Head-to-head comparison of azvudine and nirmatrelvir/ritonavir for the hospitalized patients with COVID-19: a real-world retrospective cohort study with propensity score matching.

Background: Nirmatrelvir/ritonavir and azvudine have been approved for the early treatment of COVID-19 in China, however, limited real-world data exists regarding their effectiveness and safety. Methods: We conducted a retrospective cohort study involving the hospitalized COVID-19 patients in China between December 2022 and January 2023. Demographic, clinical, and safety variables were recorded. Results: Among the 6,616 hospitalized COVID-19 patients, we included a total of 725 patients including azvudine recipients (N = 461) and nirmatrelvir/ritonavir (N = 264) recipients after exclusions and propensity score matching (1:2). There was no significant difference in the composite disease progression events between azvudine (98, 21.26%) and nirmatrelvir/ritonavir (72, 27.27%) groups (p = 0.066). Azvudine was associated with a significant reduction in secondary outcomes, including the percentage of intensive care unit admission (p = 0.038) and the need for invasive mechanical ventilation (p = 0.035), while the in-hospital death event did not significantly differ (p = 0.991). As for safety outcomes, 33 out of 461 patients (7.16%) in azvudine group and 22 out of 264 patients (8.33%) in nirmatrelvir/ritonavir group experienced drug-related adverse events between the day of admission (p = 0.565). Conclusion: In our real-world setting, azvudine treatment demonstrated similar safety compared to nirmatrelvir/ritonavir in hospitalized COVID-19 patients. Additionally, it showed slightly better clinical benefits in this population. However, further confirmation through additional clinical trials is necessary.

Differential Characteristics of Patients for Hospitalized Severe COVID-19 Infected by the Omicron Variants and Wild Type of SARS-CoV-2 in China.

Background: As multiple mutations of SARS-Cov-2 exist, there are now many viral variants with regional differences in distribution. The clinical characteristics of patients hospitalized with the virus also vary significantly, with those of the Omicron variants being strikingly different from those of the earliest wild-type variant. However, comprehensive data on this subject is lacking. It is therefore crucial to explore these differences to develop better clinical strategies for the management of COVID-19. Methods: A total of 554 confirmed COVID-19 cases in China were clinically classified as mild, moderate, severe, and critical according to their diagnoses and treatment plans. We compared the demographics and clinical characteristics of patients infected with the Omicron vs wild-type strains, between severe and non-severe cases. Bacterial co-infections with SARS-CoV-2 and correlation between inflammatory factors and T cells were analyzed. Results: Compared to the wild-type cases, the severe Omicron cases were older (median age 48.36 vs 73.24), and had more upper-respiratory symptoms and comorbidities. Decreased leukocyte counts were less pronounced, although more instances of significantly decreased CD4+ and CD8+ T-cell counts, elevated infection-related biomarkers (eg procalcitonin and C-reactive protein), and abnormal coagulation factors (including increased D-dimer and fibrinogen levels) were detected in the severe Omicron cases. The mean length of hospital stay was significantly shorter in the severe Omicron cases. CD4+ and CD8+ T cell numbers were negatively correlated with neutrophil-to-lymphocyte ratios, as well as serum interleukin-6, procalcitonin, and C-reactive protein levels. Conclusion: There were significant clinical differences between patients hospitalized with severe cases of Omicron- variant COVID-19 vs wild-type. The Omicron cases tended to be older and had more upper respiratory tract symptoms, comorbidities and bacterial co-infections. Elevated levels of inflammatory cytokines with T-cell depletion correlated with poor disease progression and prognosis. We hope these data provide a theoretical basis for future integrated prevention and control plans for COVID-19.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

UV-induced mutagenesis of Beauveria bassiana (Hypocreales: Clavicipitaceae) yields two hypervirulent isolates with different transcriptomic profiles.

