IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.

[Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis].

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).

STUDY QUESTION: Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? SUMMARY ANSWER: Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. WHAT IS KNOWN ALREADY: SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. STUDY DESIGN SIZE DURATION: In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. PARTICIPANTS/MATERIALS SETTING METHODS: A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). MAIN RESULTS AND THE ROLE OF CHANCE: Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). LIMITATIONS REASONS FOR CAUTION: The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. WIDER IMPLICATIONS OF THE FINDINGS: The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. STUDY FUNDING/COMPETING INTERESTS: The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

[Application of CRISPR/Cas systems in the nucleic acid detection of pathogens: a review].

Rapid, sensitive and specific detection tools are critical for the prevention and control of infectious diseases. The in vitro nucleic acid amplification assays, including polymerase chain reaction and isothermal amplification technology, have been widely used for the detection of pathogens. Recently, nucleic acid detection-based on clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) have been developed, which are rapid, highly sensitive, highly specific, and portable. This review describes the classification and principle of CRISPR/Cas systems and their applications in pathogen detection, and discusses the prospects of CRISPR/Cas systems.

Shared genetic architecture between type 2 diabetes and COVID-19 severity.

PURPOSE: Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. RESULTS: Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization (rg = 0.156, SE = 0.057, p = 0.005) or severe disease (rg = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having pgene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. CONCLUSIONS: Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets.

[Study on the distribution pattern of allergen sIgE in patients with respiratory allergic diseases in a hospital in Shanxi Province].

To explore the allergen sensitization status of patients with respiratory allergic diseases in Shanxi Province, and to provide a basis for the diagnosis, treatment and prevention of allergic diseases. It is a cross-sectional study, a total of 1 680 patients with allergic rhinitis and/or asthma diagnosed at the Department of Allergic Reaction of Shanxi Bethune Hospital from July 2021 to June 2023 who underwent allergen sIgE testing and/or skin prick test were retrospectively enrolled.There were 772 males and 908 females.The age range was 3 to 88 years. The median age was 35 years.There were 108 cases in the child group (≤12 years old), 102 cases in the adolescent group (13-17 years old), 819 cases in the youth group (18-40 years old), 498 cases in the middle-aged group (41-65 years old), and 153 cases in the elderly group (>65 years old). There were 333 cases in the allergic rhinitis group, 827 cases in the allergic asthma group, and 520 cases in the allergic rhinitis with asthma group. There were 1 254 urban patients and 426 rural patients.There were 253 cases in the northern Shanxi region, 1 195 cases in the central Shanxi region, and 232 cases in the southern Shanxi region. Statistical analyses were performed using the χ 2 test or Fisher's exact probability method to compare the differences in allergen sIgE positivity rates by sex, age, disease, living environment, and geography. The results showed that 1 027 patients (61.1%) were positive for at least one allergen sIgE, with Artemisia having the highest rate of positivity (603/1 680, 35.9%), followed by ragweed (302/1 680, 18.0%) and dust mite combinations (245/1 680, 14.6%). The number of individuals with single-allergen sIgE positivity was 357 (357/1 027, 34.8%), with the highest number of single-allergen sIgE positive results associated with Artemisia (114/357, 31.9%). The number of multiple-allergen sIgE positive results was 670 cases (670/1 027, 65.2%), with the highest number of patients having 2 allergen sIgE positive results (243/670, 36.3%). The overall positivity rate for allergen sIgE was significantly higher among males than among females (65.7% vs. 57.3%, χ2=12.405, P<0.001). Overall positivity for inhalant allergen sIgE was higher in the child and adolescent groups (88.0% vs. 88.2% vs. 59.8% vs. 40.2% vs. 19.0%, χ2=223.372, P<0.001), and food allergen sIgE positivity was highest in the child group (54.6% vs. 36.3% vs. 26.0% vs. 18.9% vs. 21.6%,χ2=66.383,P<0.001). The sIgE positivity rate of inhalant allergens was significantly higher in the allergic rhinitis group and the allergic rhinitis with asthma group than in the allergic asthma group, except for cockroaches and molds (P<0.05). The overall positive rate of allergen sIgE was significantly higher among urban patients than among rural patients (66.2% vs. 46.2%, χ2=53.230, P<0.001). The difference in the overall positive rate of allergen sIgE among patients from different regions was not statistically significant (56.1% vs. 62.0% vs. 62.1%, χ2=3.140, P=0.208). The sIgE positivity of dust mite combinations was significantly higher in the central Shanxi region and the southern Shanxi region than in the northern Shanxi region (15.5% vs. 18.1% vs. 7.1%,χ2=14.411, P=0.001). In conclusion, artemisia was the most important sensitizer for respiratory allergic diseases in Shanxi Province. The types of allergens and positivity rates were different for different sexes, ages, diseases, living environments, and regions. Therefore, patients with allergic diseases should be tested for allergens to help with the diagnosis, treatment and prevention of allergic diseases.

