Design and Synthesis of Cyclolipopeptide Mimics of Dysoxylactam A and Evaluation of the Reversing Potencies against P-Glycoprotein-Mediated Multidrug Resistance.

Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, 56, with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 µM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that 56 reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression. Notably, compound 56 effectively restored the sensitivity of MDR tumors to VNR in vivo at a dosage without obvious toxicity.

Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level: A single-center, retrospective cohort study.

BACKGROUND: Autoimmune pancreatitis (AIP) has been linked with elevated immunoglobulin (Ig) G4 levels. The characteristics and outcomes of AIP based on serum markers have not been fully evaluated. AIM: To compare clinical features, treatment efficacy, and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse. METHODS: A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021. According to the serum IgG4 level, all patients were divided into two groups, the abnormal group (n = 148) with a high level of IgG4 [> 2 × upper limit of normal (ULN)] and the normal group (n = 65). The t-test or Mann-Whitney U test was used to compare continuous variables. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were established to assess the cumulative relapse rates. Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse. RESULTS: Compared with the normal group, the abnormal group had a higher average male age (60.3 ± 10.4 vs 56.5 ± 12.9 years, P = 0.047); higher level of serum total protein (72.5 ± 7.9 g/L vs 67.2 ± 7.5 g/L, P < 0.001), IgG4 (1420.5 ± 1110.9 mg/dL vs 252.7 ± 106.6 mg/dL, P < 0.001), and IgE (635.6 ± 958.1 IU/mL vs 231.7 ± 352.5 IU/mL, P = 0.002); and a lower level of serum complement C3 (100.6 ± 36.2 mg/dL vs 119.0 ± 45.7 mg/dL, P = 0.050). In addition, a lower number of cases with abnormal pancreatic duct and pancreatic atrophy (23.6% vs 37.9%, P = 0.045; 1.6% vs 8.6%, P = 0.020, respectively) and a higher rate of relapse (17.6% vs 6.2%, P = 0.030) were seen in the abnormal group. Multivariate analyses revealed that serum IgG4 [(> 2 × ULN), hazard ratio (HR): 3.583; 95% confidence interval (CI): 1.218-10.545; P = 0.020] and IgA (> 1 × ULN; HR: 5.908; 95%CI: 1.199-29.120; P = 0.029) and age > 55 years (HR: 2.383; 95%CI: 1.056-5.378; P = 0.036) were independent risk factors of relapse. CONCLUSION: AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate. Several factors, such as IgG4 and IgA, are associated with relapse.

Update and latest advances in mechanisms and management of colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.

Altered fear engram encoding underlying conditioned versus unconditioned stimulus-initiated memory updating.

It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Research progress on main disease-related factors of healthy life expectancy / 中华预防医学杂志

International research on healthy life expectancy (HALE) focuses on inequality of socioeconomic status and individual natural attributes. With the acceleration of population ageing and the increase in average life expectancy, the extension of unhealthy life expectancy and the increase of social and economic burden caused by diseases have gradually attracted the attention of countries around the world. Therefore, the evaluation of disease factors affecting HALE is a meaningful direction in the future. This study introduces the development process and commonly used measurement methods of HALE. According to the definition of health from the Global Burden of Disease Study and World Health Organization, physical and mental diseases such as cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes, malignant tumors and depression were selected to summarize the impact of these diseases and pre-disease states on HALE. It is expected to provide a theoretical basis for the formulation of relevant public health policies and the improvement of quality of life in China.

Association between serum lysophosphatidylcholine level and elderly health index in older people from longevity areas of Guangxi Province / 中华预防医学杂志

Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: We included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Nanocrystalline (AlTiVCr)N Multi-Component Nitride Thin Films with Superior Mechanical Performance.

Multi-component nitride thin films usually show high hardness and good wear resistance due to the nanoscale structure and solid-solution strengthening effect. However, the state of N atoms in the thin film and its effects on the compressive strength is still unclear. In this work, (AlTiVCr)N multi-component nitride thin films with a face-centered cubic (FCC) structure prepared by the direct current magnetron sputtering method exhibit a superior strength of ~4.5 GPa and final fracture at a strain of ~5.0%. The excellent mechanical properties are attributed to the synergistic effects of the nanocrystalline structure, covalent bonding between N and metal atoms, and interstitial strengthening. Our results could provide an intensive understanding of the relationship between microstructure and mechanical performances for multi-component nitride thin films, which may promote their applications in micro- and nano-devices.

