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Background: The detection of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by multimeric protein complexes, known as inflammasomes, triggers an inflammatory response, which is a critical component of the innate immune system. This inflammatory response plays a pivotal role in host resistance against parasitic infections, presenting a significant global health challenge., Methods: We systematically searched for relevant articles from the Pubmed and the Web of Science database to summarize current insights into how inflammasomes function in preventing infections caused by the apicomplexan parasites Toxoplasma and Plasmodium., Results: In vivo and in vitro studies have extensively explored inflammasomes such as the absent in melanoma 2 (AIM2), NLR family pyrin-containing protein 1 (NLRP1), NLRP3, and NLRP12 inflammasomes, alongside noncanonical inflammasomes, with particular emphasis on the NLRP1 and the NLRP3 inflammasome during Toxoplasma gondii infection or the AIM2 and the NLRP3 inflammasome at various stages of Plasmodium infection. Toxoplasma gondii interacts with inflammasomes to activate or inhibit immune responses., Conclusions: Inflammasomes control parasite burden and parasite-induced cell death, contribute to immune recognition and inflammatory responses and thus influence apicomplexan parasite-associated pathogenesis and the severity of clinical outcomes. Hence, inflammasomes play crucial roles in the progression and outcomes of toxoplasmosis and malaria. A comprehensive understanding of how parasitic infections modulate inflammasome activity enhances insight into host immune responses against parasites., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The purpose of this network meta-analysis was to assess the impact of different protective ventilatory strategies on postoperative pulmonary complications (PPCs)., Methods: Several databases were searched for randomized controlled trials (RCTs) that were published before October 2023 in a network meta-analysis. We assessed the effect of different lung-protective ventilation strategies on the incidence of PPCs using Bayesian network meta-analysis., Results: We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low tidal volumes (LTVs) combined with iPEEP and recruitment manoeuvres (RM) was associated with significantly lower incidence of PPCs [HTVs: OR = 0.38, 95%CrI (0.19, 0.75), LTVs: OR = 0.33, 95%CrI (0.12, 0.82)], postoperative atelectasis[HTVs: OR = 0.2, 95%CrI (0.08, 0.48), LTVs: OR = 0.47, 95%CrI (0.11, 0.93)], and pneumonia[HTVs: OR = 0.22, 95%CrI (0.09, 0.48), LTVs: OR = 0.27, 95%CrI (0.08,0.89)] than was High tidal volumes (HTVs) or LTVs. LTVs combined with medium-to-high PEEP and RM were associated with significantly lower incidence of postoperative atelectasis, and pneumonia., Conclusion: LTVs combined with iPEEP and RM decreased the incidence of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. Individual PEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence is moderate., Trial Registration: PROSPERO identifier CRD42023399485., (© 2024. The Author(s).)

Background: To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients., Methods: Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery., Results: This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months., Conclusion: The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase., (© 2024. The Author(s).)

Malus sieversii, commonly known as wild apples, represents a Tertiary relict plant species and serves as the progenitor of globally cultivated apple varieties. Unfortunately, wild apple populations are facing significant degradation in localized areas due to a myriad of factors. To gain a comprehensive understanding of the nutrient status and spatiotemporal variations of M. sieversii, green leaves were collected in May and July, and the fallen leaves were collected in October. The concentrations of leaf nitrogen (N), phosphorus (P), and potassium (K) were measured, and the stoichiometric ratios as well as nutrient resorption efficiencies were calculated. The study also explored the relative contributions of soil, topographic, and biotic factors to the variation in nutrient traits. The results indicate that as the growing period progressed, the concentrations of N and P in the leaves significantly decreased (P < 0.05), and the concentration of K in October was significantly lower than in May and July. Throughout plant growth, leaf N-P and N-K exhibited hyperallometric relationships, while P-K showed an isometric relationship. Resorption efficiency followed the order of N < P < K (P < 0.05), with all three ratios being less than 1; this indicates that the order of nutrient limitation is K > P > N. The resorption efficiencies were mainly regulated by nutrient concentrations in fallen leaves. A robust spatial dependence was observed in leaf nutrient concentrations during all periods (70.1-97.9% for structural variation), highlighting that structural variation, rather than random factors, dominated the spatial variation. Nutrient resorption efficiencies (NRE, PRE, and KRE) displayed moderate structural variation (30.2-66.8%). The spatial patterns of nutrient traits varied across growth periods, indicating they are influenced by multifactorial elements (in which, soil property showed the highest influence). In conclusion, wild apples manifested differentiated spatiotemporal variability and influencing factors across various leaf nutrient traits. These results provide crucial insights into the spatiotemporal patterns and influencing factors of leaf nutrient traits of M. sieversii at the permanent plot scale for the first time. This work is of great significance for the ecosystem restoration and sustainable management of degrading wild fruit forests., (© 2024. The Author(s).)

Purpose: As future physicians, medical students have experienced tremendous pressure during the ongoing COVID-19 pandemic, which is associated with a high risk of depression and anxiety. We aimed to investigate an overview of the prevalence of anxiety and depression among medical students in various countries during the global COVID-19 pandemic, and discuss associated stressors., Methods: We systematically searched CINAHL, EMBASE, MEDLINE, PubMed, and Web of Science for relevant articles from December 1, 2019 to March 15, 2023. We performed meta-analysis using a random-effects model with REML method to calculate the pooled prevalence of anxiety and depression. Begg's and Egger's tests were used to identify the potential risk of publication bias. Meta-regression was used to explore potential sources of heterogeneity., Results: We identified 130 studies reporting anxiety and depression among 132,068 medical students during the COVID-19 pandemic. Eight screening tools were identified for anxiety and six for depression. The pooled prevalence of mental health outcomes for anxiety and depression was 45% (95% confidence interval [CI], 40%-49%) and 48% (95% CI, 43%-52%), respectively. The pooled prevalence of mental health outcomes for moderate and severe anxiety and moderate and severe depression was 28% (95% CI, 24%-32%) and 30% (95% CI, 26%-35%), respectively. There was high heterogeneity between studies, with I 2 ranging from 99.58%-99.66%. Continent and survey date were included in the meta-regression model. The results of meta-regression revealed that medical students in Asia had a lower prevalence of anxiety, and depression than those in other regions. The survey date (from February to June, 2020) showed a significantly positive correlation with the prevalence of anxiety and depression., Conclusions: We demonstrated the global prevalence of anxiety and depression among medical students during the COVID-19 pandemic. The data highlight that medical students worldwide are at high risk of experiencing anxiety and depression. The reported stressors can be categorized into personal, academic, environmental and cultural, and pandemic factors. Schools and institutions should ensure optimal alternative learning environments for uninterrupted provision of medical education. The appropriate authorities should prioritize the provision of adequate protection for medical students and establish policies to promote new methods of training and education during a disaster, such as via distance learning., (© 2024. The Author(s).)