[The prevention and therapy of corneal ulcers in patients with large-area thermal burns].

Objective: To evaluate the characteristics of ocular injury in patients with severe extensive thermal burns, and to explore the effective methods to prevent and treat corneal ulcers related to severe burns. Methods: A retrospective case series study. Between 2010 and 2019, Sixteen severe thermal burn patients with burn sizes>70% of the total body surface area involving the ocular region were admitted to the Burns and Plastic Surgery Division of Chinese PLA General Hospital, and consult with Ophthalmology Division. There were deep second-degree to fourth-degree burns in the eyelids. In the eleven surviving patients, 22 eyes presented ectropion. Eyelid full-thickness skin grafting (EFTSG) combined with or without tarsorrhaphy was performed in 20 eyes due to severe corneal exposure. Two eyes received partial blepharorrhaphy because of mild ectropion. The ocular manifestations and treatment outcomes were reviewed and assessed. Results: The majority of the patients were youth, and the average age was (36.8±10.4) years. The burn area was 84.0%±9.1% of the body surface area. Corneal ulcers secondary to lagophthalmos occurred at (35.1±15.6) days after burning in 75% (24/32) of eyes. Perforation was found in 18.8% (6/32) of eyes. Among the 22 operated eyes, the corneal ulcer was repaired in all 9 eyes receiving EFTSG with tarsorrhaphy, whereas ectropion recurred in 8 of 11 eyes only receiving EFTSG, and 4 eyes underwent further surgery due to corneal epithelial defects. Conclusions: In patients with severe large-area thermal burns, corneal ulcers are common complications. Prevention of corneal exposure is vital because the treatment of corneal ulceration is difficult due to eyelid deformity, inflammation and the absence of donor skin. Timely full-thickness skin grafting and blepharorrhaphy are effective approaches to preventing exposure keratopathy. To severe ulcers occur, conjunctival flap or Tenon's capsule covering combined with eyelid EFTSG and tarsorrhaphy is useful to rescue visual function.

Resolvin D2 promotes host defense in a 2 - hit model of sepsis with secondary lung infection.

In the development of sepsis, there is early, massive inflammation which can lead to multiple organ failure. Later there is an immunosuppressed phase where the host is susceptible to secondary infections or is unable to clear existing infection. Specialized Pro-resolving Mediators (SPMs) are endogenously produced lipids which resolve infection by decreasing bacteria load and reducing systemic inflammatory response. There has been little work studying if SPMs given late, can promote host defense. We examined if an SPM, Resolvin D2 (RvD2) could promote host defense in a 2-hit mouse model of cecal ligation and puncture (CLP) sepsis and secondary Pseudomonas aeruginosa lung infection. RvD2 given 48 h after mild CLP (1st hit), increased gene expression of Toll-like receptor-2 (TLR-2) and alveolar macrophage/monocyte phagocytic ability compared to CLP mice given saline vehicle. In this model, RvD2 did not affect plasma IL-6 or IL-10. These effects induced by RvD2, lowered lung bacterial load and decreased mortality after the secondary infection of Pseudomonas aeruginosa (2nd hit). Splenic T-cell numbers were also increased in RvD2 treated mice compared to saline vehicle treated animals. The results suggest that RvD2 promoted mechanisms of host defense in a 2-hit model sepsis and secondary lung infection.

Predicting lung adenocarcinoma invasiveness by measurement of pure ground-glass nodule roundness by using multiplanar reformation: a retrospective analysis.