Application of Soil and Water Assessment Tool (SWAT) to evaluate the fates of nitrogenous fertilizer in subtropical mountainous watershed tea farms.

Extensive nutrient loss is one of the most challenging issues faced by agricultural production regions worldwide. However, diffuse pollution in the subtropical mountainous watersheds is rarely simulated. A watershed model with regional parameter values is essential for watershed management. In this study, SWAT, one of the most popular models was applied to simulate daily discharge (years of 2008-2014), NO3-N flux (2012-2014), and tea yield (2012-2014) in the Ping-Lin watershed (PLW) of Taiwan, as well as to test the effectiveness of a modified fertilization strategy. The results demonstrated that SWAT was capable of simulating daily discharge variation, daily riverine NO3-N flux, and tea yield in the PLW. NO3-N yield of the tea farm (47 kg/ha/yr) was 9 times higher than that of the forest (5.1 kg/ha/yr). A significant proportion (~ 50%) of the input nitrogen (including dry/wet deposition and fertilizer) infiltrated into the soil, resulting in a poor fertilizer uptake efficiency of the tea tree. It was demonstrated that the modified fertilization strategy (apply fertilizer in small rainfall event, i.e., daily rainfall < 20 mm/day, and not in a single day) could increase the nitrogen uptake and harvest yield of the tea tree by 14% and 4%, respectively, with a 10% reduction in nitrogen input. Furthermore, this strategy significantly reduced the nitrogen yields from surface flow (75%), lateral flow (36%), percolation (50%), and groundwater (48%). A popular model with verified parameter values could help in developing a win-win strategy for both farmers and regulators, thus realizing the goals of sustainable agricultural practices.

Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis.

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2. Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model. Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT. Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.

Associations between Temperature and Influenza Activity: A National Time Series Study in China.

Previous studies have reported that temperature is the main meteorological factor associated with influenza activity. This study used generalized additive models (GAMs) to explore the relationship between temperature and influenza activity in China. From the national perspective, the average temperature (AT) had an approximately negative linear correlation with the incidence of influenza, as well as a positive rate of influenza H1N1 virus (A/H1N1). Every degree that the monthly AT rose, the influenza cases decreased by 2.49% (95%CI: 1.24%-3.72%). The risk of influenza cases reached a peak at -5.35 °C with RRs of 2.14 (95%CI: 1.38-3.33) and the monthly AT in the range of -5.35 °C to 18.31 °C had significant effects on the incidence of influenza. Every degree that the weekly AT rose, the positive rate of A/H1N1 decreased by 5.28% (95%CI: 0.35%-9.96%). The risk of A/H1N1 reached a peak at -3.14 °C with RRs of 4.88 (95%CI: 1.01-23.75) and the weekly AT in the range of -3.14 °C to 17.25 °C had significant effects on the incidence of influenza. Our study found that AT is negatively associated with influenza activity, especially for A/H1N1. These findings indicate that temperature could be integrated into the current influenza surveillance system to develop early warning systems to better predict and prepare for the risks of influenza.

Epidemiological features and spatial-temporal distribution of visceral leishmaniasis in mainland China: a population-based surveillance study from 2004 to 2019.

