained by methylation at the C5 position of uridine catalyzed by pyrimidine methylation transferase, which is related to the development of human diseases. Accurate identification of m5U modification sites from RNA sequences can contribute to the understanding of their biological functions and the pathogenesis of related diseases. Compared to traditional experimental methods, computational methods developed based on machine learning with ease of use can identify modification sites from RNA sequences in an efficient and time-saving manner. Despite the good performance of these computational methods, there are some drawbacks and limitations. Results: In this study, we have developed a novel predictor, m5U-SVM, based on multi-view features and machine learning algorithms to construct predictive models for identifying m5U modification sites from RNA sequences. In this method, we used four traditional physicochemical features and distributed representation features. The optimized multi-view features were obtained from the four fused traditional physicochemical features by using the two-step LightGBM and IFS methods, and then the distributed representation features were fused with the optimized physicochemical features to obtain the new multi-view features. The best performing classifier, support vector machine, was identified by screening different machine learning algorithms. Compared with the results, the performance of the proposed model is better than that of the existing state-of-the-art tool. Conclusions: m5U-SVM provides an effective tool that successfully captures sequence-related attributes of modifications and can accurately predict m5U modification sites from RNA sequences. The identification of m5U modification sites helps to understand and delve into the related biological processes and functions. [ABSTRACT FROM AUTHOR]

Background: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. Methods: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. Results: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. Conclusion: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously. [ABSTRACT FROM AUTHOR]