Background: Appropriate communication with dental patients enhances treatment outcomes and patient satisfaction. Implementing simulated patient interviews courses can improve patient-centered care and reduce conflict during clerkship training. Therefore, this study explored the relationship among student participation in a situational simulation course (SSC), academic performance, clerkship performance, and objective structured clinical examination (OSCE) performance., Methods: This study was conducted with a sample of fifth-year dental students undergoing clerkship training. After implementing a situational simulation course to investigate the relationship among participation in SSC, academic performance, clerkship performance, and OSCE performance, a path analysis model was developed and tested., Results: Eighty-seven fifth-year dental students were eligible for the SSC, and most (n = 70, 80.46%) volunteered to participate. The path analysis model revealed that academic performance had a direct effect on OSCE performance (β = 0.281, P = 0.003) and clerkship performance (β = 0.441, P < 0.001). In addition, SSC teaching had a direct effect on OSCE performance (β = 0.356, P < 0.001)., Conclusions: SSCs can enhance dental students' non-operational clinical competency and OSCE performance effectively. Simulated patient encounters with feedback, incorporated into the dental curricula, have led to improved communication. Based on our findings, we suggest implementing SSC teaching before the OSCE to improve communication and cognitive skills., (© 2024. The Author(s).)

Background: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells., Methods: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059). The binding capacity of GenSci059 to CD47 was evaluated using flow cytometry and surface plasmon resonance (SPR) methods, the inhibitory effect of GenSci059 on the CD47-SIRPα interaction was evaluated through competitive ELISA assays. The anti-tumor activity of GenSci059 was assessed using in vitro macrophage models and in vivo patient-derived xenograft (PDX) models. To evaluate the safety profile of GenSci059, binding assays were conducted using blood cells. Additionally, we investigated the underlying mechanisms contributing to the weaker binding of GenSci059 to erythrocytes. Finally, toxicity studies were performed in non-human primates to assess the potential risks associated with GenSci059., Results: GenSci059 displayed strong binding to CD47 in both human and monkey, and effectively inhibited the CD47-SIRPα interaction. With doses ranging from 5 to 20 mg/kg, GenSci059 demonstrated potent inhibition of the growth of subcutaneous tumor with the inhibition rates ranged from 30.3% to complete regression. Combination of GenSci059 with 2.5 mg/kg Rituximab at a dose of 2.5 mg/kg showed enhanced tumor inhibition compared to monotherapy, exhibiting synergistic effects. GenSci059 exhibited minimal binding to hRBCs compared to Hu5F9-G4. The binding of GenSci059 to CD47 depended on the cyclization of N-terminal pyroglutamic acid and the spatial conformation of CD47, but was not affected by its glycosylation modifications. A maximum tolerated dose (MTD) of 450 mg/kg was observed for GenSci059, and no significant adverse effects were observed in repeated dosages up to 10 + 300 mg/kg, indicating a favorable safety profile., Conclusion: GenSci059 selectively binds to CD47, effectively blocks the CD47/SIRPα axis signaling pathway and enhances the phagocytosis effects of macrophages toward tumor cells. This monoclonal antibody demonstrates potent antitumor activity and exhibits a favorable safety profile, positioning it as a promising and effective therapeutic option for cancer., (© 2024. The Author(s).)

Background: Costaceae, commonly known as the spiral ginger family, consists of approximately 120 species distributed in the tropical regions of South America, Africa, and Southeast Asia, of which some species have important ornamental, medicinal and ecological values. Previous studies on the phylogenetic and taxonomic of Costaceae by using nuclear internal transcribed spacer (ITS) and chloroplast genome fragments data had low resolutions. Additionally, the structures, variations and molecular evolution of complete chloroplast genomes in Costaceae still remain unclear. Herein, a total of 13 complete chloroplast genomes of Costaceae including 8 newly sequenced and 5 from the NCBI GenBank database, representing all three distribution regions of this family, were comprehensively analyzed for comparative genomics and phylogenetic relationships., Result: The 13 complete chloroplast genomes of Costaceae possessed typical quadripartite structures with lengths from 166,360 to 168,966 bp, comprising a large single copy (LSC, 90,802 - 92,189 bp), a small single copy (SSC, 18,363 - 20,124 bp) and a pair of inverted repeats (IRs, 27,982 - 29,203 bp). These genomes coded 111 - 113 different genes, including 79 protein-coding genes, 4 rRNA genes and 28 - 30 tRNAs genes. The gene orders, gene contents, amino acid frequencies and codon usage within Costaceae were highly conservative, but several variations in intron loss, long repeats, simple sequence repeats (SSRs) and gene expansion on the IR/SC boundaries were also found among these 13 genomes. Comparative genomics within Costaceae identified five highly divergent regions including ndhF, ycf1-D2, ccsA-ndhD, rps15-ycf1-D2 and rpl16-exon2-rpl16-exon1. Five combined DNA regions (ycf1-D2 + ndhF, ccsA-ndhD + rps15-ycf1-D2, rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1, ccsA-ndhD + rpl16-exon2-rpl16-exon1, and ccsA-ndhD + rps15-ycf1-D2 + rpl16-exon2-rpl16-exon1) could be used as potential markers for future phylogenetic analyses and species identification in Costaceae. Positive selection was found in eight protein-coding genes, including cemA, clpP, ndhA, ndhF, petB, psbD, rps12 and ycf1. Maximum likelihood and Bayesian phylogenetic trees using chloroplast genome sequences consistently revealed identical tree topologies with high supports between species of Costaceae. Three clades were divided within Costaceae, including the Asian clade, Costus clade and South American clade. Tapeinochilos was a sister of Hellenia, and Parahellenia was a sister to the cluster of Tapeinochilos + Hellenia with strong support in the Asian clade. The results of molecular dating showed that the crown age of Costaceae was about 30.5 Mya (95% HPD: 14.9 - 49.3 Mya), and then started to diverge into the Costus clade and Asian clade around 23.8 Mya (95% HPD: 10.1 - 41.5 Mya). The Asian clade diverged into Hellenia and Parahellenia at approximately 10.7 Mya (95% HPD: 3.5 - 25.1 Mya)., Conclusion: The complete chloroplast genomes can resolve the phylogenetic relationships of Costaceae and provide new insights into genome structures, variations and evolution. The identified DNA divergent regions would be useful for species identification and phylogenetic inference in Costaceae., (© 2024. The Author(s).)

Background: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG., Methods: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery., Discussion: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery., Trial Registration: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620., (© 2024. The Author(s).)

Background: Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. Melatonin, a natural hormone produced by the pineal gland known for its antioxidant and anti-inflammatory properties, has been explored for its potential immunomodulatory effects. Despite this, its specific role in mitigating CAR-T cell-induced CRS remains poorly understood., Methods: In this study, our aim was to investigate the potential of melatonin as an immunomodulatory agent in the context of CD19-targeting CAR-T cell therapy and its impact on associated side effects. Using a mouse model, we evaluated the effects of melatonin on CAR-T cell-induced CRS and overall survival. Additionally, we assessed whether melatonin administration had any detrimental effects on the antitumor efficacy and persistence of CD19 CAR-T cells., Results: Our findings demonstrate that melatonin effectively mitigated the severity of CAR-T cell-induced CRS in the mouse model, leading to improved overall survival outcomes. Remarkably, melatonin administration did not compromise the antitumor effectiveness or persistence of CD19 CAR-T cells, indicating its compatibility with therapeutic goals. These results suggest melatonin's potential as an immunomodulatory compound to alleviate CRS without compromising the therapeutic benefits of CAR-T cell therapy., Conclusion: The study's outcomes shed light on melatonin's promise as a valuable addition to the existing treatment protocols for CAR-T cell therapies. By attenuating CAR-T cell-induced CRS while preserving the therapeutic impact of CAR-T cells, melatonin offers a potential strategy for optimizing and refining the safety and efficacy profile of CAR-T cell therapy. This research contributes to the evolving understanding of how to harness immunomodulatory agents to enhance the clinical application of innovative cancer treatments., (© 2024. The Author(s).)