AIM: To explore the value of roundness measurement based on thin-section axial, coronal, and sagittal section computed tomography (CT) images for predicting pure ground-glass nodule (pGGN) invasiveness. MATERIALS AND METHODS: A total of 168 pGGNs in 155 patients (44 male, 111 females; mean age, 55.74 ± 10.57 years), and confirmed by surgery and histopathology, were analysed retrospectively and divided into pre-invasive (n=72) and invasive (n=96) groups. Photoshop (CS6) software was used to measure pGGN roundness based on conventional axial section, as well as coronal and sagittal sections generated by multiplanar reformation, from thin-section (1-mm-thick) CT lung images. RESULTS: pGGN roundness values, measured in axial, coronal, and sagittal thin-section CT sections from the pre-invasive group were 0.8 ± 0.049, 0.816 ± 0.05, and 0.818 ± 0.043, respectively, while those in the invasive group were 0.745 ± 0.077, 0.684 ± 0.106, and 0.678 ± 0.106; differences between the two groups were significant (all p<0.001). Binary logistic regression analysis showed that roundness values based on coronal and sagittal sections (p<0.001) were better than those from axial sections (p>0.05) in predicting pGGN invasiveness, with odds ratio (OR) values of 14.858 and 23.315, respectively. ROC analysis showed that evaluation of roundness measured in sagittal sections was better at predicting pGGN invasiveness than when coronal sections were used (AUC 0.870 versus 0.832). CONCLUSION: Roundness is useful for predicting pGGN invasiveness, with measurements from coronal and sagittal sections better than those from conventional axial sections, with sagittal section images having the best predictive value.

Hydrogen sulphide signalling in plant response to abiotic stress.

Throughout their whole life cycle, higher plants are often exposed to diverse environmental stresses, such as drought, salinity, heavy metals and extreme temperatures. In response to such stress, plant cells initiate signalling transduction, resulting in downstream responses, such as specific gene transcription and protein expression. Accumulating evidence has revealed that hydrogen sulphide (H2 S) serves as a signalling molecule in plant acclimation to stressful conditions. More important, H2 S interacts with other signalling molecules and phytohormones, contributing to transcriptional regulation and post-translational modification. Overall, the H2 S-mediated signalling pathway and its interaction with other signals remains elusive. Here, we describe the role of the H2 S signalling network in regulating physiological and molecular processes under various abiotic stresses.

Evidence for causal effects of sleep disturbances on risk for osteoarthritis: a univariable and multivariable Mendelian randomization study.

OBJECTIVE: To disentangle whether sleep disturbances have a causal effect on the risk of osteoarthritis (OA) using genetically based approaches. METHOD: We performed univariable and multivariable Mendelian randomization (MR) analyses using publicly released genome-wide association studies summary statistics to estimate the causal associations of sleep disturbances with OA risk. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas complementary methods including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were applied to detect and correct for the presence of pleiotropy. RESULTS: There were 228 independent instrumental variables (IVs) for insomnia and 78, 27 and 8 IVs for sleep duration, short sleep duration and long sleep duration, respectively. Univariable MR analysis suggested that genetically determined insomnia or short sleep duration exerted a causal effect on overall OA in an unfavorable manner (Insomnia: OR = 1.22, 95%CI = 1.15-1.30, P = 8.05 × 10-10; Short sleep duration: OR = 1.04, 95%CI = 1.02-1.07, P = 2.20 × 10-3). More compelling, increasing genetic liability to insomnia or short sleep duration was also associated with OA risk, after accounting for effects of insomnia or short sleep duration on body mass index, type 2 diabetes and depression individually, and in a combined model considering all three confounders. CONCLUSIONS: Findings suggested consisted evidence for an adverse effect of increased insomnia or short sleep duration on OA risk. Strategies to mitigate sleep disturbances may be one of the cornerstones protects against OA.

[Application of metagenomic next-generation sequencing technology in pathogen detection in patients with burns and patients with acute or chronic wounds].

