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Research on coagulation dysfunction following burns is controversial. This study aimed to describe the coagulation changes in severe burn patients by examining coagulation parameters.Patients with third-degree total body surface area (TBSA) burns of ≥30% were enrolled between 2017 and 2020. Platelet (PLT) count and coagulation indexes (including APTT, INR, FIB, DD, and AT Ⅲ) were measured at admission and once weekly for 8 weeks, and statistical analysis was performed. The patient medical profiles were reviewed to extract demographic and clinical data, including TBSA, third-degree TBSA, and inhalation injury. The total intravenous fluids and transfusions of crystalloids, fresh frozen plasma (FFP), and red blood cells (RBC) were calculated during the forty-eight-hour period. The number of sepsis cases was recorded.We enrolled 104 patients , and while the overall coagulation trend fluctuated, inflection points appeared around one week and demonstrated hypercoagulability. INR was significantly higher in the non-survival group than in the survivors' group from admission to three weeks after burn (all p0.01). From post-injury week 1 to post-injury week 3, the APTT in the non-survival group was greater than in the survival group, but the non-survival group's PLT count was lower than that in the survival group (all p0.05). At two and three weeks after burns, the FIB levels in the non-survival group were significantly lower than those of the survival group (both p0.01). The prevalence of inhalation injury and the proportion of sepsis cases were significantly higher in the non-survival group than in the survival group ( p ＜ 0.05, p ＜ 0.001, respectively). At the time of death, APTT, INR, and FDP levels were significantly higher in the non-survival group in the survivor group, and FIB, ATIII, and PLT were significantly lower than in the survivor group (all p0.01). On the day of death, nine of the 12 dead patients had disseminated intravascular coagulation (DIC).Coagulation dysfunction was most prominent in severe burn patients 1 week after injury and presented as hypercoagulability. Large-area burn injury, large amounts of fluid resuscitation, inhalation injury, and sepsis may all contribute to coagulation dysfunction, which can further develop into DIC and even death in severe burns patients.

Jiaoping Mi,1,2,&ast; Yijie Fang,3,&ast; Jianzhong Xian,4 Guojie Wang,3 Yuanqing Guo,5 Haiyu Hong,2 Mengshi Chi,2 Yong-Fang Li,2 Peng He,2 Jiebing Gao,3 Wei Liao2 1Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 4Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 5Department of Spinal Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liao, Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, 519020, People’s Republic of China, Email liaowei23@mail.sysu.edu.cn Jiebing Gao, Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China, Email Gaojb@mail.sysu.edu.cnObjective: Accurate preoperative localization of abnormal parathyroid glands is crucial for successful surgical management of secondary hyperparathyroidism (SHPT). This study was conducted to compare the effectiveness of preoperative MRI, 4D-CT, and ultrasonography (US) in localizing parathyroid lesions in patients with SHPT.Methods: We performed a retrospective review of prospectively collected data from a tertiary-care hospital and identified 52 patients who received preoperative MRI and/or 4D-CT and/or US and/or 99mTc-MIBI and subsequently underwent surgery for SHPT between May 2013 and March 2020. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of each imaging modality to accurately detect enlarged parathyroid glands were determined using histopathology as the criterion standard with confirmation using the postoperative biochemical response.Results: A total of 198 lesions were identified intraoperatively among the 52 patients included in this investigation. MRI outperformed 4D-CT and US in terms of sensitivity (P < 0.01), specificity (P = 0.455), PPV (P = 0.753), and NPV (P = 0.185). The sensitivity and specificity for MRI, 4D-CT, and US were 90.91%, 88.95%, and 66.23% and 58.33%, 63.64%, and 50.00%, respectively. The PPV of combined MRI and 4D-CT (96.52%) was the highest among the combined 2 modalities. The smallest diameter of the parathyroid gland precisely localized by MRI was 8× 3 mm, 5× 5 mm by 4D-CT, and 5× 3 mm by US.Conclusion: MRI has superior diagnostic performance compared with other modalities as a first-line imaging study for patients undergoing renal hyperparathyroidism, especially for ectopic or small parathyroid lesions. We suggest performing US first for diagnosis and then MRI to make a precise localization, and MRI proved to be very helpful in achieving a high success rate in the surgical treatment of renal hyperparathyroidism in our own experience.Keywords: MRI, 4D-CT, ultrasonography, SHPT, preoperative localization, parathyroidectomy

Integration of high-risk human papillomavirus (HPV) into the host genome is a crucial event for the development of cervical cancer, however, the underlying mechanism of HPV integration-driven carcinogenesis remains unknown. Here, we performed long-read RNA sequencing on 12 high-grade squamous intraepithelial lesions (HSIL) and cervical cancer patients, including 3 pairs of cervical cancer and corresponding para-cancerous tissue samples to investigate the full-length landscape of cross-species genome integrations. In addition to massive unannotated isoforms, transcriptional regulatory events, and gene chimerism, more importantly, we found that HPV-human fusion events were prevalent in HPV-associated cervical cancers. Combined with the genome data, we revealed the existence of a universal transcription pattern in these fusion events, whereby structurally similar fusion transcripts were generated by specific splicing in E6 and a canonical splicing donor site in E1 linking to various human splicing acceptors. Highly expressed HPV-human fusion transcripts, eg, HPV16 E6*I-E7-E1