BACKGROUND: The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae) can infest over 300 plant species and cause huge economic losses. Beauveria bassiana (Hypocreales: Clavicipitaceae) is one of the most widely used entomopathogenic fungi (EPF). Unfortunately, the efficacy of B. bassiana against S. frugiperda is quite low. Hypervirulent EPF isolates can be obtained by ultraviolet (UV)-irradiation. Here we report on the UV-induced mutagenesis and transcriptomic analysis of B. bassiana. RESULTS: The wild-type (WT) B. bassiana (ARSEF2860) was exposed to UV light to induce mutagenesis. Two mutants (named 6M and 8M) showed higher growth rates, conidial yields, and germination rates compared to the WT strain. The mutants showed higher levels of tolerance to osmotic, oxidative, and UV stresses. The mutants showed higher protease, chitinase, cellulose, and chitinase activities than WT. Both WT and mutants were compatible with the insecticides matrine, spinetoram, and chlorantraniliprole, but incompatible with emamectin benzoate. Insect bioassays showed that both mutants were more virulent against S. frugiperda and the greater wax moth Galleria mellonella. Transcriptomic profiles of the WT and mutants were determined by RNA-sequencing. The differentially expressed genes (DEGs) were identified. The gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, and hub gene analysis revealed virulence-related genes. CONCLUSION: Our data demonstrate that UV-irradiation is a very efficient and economical technique to improve the virulence and stress resistance of B. bassiana. Comparative transcriptomic profiles of the mutants provide insights into virulence genes. These results provide new ideas for improving the genetic engineering and field efficacy of EPF. © 2023 Society of Chemical Industry.

Prevalence of hematologic complications on extracorporeal membranous oxygenation in critically ill pediatric patients: A systematic review and meta-analysis.

OBJECTIVES: Despite advances in Extracorporeal Membranous Oxygenation (ECMO) equipment, hematologic complications remain significant in critically ill children. The aim of this study is to summarize prevalence of hematologic complications for children and neonates. METHODS: MEDLINE, PubMed and Scopus databases were searched focusing on the period from January 01, 2017 to October 01, 2022. The population included critically ill children and neonates with hematologic complications. The review included all aspects of related complications including hemorrhage, thrombosis, and hemolysis. We performed random effects meta-analyses. The primary outcome measure was overall hematologic complications. Secondary outcomes are changes in the prevalence of hemorrhagic complications. Risk of bias of included studies was assessed using the Joanna Briggs Institute checklist. RESULTS: The systematic search identified 37 studies totaling 10,659 critically ill pediatric patients receiving ECMO. The pooled prevalence of hemorrhagic complications, thrombotic complications and hemolysis among pediatric patients requiring ECMO was 43.7 % (95 % CI: 28.6 % to 58.9 %, P < 0.001), 27.6 % (95 % CI: 20.4 % to 34.8 %, P < 0.001), 34.3 % (95 % CI: 22.9 % to 45.7 %, P < 0.001). The prevalence of hemorrhagic complications was represented in descending order: surgical site (21.6 %, 95 % CI: 10.3 % to 32.9 %); cannulation site (20.6 %, 95 % CI: 11.8 % to 29.3 %); intracranial (12.2 %, 95 % CI: 9.5 % to 15.0 %); pulmonary (7.7 %, 95 % CI: 5.9 % to 9.6 %); gastrointestinal (6.0 %, 3.7 % to 8.4 %). For the assessment of thrombotic complications, thrombosis in cannulation site had a higher prevalence (28.5 %, 95 % CI: 22.1 % to 34.9 %), followed by DIC (13.5 %, 95 % CI: 8.7 % to 18.3 %) and intracranial thrombosis (4.5 %, 95 % CI: 1.4 % to 7.6 %). Predictors of increased prevalence of hemorrhagic complications included age (P = 0.017) and VV-ECMO support mode (P = 0.029). CONCLUSIONS: Among critically ill pediatric patients, there was a series of hematologic complications can occur during ECMO support. Physicians should pay special attention to the management and establish appropriate treatment programs to reduce the occurrence of hematologic complications.