BACKGROUND: Although visceral leishmaniasis (VL) was largely brought under control in most regions of China during the previous century, VL cases have rebounded in western and central China in recent decades. The aim of this study was to investigate the epidemiological features and spatial-temporal distribution of VL in mainland China from 2004 to 2019. METHODS: Incidence and mortality data for VL during the period 2004-2019 were collected from the Public Health Sciences Data Center of China and annual national epidemic reports of VL, whose data source was the National Diseases Reporting Information System. Joinpoint regression analysis was performed to explore the trends of VL. Spatial autocorrelation and spatial-temporal clustering analysis were conducted to identify the distribution and risk areas of VL transmission. RESULTS: A total of 4877 VL cases were reported in mainland China during 2004-2019, with mean annual incidence of 0.0228/100,000. VL incidence showed a decreasing trend in general during our study period (annual percentage change [APC] = -4.2564, 95% confidence interval [CI]: -8.0856 to -0.2677). Among mainly endemic provinces, VL was initially heavily epidemic in Gansu, Sichuan, and especially Xinjiang, but subsequently decreased considerably. In contrast, Shaanxi and Shanxi witnessed significantly increasing trends, especially in 2017-2019. The first-level spatial-temporal aggregation area covered two endemic provinces in northwestern China, including Gansu and Xinjiang, with the gathering time from 2004 to 2011 (relative risk [RR] = 13.91, log-likelihood ratio [LLR] = 3308.87, P < 0.001). The secondary aggregation area was detected in Shanxi province of central China, with the gathering time of 2019 (RR = 1.61, LLR = 4.88, P = 0.041). The epidemic peak of October to November disappeared in 2018-2019, leaving only one peak in March to May. CONCLUSIONS: Our findings suggest that VL is still an important endemic infectious disease in China. Epidemic trends in different provinces changed significantly and spatial-temporal aggregation areas shifted from northwestern to central China during our study period. Mitigation strategies, including large-scale screening, insecticide spraying, and health education encouraging behavioral change, in combination with other integrated approaches, are needed to decrease transmission risk in areas at risk, especially in Shanxi, Shaanxi, and Gansu provinces.

Membrane Nanopores Induced by Nanotoroids via an Insertion and Pore-Forming Pathway.

The formation of membrane nanopores is one of the crucial activities of cells and has attracted considerable attention. However, the understanding of their types and mechanisms is still limited. Herein, we report a novel nanopore formation phenomenon achieved through the insertion of polymeric nanotoroids into the cellular membrane. As revealed by theoretical simulations, the nanotoroid can embed in the membrane, leaving a nanopore on the cell. The through-the-cavity wrapping of lipids is critical for the retention of the nanotoroid in the membrane, which is attributed to both a relatively large inner cavity of the nanotoroid and a moderate attraction between the nanotoroid and membrane lipids. Under the guidance of the simulation predictions, experiments using polypeptide toroids as pore-forming agents were performed, confirming the unique biophysical phenomenon. This work demonstrates a distinctive pore-forming pathway, deepens the understanding of the membrane nanopore phenomenon, and assists in the design of advanced pore-forming materials.

Early Spatiotemporal Patterns and Population Characteristics of the COVID-19 Pandemic in Southeast Asia.

This observational study aims to investigate the early disease patterns of coronavirus disease 2019 (COVID-19) in Southeast Asia, consequently providing historical experience for further interventions. Data were extracted from official websites of the WHO and health authorities of relevant countries. A total of 1346 confirmed cases of COVID-19, with 217 recoveries and 18 deaths, were reported in Southeast Asia as of 16 March 2020. The basic reproductive number (R0) of COVID-19 in the region was estimated as 2.51 (95% CI:2.31 to 2.73), and there were significant geographical variations at the subregional level. Early transmission dynamics were examined with an exponential regression model: y = 0.30e0.13x (p < 0.01, R2 = 0.96), which could help predict short-term incidence. Country-level disease burden was positively correlated with Human Development Index (r = 0.86, p < 0.01). A potential early shift in spatial diffusion patterns and a spatiotemporal cluster occurring in Malaysia and Singapore were detected. Demographic analyses of 925 confirmed cases indicated a median age of 44 years and a sex ratio (male/female) of 1.25. Age may play a significant role in both susceptibilities and outcomes. The COVID-19 situation in Southeast Asia is challenging and unevenly geographically distributed. Hence, enhanced real-time surveillance and more efficient resource allocation are urgently needed.

Epidemiological Trends and Hotspots of Other Infectious Diarrhea (OID) in Mainland China: A Population-Based Surveillance Study From 2004 to 2017.

