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Objective: To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns. Methods: This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing. Results: Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P <0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P <0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group ( Z =-4.67, P <0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P <0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P <0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ 2 values of 4.13 and 3.91, respectively, P <0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups ( P >0.05). Conclusions: For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.

Objective: To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism., Methods: Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang , spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang -medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively., Results: The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang . In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells., Conclusion: Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Objective: To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network. Methods: Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia. Results: The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension ( OR =3.99, 95% CI : 1.81-8.80), diabetes ( OR =4.64, 95% CI : 1.64-13.15) and dyslipidemia ( OR =4.26, 95% CI : 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions: The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.

The objective was to evaluate the efficacy of curcumin in improving mouth opening (MO), burning sensation (BS), and tongue protrusion (TP) symptoms in patients with oral submucous fibrosis (OSF). An electronic search up to November 2022 was conducted in the PubMed, Web of Science, Embase, EBSCO, ProQuest, and Cochrane Library databases to identify studies using curcumin in the treatment of OSF with comparison to control groups (drugs previously proven to be effective for OSF treatment) or placebo. Only randomized controlled trials (RCTs) were considered. RevMan 5.3 software was used for the meta-analysis. Thirteen RCTs met the eligibility criteria and were included in the analysis. The results showed no significant improvement in MO (in millimetres) for curcumin when compared to control at 1 month (P = 0.91), 2 months (P = 0.54), 3 months (P = 0.56), or 6 months (P = 0.17) of treatment. There was no significant difference in BS (assessed using a visual analogue scale) between curcumin and control after 1 month (P = 0.05), 2 months (P = 0.64), 3 months (P = 0.13), or 6 months (P = 0.56) of treatment. Compared with the control groups, treatment with curcumin for 1 month (P = 0.32), 2 months (P = 0.07), and 3 months (P = 0.14) did not significantly improve the TP (in millimetres) of patients. The administration of curcumin, whether topically applied or taken orally, did not confer statistically significant improvements in MO, BS, or TP in comparison to the control treatments, among patients with OSF. The results of this meta-analysis showed that compared to placebo, the application of curcumin for 6 months markedly alleviated BS (P < 0.001). Curcumin treatment in OSF reaches a clinically effective range, but more bioavailability-centred outcomes should be reported. Robust multicentre RCTs are warranted to elucidate the efficacy of curcumin in improving specific outcomes like MO, BS, and TP in patients with this condition. Defining the therapeutic role of this natural compound may provide an effective botanical alternative for managing OSF., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of allogeneic nanofat combined with platelet-rich plasma (PRP) for treatment of pressure injury wounds in rats., Methods: Forty SD rat models with pressure injury wounds were randomly divided into 4 groups ( n =10) for treatment with nanofat, PRP (platelet count about 6.2 times that of normal whole blood), nanofat combined with PRP, or PBS only (control group).Wound healing was observed on days 1, 3, 5, 7, 10 and 14 and wound healing rate was calculated. On days 5, 10 and 14, tissue samples were taken from the wounds for HE staining, Masson staining, immunohistochemistry, and Western blotting to observe inflammatory cell infiltration, collagen formation, deposition and arrangement, angiogenesis, inflammatory factor expression and VEGF expression in the wounds., Results: The combined treatment with nanofat and PRP achieved the highest wound healing rates at all the time points of observation ( P < 0.05), enhanced inflammatory cell infiltration on day 5, and accelerated dermal and epidermal growth compared with the other treatments ( P < 0.05). The combined treatment also more effectively promoted collagen expression and its regular arrangement ( P < 0.05) and enhanced angiogenesis in the wounds than nanofat and PRP alone, without significant difference between the latter two treatments ( P > 0.05). Immunohistochemistry and Western blotting showed that the expressions of MCP-1 and VEGF in the wounds were the highest in the combined treatment group ( P < 0.05) and were higher in nanofat and PRP treatment groups than in the control group ( P < 0.05)., Conclusion: Nanofat combined with PRP can significantly promote healing of pressure injury wounds in rats, and their synergistic effect sheds light on a new strategy for treatment of pressure injury wounds.

Objective: To evaluate the efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi. Methods: From May 2021 to July 2022, patients diagnosed with urinary calculi were screened in four medical centers. Those who met the criteria were treated with superpulse thulium fiber laser under endoscope. The patients' perioperative conditions were recorded. The main effective index was stone-free rate (SFR) 4 weeks after operation, the main safety index was the failure rate of the experimental instruments during operation, and the secondary safety index was the incidence rate of perioperative complications. Results: A total of 76 eligible patients completed superpulse thulium fiber laser lithotripsy, with an average age of (52.0±11.1) years, 54 males and 22 females. There were 31 renal stones, 43 ureteral stones and 2 bladder stones. Percutaneous nephrolithotomy was performed in 17 patients. Ureteroscopy lithotripsy/flexible ureteroscopy lithotripsy was performed in 57 patients and transurethral bladder lithotripsy was in 2 patients. The lithotripsy time of all patients was (50.9±31.4) minutes. There was no failure of experimental instruments during the operation. Six patients refused follow-up examination after operation. The incidence of postoperative adverse events was 61.8% (47/76). One patient needed hospitalization due to inguinal hernia after operation, and the rest were classified as Clavien-dindo grade 1-2. The SFR was 94.3% (66/70) at 4 weeks after operation. Conclusion: It is effective and safe to use superpulse thulium fiber laser in the treatment of urinary calculi.