Background: Chrysanthemum is one kind of ornamental plant well-known and widely used in the world. However, its quality and production were severely affected by low temperature conditions in winter and early spring periods. Therefore, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze chrysanthemum (Dendranthema grandiflorum) transcription response to low temperature. Results: Using Illumina sequencing technology, a total of 86,444,237 high-quality clean reads and 93,837 unigenes were generated from four libraries: T01, controls; T02, 4 °C cold acclimation (CA) for 24 h; T03, − 4 °C freezing treatments for 4 h with prior CA; and T04, − 4 °C freezing treatments for 4 h without prior CA. In total, 7583 differentially expressed genes (DEGs) of 36,462 annotated unigenes were identified. We performed GO and KEGG pathway enrichment analyses, and excavated a group of important cold-responsive genes related to low temperature sensing and signal transduction, membrane lipid stability, reactive oxygen species (ROS) scavenging and osmoregulation. These genes encode many key proteins in plant biological processes, such as protein kinases, transcription factors, fatty acid desaturase, lipid-transfer proteins, antifreeze proteins, antioxidase and soluble sugars synthetases. We also verified expression levels of 10 DEGs using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we performed the determination of physiological indicators of chrysanthemum treated at low temperature, and the results were basically consistent with molecular sequencing results. Conclusion: In summary, our study presents a genome-wide transcript profile of Dendranthema grandiflorum var. jinba and provides insights into the molecular mechanisms of D. grandiflorum in response to low temperature. These data contributes to our deeper relevant researches on cold tolerance and further exploring new candidate genes for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) have emerged as a class of factors that are important for regulating development and cancer. Computational prediction of lncRNAs from ultra-deep RNA sequencing has been successful in identifying candidate lncRNAs. However, the complexity of handling and integrating different types of genomics data poses significant challenges to experimental laboratories that lack extensive genomics expertise. Result: To address this issue, we have developed lncRNA-screen, a comprehensive pipeline for computationally screening putative lncRNA transcripts over large multimodal datasets. The main objective of this work is to facilitate the computational discovery of lncRNA candidates to be further examined by functional experiments. lncRNAscreen provides a fully automated easy-to-run pipeline which performs data download, RNA-seq alignment, assembly, quality assessment, transcript filtration, novel lncRNA identification, coding potential estimation, expression level quantification, histone mark enrichment profile integration, differential expression analysis, annotation with other type of segmented data (CNVs, SNPs, Hi-C, etc.) and visualization. Importantly, lncRNA-screen generates an interactive report summarizing all interesting lncRNA features including genome browser snapshots and lncRNA-mRNA interactions based on Hi-C data. Conclusion: lncRNA-screen provides a comprehensive solution for lncRNA discovery and an intuitive interactive report for identifying promising lncRNA candidates. lncRNA-screen is available as open-source software on GitHub. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore the association between long-term exposure to particulate matter ≤ 2.5 µm (PM2.5) and metabolic syndrome (MetS) and its components including fasting blood glucose (FBG), blood pressure, triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and waist circumference among adults and elderly in south China.Methods: We surveyed 6628 participants in the chronic disease and risk factors surveillance conducted in 14 districts of Guangdong province in 2015. MetS was defined based on the recommendation by the Joint Interim Societies' criteria. We used the spatiotemporal land-use regression (LUR) model to estimate the two-year average exposure of ambient air pollutants (PM2.5, PM10, SO2, NO2, and O3) at individual levels. We recorded other covariates by using a structured questionnaire. Generalized linear mixed model was used for analysis.Results: A 10-μg/m3 increase in the two-year mean PM2.5 exposure was associated with a higher risk of developing MetS [odd ratio (OR): 1.17, 95% confidence interval (CI): 1.01, 1.35], increased risk of fasting blood glucose level. (OR: 1.18, 95% CI: 1.02, 1.36), and hypertriglyceridemia (OR: 1.36, 95% CI: 1.18, 1.58) in the adjusted/unadjusted models (all P < 0.05). We found significant interaction between PM2.5 and the region, exercise on the high TG levels, and an interaction with the region, age, exercise and grain consumption on FBG (P interaction < 0.05).Conclusions: Long-term exposure to PM2.5 was associated with MetS, dyslipidemia and FBG impairment. Efforts should be made for environment improvement to reduce the burden of MetS-associated non-communicable disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: To evaluate the clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) combined with whole brain radiotherapy (WBRT) in patients with brain metastases (BMs).Materials and Methods: From May 2018 to July 2020, 50 patients (111 lesions) received HFSRT (18 Gy/3F) + WBRT (40 Gy/20F). The RECIST 1.1 and RANO-BM criteria were used to evaluate treatment efficacy. Five prognostic indexes (RPA, GPA, SIR, BS-BM, and GGS) were applied. The primary endpoint was intracranial local control (iLC). Secondary endpoints were overall survival (OS) and the safety of treatment.Results: Intracranial objective response rates (iORR) using the RECIST 1.1 and RANO-BM criteria were 62.1% and 58.6%, respectively. The iLC rate was 93.1%, the 6- and 12-month iLC rates were 90.8% and 57.4%, respectively. The median intracranial progression-free survival (iPFS) was not reached (range 0-23 months). The 6-, 12-, and 24-month OS rates were 74.2%, 58.2%, and 22.9%, respectively. The KPS score showed statistical significance in univariate analysis of survival. The 6, 12, and 24 month OS rates for patients with KPS ≥ 70 were 83.8%, 70.5%, and 29.7%, respectively. The median survival time (MST) for all patients and for patients with KPS ≥ 70 were 13.6 and 16.5 months, respectively. Sex, KPS score, and gross tumor volume were significant factors in the multivariate analysis of survival. OS was significantly associated with RPA, SIR, BS-BM, and GGS classes. No acute toxicities of grade 3 or higher were noted.Conclusion: HFSRT combined with WBRT is a safe and effective local treatment modality for BM patients. [ABSTRACT FROM AUTHOR]