Diagnostic value of circulating microRNAs for esophageal cancer: a meta-analysis based on Asian data.

BACKGROUND AND OBJECTIVE: esophageal cancer (EC) is one of the most common gastrointestinal malignant diseases. We conducted a comprehensive meta-analysis to explore the clinical applicability of circulating microRNA for the diagnosis of EC. METHODS: as of September 10, 2021, a comprehensive literature search was conducted on PubMed, Embase, Web of Science, Cochrane Library, Wanfang Database, and China National Knowledge Infrastructure (CNKI) to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to evaluate the test performance. The potential sources of heterogeneity were analyzed by subgroup analysis. Deeks' funnel plot was used to assess publication bias. RESULTS: 85 studies from 50 articles were included in the current meta-analysis. The overall pooled sensitivity was 0.82 (95 % CI, 0.79-0.84), specificity was 0.84 (95 % CI, 0.81-0.86), PLR was 4.9 (95 % CI, 4.2-5.9), NLR was 0.22 (95 % CI, 0.19-0.25), DOR was 22 (95 % CI, 17-29) and AUC was 0.89 (95 % CI, 0.86-0.92), respectively. Subgroup analysis suggested that miRNA clusters with a large sample size showed better diagnostic accuracy. Publication bias was not found. CONCLUSIONS: circulating miRNAs can be used as a potential non-invasive biomarker for the diagnosis of EC in Asian populations.

Circulating microRNAs as Potential Biomarkers for the Diagnosis of Endometrial Cancer: a Meta-Analysis.

Endometrial cancer (EC) is the most common female genital tract malignancy worldwide. Many investigators have confirmed the possibility of using circulating miRNAs to diagnose EC; however, the results were inconsistent. Therefore, we performed the current meta-analysis to systematically evaluate the diagnostic value of circulating miRNAs in EC. We carefully searched relevant articles published prior to February 15, 2022 in the databases of PubMed, Embase, Web of Science, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure (CNKI) based on PRISMA statement. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to test the diagnostic accuracy. Furthermore, subgroup analyses were performed to identify the potential sources of heterogeneity, and the Deeks' funnel plot asymmetry test was used to evaluate the potential publication bias. Twenty-one studies from 12 articles including a total of 2305 participants (1341 EC patients and 964 controls) were included in the current diagnostic meta-analysis. The overall pooled results of miRNA for EC diagnosis were: sensitivity, 0.84 (95% CI: 0.79-0.88); specificity, 0.87 (95% CI: 0.79-0.91); PLR, 6.3 (95% CI: 3.9-10.0); NLR, 0.18 (95% CI: 0.13-0.25); DOR, 35 (95% CI: 17-71); and AUC was 0.91 (95% CI: 0.89-0.94). Subgroup analysis suggested that miRNA cluster, serum type, and large sample sizes showed a better diagnostic accuracy. Moreover, there was no significant publication bias. Circulating miRNAs have great potential as novel non-invasive biomarkers for EC diagnosis.

Toxicological and transcriptomic effects in Mythimna separata (Lepidoptera: Noctuidae) exposed to chlorantraniliprole and functional characterization of glutathione S-transferases.

BACKGROUND: Chlorantraniliprole (CAP) is an efficient anthranilic diamide insecticide against economically important pests such as the oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae). Resistance to CAP may develop due to enhanced enzymatic detoxification. The glutathione S-transferase (GST) superfamily in M. separata has not been systematically characterized. The aim of this study was therefore to explore the effects of lethal and sublethal doses of CAP on M. separata larvae, screen differentially expressed genes (DEGs) responding to CAP exposure, identify and characterize the GST superfamily, and analyze the metabolism of CAP by recombinant GSTs. RESULTS: The toxicity bioassay showed that CAP was active against M. separata third-instar larvae. LC50 was 17.615, 3.127, and 1.336 mg/L after 24, 48, and 72 h, respectively. Poisoned larvae showed contracted somites and disrupted midgut. Total GST activity in larvae was significantly elevated 24 h after CAP exposure. RNA-sequencing generated 43 055 unigenes with an average length of 1010 bp, and 567 up-regulated and 692 down-regulated DEGs responding to CAP treatment were screened. Thirty-five GST genes were identified from unigenes, including 31 cytosolic, three microsomal, and one unclassified. The expression profile of GST genes was analyzed using samples from different developmental stages, adult tissues, and CAP treatments. Metabolic assays indicated that CAP was depleted by recombinant MseGSTe2 and MseGSTs6. CONCLUSIONS: This study provides insight into the toxicological and transcriptomic effects in M. separata larvae exposed to CAP. The identification and functional characterization of the GST superfamily will improve our understanding of CAP detoxification by GSTs. © 2022 Society of Chemical Industry.