Background: The search for prognostic biomarkers indicating sensitivity to immunotherapy in lung adenocarcinoma patients has zeroed in on genes in the switch/sucrose non-fermentable (SWI/SNF) pathway. The mutational profiles of key genes are not clearly defined, however, and no comparisons have been conducted on whether mutations in the genes involved provide the same predictive value., Methods: In this study, analysis of clinical factors, tumor mutation burden (TMB), chromosomal instability, and co-alterations was conducted for 4344 lung adenocarcinoma samples. Independent online cohorts (N = 1661 and 576) were used to supplement the analysis with survival and RNA-seq data., Results: Mutational burden and chromosomal instability analysis showed that ARID family mutations (including ARID1A, ARID1B, or ARID2 mutations) and SMARC family mutations (including SMARCA4 or SMARCB1 mutations) display different profiles from wild-type (WT) samples (TMB: ARID versus WT: P < 2.2 × 10 -16 , SMARC versus WT: P < 2.2 × 10 -16 ; CIN: ARID versus WT: P = 1.8 × 10 -5 , SMARC versus WT: P = 0.027). Both mutant groups have a higher proportion of transversions than transitions, whereas the ratio is more equal for wild-type samples. Survival analysis shows that patients with ARID mutations were more sensitive to immunotherapy treatment than wild-type and SMARC-mutated patients (P < 0.001 and P = 0.013, respectively), and multivariate Cox analysis reveals that the presence of ARID mutations is likely the main cause., Conclusions: The research presented in this study shows that mutations in the ARID gene family, including ARID1A, ARID1B, and ARID2, are primarily responsible for the sensitive response to immunotherapy treatment in patients with lung adenocarcinoma., Competing Interests: Disclosure HT, HB, XW, YS are employees of Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest. Data Sharing The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. The data retrieved for the online validation section can be found on www.cbioportal.org and GDC Data Portal (https://portal.gdc.cancer.gov/)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Corona Virus Disease 2019 (COVID-19) has caused several pandemic peaks worldwide due to its high variability and infectiousness, and COVID-19 has become a long-standing global public health problem. There is growing evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) frequently causes multi-organ injuries and more severe neurological manifestations. Therefore, increased awareness of possible neurological complications is beneficial in preventing and mitigating the impact of long-term sequelae and improving the prognostic outcome of critically ill patients with COVID-19. Here, we review the main pathways of SARS-CoV-2 neuroinvasion and the potential mechanisms causing neurological damage. We also discuss in detail neurological complications, aiming to provide cutting-edge basis for subsequent related basic research and clinical studies of diagnosis and treatment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We visualized negative refraction of phonon polaritons, which occurs at the interface between two natural crystals. The polaritons-hybrids of infrared photons and lattice vibrations-form collimated rays that display negative refraction when passing through a planar interface between the two hyperbolic van der Waals materials: molybdenum oxide (MoO 3 ) and isotopically pure hexagonal boron nitride (h 11 BN). At a special frequency ω 0 , these rays can circulate along closed diamond-shaped trajectories. We have shown that polariton eigenmodes display regions of both positive and negative dispersion interrupted by multiple gaps that result from polaritonic-level repulsion and strong coupling.

Rhegmatogenous retinal detachment (RRD) is a retinal vitreous disease, with increasing incidence in recent years. Pars plana vitrectomy is one of the most common treatments for RRD. To prevent re-detachment after the primary surgery and guarantee the visual outcome of the patients, we highlight the techniques for RRD during the PPV, including the surgical skills to manipulate the breaks, peripheral retina and vitreous base, meanwhile, empathized on the posterior vitreous detachment and posterior vitreous cortex. The aim is to increase the rate of anatomical re-attachment and to improve visual function.

Background: We evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients., Design: Patients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/m 2 or cisplatin 40 mg/m 2 concurrently., Results: One hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness., Conclusions: Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the correlation of MYB proto-oncogene like 2 (MYBL2) with biological behaviors and clinical prognosis of prostate cancer (PCa)., Methods: We detected Mybl2 mRNA expression in 45 pairs of PCa and adjacent tissues using real-time quantitative PCR, and analyzed the correlation of high (23 cases) and low expression (22 cases) of Mybl2 with clinicopathological features and prognosis of the patients using nonparametric test, Kaplan-Meier survival analysis and univariate and multivariate Cox regression. The results were verified by analysis of the data from Cancer Genome Atlas (TCGA) microarray database, and the molecular pathways were identified by gene set enrichment analysis (GSEA). The CIBERPORT algorithm was used to identify the correlations between Mybl2 expression and tumor microenvironment of PCa. We also tested the effects of MYBL2 knockdown on proliferation and invasion of PCa cell lines using cell counting kit-8 and Transwell assays and observed the growth of PC3 cell xenograft with MYBL2 knockdown in nude mice and the expression levels of Ki-67 in the xenograft using immunohistochemistry., Results: Mybl2 expression was significantly elevated in PCa tissues in close correlation with Gleason score and clinical and pathological stage of the tumor ( P < 0.01) but not with the patients' age. Kaplan-Meier analysis indicated a significant negative correlation of high Mybl2 expression with recurrence-free survival ( P < 0.05), but not with the overall survival of the patients. The data from TCGA suggested that clinical and pathological stages were independent prognostic factors for recurrence-free survival, and our data indicated that clinical stage and Gleason score were independent prognostic factors of PCa ( P < 0.05). GSEA suggested that Mybl2 expression was related with the pathways involving immune function, cell adhesion, and cytokine secretion; CIBERPORT analysis suggested the involvement of Mybl2 expression with memory B cells and resting mast cells ( P < 0.05). In LNCaP and PC-3 cells, MYBL2 knockdown significantly inhibited cell proliferation and invasion ( P < 0.05); in the tumor-bearing nude mice, the xenografts derived from PC-3 cells with MYBL2 knockdown exhibited a lowered mean tumor weight and positivity rate for Ki67 ( P < 0.05)., Conclusion: Mybl2 is an oncogene related with multiple pathological indicators of PCa and can serve as a potential prognostic marker as well as a therapeutic target for patients with PCa.

A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.

This study aims to investigate the effect of resveratrol on intrahepatic cholestasis of pregnancy (ICP) and its effect on the gut microbiome profiles, thus contributing to the potential therapeutic strategies for ICP. ICP rat models were established by injecting 17α-ethinylestradiol (EE) subcutaneously from the thirteenth day of gestation for four days and then treated with EE (D group, n=5), resveratrol (R group, n=5), or ursodeoxycholic acid (UDCA; U group, n=5) from the seventeenth to the twentieth day of gestation. Fecal samples were analyzed with 16S ribosomal RNA (rRNA) sequencing. In results: the gut microbiota of pregnant rats was characterized with reduced alpha diversity (Chao1 index), and significant variation in the microbiota structure (ANOSIM) was also observed after being treated with EE. The richness of four phyla and ten genera was upregulated, and five phyla and ten genera were downregulated by EE treatment. The dysbiosis of Bilophila, Ruminococcus, and Actinobacteria caused by EE treatment was reversed by resveratrol administration. There was a correlation between total bile acid and alanine aminotransferase in ICP rats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results suggested that the secondary bile acid biosynthesis was decreased, and the alanine, aspartate, and glutamate metabolism was increased after being treated with EE in pregnant rats. In conclusion, EE treatment could lead to gut microbiome dysbiosis and bile acid metabolism dysregulation in pregnant rats. Resveratrol could partially rescue gut microbiota dysbiosis and improve the biochemical characteristics caused by EE treatment.