Aim This study aimed to evaluate the effectiveness of melatonin in treating insomnia in children with autism spectrum disorder (ASD). Methods Comprehensive searches were conducted in the PubMed, EMBASE, and Web of Science databases from their inception to April 20, 2022. Data were extracted and assessed for quality by two researchers. Statistical analysis was performed using the Stata 15.0 software. Results Four studies including 238 patients were included. The results showed that compared with the control group, melatonin could shorten the sleep-onset latency (standardized mean difference [SMD] = − 1.34, 95% CI: −2.19 to −0.48), reduce the number of awakenings (SMD = -2.35, 95% CI: −4.62 to −0.08), and prolong the total sleep time (SMD = 1.42, 95% CI: 0.5–2.33) in children with ASD. Conclusion Melatonin has a certain effect on relieving sleep disturbances in children with ASD, which can shorten sleep latency, reduce the number of awakenings, and prolong total sleep time. Larger studies are required to verify this hypothesis.

Background. Ingrown nails are a type of nonspecific inflammation of nail folds. Intralesional injection is a rarely reported nonsurgical therapy for ingrown nails. Objective. To observe the efficacy of treating ingrown nails with intralesional injection, and to evaluate at which stage ingrown nails are applicable for this therapy. Methods. Ingrown nails were randomly divided into treatment (n = 87) and control (n = 37) groups. The treatment group received local injections combined with basic nursing, whereas the control group was only treated with basic nursing. Patients were followed up at 1 week, 1 month, 3 months, and 6 months after the first treatment. Results. A statistically significant difference of the efficacy rates was observed between the two groups ( P P = 0.019). Conclusion. Intralesional injection is an effective therapy for ingrown nails, especially in the short term. This therapy is more applicable for Martinez-Nova stage I and IIA ingrown nails and can be used as a symptomatic treatment to relieve the acute inflammation of ingrown nails at stages IIB, III, and IV.

Accumulating evidence has noted the circRNA-microRNA- (circRNA-miRNA-) mRNA competing endogenous RNA (ceRNA) regulatory network in disease development and progression. The current study explored the ceRNA network in acute traumatic coagulopathy (ATC). Potential ATC-related genes were screened, and upstream miRNAs and circRNAs of VWF (the candidate target) were assayed through database searching and high-throughput sequencing technology. circ_0001274/miR-143-3p/VWF ceRNA regulatory network was constructed and validated. The expression of circ_0001274/miR-143-3p/VWF was determined in the peripheral blood samples from ATC patients and ATC mouse models. Online database and circRNA sequencing analysis results identified VWF as a key gene in ATC as supported by assays and that VWF was lowly expressed in ATC patients and mice. Further experiments demonstrated that miR-143-3p could target and inhibit VWF, and circ_0001274 could competitively sponge miR-143-3p. Functionally, circ_0001274 could competitively sequester miR-143-3p to upregulate VWF expression, potentially improving ATC. Our study highlights the critical role of circ_0001274/miR-143-3p/VWF axis in improving ATC.

It is difficult to identify those preterm infants who require surgical intervention. This study examined the predictive factors for bowel resection in infants with definitive and advanced necrotizing enterocolitis (NEC). We then developed a scoring system to better predict the need for surgical intervention.A total of 203 infants with modified Bell's stage 2 or higher NEC from January 2018-December 2020 were identified for this study. A retrospective study evaluated the association between several comprehensive variables and surgical intervention using a multiple logistic regression analysis, and then a scoring system was developed based on the sum of coefficients (β).Of the 135 patients who met the inclusion criteria, 57 infants underwent a surgical intervention. The multivariable logistic regression analysis showed that birth weight (regression coefficient, β = 1.30), PCT (β = 2.33), not having received enteral nutrition before the diagnosis of NEC (β = 2.13), acidosis (β = 1.57), respiratory alkalosis (β = 2.42), hypokalemia (β = 2.14), peritonitis (β = 2.87) and coagulation disorders (β = 1.78) were associated with the occurrence of bowel resection. A scoring system ranging from 0-17 was developed based on the total coefficient obtained. It was found that a cut-off score of 5 may distinguish those infants needing surgical intervention from other infants with NEC.We successfully developed a clinical decision-making tool associated with the need for surgical intervention among infants with advanced NEC. The risk scoring system could accurately identify infants who would benefit from surgical intervention.