Background: The incidence of other infectious diarrhea (OID) ranked second in class C notifiable disease in China. It has posed a great threat to public health of all age groups. The aim of this study was to investigate the epidemiological trends and hotspots of OID in mainland China. Materials and Methods: Incidence and mortality data for OID stratified by date, age and region from 2004 to 2017 was extracted from the data-center of China public health science. Joinpoint regression and space-time analyses were performed to explore the epidemiological trends and hotspots of OID. Results: The average annual incidence of OID was 60.64/100,000 and it showed an increased trend in the mainland China especially after 2006 (APC = 4.12, 95 CI%: 2.06-6.21). Children of 0-4 year age group accounts for 60.00% (5,820,897/11,414,247) of all cases and its incidence continuously increased though 2004-2017 (APC = 6.65, 95 CI%: 4.39-8.96). The first-level spatial and temporal aggregation areas were located in Beijing and Tianjin, with the gathering time from 2005/1/1 to 2011/12/31 (RR = 5.52, LLR = 572893.59, P < 0.001). The secondary spatial and temporal aggregation areas covered Guangdong, Guangxi, Hainan and Guizhou from 2011/1/1 to 2017/12/31 (RR = 1.98, LLR = 242292.72, P < 0.001). OID of Tianjin and Beijing presented a decreased trend since 2006. However, the incidence of OID in Guangdong, Guangxi, Hainan and Guizhou showed increased trends through 2004-2017. Conclusion: Our study showed that OID showed a constantly increasing trend and brought considerable burden in China especially in the 0-4 age group. The high-risk periods and clusters of regions for OID were identified, which will help government develop disease-specific and location-specific interventive measures.

Fecal Fusobacterium nucleatum harbored virulence gene fadA are associated with ulcerative colitis and clinical outcomes.

OBJECT: Fusobacterium nucleatum (F.nucleatum), a gram-negative, obligately anaerobe of oral commensal，has been regarded as culprit of periodontal diseases previously and is being unveiled as possible pathogen of gastrointestinal disorders. The key virulence factor of F.nucleatum is FadA adhesin for binding and invading of the host's epithelial cells. Here, we detected fecal F.nucleatum and virulence gene fadA in patients with ulcerative colitis(UC) and evaluated the clinical relevance with UC. METHODS AND SUBJECTS: A total of 310 subjects were enrolled including 100 patients with UC, 70 healthy controls (HC), 70 patients with irritable bowel syndrome subtype diarrhea(IBS-D), and 70 colorectal cancer patients(CRC). Stool samples of UC patients compared with healthy controls as well as IBS-D and CRC patients were collected for Polymerase Chain Reaction(PCR) detection of F.nucleatum (based on 16s rRNA) and virulence gene fadA. RESULTS: The detection rate of 16s rRNA based PCR for F.nucleatum of UC patients(39/100, 39.00%) and CRC(26/70, 37.14%) patients are significantly higher than HC (12/70, 17.14%, P < 0.01) and IBS-D patients (14/70, 20.00%, P < 0.01). Moreover, 19 samples were detected fadA positive from 39 F.nucleatum positive samples of UC patients (19/39, 48.72%), which is significantly higher than HC(2/12, 16.66%, P < 0.05). There were 3 samples detected fadA positive from 14 F.nucleatum positive samples of IBS-D patients(3/14, 21.43%) and 13 out of 26(50.00%) of CRC patients, which were both no significant differences compared with UC patients(21.4% vs 48.72%, P > 0.05; 50.00% vs 48.72%, P > 0.05). For both F.nucleatum and fadA gene positive patients, there were no statistical significances between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cells(WBC), and hemoglobin compared with negative patients(defined by either F.nucleatum or fadA negative, or both negative). However, it is worth noting that detection rate of F.nucleatum with virulence gene fadA in patients of severe ulcerative colitis was significantly higher than patients with mild and moderate colitis(28.89% vs 10.91%, P < 0.05). In addition, the fecal F.nucleatum and fadA gene positive patients were more likely to have pancolitis other than left-sided colitis(pancolitis/left-sided colitis: 26.92% vs 10.42%, P < 0.05). CONCLUSIONS: The presence of F.nucleatum and fadA gene increased in UC patients, especially in patients with severe colitis and pancolitis. Strains of F.nucleatum harbored virulence gene fadA are suggested to play a role in the pathogenesis of UC.