Background: Little is known about how the obesogenic environment influences emotional states associated with glial responses and neuronal function. Here, we investigated glial reactivation and neuronal electrophysiological properties in emotion-related brain regions of high-fat diet (HFD) and ob/ob mice under chronic stress.Methods: The glial reactivation and neuronal activities in emotion-related brain regions were analyzed among normal diet mice (ND), HFD mice, wild-type mice, and ob/ob mice. To further activate or inhibit astrocytes in medial prefrontal cortex (mPFC), we injected astrocytes specific Gq-AAV or Gi-AAV into mPFC and ongoing treated mice with CNO.Results: The results showed that obesogenic factors per se had no significant effect on neuronal activities in emotion-related brain regions, or on behavioral performance. However, exposure to a chronic stressor profoundly reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs) in the mPFC; depressive-like behaviors were seen, accompanied by significant upregulation of astrocyte reactivation. We identified resilient and susceptible mice among chronic social defeat stress-exposed HFD mice. As expected, astrocyte reactivity was upregulated, while neuronal activity was depressed, in the mPFC of susceptible compared to resilient mice. Furthermore, activating astrocytes resulted in similar levels of neuronal activity and depressive-like behaviors between resilient and susceptible mice. Additionally, inhibiting astrocyte reactivation in the mPFC of HFD mice upregulated neuronal activities and inhibited depressive-like behaviors.Conclusions: These observations indicate that obesogenic factors increase the risk of depression, and improve our understanding of the pathological relationship between obesity and depression. [ABSTRACT FROM AUTHOR]

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are frequent in low-grade gliomas and secondary glioblastomas (sGBM). Because they yield the same oncometabolite, D-2-hydroxyglutarate, they are often treated as equivalent and pooled. The objective of this study was to provide insight into the differences between IDH1 and IDH2 mutant gliomas. Methods: To investigate the different clinical and molecular characterization between IDH1 mutant and IDH2 mutant gliomas, we studied 811 patients with IDH1 mutations, IDH2 mutations and IDH1/2 wild-type. In addition, whole-transcriptome sequencing and DNA methylation data were used to assess the distribution of genetic changes in IDH1 and IDH2 mutant gliomas in a Chinese population-based cohort. Results: Among 811 gliomas in our cohort, 448 cases (55.2 %) harbored an IDH1 mutation, 18 cases (2.2 %) harbored an IDH2 mutation and 345 cases (42.6 %) harbored an IDH1/2 wild-type. We found that IDH1 and IDH2 are mutually exclusive in gliomas, and IDH2 mutations are mutually exclusive with PTEN, P53 and ATRX mutations. Patients with IDH2 mutations had a higher frequency of 1p/19q co-deletion (p < 0.05) than IDH1 mutant patients. In addition, a Gene Set Enrichment Analysis (GSEA) showed that IDH2 mutant gliomas were associated with the oxidative phosphorylation gene set, and the four most representative biological processes for genes commonly altered by hypermethylation in IDH2 mutant gliomas were the regulation of cell proliferation, cell motion, cell migration and response to hypoxia. Patients with IDH2 mutant gliomas exhibited longer Overall survival (OS) (p < 0.05) and longer Progression-free survival (PFS) (p < 0.05) than patients with IDH1/2 wild-type gliomas. However, their OS and PFS did not differ from that of IDH1 mutant patients. Conclusions: Our study revealed an intrinsic distinction between IDH1 and IDH2 mutant gliomas, and these mutations should be considered separately because their differences could have implications for the diagnosis and treatment of IDH1/2 mutant gliomas. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess Chinese medical students' smartphone addiction and its effects on subhealth and insomnia. Methods: A cross-sectional survey was conducted from October 14, 2020 to November 14, 2020 by administering an online questionnaire to Wannan Medical College students. Results: Of 2741 students who completed the survey, 1,447 (52.8%) had smartphone addiction. Medical specialty (p = 0.004), alcohol consumption (p = 0.001), smartphone use in bed (p = 0.000), depression (p = 0.000) and anxiety (p = 0.000) were strongly associated with smartphone addiction. The impacts of smartphone addiction on subhealth (p = 0.000) and insomnia (p = 0.000) were significant. Conclusion: This survey shows that the smartphone addiction detection rate among medical students was 52.8%. Students who did not like their medical specialty, consumed alcohol, used their smartphones in bed, and suffered from depression and anxiety had a higher smartphone addiction detection rate. The subhealth and insomnia of medical students are adversely associated with smartphone addiction. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty about the best approaches for advanced airway management (AAM) and the effectiveness of adrenaline treatments in Out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate whether AAM and adrenaline administration provided by Emergency Medical Service (EMS) can improve the outcomes of OHCA.Methods: This study was a prospective analysis of collected data based on OHCA adult patients treated by the EMS in China from January 2019 to December 2020.The patients were divided into AAM group and no AAM group, and into subgroups according to whether adrenaline was used. The outcome was rate of return of spontaneous circulation (ROSC), survival to admission and hospital discharge.Results: 1533 OHCA patients were reported. The probability of ROSC outcome and survival admission in the AAM group was significantly higher, compared with no AAM group. The probability of ROSC outcome in the AAM group increased by 66% (adjusted OR: 1.66, 95%CI, 1.02-2.71). There were no significant differences in outcomes between the adrenaline and no adrenaline groups. The combined treatment of AAM and adrenaline increased the probability of ROSC outcome by 114% (adjusted OR, 2.14, 95%CI, 1.20-3.81) and the probability of survival to admission increased by 115% (adjusted OR, 2.15, 95%CI, 1.16-3.97).Conclusions: The prehospital AAM and the combined treatment of AAM and adrenaline in OHCA patients are both associated with an increased rate of ROSC. The combined treatment of AAM and adrenaline can improve rate of survival to admission in OHCA patients. [ABSTRACT FROM AUTHOR]