[Clinical features of intestinal polyps and risk factors for secondary intussusception in children: an analysis of 2 669 cases]. / 2 669ä¾‹å„¿ç«¥è‚ æ¯è‚‰çš„ä¸´åºŠç‰¹å¾åŠç»§å‘è‚ å¥—å çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children. METHODS: A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception. RESULTS: Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception. CONCLUSIONS: Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.

Association of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Coffee Consumption With All-Cause and Cause-Specific Mortality : A Large Prospective Cohort Study.

BACKGROUND: Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without. OBJECTIVE: To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: Data were extracted from the UK Biobank. PARTICIPANTS: A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018. MEASUREMENTS: Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated. RESULTS: During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (>0 to 1.5, >1.5 to 2.5, >2.5 to 3.5, >3.5 to 4.5, and >4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee. LIMITATION: Exposure assessed at baseline might not capture changes in intake over time. CONCLUSION: Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

The epidemiological status of osteoporotic hip fractures: A bicentric comparative and retrospective study.

BACKGROUND: Osteoporotic hip fractures have posed a significant burden to society, and more epidemiological data is required. OBJECTIVE: To compare the epidemiological differences of hip fracture patients in Spain and China. METHOD: This was a retrospective comparative study. Comparisons were made in terms of morbidity, demographic and anthropometric characteristics, length of stay, cost of hospitalization, and mortality by consulting the medical histories of osteoporotic hip fractures in two hospitals. The t test was used for measurement data, and the X2 test was used for count data. The difference is statistically significant when p< 0.05. RESULTS: A total of 757 patients were enrolled in this study, with 426 from Virgen Macarena University Hospital (HUVM) and 331 from Xi'an Daxing Hospital (XDH). The average age was 81.4 ± 9.26 and 76.0 ± 8.08 years; the proportion of women was 74.9% and 68.0%, respectively. The incidence of osteoporotic hip fractures in Seville residents over 50 years old was approximately 239 per 100,000 residents, compared to 158 per 100,000 residents in Xi'an. The timing of surgery in Spanish patients was significantly longer than in Chinese patients, 78.7 ± 48.2 vs. 60.7 ± 43.1 hours, p= 0.000. There were 81 deaths in Spain and 43 deaths in China during the one-year follow-up period (p= 0.026). CONCLUSIONS: In terms of incidence, demographics, surgical methods, and mortality, there are significant differences between hip fracture patients in Seville, Spain and Xi'an, China.

Association between Dietary Diversity Changes and Cognitive Impairment among Older People: Findings from a Nationwide Cohort Study.