Background: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer., Methods: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196)., Results: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups., Conclusion: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study., (© 2023. The Author(s).)

Background: The Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development., Methods: MKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis., Results: MKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-β (TGF-β) signalling, and MKRN1 promotes TGF-β signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group., Conclusions: High MKRN1 levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-β axis may be a potential therapeutic target in CRC., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Glycolytic reprogramming is one of the most important features of cancer and plays an integral role in the progression of cancer. In cancer cells, changes in glucose metabolism meet the needs of self-proliferation, angiogenesis and lymphangiogenesis, metastasis, and also affect the immune escape, prognosis evaluation and therapeutic effect of cancer. The n6-methyladenosine (m6A) modification of RNA is widespread in eukaryotic cells. Dynamic and reversible m6A modifications are widely involved in the regulation of cancer stem cell renewal and differentiation, tumor therapy resistance, tumor microenvironment, tumor immune escape, and tumor metabolism. Lately, more and more evidences show that m6A modification can affect the glycolysis process of tumors in a variety of ways to regulate the biological behavior of tumors. In this review, we discussed the role of glycolysis in tumor genesis and development, and elaborated in detail the profound impact of m6A modification on different tumor by regulating glycolysis. We believe that m6A modified glycolysis has great significance and potential for tumor treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Dexamethasone is commonly used for antiemesis in surgical patients. It has been confirmed that long-term steroid use increases blood glucose level in both diabetic and non-diabetic patients, it is unclear how a single dose of intravenous dexamethasone used pre/intraoperatively for postoperative nausea and vomiting (PONV) prophylaxis would influence the blood glucose and wound healing in diabetic patients., Methods: The Pubmed, Cochrane Library, Embase, Web of Science databases, CNKI and Google Scholar were searched. The articles reporting a single dose dexamethasone administered intravenously for antiemesis in surgical patients with diabetes mellitus (DM) were included., Results: Nine randomized controlled trials (RCTs) and 7 cohort studies were included in our meta-analysis. The results showed that dexamethasone increased glucose level intraoperatively (MD: 0.439, 95% CI: 0.137-0.581, I 2  = 55.7%, P = 0.004), at the end of surgery (MD: 0.815, 95% CI: 0.563-1.067, I 2  = 73.5%, P = 0.000), on postoperative day (POD) 1 (MD: 1.087, 95% CI: 0.534-1.640, I 2  = 88%, P = 0.000), on POD 2 (MD: 0.501, 95% CI: 0.301-0.701, I 2  = 0%, P = 0.000), and increased peak glucose level within 24 hours of surgery (MD: 2.014, 95% CI: 0.503-3.525, I 2  = 91.6%, P = 0.009) compared with control. It indicated that dexamethasone caused the increase of perioperative glucose level at different time points by 0.439 to 1.087 mmol/L (7.902 to 19.566 mg/dL), and the increase of peak glucose level within 24 hours of surgery by 2.014 mmol/L (36.252 mg/dL) compared with control. Dexmethasone had no impact on wound infection (OR: 0.797, 95%CI: 0.578-1.099, I 2  = 0%, P = 0.166) and healing (P < 0.05)., Conclusion: Dexamethasone could increase blood glucose by only 2.014 mmol/L (36.252 mg/dL) of peak glucose level within 24 hours of surgery in surgery patients with DM, the increase of glucose level at each time point perioperatively was even lower, and had no effect on wound healing. Thus, dexamethasone with a single dose could be safely used for PONV prophylaxis in diabetic patients., Trial Registration: The protocol of this systematic review was registered in INPLASY with the registration number INPLASY202270002., (© 2023. The Author(s).)

Background: Aberrant cytokeratin 7 expression by hepatocytes (CK7 + Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients., Methods: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0., Results: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7 + Hs (2 +), CK7 + Hs (1 +), and CK7 - Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7 - Hs and CK7 + Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7 + Hs (2 +) and CK7 + Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7 + Hs (2 +) and CK7 + Hs (1 +) into CK7 + Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7 + Hs and CK7 - Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7 + Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7 + Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively., Conclusion: CK7 + Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis., (© 2022. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, and about 10% of DLBCL cases primarily occur in the gastrointestinal tract. Previous reports have revealed that primary gastrointestinal-DLBCL (pGI-DLBCL) harbors different genetic mutations from other nodal or extranodal DLBCL. However, the exonic mutation profile of pGI-DLBCL has not been fully addressed., Methods: We performed whole-exome sequencing of matched tumor tissues and blood samples from 53 pGI-DLBCL patients. The exonic mutation profiles were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed., Results: A total of 6,588 protein-altering events were found and the five most frequent mutated genes in our pGI-DLBCL cohort were IGLL5 (47%), TP53 (42%), BTG2 (28%), P2RY8 (26%) and PCLO (23%). Compared to the common DLBCL, significantly less or absence of MYD88 (0%), EZH2 (0%), BCL2 (2%) or CD79B (8%) mutations were identified in pGI-DLBCL. The recurrent potential driver genes were mainly enriched in pathways related to signal transduction, infectious disease and immune regulation. In addition, HBV infection had an impact on the mutational signature in pGI-DLBCL, as positive HBsAg was significantly associated with the TP53 and LRP1B mutations, two established tumor suppressor genes in many human cancers. Moreover, IGLL5 and LRP1B mutations were significantly correlated with patient overall survival and could serve as two novel prognostic biomarkers in pGI-DLBCL., Conclusions: Our study provides a comprehensive view of the exonic mutation profile of the largest pGI-DLBCL cohort to date. The results could facilitate the clinical development of novel therapeutic and prognostic biomarkers for pGI-DLBCL., (© 2022. The Author(s).)

Background: Long non-coding RNAs (lncRNAs) are critical regulators in lung adenocarcinoma (LUAD). M2-type tumor-associated macrophages (TAMs) also play oncogenic roles in LUAD. However, the involvement of lncRNAs in TAM activation is still largely unknown., Methods: The expressions of LARRPM, LINC00240 and CSF1 were determined by RT-qPCR. The regulation of LINC00240 and CSF1 by LARRPM was investigated by RNA-protein pull-down, RNA immunoprecipitation, chromatin immunoprecipitation and bisulfite DNA sequencing. In vitro and in vivo gain- and loss-of-function assays were performed to investigate the roles of LARRPM., Results: The lncRNA LARRPM was expressed at low levels in LUAD tissues and cells. The low expression of LARRPM was correlated with advanced stage and poor survival of patients with LUAD. Functional experiments revealed that LARRPM suppressed LUAD cell proliferation, migration and invasion, and promoted apoptosis. LARRPM also repressed macrophage M2 polarization and infiltration. Taken together, LARRPM significantly restricted LUAD progression in vivo. Mechanistically, LARRPM bound and recruited DNA demethylase TET1 to the promoter of its anti-sense strand gene LINC00240, leading to a decrease in DNA methylation level of the LINC00240 promoter and transcriptional activation of LINC00240. Functional rescue assays suggested that the lncRNA LINC00240 was responsible for the roles of LARRPM in the malignant behavior of LUAD cells. LARRPM decreased the binding of TET1 to the CSF1 promoter, resulting in increased DNA methylation of the CSF1 promoter and transcriptional repression of CSF1, which is responsible for the roles of LARRPM in macrophage M2 polarization and infiltration. The TAMs educated by LUAD cells exerted oncogenic roles, which was negatively regulated by LARRPM expressed in LUAD cells., Conclusions: LARRPM restricts LUAD progression through repressing both LUAD cell and macrophages. These data shed new insights into the regulation of LUAD progression by lncRNAs and provide data on the potential utility of LARRPM as a target for LUAD treatment., (© 2022. The Author(s).)