Introduction: To compare structural and vascular parameters in the central and peripheral retina and choroid of eyes diagnosed with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) with or without pan-retinal photocoagulation (PRP) using ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA). Methods: All participants underwent SS-OCTA imaging centered on the fovea. Retinal and choroidal thickness, vessel density of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary plexus (CCP), and choroidal Sattler’s and Haller’s layer (CSHL) were analyzed in nine grids using built-in angiography analysis software. Results: A total of 82 eyes from 82 participants were enrolled in this study, including 40 eyes diagnosed with severe NPDR or PDR without PRP and 42 eyes with PRP. Retinal thickness in part grids was higher in eyes with PRP than in eyes without PRP. Vessel density of the SCP in nasal-superior (p = 0.003) grid was lower in eyes with PRP than in eyes without PRP. No significant difference was found in the vessel density of the DCP between the two groups (all p > 0.05). The choroidal thickness and vessel density of the CSHL of all grids were significantly lower in eyes with PRP than in eyes without PRP (all p < 0.05). A statistically significant decrease in vessel density in CCP was found in the superior (p = 0.043), nasal-superior grid (p = 0.003), macular grid (p < 0.001), and optic disc grid (p = 0.001) of eyes with PRP, compared to eyes without PRP. A significant decrease in the vessel density of CSHL was observed in all grids of PDR eyes with PRP compared to PDR eyes without PRP (all p < 0.05). Significant decrease in choroidal thickness was observed in most grids of PDR eyes with PRP, except for macular grid (p = 0.090) and optic disc grid (p = 0.057). Conclusion: Structural and vascular parameters in the central and peripheral retinal and choroidal layers in eyes diagnosed with severe NPDR or PDR with or without PRP could be quantified using a ultrawide-field SS-OCTA. Eyes with PRP showed a significant decrease in choroidal thickness and vessel density of CCP and CSHL, compared with eyes without PRP. This trend was more obvious in eyes with PDR.

Aberrant expression of the SRY-related HMG-box (SOX) genes contributes to tumor development and progression. This research aimed to identify the regulation of the SOX genes in stomach adenocarcinoma (STAD). Expression profiles downloaded from The Cancer Genome Atlas (TCGA) were conducted to analyze the expression and function of the SOX genes. A competing endogenous RNAs (ceRNA) network mediated by the SOX genes was effectively constructed consisting of 64 lncRNAs, 29 miRNAs, and 11 SOX genes based on predicted miRNAs shared by lncRNAs and mRNAs using miRDB, TargetScan, miRTarBase, miRcode, and starBase v2.0. SOX9 was identified as a prognostic signature, which showed the usefulness of diagnosis and prognosis of STAD by the receiver operating characteristic (ROC) and Kaplan-Meier curves. SOX9 was also shown specifically in STAD and identified as highly expressed in the gastrointestinal tract. Gene Ontology (GO) enrichment analysis showed that SOX9 might influence the genes related to the pattern specification process, sodium ion homeostasis, and potassium ion transport, mainly including FEZF1, HOXC13, HOXC10, HOXC9, HOXA11, DPP6, ATP4B, CASQ2, KCNA1, ATP4A, and SFRP1. Furthermore, HOTAIR knockdown, miR-206-mimic transfection, the Cell Count Kit-8 (CCK-8) assay were performed to verify the function of HOTAIR/miR-206/SOX9 axis, which was identified in the ceRNA network analysis. HOTAIR could induce proliferation potentially by competitively binding miR-206/SOX9 axis in STAD. These findings provide new clues with prognostic and therapeutic implications in STAD and suggest that HOTAIR/miR-206/SOX9 might be a potential new strategy for therapeutic targeting of gastric cancer.

Japanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus Flavivirus of the family Flaviviridae and has caused huge threat to public health. It is still obscure regarding the functions of stem-loop (SL) and dumbbell (DB) domains of JEV 3��� UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3��� UTR to investigate their effects on virus replication. The results showed that partial deletions within SL or DB domain had no apparent effects on virus replication in both mammalian (BHK-21) and mosquito (C6/36) cells, suggesting that they were not involved in viral host-specific replication. However, the entire SL domain deletion (��VR) significantly reduced virus replication in both cell lines, indicating the important role of the complete SL domain in virus replication. The revertant of ��VR mutant virus was obtained by serial passage in BHK-21 cells that acquired a duplication of DB domain (DB-dup) in the 3��� UTR, which greatly restored virus replication as well as the capability to produce the subgenomic flavivirus RNAs (sfRNAs). Interestingly, the DB-dup mutant virus was highly attenuated in C57BL/6 mice despite replicating similar to WT JEV. These findings demonstrate the significant roles of the duplicated structures in 3��� UTR in JEV replication and provide a novel strategy for the design of live-attenuated vaccines.

In view of the devastating impact of neonatal necrotizing enterocolitis (NEC) on newborns, the research on its intervention is particularly important. Although exosomes from human amniotic fluid stem cells (AFSC) and human breast milk (HBM) can protect against NEC, their mechanisms remain unclear. Here, we intend to compare the intervention effects of two types of exosomes on NEC mouse model and reveal their respective regulatory mechanisms. In general, both AFSC-derived exosomes (AFSC-exos) and HBM-derived exosomes (HBM- exos) can alleviate NEC- associated intestinal injury, significantly reduce NEC score, and reduce systemic and ileal inflammation and NEC related brain injury during experimental NEC. However, the mode and mechanism of action of the two sources of exosomes were not identical. In vivo, the number of ileal crypts was more significantly restored after HBM-exos intervention than AFSC-exos, and in vitro, HBM-exos preferentially inhibited the inflammatory response of intestinal epithelial cells (IECs), whereas AFSC-exos preferentially regulated the migration of IECs. Mechanistically, GO and KEGG analyses revealed the different therapeutic mechanisms of AFSC-exos and HBM-exos in NEC. Taken together, our results illustrate that AFSC-exos and HBM-exos reduce the severity of experimental NEC and intestinal damage through different mechanisms, supporting the potential of cell-free or breast milk free exosome therapy for NEC. Graphical Abstract