Objective: To explore the value of using metagenomic next-generation sequencing (mNGS) technology to detect pathogens in patients with burns and patients with acute or chronic wounds. Methods: A retrospective observational study was conducted. From March 2019 to June 2020, 11 patients with burns and patients with acute or chronic wounds (including 10 males and 1 female, aged 23 to 85 years) in the Fourth Medical Center of PLA General Hospital met the inclusion criteria and were recruited. A total of 23 specimens were collected, including 6 whole blood specimens, 1 skin tissue specimen, 1 drained pus specimen, and 15 wound secretion swab specimens. Each specimen was divided into two parts, which were subjected for pathogen detection using microbial culture method and mNGS method, respectively. The number and types of pathogens detected by the 2 methods and the relative abundance detected by the mNGS method were recorded, and the consistency of the two methods were compared. Data were statistically analyzed with paired Wilcoxon rank sum test. Results: With the microbial culture method, no pathogen was detected in 5 of the 23 specimens, while 35 pathogens were detected in the remaining 18 specimens, belonging to 9 species of bacteria and 2 species of fungi. Five specimens had one pathogen while 9 specimens had 2 pathogens and 4 specimens had 3 pathogens detected in each specimen. With the mNGS method, no pathogen was detected in one of the 23 specimens, while 75 pathogens were detected in the remaining 22 specimens, belonging to 28 species of bacteria, 3 species of fungi, and 3 species of viruses. Eight specimens had one pathogen, 5 specimens had 2 pathogens, 2 specimens had 3 pathogens, 3 specimens had 4 pathogens, 2 specimens had 6 pathogens, and 1 specimen had 7 pathogens, and 1 specimen had 20 pathogens detected in each specimen. The number of pathogens detected in each specimen by microbial culture method was 2 (1, 2) types, which was significantly less than 2 (1, 4) types by mNGS method (Z=3.359, P<0.01). In 5 specimens, no bacteria were detected by microbial culture method but mNGS method detected bacteria in 2 specimens and virus in 2 different specimens. The mNGS method detected two or more types of bacteria in 13 specimens, the relative abundance of bacteria with the 1st relative abundance ranking ranged from 28.8% to 95.9% in each specimen. Of the 23 specimens detected by two detection methods, 7 specimens (30.4%) showed identical detection results, 5 specimens (21.7%) showed totally different detection results, and 11 specimens (47.8%) had partially consistent detection results. Conclusions: Compared with the traditional microbial culture method, the mNGS method has higher detection sensitivity and stronger capacity to detect pathogens, and can determine the relative abundance of pathogens in mixed infections. As a supplement to the culture method, the mNGS method is expected to play an important role in the diagnosis of infectious pathogens in burns and acute or chronic wounds.

Single-nucleus RNA-seq2 reveals functional crosstalk between liver zonation and ploidy.

Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for the comprehensive analysis of the nuclear transcriptome from frozen tissues, allowing the dissection of all cell types present in the liver, regardless of cell size or cellular fragility. We use this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that ploidy states are associated with different metabolic potential, and gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobule. Our work reveals a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.

Lipoxin A4 promotes reduction and antibiotic efficacy against Pseudomonas aeruginosa biofilm.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic bacterium commonly found in wound infections and airways of cystic fibrosis patients. P. aeruginosa readily forms biofilms which can reduce the efficacy of antibiotics used to eradicate the pathogen. We have previously shown that a Specialized Pro-resolving Mediator (SPM), Lipoxin A4 (LxA4) is a quorum sensing inhibitor which can reduce P. aeruginosa virulence. In this study, we examined the direct actions of LxA4 and RvD2 on P. aeruginosa biofilm formation and virulence gene expression. The influence of LxA4 on antibiotic efficacy and the combined effects on biofilm formation were also investigated. LxA4 and RvD2 reduced P. aeruginosa biofilm formation and virulence gene expression. LxA4 increased ciprofloxacin inhibition on biofilm formation but did not affect ciprofloxacin's action on non-adherent bacteria. On the other hand, LxA4 increased bacterial killing action of imipenem but did not affect imipenem's action on biofilm. We also found that LxA4 can increase ciprofloxacin's bacterial killing ability in established biofilm. Together these results suggest that LxA4 has direct effects on P. aeruginosa biofilm formation and can increase antibiotic efficacy directly.

[Analysis of drug - resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province in 2015 and 2016].

OBJECTIVE: To investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. METHODS: From 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. RESULTS: The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. CONCLUSIONS: There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.

[Ten cases of wound hemostasis with glove bandaging in hand skin grafting].

From July 2018 to April 2019, 10 patients (8 males and 2 females, aged 5 to 53 years) who need skin grafting with 17 hands were admitted to the Fourth Medical Center of PLA General Hospital. The method of glove bandaging was used for wound hemostasis in skin grafting. After the initial hemostasis, sterile latex gloves were used as the inner cover of hand, and then pressure-wrapped with gauze. After 20 minutes, the gauze and gloves were removed in order from the near to the far, then thorough hemostasis was conducted again, and finally skin grafting was performed. The use of gloves as inner cover can avoid the adhesion of gauze fibers to the wound surface, so that it will not cause small blood vessels to re-bleed when the gauze is removed, therefore reducing the excessive use of electrocoagulation and secondary damage to the wound. As a result, blood loss can be reduced and hemostatic time can be shortened.

[Epidemiological investigation of 169 inpatients with high-voltage electrical burns on the wrist].