BACKGROUND: Little is known about the role of dietary diversity changes in affecting cognitive function among older people. Therefore, we aimed to evaluate the associations between dietary diversity scores (DDS) changes with cognitive impairment among older adults in a large prospective cohort. METHODS: Cognitive function was assessed using the Mini-Mental State Examination questionnaire at baseline and follow-up. A total of 9726 participants without Parkinson's disease, dementia, or cognitive impairment were enrolled at baseline. Nine food groups were collected using simplified FFQ at baseline and follow-up surveys. Then nine food groups change patterns and DDS change patterns (overall, plant-based and animal-based) were assessed. The associations of above DDS changes patterns with subsequent cognitive impairment were evaluated. A multivariable-adjusted Cox proportional hazards model was used to estimate HRs and 95%CIs. RESULTS: We documented 2805 cognitive impairments during 52,325 person-years of follow-up. Compared to high-to-high overall DDS change patterns, the multivariable adjusted HRs (95%CI) for high-to-medium, medium-to-medium, medium-to-low, low-to-medium and low-to-low DDS change patterns were 1.33 (1.12-1.57), 1.11 (0.94-1.32), 1.61 (1.39-1.86), 2.00 (1.66-2.40), 2.30 (1.90-2.78) and 2.80 (2.23-3.53), respectively. Compared with participants with stable DDS change pattern, those who in large improvement of DDS had a 13% lower risk of cognitive impairment (HRs, 0.87; 95%CI: 0.78-0.98). The associations of plant-based DDS, animal-based DDS, or nine food groups DDS change patterns with cognitive impairment were in a similar direction to the main result. CONCLUSIONS: Protective associations between maintaining high DDS and a reduced risk of cognitive impairment were observed. In contrast, lowering or maintaining a lower DDS increases the risk of cognitive impairment.

Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn. / ä¸å¯¹ç§°äºŒç”²åŸºç²¾æ°¨é ¸ä¸Žæ–°ç”Ÿå„¿æŒç»­æ€§è‚ºåŠ¨è„‰é«˜åŽ‹ç— ç†è¿›ç¨‹çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response. METHODS: A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA). RESULTS: For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg. CONCLUSIONS: There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

Virulence of the Bio-Control Fungus Purpureocillium lilacinum Against Myzus persicae (Hemiptera: Aphididae) and Spodoptera frugiperda (Lepidoptera: Noctuidae).

Eco-friendly entomopathogenic fungi are widely used to control agricultural insect pests. Purpureocillium lilacinum (Thom.) Luangsa-ard et al. (Hypocreales: Ophiocordycipitaceae) is a nematophagous fungus used for the bio-control of destructive root-knot nematodes. However, its insecticidal activities against agricultural insect pests haven't been widely studied. In this study, P. lilacinum PL-1 was isolated from soil (Hefei, China) and identified by molecular and morphological analyses. The growth rate, spore production, proteinase, and chitinase activities of the isolate were analyzed. Virulence tests against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae) and fall armyworm (FAW), Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) were performed. The median lethal concentration (LC50) and median lethal time (LT50) against aphids (via immersion) and LT50 against FAW (via injection) were determined. FAW eggs immersed in aqueous conidia suspension were infected after 60 h. Differentially expressed genes (DEGs) in the infection of FAW larvae by P. lilacinum were analyzed by quantitative reverse transcription PCR. The significantly upregulated DEGs include FAW immune genes (antimicrobial peptides, C-type lectins, lysozymes, prophenoloxidase, and peptidoglycan recognition proteins) and fungal pathogenic genes (ligase, chitinase, and hydrophobin). Our data demonstrate that P. lilacinum can be used as an entomopathogenic fungus against agricultural insect pests.