Neural tube defect (NTD) is the most common and severe embryopathy causing embryonic malformation and even death associated with gestational diabetes mellitus (GDM). Leu-Pro-Phe (LPF) is an antioxidative tripeptide isolated from hydrolysates of corn protein. However, the biological activity of LPF in vivo and in vitro remains unclear. This study is aimed at investigating the protective effects of tripeptide LPF against NTD in the high glucose exposure condition and delineate the underlying biological mechanism. We found that LPF alleviated NTD in the high glucose-exposed chicken embryo model. In addition, DF-1 chicken embryo fibroblast was loaded with high glucose for induction of oxidative stress and abnormal O-GlcNAcylation in vitro. LPF significantly decreased accumulation of reactive oxygen species and content of malondialdehyde in DF-1 cells but increased the ratio of reduced glutathione and oxidized glutathione in chick embryo. Oxygen radical absorbance capacity results showed that LPF itself had good free radical scavenging capacity and could enhance antioxidant activity of the cell content. Mechanistic studies suggested that the resistance of LPF to oxidative damage may be related to promotion of NRF2 expression and nuclear translocation. LPF alleviated the overall O-GlcNAcylation level of cellular proteins under high glucose conditions and restored the level of Pax3 protein. Collectively, our findings indicate that LPF peptide could act as a nutritional supplement for the protection of development of embryonic neural tube affected by GDM.

The outcome of patients with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is variable. We aim to study if baseline 18 F-FDG PET/CT has some prognostic significance in WM/LPL.Thirty-three patients with newly diagnosed WM/LPL who underwent baseline 18 F-FDG PET/CT and received active treatment thereafter were recruited in this retrospective study. Semiquantitative indices of baseline 18 F-FDG PET/CT were measured as total lesion glycolysis (TLG), metabolic tumor volume (MTV), and SUV max . The patients were followed up for at least 3 years or until reaching the endpoint, which were defined as progression-free survival (PFS) and the time to next treatment (TTNT).The overall response rate of the first-line treatment in the recruited patients was 84.8% (28/33). The 3-year PFS and overall survival rates were 56.3% and 89.3%, respectively. Patients with PFS36 months and TTNT36 months showed TLG and MTV significantly higher than those with PFS ≥36 months and TTNT ≥36 months ( P0.05). SUV max in patients with PFS36 months was significantly higher than those with PFS ≥36 months ( P = 0.033). Receiver operating characteristic analysis demonstrated that cutoff values of TLG291.28 SUVbw * mL, MTV108.78 mL, and SUV max3.16 were optimal for predicting PFS36 months. Kaplan-Meier analysis showed that TLG291.28 SUVbw * mL and MTV108.78 mL were predictive for shorter PFS ( P = 0.003) and TTNT ( P = 0.002). In multivariate analysis, TLG291.28 SUVbw * mL and MTV108.78 mL were independent predictors for shorter PFS (hazard ratio, 3.06; 95% confidence interval, 1.09-8.57; P = 0.033) and TTNT (hazard ratio, 10.01; 95% confidence interval, 2.56-39.22; P = 0.001).The metabolic indices of TLG and MTV in baseline 18 F-FDG PET/CT were independent prognostic factors to predict PFS and TTNT in patients with WM/LPL.

To produce high concentrations of hyperoside from quercetin using recombinant Escherichia coli with in situ regeneration of UDP-galactose.Sucrose synthase from Glycine max (GmSUS) was co-expressed with UDP-glucose epimerase from E. coli (GalE) in E. coli for regenerating UDP-galactose from UDP and sucrose. Glycosyltransferase from Petunia hybrida (PhUGT) was introduced to synthesize hyperoside from quercetin through the regeneration system of UDP-galactose. Co-expressing with molecular chaperones GroEL/ES successfully enhanced the catalytic efficiency of the recombinant strain, which assisted the soluble expression of PhUGT. By using a fed-batch approach, the production of hyperoside reached 863.7 mg LThe method described herein for hyperoside production can be widely applied for the synthesis of isorhamnetin-3-O-galactoside, kaempferol-3-O-galactoside and other flavonoids.

Lung cancer (LC) remains a threatening health issue worldwide. Methyltransferase-like protein 3 (METTL3) is imperative in carcinogenesis via m6A modification of microRNAs (miRNAs). This study estimated the effect of METTL3 in LC by regulating m6A methylation-mediated pri-miR-663 processing.miR-663 expression in 4 LC cell lines and normal HBE cells was determined using RT-qPCR. A549 and PC9 LC cells selected for in vitro studies were transfected with miR-663 mimics or inhibitor. Cell viability, migration, invasion, proliferation, and apoptosis were detected by CCK-8, Transwell, EdU, and flow cytometry assays. The downstream target genes and binding sites of miR-663 were predicted via Starbase database and validated by dual-luciferase assay. LC cells were delivered with oe-METTL3/sh-METTL3. Crosslinking between METTL3 and DGCR8 was verified by co-immunoprecipitation. Levels of m6A, miR-663, and pri-miR-663 were measured by m6A dot blot assay and RT-qPCR. m6A modification of pri-miR-663 was verified by Me-RIP assay. Finally, the effects of METTL3 in vivo were ascertained by tumor xenograft in nude mice.miR-663 was upregulated in LC cells, and miR-663 overexpression promoted cell proliferation, migration, invasion, and inhibited apoptosis, but miR-663 knockdown exerted the opposite effects. miR-663 repressed SOCS6 expression. SOCS6 overexpression annulled the promotion of miR-663 on LC cell growth. METTL3 bound to DGCR8, and METTL3 silencing elevated the levels of pri-miR-663 and m6A methylation-modified pri-miR-663, and suppressed miR-663 maturation and miR-663 expression. METTL3 facilitated tumor growth in mice through the miR-663/SOCS6 axis.METTL3 promotes LC progression by accelerating m6A methylation-mediated pri-miR-663 processing and repressing SOCS6.