Competing Interests: None to declare.

Background: Sequential treatment with different generations of anaplastic lymphoma kinase (ALK) inhibitors have been widely applied to ALK-positive lung cancer; however, resistance mutations inevitably developed. Further characterization of ALK resistance mutations may provide key guidance to subsequent therapies. Here we explored the emergence of secondary ALK mutations during sequential ALK tyrosine kinase inhibitor (TKI) treatment in a real-world study of Chinese lung adenocarcinoma (ADC) patients., Methods: A clinical-genomic database was queried for lung ADC patients with at least one ALK inhibitor treatment and at least one plasma sample collected following ALK inhibitor treatment. Targeted genome profiling was performed with a 139-gene panel in baseline tumor tissue and serial plasma samples of patients., Results: A total of 116 patients met inclusion criteria. ALK G1202R was more common in patients with echinoderm microtubule-associated protein-like 4 (EML4)-ALK v3 fusion, whereas ALK L1196M was more common in v1. TP53 mutant patients were significantly associated with harboring multiple ALK resistance mutations (P = 0.03) and v3+/TP53 mutant patients had the highest rate of multiple ALK resistance mutations. The sequential use of ALK TKI led to an increased incidence of concurrent ALK mutations along the lines of therapies. Alectinib had a lower rate (9%) harboring ALK resistance mutation as first-line ALK TKI compared with crizotinib (36%). ALK compound mutations identified included ALK D1203N/L1196M, ALK G1202R/L1196M, and ALK G1202R/F1174C, which may be lorlatinib resistant. Using paired pretreatment and post-treatment samples, we identified several ALK-independent resistance-related genetic alterations, including PTPRD and CNKN2A/B loss, MYC, MYCN and KRAS amplification, and EGFR 19del ., Conclusions: Sequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making., Competing Interests: Disclosure XC, RY, HB, JL, XW, and YS are employees of Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) has become a promising surrogate for genomic profiling of central nervous system tumors. However, suboptimal ctDNA detection rates from CSF limit its clinical utility. Thus precise screening of suitable patients is needed to maximize the clinical benefit., Patients and Methods: Between February 2017 and December 2020, 66 newly diagnosed non-small-cell lung cancer (NSCLC) patients with brain parenchymal metastases were prospectively enrolled as a training cohort and 30 additional patients were enrolled as an external validation cohort. CSF samples and matched primary tumor tissues were collected before treatment and subjected to next-generation sequencing (NGS). The imageological characteristics of patients' brain tumors were evaluated by radiologists using enhanced magnetic resonance imaging images. The clinical and imageological characteristics were evaluated by complete subsets regression, Akaike information criteria, and Bayesian information criteria methods to establish the prediction model. A nomogram was then built for CSF ctDNA detection prediction., Results: The somatic mutation detection rate of genes covered by our targeted NGS panel was significantly lower in CSF ctDNA (59.09%) than tumor tissue (91.84%). The T size (diameter of the largest intracranial lesion) and LVD min (minimum lesion-ventricle distance for all intracranial lesions) were significantly associated with positive CSF ctDNA detection, and thus, were selected to establish the prediction model, which achieved an area under the ROC curve (AUC) of 0.819 and an accuracy of 0.800. The model's predictive ability was further validated in the independent external cohort (AUC of 0.772, accuracy of 0.767) and by internal cross-validation. The CSF ctDNA detection rate was significantly improved from 58.18% (32/55) to 81.81% (27/33) in patients after model selection (P = 0.022)., Conclusions: This study developed a regression model to predict the probability of detecting CSF ctDNA using the phenotypic characteristics of metastatic brain lesions in NSCLC patients, thus, maximizing the benefits of CSF liquid biopsies., Competing Interests: Disclosure YM and YS are employees of Nanjing Geneseeq Technology Inc. The other authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diabetic retinopathy is one of the three major microvascular complications of diabetes. Proliferative diabetic retinopathy (PDR) is an important ocular complication that affects the vision and quality of life of patients. Vitrectomy is the most effective treatment option. The characteristic of fibrovascular membranes in PDR varies at different stages of the disease, which requires specific treatment strategy and techniques. In order to improve the clinical diagnosis and treatment of PDR, this article proposes that different treatment methods should be correctly adopted for different types of proliferative membranes on the basis of fully understanding the tissue morphology of these membranes, and more attention should be paid to the treatment of the vitreous body to achieve more effective therapeutic effects. (Chin J Ophthalmol, 2021, 57: 881-885) .

Twisted two-dimensional van der Waals (vdW) heterostructures have unlocked a new means for manipulating the properties of quantum materials. The resulting mesoscopic moiré superlattices are accessible to a wide variety of scanning probes. To date, spatially-resolved techniques have prioritized electronic structure visualization, with lattice response experiments only in their infancy. Here, we therefore investigate lattice dynamics in twisted layers of hexagonal boron nitride (hBN), formed by a minute twist angle between two hBN monolayers assembled on a graphite substrate. Nano-infrared (nano-IR) spectroscopy reveals systematic variations of the in-plane optical phonon frequencies amongst the triangular domains and domain walls in the hBN moiré superlattices. Our first-principles calculations unveil a local and stacking-dependent interaction with the underlying graphite, prompting symmetry-breaking between the otherwise identical neighboring moiré domains of twisted hBN., (© 2021. The Author(s).)