Chemical profiling of Fritillariae thunbergii Miq prepared by different processing methods reveals two new quality markers: Zhebeininoside and imperialine-3-ß-D-glucoside.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae thunbergii Miq (FTM)exhibit versatile biological activities including the significant antitussive and expectorant activities. As a herbal medicine, the therapeutic effects of FTM may be expressed by multi-components which have complicated integration effects on multi-targets. With the time going, the different processing methods of FTM has been changed a lot. Thus，the study described the effect of processing methods to FTM and its quality. MATERIAL AND METHOD: Studies were undertaken by using UHPLC-LTQ Orbitrap MS and pharmacodynamic models. All reagents were involved of analytical grade. While a HPLC-ELSD's method has been developed and validated, a certified Quality System is conformed to ICH requirements. The experimental animals followed the animal welfare guidelines. AIM OF THE STUDY: We aimed to found the differences after the different processing methods of FTM, and to demonstrate the changes could be selected as quality control indicators, and established a method for simultaneous determination of these for quality control. RESULTS: we have previously found two new steroidal alkaloids: zhebeininoside and imperialine-3-ß-D-glucoside from the different processing methods of FTM, which is the difference between the different processing methods of FTM, mainly on the steroidal alkaloids. The activity analysis of zhebeininoside, imperialine-3-ß-D-glucoside, verticine and verticinone showed that the mouse model of cough expectorant has antitussive effect. The positive drug selected was dextromethorphan syrup. The positive group showed biological activity, but the blank group showed nothing. The model group showed illness which means that the model was effective. There are two ways of the mechanism of action of the expectorant action which can make sputum thin, reduce its viscosity, and be easy to cough up, or can accelerate the movement of mucous cilia in the respiratory tract and promote the discharge of sputum. In our study, the content of phenol red was significantly reduced in the administration group. CONCLUSIONS: To sum up, our results suggest that zhebeininoside and other three components cloud be selected as quality control indicators, and a method for simultaneous determination of zhebeininoside and other three components was established for quality control.

Diagnostic accuracy of circulating microRNA in hepatitis B virus-related hepatocellular carcinoma: a meta-analysis based on Asian data.

BACKGROUND AND AIM: hepatitis B virus (HBV) is the main risk factor for hepatocellular carcinoma (HCC). We performed a meta-analysis based on Asian data to evaluate the diagnostic accuracy of circulating microRNA as a non-invasive biomarker in the diagnosis of HBV-related HCC. METHODS: a comprehensive literature search (updated to May 12, 2021) in PubMed, Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing HBV-related HCC were pooled in this meta-analysis. A subgroup analysis was performed to explore heterogeneity, and Deeks' funnel plot was used to assess publication bias. RESULTS: a total of 19 articles including 32 studies were included in the current meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.83 (95 % CI: 0.79 to 0.87), 0.78 (95 % CI: 0.73 to 0.83), 3.9 (95 % CI: 3.0 to 4.9), 0.21 (95 % CI: 0.16 to 0.27), 18 (95 % CI: 12 to 27) and 0.88 (95 % CI: 0.85 to 0.91), respectively. Subgroup analysis shows that miRNA clusters with a large sample size showed better diagnostic accuracy. Although there is no publication bias, the research still has some limitations. CONCLUSIONS: circulating miRNAs could serve as a potential non-invasive biomarker in diagnosing HBV-related HCC in Asian populations.

CTL10 has multiple functions in the innate immune responses of the silkworm, Bombyx mori.

Insect C-type lectins (CTLs) play crucial roles in modulating the humoral and cellular immune responses. In the domesticated silkworm Bombyx mori L., BmCTL10 gene encodes an immulectin containing two carbohydrate recognition domains (CRDs). The phylogenetic analysis showed that BmCTL10 didn't cluster with other immulectin homologs in B. mori. BmCTL10 was mainly expressed in second to fifth instar larvae, wandering stage larvae, prepupa, and adults. In naïve fifth instar larvae, BmCTL10 was predominantly expressed in the fat body and epidermis. In second instar larvae, the topical application of Beauveria bassiana by immersion caused down-regulation of BmCTL10. The intra-hemocoel injection of E. coli, S. aureus, B. bassiana, and 20-hydroxyecdysone in fifth instar larvae caused tissue and time-specific inductions. The recombinant protein (rBmCTL10) can bind to larval hemocytes and various pathogen-associated molecular patterns to enhance hemocyte-mediated nodulation, phagocytosis, and encapsulation. rBmCTL10 caused significant upregulation of most antimicrobial peptides and nitric oxide synthase 1 in hemocytes in vivo. Yeast two-hybrid demonstrated that integrin ß3 and ß4 subunits can interact with BmCTL10. Furthermore, only CRD2 can interact with the ß3, while both CRD1 and CRD2 can interact with the ß4. Taken together, this study showed that BmCTL10 has multiple functions in the innate immune responses of B. mori and two integrin ß subunits are their potential receptors.