Background. Interleukin 8 (IL-8) is a chemotactic cytokine released by various cells including leukocytes, endothelial cells, and epithelial cells. IL-8 has multiple functions in inflammation, tumour invasion, or angiogenesis. Human odontogenic cystic lesions are chronic and frequently inflamed. Tissue-derived extracellular vesicles (Ti-EVs) are widely present in various tissues and could more accurately reflect the characteristics of the primary tissue. However, the involvement of IL-8 in Ti-EVs of human odontogenic lesions is still unclear. This study aimed to explore the expression of IL-8 in Ti-EVs of human odontogenic lesions and the potential roles of Ti-EVs that carried IL-8. Methods. Fresh tissue samples of dentigerous cyst (DC, n = 5 ) and odontogenic keratocyst (OKC, n = 5 ) were collected for Ti-EVs isolation. Ti-EVs were characterised by transmission electron microscopy and nano-flow cytometry analysis. The cytokine profile of Ti-EVs was explored by cytokine antibody array. The IL-8 expression was examined by immunochemical staining in tissue of odontogenic lesions (DC, n =12; OKC, n =28). Antioxidants (N-acetyl-L-cysteine and diphenyleneiodonium) were employed to treat HaCaT cells, and the expression of IL-8 was detected by enzyme-linked immunosorbent assay. The gene expression of MMP9 was explored by quantitative real-time polymerase chain reaction in co-culture system of fibroblasts of OKC with Ti-EVs. Results. Compared with DC, the expression of IL-8 in Ti-EVs and fixed tissue specimens of OKC was markedly upregulated. The antioxidants decreased the expression level of IL-8 protein in the supernatant of HaCaT cells. The Ti-EVs treatment (10 μg/ml) of fibroblasts significantly induced the MMP9 mRNA expressions in OKC fibroblasts. Conclusions. IL-8 was upregulated in Ti-EVs of OKC and might be involved in the tissue destruction of OKC.

The objective of this study was to explore the association between disordered vaginal microbiota and missed abortion to ascertain potential causes of missed abortion related to vaginal microbiology.This study was a prospective cohort study with a comparison group (reference group). Vaginal secretions from the posterior fornix of women in the early stages of pregnancy were collected in the Xiangya Third Hospital of Central South University in Changsha, Hunan, China, from November 2018 to November 2019. A total of 54 cases of missed abortion (case group) and 50 cases of normal pregnancy requiring induced abortion (reference group) were analyzed. Bacterial DNA was extracted, hybridized with gene-specific primers, and then detected using a bacterial chip. The composition and relative abundance of vaginal microbiota in the two groups were compared using α-diversity analysis, β-diversity analysis, and the linear discriminant analysis effect size method.The α-diversity analysis showed that the Simpson index of the case group was lower than that of the reference group, whereas the Shannon index in the case group was higher. The relative abundance of Firmicutes in the case group (42.52%) was lower than in the reference group (51.03%, p 0.05), as was the relative abundance of Lactobacillus (case group 16.51%, reference group 23.00%; p 0.05). Interestingly, levels of Mycoplasma genitalium and Ureaplasma were lower in the case group (p 0.05). The relative abundance of Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus gasseri was also significantly lower in the case group than in the reference group (p 0.05). The pathways enriched in the case group were predominantly related to metabolism, whereas the genetics-related pathways were predominantly enriched in the reference group.Bacteria are more diverse and unevenly distributed in patients with missed abortion. Decreases in the proportion of vaginal Lactobacillus and changes in Lactobacillus species in these patients may increase the chance of genital tract pathogenic bacterial infection. To our knowledge, our study was the first to observe that a decrease of Firmicutes levels in the vaginal microbiota might impair energy metabolism and have an association with missed abortion.