Characteristics of Viral Shedding Time in SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis.

Background: The viral shedding time (VST) of SARS-CoV-2 mainly determines its transmission and duration of infectiousness. However, it was heterogeneous in the existing studies. Here, we performed a meta-analysis to comprehensively summarize the VST of SARS-CoV-2. Methods: We searched PubMed, Web of Science, MedRxiv, BioRxiv, CNKI, CSTJ, and Wanfang up to October 25, 2020, for studies that reported VSTs of SARS-CoV-2. Pooled estimates and 95% CIs for the VSTs were calculated using log-transformed data. The VSTs in SARS-CoV-2 infections based on different demographic and clinical characteristics, treatments and specimens were stratified by subgroup analysis. Results: A total of 35 studies involving 3,385 participants met the inclusion criteria. The pooled mean VST was 16.8 days (95% CI: 14.8-19.4, I2 = 99.56%) in SARS-CoV-2 infections. The VST was significantly longer in symptomatic infections (19.7 days, 95% CI: 17.2-22.7, I2 = 99.34%) than in asymptomatic infections (10.9 days, 95% CI: 8.3-14.3, I2 = 98.89%) (P < 0.05). The VST was 23.2 days (95% CI: 19.0-28.4, I2 = 99.24%) in adults, which was significantly longer than that in children (9.9 days, 95% CI: 8.1-12.2, I2 = 85.74%) (P < 0.05). The VST was significantly longer in persons with chronic diseases (24.2 days, 95% CI: 19.2-30.2, I2 = 84.07%) than in those without chronic diseases (11.5 days, 95% CI: 5.3-25.0, I2 = 82.11%) (P < 0.05). Persons receiving corticosteroid treatment (28.3 days, 95% CI: 25.6-31.2, I2 = 0.00%) had a longer VST than those without corticosteroid treatment (16.2 days, 95% CI: 11.5-22.5, I2 = 92.27%) (P = 0.06). The VST was significantly longer in stool specimens (30.3 days, 95% CI: 23.1-39.2, I2 = 92.09%) than in respiratory tract specimens (17.5 days, 95% CI: 14.9-20.6, I2 = 99.67%) (P < 0.05). Conclusions: A longer VST was found in symptomatic infections, infected adults, persons with chronic diseases, and stool specimens.

Concurrence and impact of hepatic steatosis on chronic hepatitis B patients: a systematic review and meta-analysis.

BACKGROUND: The association between hepatic steatosis (HS) and chronic hepatitis B (CHB) remains controversial. We performed a systematic review and meta-analysis to investigate the latest concurrence rate and impact of HS on CHB patients. METHODS: Relevant studies were identified by searching PubMed, EMBASE, and the Cochrane Library from January 1, 2000 to December 2, 2020. We calculated the pooled prevalence of HS in CHB patients using a random effects model. A subgroup analysis was performed to explore the impact of HS on CHB patients. This study is registered with PROSPERO (No. CRD42021242584). RESULTS: A total of 98 studies with a population of 48,472 patients were included. The global prevalence of HS in CHB patients was 34.93% [95% confidence interval (CI): 32.01-37.90%]. Overweight status, hypertension, diabetes, hyperlipidemia, and metabolic syndrome showed a higher risk for developing HS in CHB patients, while positive hepatitis B e antigen (HBeAg) status was negatively associated with the presence of HS [odds ratio (OR) =0.81, 95% CI: 0.70-0.93]. The pooled analysis showed no significant association between HS and fibrosis progression (OR =0.68, 95% CI: 0.44-1.05). However, the coexistence of HS was negatively associated with the antiviral therapy response in CHB patients, including virological response (OR =0.69, 95% CI: 0.48-0.99) and alanine aminotransferase (ALT) normalization (OR =0.44, 95% CI: 0.28-0.69). DISCUSSION: The global prevalence of HS in CHB patients is higher than previously estimated. The concurrence of HS could impact the replication of HBV and the effectiveness of antiviral therapy in CHB patients. However, coexistence with HS did not show a higher risk of developing advanced fibrosis in CHB patients.

Coronaviruses and gastrointestinal diseases.

The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.