Objective: To investigate the impact of non-alcoholic fatty liver disease (NAFLD) on the incidence of type 2 diabetes mellitus (T2DM) in an elderly population. Methods: A rural elderly population of Kunshan city, Jiangsu Province were used as the research subject. Prior diabetes mellitus, heavy alcohol consumption and incomplete data were excluded from prospective cohort study analysis. Annual physical examination and follow-up were conducted from 2007 to 2016. T2DM onset, death and loss to follow-up visits were observed as the research subject end points. According to the baseline physical examination results, the study subjects were divided into NAFLD and control groups, and further baseline data of both groups were analyzed whether there were match. The cumulative incidence rate of T2DM were statistically analyzed and compared between the two groups. Simultaneously, the relationship between the two groups of various indexes and the newly developed T2DM were analyzed using Kaplan-Meier. The variables with P < 0.1 were selected and incorporated into the Cox proportional hazard regression model. The impact of NAFLD on the incidence of T2DM was analyzed in an elderly population. Results: At baseline, there were statistically significant differences in the distribution of age, sex, waist circumference, body mass index, systolic blood pressure, diastolic blood pressure, direct bilirubin, blood urea nitrogen and triglycerides between NAFLD and non-NAFLD groups. However, fasting blood glucose, serum creatinine, total bilirubin, total cholesterol, low density lipoprotein cholesterol and high-density lipoprotein cholesterol had no statistically significant differences between the two groups. After nine years of follow-up, 207 newly developed T2DM cases, 52 NAFLD cases and 155 control group were selected as the study subjects. The cumulative incidence rates were 4.25%, 10.34%, and 3.55%, respectively. Kaplan-Meier analysis result showed that there were statistically significant differences in the cumulative incidence rates between the two groups from five-year. NAFLD had increased the T2DM risk in an elderly population by approximately 2.14 times (2.14 CI : 1.132 ~ 4.047) at five-year, and then had increased year by year thereafter. Univariate analysis showed that T2DM risk was 2.76 times higher in NAFLD than non-NAFLD groups (95% CI : 2.015 ~ 3.777). After adjustment for gender, age, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, serum creatinine, triglyceride, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, T2DM risk ratio was 1.68 times higher in NAFLD than control groups (95% CI : 1.163 ~ 2.425). Conclusion: NAFLD is an independent long-term risk factor for the T2DM onset in an elderly population.

Objectives: To investigate the clinicopathological and prognostic significance of International Endocervical Adenocarcinoma Criteria and Classification (IECC) in classifying endocervical adenocarcinomas among Chinese women. Methods: A total of 286 endocervical adenocarcinomas diagnosed from January 2013 to December 2019 at the Women's Hospital, Zhejiang University School of Medicine were identified and included. The cases were reviewed and reclassified based on IECC. The histological types were correlated with p16 immunostaining, human papilloma virus (HPV) mRNA status, the clinicopathological parameters including the International Federation of Gynecologic Oncology (FIGO) stage, and clinical follow-up data. Results: The patients aged from 19 to 77 (median 47) years. There were 223 patients at FIGO stage Ⅰ, 22 at stage Ⅱ, 38 at stage Ⅲ and 3 at stage Ⅳ. The IECC types included 213 (74.5%) HPV-related adenocarcinomas (HPVA), 60 (21%) non-HPV-related adenocarcinomas (NHPVA), and 13 (4.5%) adenocarcinomas, no other specified (NOS). The major histological subtypes in HPVA and NHPVA were common type ( n =156, 54.5%) and gastric type (GAC, n =46, 15.9%), respectively. The p16 positive rates in HPVA, NHPVA and adenocarcinoma, NOS were 92% (173/188), 26.6% (17/64) and 61.5% (8/13), respectively, and those of HPV mRNA hybridization in situ were 89.4% (144/161), 0/18 and 7/13, respectively. Compared to HPVA, NHPVA was more frequently associated with older age, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression ( P <0.05). Univariate survival analysis showed that age (>47 years), NHPVA, GAC, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression were indicators for a poorer overall survival and tumor recurrence ( P <0.05). Mucinous HPVA showed worse clinical outcomes compared to usual-type HPVA ( P <0.01). Multivariate survival analysis demonstrated that FIGO stage Ⅱ-Ⅳ, NHPVA and aberrant p53 expression were independent indicators for poor overall survival while FIGO stage Ⅱ-Ⅳ and GAC were independently associated with tumor recurrence ( P <0.05). Conclusions: The two broad IECC categories, HPVA and NHPVA, not only provide morphological links to the etiology (HPV infection), but also have significant clinicopathological and prognostic relevance.

Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case ( P >0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations ( P >0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.

Escherichia coli is a symbiotic bacterium in humans and animals and an important pathogen of humans and animals. Prevention and suppression of E. coli infection is of great concern. In this study, we isolated a strain of Lactobacillus agilis 32 from pig manure and evaluated its biological characteristics, and found that its bacterial survival rate was 25% after 4 h of treatment at pH 2, and under the condition of 0·5% bile concentration, its survival rate exceeds 30%. In addition, L. agilis 32 has a cell surface hydrophobicity of 77·8%, and exhibits 67·1% auto-aggregation and 63·2% aggregation with Enterotoxigenic E. coli 10 (ETEC 10). FITC fluorescence labelling showed that the fluorescence intensity of cecum was significantly higher than that of duodenum, jejunum or colon (P < 0·05), but no significant difference from ileum. Lactobacillus agilis 32 bacterial culture and CFS showed average inhibition zone diameters of 14·2 and 15·4 mm respectively. Lactobacillus agilis 32 CFS treatment can significantly reduce the pathogenicity of ETEC 10. These results show that L. agilis 32 is an active and potential probiotic, and it has a good antibacterial effect on ETEC10, which provides basic research for probiotics to prevent and treat intestinal diarrhoea pathogen infection., (© 2020 The Society for Applied Microbiology.)

Objective: To explore the biomechanical mechanism of blunt spleen injury based on finite element analysis., Objective: A fist finite element model was used to simulate the impact at 4-8 m/s in the spleen area of THUMS4.0 human body model from the front of the left costal area, the left anterior axillary line and the rear scapular line. The strain distribution and damage of the spleen under different conditions were observed. The simulation results were compared with the clinical cases of spleen rupture to analyze the mechanism of spleen injury., Objective: The damage location and strain distribution of the spleen could vary under different conditions. Due to the special anatomical location of the spleen, a blunt impact at the speed of 4-8 m/s on the front side did not easily cause spleen injury, and the strain was distributed mainly in the front of the spleen and the spleen hilum; a similar blunt impact on the left side was likely to cause spleen diaphragmatic surface injury, the splenic visceral surface could be injured by the compression of the medial tissue and organs and the traction of the splenic pedicle, and the strain was distributed in the spleen diaphragmatic and visceral surfaces; an impact on the back side was likely to cause injuries in the posterior portion and hilum of the spleen, and the strain was mainly concentrated in the injured area., Objective: Blunt spleen injuries caused by punches on the abdomen are mostly caused by direct impact on the ribs, the compression by the surrounding tissues and organs and the traction by the spleen pedicle.