Background: Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. Methods: Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. Results: Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. Conclusion: NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice. [ABSTRACT FROM AUTHOR]

Background: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge.Methods: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated.Results: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores.Conclusion: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics.Methods: Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People's Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients' access to neurologists and prescriptions of individual ASMs.Results: A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine.Conclusions: This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups. [ABSTRACT FROM AUTHOR]

Background: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. Methods: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. Results: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. Conclusion: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus. Key Points: Currently bacterial and viral agents in the gastrointestinal tract are under-detected and poorly defined in developing countries. A new sensitive TAC assay provided comprehensive identification of microorganisms, including neglected pathogens, in Chinese children with moderate and severe diarrhea. [ABSTRACT FROM AUTHOR]

Background: More than 210,000 medical workers have fought against the outbreak of Coronavirus Disease 2019 (COVID-19) in Hubei in China since December 2019. However, the prevalence of mental health problems in frontline medical staff after fighting COVID-19 is still unknown.Methods: Medical workers in Wuhan and other cities in Hubei Province were invited to participate a cross-sectional and convenience sampling online survey, which assessed the prevalence of anxiety, insomnia, depression, and post-traumatic stress disorder (PTSD).Results: A total of 1,091 responses (33% male and 67% female) were valid for statistical analysis. The prevalence was anxiety 53%, insomnia 79%, depression 56%, and PTSD 11%. Healthcare workers in Wuhan were more likely to face risks of anxiety (56% vs. 52%, P = 0.03) and PTSD (15% vs. 9%, P = 0.03) than those in other cities of Hubei. In terms of educational attainment, those with doctoral and masters' (D/M) degrees may experience more anxiety (median of 7.0, [interquartile range (IQR) 2.0-8.5] vs. median 5.0 [IQR 5.0-8.0], P = 0.02) and PTSD (median 26.0 [IQR 19.5-33.0] vs. median 23.0 [IQR 19.0-31.0], P = 0.04) than those with lower educational degrees.Conclusions: The mental problems were an important issue for the healthcare workers after COVID-19. Thus, an early intervention on such mental problems is necessary for healthcare workers. [ABSTRACT FROM AUTHOR]