Objective: To analyze the epidemiological characteristics of inpatients with high-voltage electrical burns on the wrist in Beijing Jishuitan Hospital (hereinafter referred to as the author's unit), so as to provide reference for the prevention and treatment of high-voltage electrical burns on the wrist. Methods: The medical records of inpatients suffered from high-voltage electrical burns on the wrist in the author's unit from January 2008 to December 2019 were collected. The patients' gender, age, population category, injury situation, injury season, total burn area, electrical burn type on the wrist of the affected limbs, the time from injury to first flap/myocutaneous flap transplantation, vascular reconstruction and flap/myocutaneous flap transplantation of the affected limbs, the total amputation rate of the affected limbs and the amputation rate of the affected limbs with type Ⅲelectrical burns on the wrist, the number of operation, postoperative infection rate of flap/myocutaneous flap, length of hospital stay, hospitalization expense, and treatment outcome were retrospectively analyzed. Comparison of the aforementioned statistical items between patients admitted from January 2008 to December 2013 (hereinafter referred to as the pre-stage) and January 2014 to December 2019 (hereinafter referred to as the post-stage) except gender, the total amputation rate of the affected limbs, treatment outcome were performed. Data were statistically analyzed with chi-square test, Fisher's exact probability test, and Wilcoxon rank-sum test. Results: During the 12 years, a total of 169 patients with high-voltage electrical burns on the wrist were admitted to the author's unit, including 162 males and 7 females, aged (35±13) years, and 75.15% (127/169) of patients were 21-50 years old. The top three groups in population category from high to low were workers, migrant workers, and primary and secondary school students, accounting for 48.52% (82/169), 28.99% (49/169), and 9.47% (16/169), respectively. At work of non-electric power accounted for 47.93% (81/169) and ranked the first in the proportion of injury situation. The injury occurred mostly in summer and autumn, accounting for 39.05% (66/169) and 28.99% (49/169), respectively. About 65.09% (110/169) of the patients were with total burn area less than 10% total body surface area. There were totally 216 affected limbs with high-voltage electrical burns on the wrist, of which the numbers of wrist with type Ⅲ and type Ⅳ injury were 25 (11.57%) and 21 (9.72%), respectively. The time from injury to first flap/myocutaneous flap transplantation was 6.00 (3.75, 8.00) d. There were 45 affected limbs operated with vascular reconstruction, 75 affected limbs transplanted with pedicled axial flap, and 86 affected limbs transplanted with free flap/myocutaneous flap. The total amputation rate of affected limbs was 12.96% (28/216), and the amputation rate of the affected limbs with type Ⅲ electrical burns on the wrist was 28% (7/25). The number of operation was 4 (3, 5) times, the postoperative infection rate of flap/myocutaneous flap was 7.18% (13/181), the hospitalization time was 39.00 (25.00, 50.00) d, and the hospitalization cost was 123 553.00 (50 656.50, 216 003.00) yuan. Compared with those of the pre-stage, the time from injury to first flap/myocutaneous flap transplantation was significantly shortened (Z=-4.038, P<0.01), the ratio of free flap/myocutaneous flap transplantation on affected limbs was significantly increased (χ(2)=13.478, P<0.01), the ratio of pedicled axial flap transplantation on affected limbs was significantly decreased (χ(2)=10.242, P<0.01), the number of operation was significantly reduced (Z=-5.903, P<0.01), the postoperative infection rate of flap/myocutaneous flap was significantly decreased (χ(2)=4.492, P<0.05), the length of hospital stay was significantly shortened (Z=-2.723, P<0.01), and the hospitalization expense was significantly decreased among patients hospitalized in the post-stage (Z=-2.121, P<0.05). The other items were close between patients hospitalized in the pre-stage and those in the post-stage. Conclusions: Men were more likely than women to suffer from high-voltage electrical burns on the wrist in the author's unit. Young workers and migrant workers may be the key groups for the prevention of high-voltage electrical burns on the wrist. It is very important to strengthen the management of high voltage safety education for non-electric power staff, warn and protect the surrounding area of high voltage environment, and prohibit non staff for entering the high voltage environment, especially in summer and autumn. In the last 6 years, the patients with high-voltage electrical burns on the wrist may benefit from the active vascular reconstruction at early stage and free flap/myocutaneous flap repair in the author's unit.

[An epidemiological survey on clinical features, self-management and cognitive level of elderly asthmatics in China].