Collective electronic modes or lattice vibrations usually prohibit propagation of electromagnetic radiation through the bulk of common materials over a frequency range associated with these oscillations. However, this textbook tenet does not necessarily apply to layered crystals. Highly anisotropic materials often display nonintuitive optical properties and can permit propagation of subdiffractional waveguide modes, with hyperbolic dispersion, throughout their bulk. Here, we report on the observation of optically induced electronic hyperbolicity in the layered transition metal dichalcogenide tungsten diselenide (WSe 2 ). We used photoexcitation to inject electron-hole pairs in WSe 2 and then visualized, by transient nanoimaging, the hyperbolic rays that traveled along conical trajectories inside of the crystal. We establish here the signatures of programmable hyperbolic electrodynamics and assess the role of quantum transitions of excitons within the Rydberg series in the observed polaritonic response., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

In this study, we analyzed 93 whole genomes from Chinese spot-billed ducks (CSB), meat-type ducks (MET), and egg and dual purpose-type ducks (EDT) to characterize the genetic material flowing between the CSB and modern ducks. Using a frequency of shared identical-by-descent method, approximately 10.9 Mb introgression segments containing 140 genes were identified showing the signatures of introgression between CSB and EDT. Meanwhile, nearly 10.6 M introgression regions containing 149 genes were identified between CSB and MET. Based on the haplotypes tree of each segment, we found that the introgression between CSB and domesticated ducks was asymmetric with a high level of gene flow from domestic to CSB and a low level of migration in the opposite direction. Moreover, we identified several genes that were introgressions from CSB and showed the signature of positive selection, which may contribute to the breeding of modern ducks. Our results provide new insight into the evolution and breeding history of domestic ducks and may be useful for the future management of wild and domestic duck populations., (© 2020 Stichting International Foundation for Animal Genetics.)

Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population 1-3 . Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology 4 to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future.

Objectives: To investigate the seroreversion time in HIV-1-exposed but uninfected infants from two tertiary hospitals in China., Methods: This study retrospectively investigated the data of perinatal, HIV-1-exposed infants from hospitals in Beijing and Shenzhen. Maternal and infant medical records from both hospitals from January 2009 to December 2019 were reviewed, and the HIV antibody seroreversion times of infants were determined. From 2009 to 2019, a total of 485 HIV-1-exposed but uninfected infants were enrolled. The majority of infants were born at term with normal birth weight., Results: The seroreversion rates were 89.3%, 94.2% and 100% at 12, 18 and 24 months of age, respectively. There were no significant associations between seroreversion and several risk factors, such as gender, birth weight, gestational age, mode of delivery, postpartum prophylaxis and antiretroviral treatment duration. The mean value of HIV-specific immunoglobulin G concentration decreased from 15.4 at day 42 to 0.03 after 24 months in HIV-exposed, uninfected infants., Conclusions: Clearance of HIV antibodies could take more than 18 months in a small number of perinatally exposed infants. Caution should be used in excluding or diagnosing perinatal HIV infection in children with long persistence of HIV antibodies., (© 2020 British HIV Association.)

To date, skin substitute that can provide permanent wound closure is still autologous tissue-engineered skin using autologous skin cells as seed cells. The development of cultured epithelial autograft has experienced a long and tortuous process. Autologous tissue-engineered composite skin is closer to autologous split-thickness skin graft in terms of structure, function, and efficacy, which has become a research focus in recent years. Based on the actual status of research on tissue-engineered skin application, this paper reviewed the main research progresses and existing problems, and the prospect of research and development and clinical application of autologous tissue-engineered skin as permanent graft in order to provide a reference for the improvement and application of autologous tissue-engineered skin.

Objective: To evaluate the safety and immune effect of recombinant hepatitis B vaccine （CpG ODN adjuvant). Methods: On Oct. 26, 2016, we launched volunteer recruitment in Kaihua county, Quzhou city, Zhejiang Province. In the randomized, double-blind, controlled trial, a total of 48 subjects with negative HBV screening tests and normal hepatorenal function among 18 and 60 years old were selected and divided into two groups randomly, 24 cases each. The experimental group was given 250 μg of CpG ODN recombinant （Hansenula polymorpha) Hepatitis B vaccine and the control group was given 10 μg of commercial Hepatitis B vaccine with timed at 0, 1and 6 months. The inoculation reactions were compared the difference between the two groups after observed and recorded in time periods. We also collected serum before and after immunization to compare the two groups of anti-HBs positive rate, geometric mean concentration（GMC). Results: During the study period, the incidence of adverse events was 66.67%（16/24) in the experimental group and 54.17%（13/24) in the control group, with no significant difference（ P =0.556). The severities of adverse events were level 1 or level 2, and no level 3 or above adverse reactions occurred. After full-course immunization, in the FAS data set, the anti-HBs GMC in the experimental group [2 598.56（1 127.90-5 986.90) mIU/ml] was higher than that in the control group[371.97（164.54-840.91) mIU/ml] In the PPS set, the GMC of test group was 7 808.21（3 377.00-18 052.00) mIU/ml, which was higher than that of the control group [843.22（213.80-3 325.90) mIU/ml]. The anti-HBs positive rate of FAS（PPS) was 95.83%（100.00%) in the experimental group and the control group; The anti-HBs strongly positive rate of FAS（PPS) was 79.17%（90.00%) in the experimental group and 33.33%（50.00%) in the control group, with statistically significant differences among the FAS set（ P =0.003) and no statistically significance differences among the PPS set（ P =0.074). Conclusion: CpG Hepatitis B Vaccine is safe and shows better immunogenicity than the control vaccine.