Background: Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. Methods: Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. Results: Targeted antigen showed a surface antigen expression pattern, and the 43–55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. Conclusions: ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of miRNA in EV secretion from cancer cells remains unknown. Methods: qPCR and bioinformatics analysis were applied for determining extracellular let-7a expression from CRC patient serum and cells. Nanosight particle tracking analysis was performed for investigating the effect of let-7a on EV secretion. Luciferase reporter assays was used for identifying targeted genes synaptosome-associated protein 23 (SNAP23). In vitro and in vivo assays were used for exploring the function of let-7a/SNAP23 axis in CRC progression. Bioenergetic assays were performed for investigating the role of let-7a/SNAP23 in cellular metabolic reprogramming. Results: let-7a miRNA was elevated in serum EVs from CRC patients and was enriched in CRC cell-derived EVs. We determined that let-7a could suppress EV secretion directly targeting SNAP23. In turn, SNAP23 promotes EV secretion of let-7a to downregulate the intracellular let-7a expression. In addition, we found a novel mechanism of let-7a/SNAP23 axis by regulating mitochondrial oxidative phosphorylation (OXPHOS) through Lin28a/SDHA signaling pathway. Conclusions: Let-7a plays an essential role in not only inhibiting EV secretion, but also suppressing OXPHOS through SNAP23, resulting in the suppression of CRC progression, suggesting that let-7a/SNAP23 axis could provide not only effective tumor biomarkers but also novel targets for tumor therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Precise disease module is conducive to understanding the molecular mechanism of disease causation and identifying drug targets. However, due to the fragmentization of disease module in incomplete human interactome, how to determine connectivity pattern and detect a complete neighbourhood of disease based on this is still an open question. Results: In this paper, we perform exploratory analysis leading to an important observation that through a few intermediate nodes, most separate connected components formed by disease-associated proteins can be effectively connected and eventually form a complete disease module. And based on the topological properties of these intermediate nodes, we propose a connect separate connected components (C3) method to detect a succinct disease module by introducing a relatively small number of intermediate nodes, which allows us to obtain more pure disease module than other methods. Then we apply C3 across a large corpus of diseases to validate this connectivity pattern of disease module. Furthermore, the connectivity of the perturbed genes in multi-omics data such as The Cancer Genome Atlas also fits this pattern. Conclusions: C3 tool is not only useful in detecting a clearly-defined connected disease neighbourhood of 299 diseases and cancer with multi-omics data, but also helpful in better understanding the interconnection of phenotypically related genes in different omics data and studying complex pathological processes. [ABSTRACT FROM AUTHOR]

Background: Feelings of depression can be caused by negative life events (NLE) such as the death of a family member, a quarrel with one's spouse, job loss, or strong criticism from an authority figure. The automatic and accurate identification of negative life event language patterns (NLE-LP) can help identify individuals potentially in need of psychiatric services. An NLE-LP combines a person (subject) and a reasonable negative life event (action), e.g. or < boyfriend:break_up>.Methods: This paper proposes an analogical reasoning framework which combines a word representation approach and a pattern inference method to mine/extract NLE-LPs from psychiatric consultation documents. Word representation approaches such as skip-gram (SG) and continuous bag-of-words (CBOW) are used to generate word embeddings. Pattern inference methods such as cosine similarity (COSINE) and cosine multiplication similarity (COSMUL) are used to infer patterns.Results: Experimental results show our proposed analogical reasoning framework outperforms the traditional methods such as positive pairwise mutual information (PPMI) and hyperspace analog to language (HAL), and can effectively mine highly precise NLE-LPs based on word embeddings. CBOW with COSINE of analogical reasoning is the best word representation and inference engine. In addition, both word embeddings and the inference engine provided by the analogical reasoning framework can further be used to improve the HAL model.Conclusions: Our proposed framework is a very simple matching function based on these word representation approaches and is applied to significantly improve HAL model mining performance. [ABSTRACT FROM AUTHOR]