Background: To evaluate the myocardial microcirculation perfusion of patients with acute ST-segment elevation myocardial infarction (STEMI) with a different index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and analyse the value of MCE in predicting myocardial perfusion after PCI., Methods: Fifty-six patients with acute STEMI who underwent an emergency PCI were selected from October 2018 to October 2019 in our hospital. According to the IMR values measured during PCI treatment, the patients were divided into three groups. Traditional ultrasound and MCE were performed one week after PCI. The left ventricular ejection fraction (LVEF), ventricular wall motion score index (WMSI), A value, β value and A × β value (which refers to the patient's myocardial blood flow) were measured. The receiver operating characteristic curve was drawn to evaluate the effectiveness of the MCE parameters in the diagnosis of myocardial microcirculation perfusion disorders., Results: The results showed that there was no significant difference in the LVEF among the groups. The WMSI in Group 3 was statistically different from that in Groups 1 and 2 (P < 0.05), but there was no statistically significant difference in the WMSI between Groups 1 and 2. Among the three groups, the A value, β value and A × β value were significantly different (P < 0.05). According to Spearman's correlation analysis, the MCE quantitative parameters (i.e. the A value, β value and A × β value) were negatively correlated with the IMR value (r = -0.523, -0.471, -0.577, P < 0.01)., Conclusions: The A value, β value and A × β value were negatively correlated with the IMR value. Furthermore, MCE could be used to observe the myocardial perfusion in patients with acute STEMI after PCI and may be one of the indicators used to accurately evaluate myocardial microcirculation., (© 2022. The Author(s).)

Background: Isobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol's toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol., Results: A S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism., Conclusions: The importance of tryptophan in yeast's tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast's isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance., (© 2021. The Author(s).)

Background: Cold stress caused by low temperatures is an important factor restricting rice production. Identification of cold-tolerance genes that can stably express in cold environments is crucial for molecular rice breeding., Results: In this study, we employed high-throughput quantitative trait locus sequencing (QTL-seq) analyses in a 460-individual F 2:3 mapping population to identify major QTL genomic regions governing cold tolerance at the seedling stage in rice. A novel major QTL (qCTS6) controlling the survival rate (SR) under low-temperature conditions of 9°C/10 days was mapped on the 2.60-Mb interval on chromosome 6. Twenty-seven single-nucleotide polymorphism (SNP) markers were designed for the qCST6 region based on re-sequencing data, and local QTL mapping was conducted using traditional linkage analysis. Eventually, we mapped qCTS6 to a 96.6-kb region containing 13 annotated genes, of which seven predicted genes contained 13 non-synonymous SNP loci. Quantitative reverse transcription PCR analysis revealed that only Os06g0719500, an OsbZIP54 transcription factor, was strongly induced by cold stress. Haplotype analysis confirmed that +376 bp (T>A) in the OsbZIP54 coding region played a key role in regulating cold tolerance in rice., Conclusion: We identified OsbZIP54 as a novel regulatory gene associated with rice cold-responsive traits, with its Dongfu-104 allele showing specific cold-induction expression serving as an important molecular variation for rice improvement. This result is expected to further exploration of the genetic mechanism of rice cold tolerance at the seedling stage and improve cold tolerance in rice varieties by marker-assisted selection.

Background: The surgical approaches remain controversial for the treatment of middle and distal-third humeral shaft (MDTHS) fractures. This study compared clinical effects of the anterolateral approach with two incisions (AATI) and the posterior median approach (PMA) in the treatment of MDTHS fractures., Methods: A retrospective analysis was carried out. One hundred sixty-six patients with MDTHS fractures were selected from January 2015 to January 2017 in Xi'an Hong Hui Hospital. According to surgical approaches, patients were divided into AATI (86 cases) and PMA group (80 cases). All patients were treated with open reduction and plate fixation. Operation indexes were compared, including incision length, operation time, and bleeding. Bryan-Morrey score was used to evaluate elbow joint function. Complication incidence was compared, such as incision infection, iatrogenic radial nerve injury, and nonunion., Results: The AATI group showed smaller incision length, less bleeding, lower iatrogenic radial nerve injury rate, and better elbow function than that of PMA group (P<0.05)., Conclusions: The middle and distal-third humeral shaft fractures can be successfully cured by both approaches. Compared with the posterior median approach, it has better clinical effects of the anterolateral approach with two incisions, which is worthy of clinical application and promotion.

Background: The Saccharomyces cerevisiae Snf1 complex is a member of the AMP-activated protein kinase family and plays an important role in response to environmental stress. The α catalytic subunit Snf1 regulates the activity of the protein kinase, while the β regulatory subunits Sip1/Sip2/Gal83 specify substrate preferences and stress response capacities of Snf1. In this study, we aim to investigate the effects of SNF1 overexpression on the cell tolerance and glucose consumption of S. cerevisiae in high glucose, ethanol, and heat stresses and to explore the valid Snf1 form in the light of β subunits in these stresses., Results: The results suggest that overexpression of SNF1 is effective to improve cell resistance and glucose consumption of S. cerevisiae in high glucose, ethanol, and heat stresses, which might be related to the changed accumulation of fatty acids and amino acids and altered expression levels of genes involved in glucose transport and glycolysis. However, different form of β regulatory subunits dominated in stresses with regard to cell tolerance and glucose utilization. The Sip1 isoform was more necessary to the growth and glucose consumption in ethanol stress. The glucose uptake largely depended on the Sip2 isoform in high sugar and ethanol stresses. The Gal83 isoform only contributed inferior effect on the growth in ethanol stress. Therefore, redundancy and synergistic effect of β subunits might occur in high glucose, ethanol, and heat stresses, but each subunit showed specificity under various stresses., Conclusions: This study enriches the understanding of the function of Snf1 protein kinase and provides an insight to breed multi-stress tolerant yeast strains.

Background and Objective: As the pathological mechanisms of AD are complex, increasing evidence have demonstrated Chinese Medicine with multi-ingredients and multi-targets may be more suitable for the treatment of diseases with complex pathogenesis. Therefore, the study was to preliminarily decipher the bioactive compounds and potential mechanisms of Qiong Yu Gao (QYG) for AD prevention and treatment by an integrated network pharmacology approach., Methods: Putative ingredients of QYG and significant genes of AD were retrieved from public database after screening. Then QYG ingredients target proteins/genes were obtained by target fishing. Compound-target-disease network was constructed using Cytoscape to decipher the mechanism of QYG for AD. KEGG pathway and GO enrichment analysis were performed to investigate the molecular mechanisms and pathways related to QYG for AD treatments., Results: Finally, 70 compounds and 511 relative drug targets were collected. In which, 17 representative direct targets were found. Gene ontology enrichment analysis revealed that the adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway was the key biological processes and were regulated simultaneously by the 17 direct targets. The KEGG pathway enrichment analysis found that three signaling pathways were closely related to AD prevention and treatment by QYG, including PI3K-Akt signaling pathway, regulation of actin cytoskeleton pathway and insulin resistance pathway., Conclusion: This study demonstrated that QYG exerted the effect of preventing and treating AD by regulating multi-targets with multi-components. Furthermore, the study demonstrated that a network pharmacology-based approach was useful for elucidation of the interrelationship between complex diseases and interventions of Chinese herbal medicines., Competing Interests: Competing interestsThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Background: Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs., Methods: We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded., Results: A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%., Conclusion: Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.