The rapid growth of the coronavirus disease 2019 (COVID-19) pandemic, limited availability of personal protective equipment, and uncertainties regarding transmission modes of severe acute respiratory syndrome coronavirus-2 have heightened concerns for the safety of healthcare workers (HCWs). Systematic studies of occupational risks for COVID-19 in the context of community risks are difficult and have only recently started to be reported. Ongoing quality improvement studies in various locales and within many affected healthcare institutions are needed. A template design for small-scale quality improvement surveys is proposed. Such surveys have the potential for rapid implementation and completion, are cost-effective, impose little administrative or workforce burden, can reveal occupational risks while taking community risks into account, and can be repeated easily with short time intervals between repetitions. This article describes a template design and proposes a survey instrument that is easily modifiable to fit the particular needs of various healthcare institutions in the hope of beginning a collaborative effort to refine the design and instrument. These methods, along with data management and analytic techniques, can be widely useful and shared globally. The authors' goal is to facilitate quality improvement surveys aimed at reducing the risk of occupational infection of HCWs during the COVID-19 pandemic., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

The article "Long non-coding RNA PVT1 regulates glioma proliferation, invasion, and aerobic glycolysis via miR-140-5p, by Y. Shao, H.-T. Chen, Q.-R. Ma, Y.-W. Zhang, Y.-Q. He, J. Liu published in Eur Rev Med Pharmacol Sci 2020; 24(1): 274-283-DOI: 10.26355/eurrev&#95;202001&#95;19922-PMID: 31957841" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19922.

The article "Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy via MAPK pathway, by Y. Ma, Q. Zhao, Y. Shao, M.-Z. Cao, M. Zhao, D. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (3 Suppl): 1-8-DOI: 10.26355/eurrev&#95;201908&#95;18620-PMID: 31389568" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18620.

Abstract: Objective To study the mechanism of rib fracture caused by landing on different parts of the trunk using finite element method, and to provide some new techniques and new ideas for the reconstruction of the whole process of falls from height. Methods The finite element method was used to study the rib fracture of human security model THUMS4.0 caused by landing on different parts of the trunk. Then the model was compared with actual cases and the mechanism of rib fracture caused by falls from height was analyzed from a biomechanical point of view. Results There were some differences in the stress and strain distribution as well as the rib fracture sites when different parts touched the ground. Ribs on both sides of the body were fractured when the front of the trunk touched the ground, and the fractures were mainly located in the junction of the ribs and costal cartilage and the midaxillary line area. When the right anterior part of the trunk touched the ground, rib fracture occurred first on the side that touched the ground, and rib fractures were mainly located in the area from the right midaxillary line to the posterior axillary line, and junction of ribs on both sides and costal cartilage. When the back of the trunk touched the ground, the fracture sites were mainly located on the back of the ribs on both sides. When the right posterior part of the trunk touched the ground, multiple rib fractures were likely to occur in the parts that touched the ground. The plastic strains were mainly concentrated at the fracture sites, while the von Mises stresses were not only concentrated at the fracture sites, but also at other sites. Conclusion There are some differences in rib fracture location sites and injury mechanisms when different parts of the trunk touch the ground., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Background: Inflammatory bowel disease is a chronic immunoinflammatory disease of the gastrointestinal tract. Piperine, an alkaloid, has been reported to possess antioxidant, anti-inflammatory, antiapoptotic, and antiulcer potential., Aim: To elucidate the plausible mechanisms of action of piperine on experimental trinitrobenzenesufonic acid (TNBS)-induced colitis by assessing various biochemical, molecular, histological, and ultrastructural modifications., Methods: Colitis was induced in male Sprague-Dawley rats via intrarectal instillation of TNBS. Then, the rats were treated with piperine (10, 20, and 40 mg/kg, p.o.) for 14 days., Results: TNBS induced significant ( p < 0.05) colonic damage, which was assessed by disease activity index, macroscopic score, and stool consistency. The administration of piperine (20 and 40 mg/kg) significantly inhibited ( p < 0.05) these damages. Treatments with piperine (20 and 40 mg/kg) notably inhibited ( p < 0.05) the TNBS-induced elevation of oxido-nitrosative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), 5-hydroxytryptamine, and hydroxyproline content in the colon. Furthermore, colonic inducible nitric oxide synthase (iNOs), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma, and cyclooxygenase-2 (COX-2) messenger RNA (mRNA) expressions were upregulated after TNBS instillation and piperine (20 and 40 mg/kg) significantly attenuated ( p < 0.05) these elevated mRNA expressions. TNBS decreased the expressions of tight junction (TJ) protein (claudin-1, occludin, and zonula occludens-1 (ZO-1)) and increased the expressions of proapoptotic (caspase-1) protein. These expressions were markedly inhibited ( p < 0.05) by piperine treatment. Histological and ultrastructural studies of transmission electron microscopy suggested that piperine significantly ameliorated ( p < 0.05) TNBS-induced colonic aberrations., Conclusion: Piperine ameliorated the progression of TNBS-induced colitis by modulating the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha/nuclear factor-kappa B signaling pathway, thus inhibiting the overexpression of proinflammatory cytokines (TNF-α and IL's), COX-2, iNOs, oxido-nitrosative stress, and proapoptotic proteins (caspase-1) that may improve the expression of TJ protein (claudin-1, occludin, and ZO-1).

Objective: To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p., Patients and Methods: Sixty patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p., Results: PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression., Conclusions: PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p.

Despite its importance in central nervous system development, development of the human neural tube (NT) remains poorly understood, given the challenges of studying human embryos, and the developmental divergence between humans and animal models. We report a human NT development model, in which NT-like tissues, neuroepithelial (NE) cysts, are generated in a bioengineered neurogenic environment through self-organization of human pluripotent stem cells (hPSCs). NE cysts correspond to the neural plate in the dorsal ectoderm and have a default dorsal identity. Dorsal-ventral (DV) patterning of NE cysts is achieved using retinoic acid and/or sonic hedgehog and features sequential emergence of the ventral floor plate, P3, and pMN domains in discrete, adjacent regions and a dorsal territory progressively restricted to the opposite dorsal pole. This hPSC-based, DV patterned NE cyst system will be useful for understanding the self-organizing principles that guide NT patterning and for investigations of neural development and neural disease., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Abstract: Postmortem changes on corpses appear immediately after death, and can transform the original structure characteristics of the corpse to different degrees as well as show specific changes on computed tomography （CT） images, sometimes with false positives and false negatives, influencing the identification of injuries or diseases. This paper systematically summarizes the postmortem changes of computed tomography imaging characteristics on corpses, to further expand the application of virtopsy in the practices of forensic pathology identification, and provide reference for the identification of injuries, diseases and changes after normal death., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

The co-occurrence of hepatic cystic echinococcosis (CE) and alveolar echinococcosis (AE) is extremely rare. Here, we present the clinical manifestations and treatment outcomes of three cases with co-occurring CE and AE in the liver. Computed tomography (CT), magnetic resonance imaging and 18FFluorodeoxyglucose Positron Emission Tomography-CT were used for preoperative diagnosis. Specimens were taken intraoperatively and sent for pathological studies to confirm the coexistence of CE and AE by laminated membrane, daughter cysts or germinal layer and infiltration structure. Albendazole was prescribed after operation for 12 months. All patients were completely recovered and showed no recurrence at last follow-up. Therefore, surgical intervention and postoperative application of albendazole are recommended for patients with concurrence of hepatic AE and CE.