Objective: To investigate the prevalence of asthma among the elderly people in China and to analyze the clinical features, self-management and cognitive level of elderly asthma patients. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the last epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) and seven regions (north, northeast, southern china, east, south, southwest and northwest) in China from February 2010 to August 2012. 2 034 were diagnosed as asthma. The elderly patients aged ≥65 years were selected from the 2 034 asthma patients. The clinical characteristics, comorbidities, the status of asthma control and self-management and insights of the disease in elderly asthma patients were analyzed. Results: Among the 2 034 asthma patients, 584 (28.7%) were elderly asthmatics aged ≥65 years old and 1 450 (71.3%) were<65 years old. In the elderly asthma group, Early-onset asthma accounted for 439 (75.2%) and 145 (24.8%) were late-onset. The common clinical manifestations of elderly asthma patients were: chest distress 395 (67.6%), wheezing 304 (52.1%), cough 298 (51.0%). Common comorbidities of elderly asthmatics were: chronic obstructive pulmonary disease 144 (24.7%), allergic rhinitis 122(20.9%), gastroesopheal reflux disease (GERD) 114(19.5%), allergic conjunctivitis 86 (14.7%), eczema 82 (14.0%), chronic bronchitis 76 (13.0%). The Asthma Control Test (ACT) scores of elderly asthmatics and non-elderly asthmatics were (18.5±3.2) and (21.7±3.4) respectively. There was a significant difference between the two groups (P=0.042). Of the elderly asthmatics, only 13 (2.2%) patients monitored daily using a peak flow meter. 93 (15.9%) patients aware that asthma was characterized by chronic airway inflammation. 64 (11.0%) asthmatics understood that the treatment goal. Conclusions: The clinical manifestations of elderly asthmatics are atypical, especially paroxysmal wheezing. Asthma in elderly people causes more comorbidities and mortality. The self-management and cognitive level of patients with asthma needs to be improved.

[A survey on clinical characteristics and risk factors of severe asthma in China].

Objective: To investigate the clinical characteristics and risk factors of severe bronchial asthma in Chinese people over 14 years old. Methods: According to the multi-stage random cluster sampling methods, a total of 164 215 subjects were visited by a questionnaire in the epidemiology survey from eight provinces (Beijing, Shanghai, Guangdong, Liaoning, Henan, Shanxi, Jiangsu, Sichuan provinces) located in seven regions (north, northeast, east, central China, south, southwest and northwest) of China from February 2010 to August 2012. A total of 2 034 were diagnosed as asthma. The clinical characteristics and related risk factors of patients with severe asthma in China were analyzed. Results: Among all asthma patients, 560 were newly diagnosed, accounting for 27.5% (560/2 034) and the percentage of previously confirmed patients was 72.5% (1 474/2 034). A total of 145 were eligible for severe asthma, accounting for 9.8% (145/1 474) of previously confirmed asthmatics and 7.1% (145/2 034) of all asthmatics. 83.5% (121/145) severe asthmatics had at least one trigger factor. Correlation analysis showed that the risk factors of severe asthma were: smoking (OR=1.543, 95%CI: 1.250-1.814), obesity (OR=2.186, 95%CI: 1.972-2.354), petting (OR=2.135, 95%CI: 1.904-2.283), combined with allergic rhinitis (OR=3.456, 95%CI: 2.721-4.326), gastroesophageal reflux disease (OR=1.842, 95%CI: 1.682-2.140), bronchiectasis (OR=1.665, 95%CI: 1.347-1.912) or chronic obstructive pulmonary disease (OR=1.312, 95%CI: 1.171-1.694). Conclusions: The most common comorbidities in severe asthmatics in China are allergic rhinitis and gastroesophageal reflux disease. The risk factors of severe asthma include obesity, allergic rhinitis, gastroesophageal reflux disease, chronic obstructive pulmonary disease, bronchiectasis, smoking and petting.

Application Prospects of Virtual Autopsy in Forensic Pathological Investigations on COVID-19.

ABSTRACT: Autopsy of patients who died of infectious diseases is of significance for public health management. Few forensic autopsies have been performed since the outbreak of the corona virus disease 2019 （COVID-19） due to some limitations, thus forensic pathological examination failed to contribute to the prevention and treatment of infectious diseases. Virtual autopsy has unique advantages in the forensic examination of patients who died of infectious diseases. Accumulated virtual autopsy image data are of great value to the study of the pathological mechanism and diagnosis of COVID-19. This article reviews the relationship between imaging changes and pathology of the COVID-19 as well as the application of virtual autopsy in autopsy of patients who died of infectious diseases, in order to provide reference for performing virtual autopsy in the outbreak of COVID-19.