Background: The comparative efficacy of epidural bupivacaine alone and bupivacaine combined with magnesium sulfate in providing postoperative analgesia remains controversial., Methods: We searched Mediline (OvidSP), EMBASE (OvidSP) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify trials that compared epidural bupivacaine and magnesium sulfate combination (intervention) with bupivacaine alone (control). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework was used to assess the quality of evidence., Results: Eleven studies fulfilled our inclusion criteria after screening. We found that epidural bupivacaine combined with magnesium sulfate could prolong the time for first rescue analgesics (SMD 4.96; 95% CI [2.75, 7.17], P < 0.00001, I 2  = 98%), reduce the number of patients who need rescue analgesics (RR 0.38; 95% CI [0.20, 0.74], P = 0.004, I 2  = 75%) and requirement for rescue analgesics (SMD -2.65; 95% CI [- 4.23, - 1.06], P = 0.001, I 2  = 96%)., Conclusions: Magnesium suifate as an adjuvant of epidural bupivacaine improved postoperative analgesia. However, we rated the quality of evidence to be very low because of high heterogeneity, imprecise of results and small sample sizes. Furthermore, further large high-quality trials are still needed to confirm the effects of magnesium sulfate on postoperative analgesia.

Background: Several reports were published on the relationship between the vascular endothelial growth factor (VEGF) -2578C > A gene polymorphism and lung cancer risk; however, the results are debatable. This meta-analysis was conducted to assess the relationship between VEGF -2578C > A gene polymorphism and lung cancer risk., Methods: The associated literatures were identified on the 1st of September 2018 from CBM-disc (China Biological Medicine Database) and PubMed., Result: A total of 14 reports were recruited into our meta-analysis to assess the association between VEGF -2578C > A gene polymorphism and lung cancer susceptibility. There was a marked association between VEGF -2578C > A A allele / CC genotype and lung cancer risk in overall and Asian populations (overall populations: A allele: OR = 1.26, 95% CI: 1.08-1.46, P = 0.003; CC genotype: OR = 0.72, 95% CI: 0.54-0.95, P = 0.02; Asians: A allele: OR = 1.33, 95% CI: 1.15-1.55, P = 0.0002; CC genotype: OR = 0.68, 95% CI: 0.50-0.93, P = 0.01). However, VEGF -2578C > A gene polymorphism was not associated with the risk of lung cancer in Caucasians., Conclusion: VEGF -2578C > A A allele / CC genotype is associated with the lung cancer susceptibility in Asians and in overall populations.

Background: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction., Methods/design: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine., Discussion: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development., Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

Background: Knee osteoarthritis (KOA) is one of the most common bone and joint diseases. As one of the main non-drug therapies, acupuncture is widely used to treat KOA, although the evidence for its efficacy is inconclusive. The objective of this pilot trial is to clarify the clinical efficacy and safety of fire acupuncture in the treatment of mild to moderate KOA and to provide high-quality data for further research., Methods/design: This study is a prospective randomized controlled pilot trial in which 120 patients with mild to moderate KOA will be randomly allocated in equal proportions to a fire acupuncture group or a general acupuncture group. They will receive acupuncture for six sessions over 2 weeks. The primary end point is success rate, which will be calculated based on the change from baseline of the pain and function scores in the Western Ontario and McMaster Universities Osteoarthritis Index at 4 weeks. Secondary end points include the proportion of patients achieving clinical improvement based on: (1) the OMERACT-OARSI responder criteria, (2) levels of matrix metalloproteinase 3, interleukin 1β, and tumor necrosis factor α in blood, and (3) a subjective efficacy evaluation from patients., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800019162. Registered on 29 October 2018.

Background: Plant homeodomain (PHD) finger proteins are widely present in all eukaryotes and play important roles in chromatin remodeling and transcriptional regulation. The PHD finger can specifically bind a number of histone modifications as an "epigenome reader", and mediate the activation or repression of underlying genes. Many PHD finger genes have been characterized in animals, but only few studies were conducted on plant PHD finger genes to this day. Brassica rapa (AA, 2n = 20) is an economically important vegetal, oilseed and fodder crop, and also a good model crop for functional and evolutionary studies of important gene families among Brassica species due to its close relationship to Arabidopsis thaliana., Results: We identified a total of 145 putative PHD finger proteins containing 233 PHD domains from the current version of B. rapa genome database. Gene ontology analysis showed that 67.7% of them were predicted to be located in nucleus, and 91.3% were predicted to be involved in protein binding activity. Phylogenetic, gene structure, and additional domain analyses clustered them into different groups and subgroups, reflecting their diverse functional roles during plant growth and development. Chromosomal location analysis showed that they were unevenly distributed on the 10 B. rapa chromosomes. Expression analysis from RNA-Seq data showed that 55.7% of them were constitutively expressed in all the tested tissues or organs with relatively higher expression levels reflecting their important housekeeping roles in plant growth and development, while several other members were identified as preferentially expressed in specific tissues or organs. Expression analysis of a subset of 18 B. rapa PHD finger genes under drought and salt stresses showed that all these tested members were responsive to the two abiotic stress treatments., Conclusions: Our results reveal that the PHD finger genes play diverse roles in plant growth and development, and can serve as a source of candidate genes for genetic engineering and improvement of Brassica crops against abiotic stresses. This study provides valuable information and lays the foundation for further functional determination of PHD finger genes across the Brassica species.

Background: A microorganism engineered for non-native tasks may suffer stresses it never met before. Therefore, we examined whether a Kluyveromyces marxianus strain engineered with a carotenoid biosynthesis pathway can serve as an anti-stress chassis for building cell factories., Results: Carotenoids, a family of antioxidants, are valuable natural products with high commercial potential. We showed that the free radical removal ability of carotenoids can confer the engineered host with a higher tolerance to ethanol, so that it can produce more bio-ethanol than the wild type. Moreover, we found that this engineered strain has improved tolerance to other toxic effects including furfurals, heavy metals such as arsenate (biomass contaminant) and isobutanol (end product). Furthermore, the enhanced ethanol tolerance of the host can be applied to bioconversion of a natural medicine that needs to use ethanol as the delivery solvent of hydrophobic precursors. The result suggested that the engineered yeast showed enhanced tolerance to ethanol-dissolved hydrophobic 10-deacetylbaccatin III, which is considered a sustainable precursor for paclitaxel (taxol) bioconversion., Conclusions: The stress tolerances of the engineered yeast strain showed tolerance to several toxins, so it may serve as a chassis for cell factories to produce target products, and the co-production of carotenoids may make the biorefinary more cost-effective.