Disturbance of cholesterol homeostasis is considered as one of the manifestations of cancer. Cholesterol plays an essential role in the pleiotropic functions of cancer cells, including mediating membrane trafficking, intracellular signal transduction, and production of hormones and steroids. As a single transmembrane receptor, the low-density lipoprotein receptor (LDLR) can participate in intracellular cholesterol uptake and regulate cholesterol homeostasis. It has recently been found that LDLR is aberrantly expressed in a broad range of cancers, including colon cancer, prostate cancer, lung cancer, breast cancer and liver cancer. LDLR has also been found to be involved in various signaling pathways, such as the MAPK, NF-κB and PI3K/Akt signaling pathways, which affect cancer cells and their surrounding microenvironment. Moreover, LDLR may serve as an independent prognostic factor for lung cancer, breast cancer and pancreatic cancer, and is closely related to the survival of cancer patients. However, the role of LDLR in some cancers, such as prostate cancer, remains controversial. This may be due to the lack of normal feedback regulation of LDLR expression in cancer cells and the severe imbalance between LDLR-mediated cholesterol uptake and de novo biosynthesis of cholesterol.The imbalance of cholesterol homeostasis caused by abnormal LDLR expression provides new therapeutic opportunities for cancer. LDLR interferes with the occurrence and development of cancer by modulating cholesterol homeostasis and may become a novel target for the development of anti-cancer drugs. Herein, we systematically review the contribution of LDLR to cancer progression, especially its dysregulation and underlying mechanism in various malignancies. Besides, potential targeting and immunotherapeutic options are proposed.

The aim of the study was to comprehensively understand the combined hepatocellular and cholangiocarcinoma (CHC) and develop a nomogram for prognostic prediction of CHC.Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2004-2014). Propensity-score matching (PSM) was used to match the demographic characteristic of the CHC versus hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A nomogram model was established to predict the prognosis in terms of cancer specific survival (CSS). The established nomogram was externally validated by a multicenter cohort.A total of 71,756 patients enrolled in our study including 62,877 HCC patients, 566 CHC patients, and 8303 ICC patients. The CHC, HCC, and ICC are not exactly similar in clinical characteristic. After PSM, the CSS of CHC was better than HCC but comparable to ICC. Tumor size, M stage, surgery, chemotherapy, and surgery were independently prognostic factors of CHC and were included in the establishment of novel nomogram. The c-index of the novel nomogram in SEER training set and multicenter validation was 0.779 and 0.780, respectively, which indicated that the model was with better discrimination power. In addition, decision curve analyses proved the favorable potential clinical effect of the predictive model. Lastly, a risk classification based on nomogram also verified the reliability of the model.CHC had better survival than HCC but was comparable to ICC. The nomogram was established based on tumor size, M stage, chemotherapy, surgery, and radiotherapy and well validated by external multicenter cohort.

Caspase-8 (Casp8) suppresses receptor-interacting protein kinase-3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL)-dependent necroptosis, demonstrated by the genetic evidence that deletion of Ripk3 or Mlkl prevented embryonic lethality of Casp8-deficient mice. However, the detailed mechanisms by which Casp8 deficiency triggers necroptosis during embryonic development remain unclear. In this article, we show that Casp8 deletion caused formation of the RIPK1-RIPK3 necrosome in the yolk sac, leading to vascularization defects, prevented by MLKL and RIPK3 deficiency, or RIPK3 RHIM mutant (RIPK3 V448P), but not by the RIPK1 kinase-dead mutant (RIPK1 K45A). In addition, Ripk1K45A/K45ACasp8−/− mice died on embryonic day 14.5, which was delayed to embryonic day 17.5 by ablation of one allele in Ripk1 and was completely rescued by ablation of Mlkl. Our results revealed an in vivo role of RIPK3 RHIM and RIPK1K45A scaffold-mediated necroptosis in Casp8 deficiency embryonic development and suggested that the Casp8-deficient yolk sac might be implicated in identifying novel regulators as an in vivo necroptotic model.

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) with a widespread presence in drinking water that exhibit much higher cytotoxicity than regulated DBPs. However, the developmental neurotoxicity of HBQs has not been studied in vivo. In this work, we studied the neurotoxicity of HBQs on zebrafish embryos, after exposure to varying concentrations (0-8 µmol/L) of three HBQs, 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ) for 4 to 120 hr post fertilization (hpf). HBQ exposure significantly decreased the locomotor activity of larvae, accompanied by significant reduction of neurotransmitters (dopamine and γ-aminobutyric acid) and acetylcholinesterase activity. Furthermore, the expression of genes involved in neuronal morphogenesis (gfap, α1-tubulin, mbp, and syn-2α) were downregulated by 4.4-, 5.2-, 3.0-, and 4.5-fold in the 5 µmol/L 2,5-DCBQ group and 2.0-, 1.6-, 2.1-, and 2.3-fold in the 5 µmol/L 2,5-DBBQ group, respectively. Transcriptomic analysis revealed that HBQ exposure affected the signaling pathways of neural development. This study demonstrates the significant neurotoxicity of HBQs in embryonic zebrafish and provides molecular evidence for understanding the potential mechanisms of HBQ neurotoxicity.