AMSP-30 m as a novel HIF-1α inhibitor attenuates the development and severity of adjuvant-induced arthritis in rats: Impacts on synovial apoptosis, synovial angiogenesis and sonic hedgehog signaling pathway.

Growing evidence indicates that synovial hypoxia-inducible factor 1α (HIF-1α) can be as a promising target for RA therapy. We previously reported that AMSP-30 m as a novel HIF-1α inhibitor had potent activities of anticancer metastasis. This study clarified the therapeutic effects of HIF-1α inhibitor AMSP-30 m on adjuvant-induced arthritis (AIA) in rats and explored the possible mechanisms. AMSP-30 m was given intraperitoneally to AIA rats, and its therapeutic effects and anti-inflammatory activity were evaluated. The influences of AMSP-30 m on synovial apoptosis, angiogenesis and sonic hedgehog (Shh) pathway were examined. We found that, accompanied with the inhibition of synovial HIF-1α expression, AMSP-30 m had potent anti-arthritic and anti-inflammatory effects on AIA rats, evidenced by the reduction in paw swelling, arthritis index, histopathological scores, and the production of IL-1ß, IL-6, TNF-α in serum and synovial tissues. AMSP-30 m reduced synovial Ki67 expression and increased TUNEL-positive index, indicating its anti-proliferative and pro-apoptotic effects on AIA synovial cells, which was related to reducing Bcl-2 protein level and increasing Bax, cleaved caspase 3 protein levels. Additionally, AMSP-30 m showed anti-angiogenic effects within AIA synovium, indicated by the reduction of synovial VEGF expression and blood vessels number (especially CD31+/αSMA- immature vessels, but not CD31+/αSMA+ mature vessels). Moreover, AMSP-30 m inhibited the activation of synovial Shh pathway, suggested by the reduction of pathway-related proteins, like Shh, Smo, Gli-1, cyclin D1 and c-Myc. Collectively, HIF-1α inhibitor AMSP-30 m exerted potent anti-arthritic effects on AIA rats possibly by promoting synovial apoptosis, reducing synovial angiogenesis and inhibiting Shh pathway.

Ocular manifestations of multiple sclerosis in patients from three countries: A Web-based survey.

OBJECTIVE: This study evaluates the epidemiological characteristics, ophthalmological manifestations, and different therapeutic options available for patients with multiple sclerosis (MS) in China, Spain, and Cuba. METHODS: A self-designed questionnaire was used to conduct a comparable descriptive cross-sectional study on patients with MS. The survey included patients' demographic data, ocular manifestations related to MS, and treatment methodology followed in the three countries. The online survey was designed using the Wenjuanxing survey platform, and a survey link was circulated through WhatsApp, WeChat, and emails. Quantitative data were expressed as mean and standard deviation, the Kruskal-Wallis test was used for non-parametric variables. Qualitative data were expressed as numerical and percentage. The chi-square test (χ2) was used to compare the group's response categories. The statistical difference was considered significant when p < 0.05. RESULTS: The female-to-male ratio in all the three countries was 2-3:1, and relapsing-remitting MS (RRMS) was the most frequent in all three countries. Vision loss was slow and progressive in half of the patients from the three countries, with no significant differences (p = 0.524). A higher percentage of steroid treatment was observed in Chinese patients in comparison with the patients from other two countries (p < 0.001), and a similar trend was seen in the use of traditional medicines. Almost one-third of patients who did not receive any treatment recovered spontaneously in all the three countries (p = 0.097). CONCLUSIONS: MS occurs more frequently in the relapsing-remitting clinical form and there is a clear female predominance. The first ocular crisis or clinical debut of MS is characterized by slow and progressive visual impairment, increasing and adding to other ocular manifestations during its evolutionary course. Spontaneous recovery of vision after an attack of optic neuritis in the course of MS is possible.