Abstract: Objective Quantitative analysis and comparison of the expression of ribonucleic acid （RNA） from frozen organs and formaldehyde-fixed and paraffin-embedded （FFPE） tissues. Methods Frozen specimens of human brain, myocardium and liver tissues as well as FFPE samples at different postmortem intervals were collected and mass concentration of RNA was extracted and detected. Reverse transcription-quantitative polymerase chain reaction （RT-qPCR） technology was used to analyze the amplification efficiency and relative expression of each RNA marker. Results The mass concentration and integrity of RNA extracted from FFPE samples were relatively low compared with frozen specimens. The amplification efficiency of RNA markers was related with RNA species and the length of amplification products. Among them, glyceraldehyde-3-phosphate dehydrogenase （GAPDH） and β-actin （ACTB） with relatively long amplification products failed to achieve optimal amplification efficiency, whereas 5S ribosomal RNA （5S rRNA） achieved ideal amplification efficiency and showed quite stable expression across various tissues, therefore it was chosen as internal reference marker. The expression quantity of GAPDH and ACTB in frozen specimens with longer postmortem intervals and in FFPE samples with relatively long amplification products was decreased. The expressions of tissue-specific microRNAs （miRNAs）, GAPDH and ACTB with relatively short amplification products had consistency in the same tissues and FFPE samples. Conclusion Through standardizing the RT-qPCR experiment, selecting the appropriate RNA marker and designing primers of appropriate product length, RNA expression levels of FFPE samples can be accurately quantified., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Forensic Medicine.)

Objective: To investigate the effect of melatonin on diabetic retinopathy rats through the mitogen-activated protein kinase (MAPK) pathway., Materials and Methods: A total of 48 Sprague Dawley (SD) rats were randomly divided into normal group (n=12), model group (n=12), melatonin group (n=12), and inhibitor group (n=12). The rats in normal group received no treatment. Those in model group, melatonin group, and inhibitor group were prepared into models of diabetic retinopathy and intraperitoneally injected with normal saline, melatonin, and SB 203580, respectively. After 7 days of intervention, the materials were taken. The expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected through immunohistochemistry. Western blotting was employed to determine the protein expression levels of p38 MAPK, phosphorylated (p)-p38 MAPK, and cysteinyl aspartate specific proteinase-3 (Caspase-3). The messenger ribonucleic acid (mRNA) expression levels of Bax and Bcl-2 were measured via quantitative Polymerase Chain Reaction (qPCR). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of serum interleukin-1β (IL-1β) and IL-18. The apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL)., Results: Based on immunohistochemistry, model group, melatonin group, and inhibitor group exhibited significantly increased positive expression of Bax but notably decreased positive expression of Bcl-2 in comparison with normal group (p<0.05). Compared with those in model group, the positive expression of Bax was clearly reduced, while the positive expression of Bcl-2 was overtly raised in melatonin group and inhibitor group (p<0.05). The results of Western blotting showed that there was no difference in the protein expression of p38 MAPK among all groups (p>0.05). Compared with normal group, the other three groups had remarkably elevated protein expressions of p-p38 MAPK and Caspase-3 (p<0.05). The protein expressions of p-p38 MAPK and Caspase-3 in melatonin group and inhibitor group were significantly lower than those in model group decreased (p<0.05). QPCR assay revealed that the mRNA expression of Bax was markedly lower in normal group than that in the other three groups, while the mRNA expression of Bcl-2 was significantly higher in normal group than that in the other three groups (p<0.05). Compared with model group, melatonin group, and inhibitory group showed clearly declined mRNA expression level of Bax and notably increased mRNA expression level of Bcl-2 (p<0.05). TUNEL results revealed that the apoptosis rate was remarkably elevated in the other three groups compared with that in normal group (p<0.05). In comparison with model group, melatonin group and inhibitor group exhibited significantly reduced apoptosis rate (p<0.05)., Conclusions: Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy by repressing the MAPK pathway.

Many types of RNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles in regulating fat cell differentiation and tissue development. However, the expression profiles of these RNAs in different adipose tissues are still largely unknown. To shed light on this issue, we performed a transcriptome analysis of mRNAs, lncRNAs and circRNAs obtained from intramuscular adipose tissue, subcutaneous adipose tissue, retroperitoneal adipose tissue and mesenteric adipose tissue of Chinese Erhualian pigs. A number of differentially expressed mRNAs, lncRNAs and circRNAs were identified among the four adipose tissues. Tissue-specific analysis indicated that circRNAs exhibited the highest tissue specificity among mRNAs, lncRNAs and circRNAs, whereas intramuscular adipose tissue had the most tissue-specific genes among the four adipose tissues. Gene Ontology analysis showed that differentially expressed mRNAs among groups were involved mainly in lipid metabolism and immune inflammatory response processes. Furthermore, the co-expression network construction of mRNAs-lncRNAs revealed that several important lncRNAs, such as MSTRG.426159 and MSTRG.604206, might associate with lipid metabolic process. Taken together, these data provide a genome-wide resource of mRNAs, lncRNAs and circRNAs potentially involved in porcine fat metabolism, thus improving understanding of their function in diverse adipose tissues., (© 2019 Stichting International Foundation for Animal Genetics.)