Health care workers treating coronavirus disease 2019 (COVID-19) patients experience burnout and stress due to overwork and poor working conditions.To investigate the work experiences of frontline health care workers in Wuhan city and Qinghai province, China, during the COVID-19 outbreak.In this cross-sectional descriptive study, a self-reported questionnaire was designed to evaluate work experiences of medical staff throughout the course of the COVID-19 pandemic. A total of 178 health care workers responded to the questionnaire between February 19 and 29, 2020. Higher questionnaire dimen-sional score confirmed dimensional advantage.Of all dimensions evaluated by this questionnaire, the occupational value dimension had the highest mean score of 2.61 (0.59), followed by the support/security dimension score of 2.30 (0.74). Occupational protection scored lowest at 1.44 (0.75), followed by work environment at 1.97 (0.81). The social relationships dimension had an intermediate score of 2.06 (0.80). Significant differences in working conditions were observed across hospital departments, with the fever ward scoring lowest. Total scores also differed significantly across workplaces; the fever outpatient department scored lowest (Medical staff treating COVID-19 patients in China report poor occupational experiences strongly affected by work environment, occupational protection and social relationships. Health care managers must address the occupational needs of medical staff by ensuring a supportive and safe work environment.

Background and objective: Teaching is widely recognized as a highly stressful profession. Job stress leads to emotional exhaustion, which in turn triggers teacher attrition. The cost is estimated as USD 2.2 billion annually for teacher dropouts. It is therefore important to understand the mental state of teachers and the factors that may influence it in order to provide the appropriate early intervention. In the past, more attention has been paid to the mental status of teachers in economically developed cities, but less research has been conducted in remote cities. In this study, we selected primary and secondary school teachers in a typical area to assess their mental health, thereby contributing to the development of effective mental health education programs for teachers in primary and secondary schools. Materials and methods: In this study, 1102 teachers from a typical city in Ningxia Province, characterized by remote mountain areas, minority communities, and a low economic level, participated. The mental status of the teachers was assessed by a Symptom Checklist-90 (SCL-90). The effects of gender, age, level of education, place of work, and marital status on the total SCL-90 score were recorded and compared. The subscale scores of the SCL-90 and the differences among the respondents with various characteristics were analyzed. Results: In total, 1025 data were valid and used for statistical analysis. The effective rate of this study was 93.01%. The analysis showed that 25.17% of the subjects had possible mental problems. There were significant differences in age and marital status (p < 0.001). The score of teachers less than 30 years old was lower than that of other teachers (p = 0.001 vs. 30–39; p < 0.001 vs. 40–49; p < 0.001 vs. ≥50). The no-marriage teachers had the lowest score than the married group or others (p < 0.001 vs. married; p < 0.05 vs. others). Compared to the norm, teachers’ mental status was poor, especially in somatization (p < 0.001), obsessive-compulsive symptoms (p < 0.001), depression (p < 0.001), anxiety (p < 0.001), hostility (p < 0.001), phobic anxiety (p < 0.001), and psychosis (p < 0.001). There were gender differences in obsessive-compulsive symptoms (p < 0.05) and depression (p < 0.05). Conclusions: These data indicate that the mental status of these teachers is not optimistic, and married female teachers aged 40–55 years need to be given more attention. Mental health examinations can be incorporated into daily physical examination items to facilitate the timely detection and early intervention of negative emotions.

ObjectivesThis review aimed to summarize the recent literature on positive-pressure extubation.DesignA scoping review was conducted under the framework of the Joanna Briggs Institute.Data sourcesWeb of Science, PubMed, Ovid, Cumulative Index to Nursing & Allied Health, EBSCO, Cochrane Library, Wan Fang Data, China National Knowledge Infrastructure, and China Biology Medicine databases were searched for studies on adults and children.Study selectionAll articles describing the use of positive-pressure extubation were considered eligible for inclusion. The exclusion criteria were articles not available in English or Chinese, and those without full text available.Data extraction and synthesisThe database searches identified 8,381 articles, 15 of which could be included in this review, with an aggregated patient number of 1,544. Vital signs, including mean arterial pressure, heart rate, R-R interval, and SpO2 before and after extubation; blood gas analysis indexes, including pH, oxygen saturation, PaO2, and PaCO2 before and after extubation; and incidence of respiratory complications, including bronchospasm, laryngeal edema, aspiration atelectasis, hypoxemia, and hypercapnia, were reported in the included studies.ResultsThe majority of these studies reported that the positive-pressure extubation technique can maintain stable vital signs and blood gas analysis indices as well as prevent complications during the peri-extubation period.ConclusionsThe positive-pressure extubation technique has a safety performance similar to that of the traditional negative-pressure extubation technique and may lead to better clinical outcomes, including stable vital signs, arterial blood gas analysis, and a lower incidence of respiratory complications.

A novel bacterial strain, CDC141T, was isolated from sputum samples of a patient with pulmonary infection in Hainan Province, PR China. We performed a polyphasic study to assess the taxonomic position of the new species. Based on the results of 16S rRNA gene sequence analyses, strain CDC141T belonged to the genus Nocardia with the highest sequence similarity to Nocardia nova NBRC 15556T (98.84 %) and Nocardia macrotermiti s RB20T (98.54 %). The dapb1 gene sequence-based phylogenetic and phylogenomic trees further showed that the novel strain was clustered in a distinct clade adjacent to Nocardia pseudobrasiliensis DSM 44290T. The DNA G+C content of strain CDC141T was 68.57 mol%. The genomic diversity analysis revealed low average nucleotide identity and in silico DNA‒DNA hybridization values (T were C16 : 0, C18 : 0 10-methyl, TBSA, C16 : 1 ω6c/C16 : 1 ω7c, C18 : 1 ω9c, C18 : 0, C17 : 1 iso I/anteiso B and C17 : 0. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, unidentified glycolipids, unidentified phospholipids and unidentified lipids. MK8 (H4ω-cycl) and MK8 (H4) were the major respiratory quinones. These characteristics were consistent with the typical chemotaxonomic properties of members of the genus Nocardia . Based on the results of phenotypic and genetic analyses, strain CDC141T was identified as representing a new species of the genus Nocardia , with the proposed name Nocardia pulmonis sp. nov. (CDC141T=JCM 34955T=GDMCC 4.207T).