Background: Survival of esophageal cancer in Linzhou was seen to increase over the past few decades and is higher than the average level of China due to the implementation of comprehensive prevention and control measures. In population-based studies, relative survival is a common index to approximate disease-specific survival. However, the cure fraction maybe great interest to patients and physicians. This study aimed to investigate the cure fraction of esophageal cancer in Linzou city during 2003-2012 with a cure model.Methods: We carried out a population-based study of 8067 esophageal cancer patients in the Linzhou city during 2003-2012. Flexible parametric cure models were used to estimate cure proportions and median survival times of uncured by year of diagnosed and age. In each model, an interaction between calendar year and age were included. All variables in the model were included both as constant and time-varying effects.Results: The 5-year relative survival rate was increased in every age group from 2003 to 2012. The huge increase in the cure proportion was observed in each age group. At the year of 2011-2012, 79.8%, 58.0%, 123.4% and 162.7% improvements of cure proportion were seen in age group 19-49, 50-59, 60-69 and 70-99 years compared with year of 2003-2004. Meanwhile, survival of 'uncured' patients changed little in all age group.Conclusions: The improvement of survival in Linzhou city during 2003-2012 was mainly due to an increasing cure proportion. Huge improvement of cure fraction within short period is likely due to the organized screening of esophageal cancer in Linzhou city. [ABSTRACT FROM AUTHOR]

Background: Understanding immune phenotypes and human gastric disease in situ requires an approach that leverages multiplexed immunohistochemistry (mIHC) with multispectral imaging to facilitate precise image analyses.Methods: We developed a novel 4-color mIHC assay based on tyramide signal amplification that allowed us to reliably interrogate immunologic checkpoints, including programmed death-ligand 1 (PD-L1), cytotoxic T cells (CD8+T) and regulatory T cells (Foxp3), in formalin-fixed, paraffin-embedded tissues of various human gastric diseases. By observing cell phenotypes within the disease tissue microenvironment, we were able to determine specific co-localized staining combinations and various measures of cell density.Results: We found that PD-L1 was expressed in gastric ulcer and in tumor cells (TCs), as well as in tumor-infiltrating immune cells (TIICs), but not in normal gastric mucosa or other gastric intraepithelial neoplastic tissues. Furthermore, we found no significant reduction in CD8+T cells, whereas the ratio of CD8+T:Foxp3 cells and CD8+T:PD-L1 cells was suppressed in tumor tissues and elevated in adjacent normal tissues. An unsupervised hierarchical analysis also identified correlations between CD8+T and Foxp3+ tumor-infiltrating lymphocyte (TIL) densities and average PD-L1 levels. Three main groups were identified based on the results of CD8+T:PD-L1 ratios in gastric tumor tissues. Furthermore, integrating CD8+T:Foxp3 ratios, which increased the complexity for immune phenotype status, revealed 6-7 clusters that enabled the separation of gastric cancer patients at the same clinical stage into different risk-group subsets.Conclusions: Characterizing immune phenotypes in human gastric disease tissues via multiplexed immunohistochemistry may help guide PD-L1 clinical therapy. Observing unique disease tissue microenvironments can improve our understanding of immune phenotypes and cell interactions within these microenvironments, providing the ability to predict safe responses to immunotherapies. [ABSTRACT FROM AUTHOR]

Background: This study used a short-term de-training model to mimic the physiological weight changes during the early retirement stage in Taekwondo (TKD) athletes. This study investigates whether the negative changes in body composition, blood lipid profiles, and metabolic biomarkers occur in elite collegiate TKD athletes when experiencing a two-months de-training period. Methods: Fourteen collegiate Division Ι elite TKD athletes (age: 21.1 ± 0.2 years, BMI: 22.3 ± 1.1 kg/m2; 10 males and 4 females) participated in this study. The body composition, blood lipid profiles, atherogenic dyslipidemia indexes, metabolic biomarkers and baseline systemic inflammation states were measured before and after twomonths de-training. Results: The body weight and BMI did not change after de-training in these elite TKD athletes. The total muscle mass displayed a significant decline after de-training (−2.0%, p = 0.019), with an increase in fat mass (+24.3%, p < 0. 01). The blood triglyceride did not change, but the total cholesterol was higher after de-training (+8.3%, p = 0.047). The CHOL-to-HDL and LDL-to-HDL ratios increased by 12.4% (p < 0.001) and 13.2% (p = 0.002) after de-training, respectively. The blood platelet number, plateletcrit, and platelet-to-lymphocyte ratio increased significantly by 5.0% (p = 0.013), 7.3% (p = 0.009), and 20.6% (p = 0.018) after de-training, respectively. The McAuley’s Index decreased (−6.9%, p = 0.025) after de-training. Conclusion: We demonstrated that a two-months de-training period resulted in adverse effects on early atherogenic dyslipidemia development, progressing insulin resistance, low-grade inflammation, and visceral adiposity in young elite TKD athletes. Our findings provide clear insights into the possible deleterious impacts at early stage retirement in former combative sports athletes. [ABSTRACT FROM AUTHOR]