Background: Several studies have investigated the effects of dexamethasone on post-operative cognitive dysfunction (POCD) or post-operative delirium (POD); however, their conclusions have been inconsistent. Thus, we conducted a meta-analysis to determine the effects of dexamethasone on POCD and POD in adults following general anaesthesia., Methods: The Cochrane Central Register of Controlled Trials (2018, Issue 11 of 12) in the Cochrane Library (searched 17 November 2018), MEDLINE OvidSP (1946 to 16 November 2018) and Embase OvidSP (1974 to 16 November 2018) were searched for randomised controlled trials that evaluated the incidence of POCD and POD following dexamethasone administration in adults (age ≥ 18 years) under general anaesthesia. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess the quality of the evidence., Results: Five studies were included (three studies with 855 participants in the dexamethasone group and 538 participants in the placebo group for the incidence of POCD, and two studies with 410 participants in the dexamethasone group and 420 participants in the placebo group for the incidence of POD). There was no significant difference between the dexamethasone group and the placebo group in terms of the incidence of POCD 30 days after surgery (RR [relative risk] 1.00; 95% CI [confidence interval: 0.51, 1.96], P = 1.00, I 2  = 77%) or the incidence of POD (RR 0.96; 95% CI [0.68, 1.35], P = 0.80, I 2  = 0%). However, both analyses had some limitations because of limited evidence and clinical heterogeneity, and we considered the quality of the evidence for the post-operative incidence of POCD and POD to be very low., Conclusions: This meta-analysis revealed that prophylactic dexamethasone did not reduce the incidence of POCD and POD. Trials of alternative preventive strategies for POCD and POD, as well as a better understanding of the pathophysiology of those complex syndromes, are still needed to make progress in this field., Trial Registrationr: This study is registered with PROSPERO, 23 October 2018, number CRD42018114552. Available from  https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

Background: As a member of peroxiredoxin (PRX) family, PRX3 is predominantly located in mitochondria and plays an important role of free radical scavenging. Since a body of evidence demonstrated the involvement of PRX3 in insulin secretion, insulin sensitivity, and glucose metabolism, the present study was conducted to investigate the role of PRX3 in the pathogenesis of polycystic ovarian syndrome (PCOS) featured in insulin resistance., Methods: Enzyme-linked immunosorbent assay was performed to detect plasma PRX3 in PCOS patients and control subjects. Levels of reactive oxygen species (ROS) and oxidized PRXs were detected in mouse islet cells treated with gradient glucose., Results: We did not find significant difference of fasting plasma PRX3 between PCOS patients and controls. No association was noticed between fasting plasma PRX3 and fasting plasma glucose or insulin. After oral glucose tolerance test (OGTT), PCOS patients showed higher levels of both glucose and insulin as compared to controls. The plasma level of PRX3 was significantly increased at 2 h and began to fall back at 3 h of OGTT. There was a one-hour time lag of peak values between plasma PRX3 and insulin, and the plasma PRX3 at 2 h was positively correlated with the insulin level at 1 h of OGTT of PCOS patients. In addition, the level of ROS was significantly elevated at 1 h and oxidized PRX3 was increased dramatically at 2 h of 16.7mM glucose stimulation in mouse islet cells., Conclusion: It seems that PRX3 does not show its antioxidant function under baseline conditions. Instead, PRX3 responds to oxidative stress induced by rapid increase of insulin and glucose in patients with PCOS.

Background: Perioperative transfusion can reduce the survival rate in colorectal cancer patients. The effects of transfusion on the short- and long-term prognoses are becoming intriguing., Objective: This systematic review and meta-analysis aimed to define the effects of perioperative transfusion on the short- and long-term prognoses of colorectal cancer surgery., Results: Thirty-six clinical observational studies, with a total of 174,036 patients, were included. Perioperative transfusion decreased overall survival (OS) (hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.24 to 0.41; P < 0.0001) and cancer-specific survival (CSS) (HR, 0.34; 95% CI, 0.21 to 0.47; P < 0.0001), but had no effect on disease-free survival (DFS) (HR, 0.17; 95% CI, - 0.12 to 0.47; P = 0.248). Transfusion could increase postoperative infectious complications (RR, 1.89, 95% CI, 1.56 to 2.28; P < 0.0001), pulmonary complications (RR, 2.01; 95% CI, 1.54 to 2.63; P < 0.0001), cardiac complications (RR, 2.20; 95% CI, 1.75 to 2.76; P < 0.0001), anastomotic complications (RR, 1.51; 95% CI, 1.29 to 1.79; P < 0.0001), reoperation(RR, 2.88; 95% CI, 2.05 to 4.05; P < 0.0001), and general complications (RR, 1.86; 95% CI, 1.66 to 2.07; P < 0.0001)., Conclusion: Perioperative transfusion causes a dramatically negative effect on long-term prognosis and increases short-term complications after colorectal cancer surgery.

Background: Recent advances in semiconductor sequencing platform (SSP) have provided new methods for preimplantation genetic diagnosis/screening (PGD/S). The present study aimed to evaluate the applicability and efficiency of SSP in PGD/S., Methods: The artificial positive single-cell-like DNAs and normal single-cell samples were chosen to test our semiconductor sequencing platform for preimplantation genetic diagnosis/screening (SSP-PGD/S) method with two widely used whole-genome amplification (WGA) kits. A total of 557 single blastomeres were collected from in vitro fertilization (IVF) couples, and their WGA products were processed and analyzed by our SSP-PGD/S method in comparison with array comparative genomic hybridization (array-CGH)., Results: Our SSP-PGD/S method indicated high compatibilities with two commercial WGA kits. For 557 single blastomeres, our method with four million reads in average could detect 24-chromosome aneuploidies as well as microdeletion/microduplication of the size over 4 Mb, providing 100% consistent conclusion with array-CGH method in the classification of whether it was transplantable., Conclusions: Our studies suggested that SSP-PGD/S represents a valuable alternative to array-CGH and brought PGD/S into a new era of more rapid, accurate, and economic.

Background: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common form of deafness. Acupuncture has been used as a salvage therapy for ISSNHL in China since 200 BCE. However, the efficacy of acupuncture has not been confirmed in strictly controlled trials. We designed a randomized controlled clinical trial to evaluate the efficacy and long-term effects of acupuncture in patients with early ISSNHL., Methods/design: In this randomized controlled clinical trial, we will enroll 124 participants with ISSNHL diagnosed 2 to 4 weeks prior to enrollment, who have shown little hearing improvement after routine Western medical treatment (i.e., corticosteroids). 62 of these participants will have flat audiogram and the other 62 will have a high-frequency drop audiogram; they will all take Methycobal while half of the flat type and half of the high-frequency drop type will also receive acupuncture treatments for 4 weeks in a four-group design. The primary outcome measure will be the effective rate of hearing improvement (defined as the proportion of patients with at least 15-dB improvement in the hearing loss frequency band). The secondary outcome will measure the improvements in Pure Tone Average, Word Recognition Score, and Tinnitus Handicap Inventory. The assessments of the participants will be made at baseline, after treatment (week 4), and at follow-up (week 28)., Discussion: This study aims to explore the efficacy and long-term effects of acupuncture in patients with ISSNHL. This study will be a randomized controlled trial with strict methodology and few design deficits. If our study yields positive results, acupuncture could be recommended as a salvage therapy for patients with ISSNHL., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-ICR-15006787 . Registered on 12 July 2015.

Background: The study aimed to evaluate the efficacy and safety of gingival mesenchymal stem cells (GMSCs) from human fetal gingival tissue used for treating gingival defects in a rat model., Methods: GMSCs were isolated from human fetal gingival tissue and identified by flow cytometry for nestin, Oct4, vimentin, NANOG, CD105, and CD90. The immunogenicity of GMSCs was analyzed by mixed lymphocyte reactions; the tumorigenicity of GMSCs was evaluated by xenotransplanting into nude mice. The gingival defect animal model was established by mechanical resection in rats. GMSCs were transplanted into the defective area, and the regeneration of gingival tissue was observed twice weekly. Four weeks after transplantation, the gingival tissue was surgically cut down, and the graft was analyzed by immunohistochemistry staining for human mitochondrial antigens and rat CD3 and CD20., Results: GMSCs from human fetal gingival tissue positively expressed nestin, Oct4, vimentin, NANOG, CD105, and CD90. There was no cell aggregation after mixed lymphocyte reactions, and interleukin-2 did not increase. Inoculation of GMSCs into nude mice for 6 months showed no tumor formation. GMSCs were transplanted into the gingiva defects of rats. One week after transplantation, the defect area was reduced, and after 3 weeks the morphology and color of local gingival tissue was similar to normal gingival tissue, and gingival height was the same as the normal control group., Conclusions: Using GMSCs from human fetal gingival tissue to treat gingival defects is a safe and effective innovative treatment method.