In this experiment, a high-fat diet was used to induce hyperlipidemia in mice to determine the synergistic effect of AX and L. fermentum HFY06 on the prevention of hyperlipidemia and its potential regulatory mechanism. The results of this study showed that after the AX and L. fermentum HFY06 synergistic intervention, the body weight, epididymal fat index, blood lipid level, and liver function indexes of mice were improved. In addition, the synbiotics comprising AX and L. fermentum HFY06 increased the CAT activity in the serum of mice on a high-fat diet, reduced NO and MDA levels, and improved the body’s oxidative stress. From the perspective of molecular biology, on the one hand, AX and L. fermentum HFY06 synergistic intervention activated the AMPK pathway to regulate body lipid metabolism; up-regulated the mRNA expressions of CPT-1, PPAR-α, CYP7A1, and HSL; and down-regulated the mRNA expressions of ACC, C/EBPα, and LPL. On the other hand, the synergistic effect of AX and HFY06 enhanced the mRNA expressions of ZO-1, occludin, and claudin-1 in the small intestine of mice, increased the strength of the intestinal barrier, and optimized the composition of the intestinal microbiota. From the above results, it can be concluded that AX and L. fermentum HFY06 have a synergistic effect in improving hyperlipidemia. However, this study was only performed using animal models, and the lipid synthesis and metabolism mechanism are complicated; hence, further clinical studies are needed.

The Wisconsin upper respiratory symptom survey (WURSS) is a validated English questionnaire to evaluate the quality of life and severity of upper respiratory tract infections (URTIs). We aimed to develop a Mandarin Chinese version of WURSS-24 (WURSS-24-C) and evaluate its reliability, validity and minimal important difference (MID). The WURSS-24-C was developed using the forward-backward translation procedure. People with URTIs’ symptoms within 48 h of onset were recruited and asked to fill in the WURSS-24-C daily for up to 14 d. Exploratory and confirmatory factor analyses were used to suggest domains. The 8-Item Short Form Health Survey (SF-8) assessing general mental and physical health was used to assess validity. Reliability estimated by Cronbach’s alpha and mean day-to-day change for those indicating minimal improvement as MID were evaluated. The WURSS-24-C was found to be acceptable, relevant, and easy to complete in cognitive debriefing interviews. A total number of 300 participants (age 28.4 ± 9.3, female 70%) were monitored for 2500 person-days. Four domains (activity and function, systemic symptoms, nasal symptoms and throat symptoms) of the WURSS-24-C were confirmed (comparative fit index [CFI] = 0.93). The reliability of this 4-domain-structure is good (Cronbach’s alphas varied from 0.849 to 0.943). Convergent validity is moderate (Pearson correlation coefficients between daily WURSS-24-C and the SF-8 were −0.780 and −0.721, for the SF-8 physical and mental health, respectively). Estimates of MID for individual items varied from −0.41 to −1.14. The WURSS-24-C is a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese-speaking patients with URTIs.Key messagesThe Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs).The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs.The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs. The Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs). The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs. The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs.

The biological mechanisms linking diet-related obesity and autistic behaviors remain unclear. Metformin has proven to be beneficial in the treatment of many syndromes, including autism spectrum disorder. Therefore, the aim of this study was to assess whether metformin treatment could ameliorate metabolic and behavioral alterations in C57BL/6 mice kept on a high-fat diet (HFD), and whether these changes were related to modifications in the gut microbiota and 5-HT levels. As expected, ten weeks of HFD ingestion increased body weight, adiposity, and glucose levels. HFD-fed mice showed a marked aggravation of repetitive behaviors (marble burying and self-grooming), and this was prevented by metformin administration. In addition, HFD-fed mice increased the total distance travelled in the open field test. This hyperactivity was counteracted by metformin cotreatment. In the elevated plus maze test, HFD-fed mice showed a reduced number of entries into the open arms. Interestingly, both HFD and metformin cotreatment increased social interactions in the three-chamber test. HFD increased the levels of intestinal tryptophan and 5-hydroxyindoleacetic acid. Metformin stimulated gut tryptophan and promoted the synthesis of 5-HT in the HFD group. Lactococcus, Trichococcus, Romboutsia, and Faecalibaculum were enriched in HFD-fed mice, whereas the HFD group cotreated with metformin was enriched in Intestinimonas and L. reuteri. Faecalibacterium was positively correlated with sociability and 5-HT pathway components in mice that received metformin. In summary, HFD consumption elicited a complex phenotype comprising higher levels of anxiety-like and repetitive behaviors but also increased sociability. Metformin could potentially improve HFD-induced disorders in the autistic spectrum through a mechanism involving positive modulation of 5-HT levels in the gut and its microbiota composition.