Objective: Hepatocellular carcinoma (HCC) is a malignant cancer with a high fatality rate, and the expression of microRNA-145 (miR-145) is significantly low in HCC tissue. Therefore, the effect of miR-145 on HCC was explored., Patients and Methods: Primary hepatocellular carcinoma samples and corresponding normal samples, and HepG2 cells were analyzed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and dual-luciferase reporter assay., Results: miR-145 expression was significantly downregulated in HCC tissue and HepG2 cells as compared to normal liver tissue. After HepG2 cells were transfected with miR-145 mimics, miR-145 expression was recovered, accompanied by a significantly lower cell number, inhibition of the G1/S phase transition, and promotion of the apoptosis of HepG2 cells, as well as changes in levels of G1/S-specific cyclin-E1 (CCNE1) and activated caspase-3. Furthermore, the rho-associated protein kinase 1 (ROCK1) levels were opposite the levels of miR-145 expression in vivo and in vitro, and additional experiments with co-transfection of miR-145 mimics and pEGFP-N3-3'UTR provided the direct evidence that the ROCK1 gene is a target of miR-145. Moreover, a significant decrease or increase in the expression of ROCK1 was associated with nuclear factor-kB (NF-κB)(p65) activity, and lipopolysaccharide (LPS) significantly increased NF-κB(p65) activity, accompanied by recovery of the reduction in the number of HepG2 cells for miR-145 mimics. The NF-κB activity and cell number were significantly (p < 0.05, p < 0.01) increased in response to the overexpression of the ROCK1 gene in HepG2 cells., Conclusions: We showed that miR-145 can target and downregulate ROCK1 expression, and it controls HCC by inhibiting the cell cycle and activating apoptosis via the ROCK1/NF-κB signaling pathway. Our findings will provide a new perspective for the therapy of HCC.

Objective: To understand and analyze the incidence rate, risk factors, independent risk factors and the causes of death in elderly population with non-alcoholic fatty liver disease (NAFLD). Furthermore, analyze the relationship between metabolic syndrome (MS) and mortality rate in patients with NAFLD to provide evidence for the prevention and control of NAFLD in the elderly population. Methods: A total of 7 619 elderly people aged over 60 years, and local household registered in Kunshan city, Jiangsu province in 2016 were included as subjects to analyze the incidence rate, influencing factors and causes of death in patients with NAFLD and the relationship between MS and mortality rate in patients with NAFLD. According to different data, using Kruskal-Wallis H test, analysis of variance, t-test, chi-square test or logistic regression analysis were performed. Results: The prevalence of NAFLD was14.10% (1 074/7 619) among the elderly over 60 years in Kunshan city, Jiangsu province in 2016, and the female prevalence rate was significantly higher than that of males ( P < 0.05). When the body mass index (BMI) was < 32 (kg/m(2)), the prevalence of NAFLD increased with the increase of BMI index. When BMI was 18.5-23.9 kg/m2, 24-27.9 kg/m(2) and > 32 kg/m(2), the prevalence of NAFLD was significantly higher in females than males ( P < 0.05). There was no significant difference in prevalence between males and females with BMI <18.5 kg/m(2) and 28~31.9 kg/m(2) ( P > 0.05). BMI gradually decreased ( P < 0.05) with the increase of age, and the incidence of NAFLD showed a downward trend ( P < 0.05). An independent risk factors for NAFLD ( P < 0.01) were gender ( OR = 0.616), age ( OR = 0.970), waist circumference ( OR = 1.065), triglycerides ( OR = 1.162), BMI ( OR = 1.238), and diastolic blood pressure ( OR = 1.012). The probability of NAFLD combined with three and four kinds of MS was significantly higher than control group ( P < 0.05). Subjects' mortality rate during the follow-up period was 1.94%, 2.23% in the NAFLD group, and 1.89% in the control group. Average life expectancy was 75.58 years in NAFLD group and 78.68 years in the control group. All deaths in NAFLD groups were associated with MS, and 70.83% combined with three or more MS. The primary cause of death in NAFLD group was tumors (37.5%), followed by cardiovascular disease (16.67%) and three cases died directly from MS. Conclusion: The prevalence of NAFLD in the elderly population in Kunshan city, Jiangsu province is relatively low, which may be associated with local diet and high-intensity workouts. MS disorders represented by obesity and diabetes mellitus are closely associated to the onset of NAFLD. Obesity is the most important risk factor for the incidence of NAFLD in the local elderly population over 60 years old. However, the risk of NAFLD should not be neglected in people with normal BMI, especially in aged women, and the weight control should be the most important means to prevent and control NAFLD. NAFLD may increase mortality rate and reduce life expectancy in the elderly population. The main reason to cause death in the elderly with NAFLD is cardiovascular disease and malignant tumors. Simultaneously, multiple MS development may increase the death rate in elderly with NAFLD.

Objective: To investigate the influences of metformin on the proliferation and migration of endometrial cancer (EC) Ishikawa cells and its mechanism., Materials and Methods: After the EC Ishikawa cells were treated with metformin at a concentration of 10 mM for 24 h, the proliferation of cancer cells was detected via XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-car-boxanilide] assay and colony formation assay, and the migration and invasion of cancer cells were detected via wound healing assay and transwell assay. In addition, the expressions of epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin and Vimentin, were detected via Western blotting, and immunofluorescence staining was performed for E-cadherin in cancer cells. Finally, the protein expression level of phosphatidylinositol 3-hydroxy kinase/protein kinase B/murine double minute 2 (PI3K/AKT/MDM2) signaling pathway in cancer cells was detected via Western blotting., Results: Metformin inhibited the proliferation of Ishikawa cells in a concentration-dependent manner (0-10 mM) (p<0.05). Moreover, metformin (10 mM) also inhibited the proliferation of Ishikawa cells in a time-dependent manner (0-72 h) (p<0.05). The results of colony formation assay revealed that metformin (10 mM) could significantly inhibit the colony formation of Ishikawa cells (p<0.05). The results of wound healing assay and transwell assay showed that metformin (10 mM) significantly inhibited the migration and invasion of Ishikawa cells (p<0.05). According to further studies, metformin (10 mM) inhibited the EMT process in Ishikawa cells. Western blotting results manifested that the activation of PI3K/AKT/MDM2 signaling pathway was inhibited by metformin (p<0.05)., Conclusions: Metformin can inhibit the proliferation and migration of EC cells by inhibiting the activation of PI3K/AKT/MDM2 signaling pathway. Therefore, metformin is expected to be a new drug for the clinical treatment of EC.

We studied the magnetic ordering of thin films and bulk crystals of rutile RuO&#95;{2} using resonant x-ray scattering across the Ru L&#95;{2} absorption edge. Combining polarization analysis and azimuthal angle dependence of the magnetic Bragg signal, we have established the presence and characteristic of collinear antiferromagnetism in RuO&#95;{2} with T&#95;{N}>300  K. In addition to revealing a spin-ordered ground state in the simplest ruthenium oxide compound, the persistence of magnetic order even in nanometer-thick films lays the ground for potential applications of RuO&#95;{2} in antiferromagnetic spintronics.