Background: Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil., Methods: A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively., Results: Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P < 0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2 ± 0.5 vs. 5.2 ± 0.6; P < 0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups., Conclusion: Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia., Trial Registration: A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

The Catsper channel is a sperm-specific, Ca 2+ -permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, Ca 2+ ATPase, K + channel, Hv1 channel and HCO 3 - transporters. Furthermore, the Catsper channel is regulated by some physiological stimulants, such as progesterone, cyclic nucleotides (e.g., cAMP, cGMP), zona pellucida (ZP) glycoproteins and bovine serum albumin (BSA). All of these factors normally stimulate Ca 2+ entry into sperm through the Catsper channel. In addition, the Catsper channel may be a potential target for male infertility treatment or contraception. This review will focus on the structure, functions, regulation mechanisms and medicinal targets of the Catsper channel.

Background: Stress has been proved to impair the porcine reproduction soundly. Endocrine disruption, which is closely related to the persistent follicles, is possibly one of the results of stress, although the mechanism is unclear. Since the expression of luteinizing hormone receptor (LHR) in ovarian follicular wall and concentrations of steroid hormone in follicular fluid are related to the development of persistent follicles, this study is designed to evaluate the effect of administered adrenocorticotrophic hormone (ACTH) to weaned pigs on their ovarian steroidogenesis capacity and LHR expression., Methods: Ten multiparous sows were weaned and randomly divided into two groups (n = 5 each). Sows received 1 IU/kg ACTH (ACTH group) or saline (control group) every 8 h from days 3-9 after jugular vein intubation. Blood samples were collected throughout the experiment, and ovaries were collected after slaughter on day 10. Follicular fluid (FF) was used to determine the steroid hormone concentrations. The ovarian follicle wall was obtained and stored in liquid nitrogen to detect mRNA levels., Results: The plasma cortisol concentration was significantly (P < 0.01) elevated after ACTH injection. The estradiol (E 2 ) and androstenedione (ASD) concentrations in FF were significantly lower (P < 0.05) in the ACTH group than in the control group. The LHR, 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450 aromatase (P450arom), and cytochrome P450 17a-hydroxylase (P450c17) mRNA levels were significantly (P < 0.05) reduced in the ACTH group. The steroidogenic acute regulatory protein (StAR) level and cytochrome P450 side-chain cleavage (P450scc) was lower in the ACTH group than in the control group, but the difference was not statistically significant (P > 0.05). Immunostaining results revealed 3β-HSD,P450c17, and LHR expression in theca cells, and P450arom expression in granulosa cells. Immunohistochemical staining showed significant differences in the distribution of 3β-HSD, P450c17, LHR, and P450arom between the two groups., Conclusions: These findings indicated that ACTH significantly diminished the LHR expression and steroidogenesis capacity of the ovaries of weaned sows.

Background: Musculoskeletal pain in people with type 2 diabetes is a common issue even to this day. The study aimed to explore the 10-year cumulative incidence of musculoskeletal pain, the mean number of doctor visits for musculoskeletal pain, and the mean number of doctor visits for musculoskeletal pain by location in people with type 2 diabetes, compared with respective values for people without diabetes., Methods: The study utilized a population-based retrospective cohort study design. The subjects were randomly obtained from the Taiwan National Health Insurance Research Database. The diabetic group included 6586 people with type 2 diabetes aged 18-50 years, while the non-diabetic group consisted of 32,930 age- and sex-matched people. Based on the medical records of individuals with musculoskeletal pain in the two groups from 2001 to 2010, the 10-year cumulative incidence of musculoskeletal pain, the mean number of doctor visits for musculoskeletal pain, and the mean number of doctor visits for musculoskeletal pain by location were calculated and compared, with the aim of identifying differences between the two groups., Results: Showed that people in the diabetic group had a higher 10-year cumulative incidence of and a higher mean number of doctor visits for musculoskeletal pain than the non-diabetic group (p < 0.05). The relative risk (RR) of the 10-year cumulative incidence of musculoskeletal pain in the two groups was the highest (RR = 1.39) for people between 30 and 39 years of age. The mean number of doctor visits for musculoskeletal pain by location was significantly different between the two groups. However, the mean number of doctor visits for limb pain registered the largest difference between the two groups., Conclusion: People with type 2 diabetes aged 18-50 years had a higher 10-year cumulative incidence of and a higher mean number of doctor visits for musculoskeletal pain than the non-diabetic group. Musculoskeletal pain might directly or indirectly interfere with or decrease the physical activity levels of people with diabetes. Therefore, it is important to detect and treat musculoskeletal pain early in order to promote physical activity and optimize blood sugar control.

Background: Placenta accreta is a rare obstetric condition but can lead to life-threatening complications that was mainly diagnosed in the third trimester. We present a case of acute trophoblastic pulmonary embolism (PE) during conservative treatment of placenta accreta., Case Presentation: A 24-year-old patient who delivered vaginally at 40(+4) weeks gestation. The placenta was retained despite the use of oxytocics and attempts of manual removal. Conservative management including uterine arteria embolism, hysteroscopic resection and mifepristone was used but failed and finally the patient died from acute trophoblastic PE and allergic shock when infusing povidone-iodine into her uterine cavity., Conclusion: Although conservative treatment of placenta accreta can retain reproductive potential and trophoblastic PE is rare, clinicians should consider hysterectomy when conservative treatment failed and infusion of povidone-iodine or other liquid into the cavity should be prohibited.

Immunochromatographic sensors (ICSs) are inexpensive, simple, portable, and robust, thus making ICSs commonplace in clinical diagnoses, food testing, and environmental monitoring. However, commonly used gold nanoparticles (AuNPs) ICSs have low sensitivity. Therefore, we developed highly sensitive surface enhanced Raman scattering (SERS) ICSs. To enhance the sensitivity of SERS ICSs, rough surface core-shell Au@Ag nanoparticles (RSAu@AgNPs) were prepared by coating silver on the surface of gold nanoflowers (AuNFs). Then these nanoparticles were used as SERS substrate in the SERS ICSs, after which the SERS ICSs were implemented to detect haemoglobin and heavy metal cadmium ion (Cd(2+)). The limit of detection (LOD) of the SERS ICSs for detecting haemoglobin was 8 ng/mL, and the linear range of the SERS ICSs was from 31.3 to 2000 ng/mL. The LOD of the SERS ICSs for detecting Cd(2+) was 0.05 ng/mL and the linear analysis range was from 0.05 to 25 ng/mL. The cross reactivity of the SERS ICSs was studied and results showed that the SERS ICSs exhibited highly specific for detection of haemoglobin and Cd(2+), respectively. The SERS ICSs were then used to detect haemoglobin (spiked in serum and in stool) and Cd(2+) (spiked in tap water, river water, and soil leaching water), and the results showed high recovery. These characteristics indicated that SERS ICSs were ideal tools for clinical diagnosis and environmental pollution monitoring.