Background: Soil alkalinity shows significant constraints to crop productivity; however, much less attention has been paid to analyze the effect of soil alkalinity on plant growth and development. Shanrong No. 4 (SR4) is an alkalinity tolerant bread wheat cultivar selected from an asymmetric somatic hybridization between the bread wheat cultivar Jinan 177 (JN177) and tall wheatgrass (Thinopyrum ponticum), which is a suitable material for studying alkalinity tolerant associate genes. Results: The growth of SR4 plant seedlings was less inhibited than that of JN177 when exposed to alkalinity stress conditions. The root cytosolic Na+/K+ ratio in alkalinity stressed SR4 was lower than in JN177, while alkalinity stressed SR4 contained higher level of nutrient elements than in JN177. SR4 plant seedlings accumulated less malondialdehyde (MDA) and reactive oxygen species (ROS), it also showed higher activity of ROS scavenging enzymes than JN177 under alkalinity stress. The root intracellular pH decreased in both alkalinity stressed JN177 and SR4, however, it was much lower in SR4 than in JN177 under alkalinity stress. The transcriptomes of SR4 and JN177 seedlings exposed to alkalinity stress were analyzed by digital gene expression tag profiling method. Alkalinity stress conditions up- and down-regulated a large number of genes in the seedling roots that play the functions in the categories of transcription regulation, signal transduction and protein modification. Conclusions: SR4 expresses a superior tolerance to alkaline stress conditions which is due to its strong absorbing ability for nutrient ions, a strong regulating ability for intracellular and rhizosphere pH and a more active ROS scavenging ability. [ABSTRACT FROM AUTHOR]

Background: Since the novel H7N9 avian influenza outbreak occurred in China in 2013, neuraminidase inhibitors (NAIs) such as oseltamivir and peramivir have been used as first-line drugs to treat the influenza virus infection. This study aimed to compare the efficacy of oseltamivir-peramivir combination therapy versus oseltamivir monotherapy.Methods: A retrospective study of 82 H7N9 confirmed patients was conducted by reviewing medical charts at the First Affiliated Hospital of ZheJiang University in China from April 1, 2013 to Feb 28, 2014. The patients' clinical information was collected systematically, and we compared the virology and clinical data between oseltamivir monotherapy group (43 patients) and oseltamivir-peramivir combination group (39 patients).Results: The median duration from NAIs administration to H7N9 virus-negative in oseltamivir monotherapy group and oseltamivir-peramivir combination group was 6.50 and 7.00 days (p >0.05), respectively. The median decline of Day 2 to Day 0 (initiation of NAIs therapy) viral load was 0.00 and 0.69 log10 copies/μl (p >0.05) respectively in the monotherapy vs. combination therapy groups. The incidence of new Acute Respiratory Distress Syndrome during NAI administration was 63.89 and 77.78 % (p >0.05); while the mortality rates were 25.58 and 43.59 % (p >0.05) in the oseltamivir group vs. oseltamivir-peramivir group.Conclusions: Our results suggest that in adults with H7N9 virus infection, the use of oseltamivir-peramivir combination therapy was not superior to oseltamivir monotherapy. [ABSTRACT FROM AUTHOR]