Background: Previous studies have demonstrated that the trafficking defects of Nav1.1/Nav1.2 are involved in the dementia pathophysiology. However, the detailed mechanisms are not fully understood. Moreover, whether the impaired miRNAs regulation linked to dementia is a key player in sodium channel trafficking disturbance remains unclear. The cognitive impairment induced by chronic cerebral ischemia through chronic brain hypoperfusion (CBH) is likely reason to precede dementia. Therefore, our goal in the present study was to examine the role of microRNA-9 (miR-9) in regulating Nav1.1/Nav1.2 trafficking under CBH generated by bilateral common carotid artery occlusion (2VO)., Results: The impairment of Nav1.1/Nav1.2 trafficking and decreased expression of Navβ2 were found in the hippocampi and cortices of rats following CBH generated by bilateral 2VO. MiR-9 was increased in both the hippocampi and cortices of rats following CBH by qRT-PCR. Intriguingly, miR-9 suppressed, while AMO-miR-9 enhanced, the trafficking of Nav1.1/Nav1.2 from cytoplasm to cell membrane. Further study showed that overexpression of miR-9 inhibited the Navβ2 expression by targeting on its coding sequence (CDS) domain by dual luciferase assay. However, binding-site mutation or miR-masks failed to influence Navβ2 expression as well as Nav1.1/Nav1.2 trafficking process, indicating that Navβ2 is a potential target for miR-9. Lentivirus-mediated miR-9 overexpression also inhibited Navβ2 expression and elicited translocation deficits to cell membrane of Nav1.1/Nav1.2 in rats, whereas injection of lentivirus-mediated miR-9 knockdown could reverse the impaired trafficking of Nav1.1/Nav1.2 triggered by 2VO., Conclusions: We conclude that miR-9 may play a key role in regulating the process of Nav1.1/Nav1.2 trafficking via targeting on Navβ2 protein in 2VO rats at post-transcriptional level, and inhibition of miR-9 may be a potentially valuable approach to prevent Nav1.1/Nav1.2 trafficking disturbance induced by CBH.

Background: The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI)., Methods: In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively., Results: During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0.001]. Concomitantly, the absolute decreases in LV end-systolic volumes and end-diastolic volumes at 18 months in the WJMSC group were significantly greater than those in the placebo group (P = 0.0004, P = 0.004, respectively)., Conclusions: Intracoronary infusion of WJMSCs is safe and effective in patients with AMI, providing clinically relevant therapy within a favorable time window. This study encourages additional clinical trials to determine whether WJMSCs may serve as a novel alternative to BMSCs for cardiac stem cell-based therapy., Trial Registration: Clinical Trials NCT01291329 (02/05/2011).

Background: Interleukin-12 (IL-12) has long been considered to be effective in triggering an anticancer immune response, however, the dosage has been limited by potential systemic immunotoxicity. Since focused ultrasound (FUS) has been confirmed to temporally and locally open the blood-brain barrier (BBB), the purpose of this study was to elucidate the possibility of combining FUS-induced BBB opening with IL-12 delivery to enhance the anticancer immunological response for glioma treatment., Methods: FUS energy combined with microbubble administration was delivered transcranially to open BBB, and C-6 glioma rats were used in this study. The efficacy in inducing BBB opening and the corresponding immunological response were primarily evaluated in normal animals. The anticancer immune-triggering chemokine, IL-12, was intraperitoneally administered during the treatment phase to evaluate the effect of immunological response on tumor progression. Glioma animals were sub-grouped to evaluate the effect of the immune response in suppressing glioma when IL-12 was combined with FUS-induced BBB opening. We performed flow cytometry to verify consequent immune cell population changes of peripheral/ tissue lymphocytes as well as macrophages from the animals. Brain sections of sacrificed animals were also used for histological and immunohistochemical analysis. IL-12 level among experimental groups were measured via ELISA analysis. We also analyzed survival and followed tumor progression in vivo via T2-weighted magnetic resonance imaging., Results: FUS-induced BBB opening had no obvious effect on the T lymphocytes population in normal animals, either in the brain or systemically. Yet, it triggered mild changes in the tumor-infiltrating lymphocyte (TIL) population, particularly in numbers of CD3+CD8+ cytotoxic T lymphocytes (CTLs) in the tumor region. IL-12 administration triggered a profound increase in all TIL populations, including CD3+CD4+ T helper cells (Th), CTL, and CD4+CD25+ regulatory T cells (Treg), but combined FUS-BBB opening with IL-12 administration produced the most significant IL-12 increase, CTL increase and CTL/Treg ratio increase, thus contributing to the most significant suppression of tumor progression and increased animal survival., Conclusion: This study provides evidence that FUS-BBB opening can enhance immune-modulating agent delivery to the brain, which improve the anticancer immune response in brain tumor treatment.

Background: The identification of acid mucopolysaccharide by the liquid chromatography/tandem mass spectrometry method (LC-MS/MS) of the predominant disaccharide units of glycosaminoglycans (GAGs) (chondroitin sulfate, CS; dermatan sulfate, DS; heparan sulfate, HS) after methanolysis is validated and applicable for mucopolysaccharidosis (MPS) type determination., Methods: A total of 76 urine samples were collected and analyzed, from nine MPS I patients, 13 MPS II patients, seven MPS III patients, eight MPS VI patients, and 39 normal controls. Urinary GAG was first precipitated by the Alcian blue method followed by a treatment of 3 N HCl methanol. The protonated species of the methylated disaccharide products were detected by using a multiple reaction monitoring experiment. Internal standards, [2H6] CS, [2H6] DS and [2H6] HS, were prepared in-house by deuteriomethanolysis of CS, DS and HS., Results: One particular disaccharide for each GAG was selected, in which the parent ion and its daughter ion after collision were m/z 426.1 → 236.2 for DS (m/z 432 → 239 for dimers derived from [2H6] CS and [2H6] DS) and m/z 384.2 → 161.9 for HS (m/z 390.4 → 162.5 for the [2H6] HS dimer). The quantities of DS and HS were determined, which varied from one MPS type to the other. The results can be used to evaluate the severity of MPS subgroups, as well as urinary GAG amelioration at follow-up after enzyme replacement therapy (ERT)., Conclusions: The modified LC-MS/MS method for MPS type determination is specific, sensitive, validated, accurate, and applicable for simultaneous quantifications of urinary DS and HS. This method can help to make correct diagnosis of MPS patients and evaluate the effectiveness of ERT.

Background: Gastritis cystica profunda (GCP) is an uncommon disease characterized by multiple cystic gastric glands within the submucosa of the stomach., Case Description: Here, we present a case of a 63-year-old man with intermittent epigastric discomfort in whom gastroscopy revealed multiple irregular elevated nodular lesions with smooth surfaces at the anterior of the antrum. Surgical resection of the nodular lesions was performed, and the diagnosis of gastritis cystica profunda (GCP) was confirmed by histological examination. Another elevated nodular lesion approximately 10 mm in diameter with an ulcer was found on the gastric side of the remnant stomach near the resection side from 6 to 24 months after the surgical resection. Endoscopic ultrasonography (EUS) and repeated biopsies of the new elevated lesion were performed. Homogeneous, anechoic masses originating from the submucosa without gastric adenocarcinoma in histological examination showed GCP recurrence may occur., Conclusions: We report a case of GCP recurrence within 6 months after surgical resection. GCP should be considered in the differential diagnosis of elevated lesions in the stomach.