Soluble ORF2 protein enhances HEV replication and induces long-lasting antibody response and protective immunity in vivo.

BACKGROUND AND AIMS: The HEV is a small positive-sense RNA virus that encodes a cytoplasmic form of the capsid protein (ORF2c), essential for virion structure, and a secreted glycosylated form (ORF2s) that accumulates at high titer in serum and can mask neutralizing epitopes. We explored the contribution of ORF2s to HEV replication and its role in generating antibodies against ORF2 in a nonhuman primate model. APPROACH AND RESULTS: We used a recombinant HEV genotype 3 variant that does not express ORF2s due to the introduction of stop codons (ORF2s mut ). Rhesus macaques (RMs) were given intrahepatic injections of infectious wildtype HEV (ORF2s wt ) RNA or a variant lacking ORF2s expression (ORF2s mut ). The replication of the ORF2s mut virus was delayed by ~2 weeks compared with ORF2s wt , and peak titers were nearly tenfold lower. Reversions of the 3 mutations that blocked ORF2s expression were not detected in the ORF2s mut genomes, indicating genetic stability. However, serum antibodies against ORF2 were transiently detected in RMs infected with ORF2s mut , whereas they were long-lasting in RMs infected with ORF2s wt . Moreover, RMs infected with ORF2s mut were more susceptible to reinfection, as evidenced by the viral RNA detected in fecal samples and the expansion of HEV-specific CD8 + T cells. CONCLUSIONS: These findings indicate that ORF2s may be dispensable for viral replication in vivo but is required for long-lived antibody-mediated responses that protect against HEV re-exposure.

Guideline on treating community-acquired pneumonia with Chinese patent medicines.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

Effect of fetal calf serum on propagation of duck hepatitis A virus genotype 3 in duck embryo fibroblast cells.

BACKGROUND: Duck viral hepatitis (DVH) is a highly contagious viral disease affecting ducks. It can be caused by five agents, including duck hepatitis A virus genotypes 1 (DHAV-1), 2 (DHAV-2), and 3 (DHAV-3), as well as duck hepatitis virus 2 and duck hepatitis virus 3. Since 2007, DHAV-3 has been known to be the most prevalent in East and South Asia. So far, the information regarding the propagation of DHAV-3 in cultured cells is limited. In this study, we describe the comparative studies on the growth properties of DHAV-3 in primary duck embryo fibroblast (DEF) cells using two different strains: a virulent strain C-GY and an attenuated strain YDF120. The effect of fetal calf serum (FCS) and chick serum (CS) on DHAV-3 replication and the mechanism of the inhibitory effect conferred by FCS were also investigated. RESULTS: Following serial passages, both C-GY and YDF120 failed to produce cytopathic effect and plaques. The combined quantitative real-time PCR and indirect immunofluorescence staining methods showed that the two viruses could be propagated productively in DEF cells. Investigation of the viral growth kinetics revealed that the two viruses replicated in DEF cells with similar efficiencies, while the viral load of the virulent C-GY strain peaked more rapidly when compared with the attenuated YDF120 strain. Neutralization assay and time-of-drug-addition study indicated that FCS displayed inhibitory effect on DHAV-3 replication. Analysis on the mechanism of action of FCS against DHAV-3 demonstrated that the inhibitory effect was reflected at three steps of the DHAV-3 life cycle including adsorption, replication, and release. CONCLUSIONS: Both virulent and attenuated DAHV-3 strains can establish noncytocidal, productive infections in DEF cells. The virulent strain replicates more rapidly than the attenuated strain in early infection period. FCS has an inhibitory effect on DHAV-3 replication, which may be attributed to action of a non-specific inhibitory factor present in FCS directly on the virus. These findings may provide new insights into the development of potential antiviral agents.

Pathogenicity of a variant goose parvovirus, from short beak and dwarfism syndrome of Pekin ducks, in goose embryos and goslings.

The pathogenicity of a variant goose parvovirus (GPV), isolated from short beak and dwarfism syndrome of Pekin ducks (strain Cherry Valley), was investigated in embryonating goose eggs and goslings. The virus was easily grown in GPV antibody-free goose embryos and caused high mortality and severe lesions of goose embryos, indicating that the variant GPV has good adaptation and high pathogenicity to embryonated goose eggs similar to the classical GPV. Like the third egg-passage virus (strain H) of a classical GPV, the third egg-passage virus (strain JS1) of the variant GPV caused Derzsy's disease in 2-day-old goslings with high mortality. The findings suggest that the variant GPV strain, which had specifically adapted to Pekin ducks, still retained high pathogenicity for its original host. The mortality (73.3-80%) caused by the first and third egg-passages of the variant GPV was somewhat lower than that (93.3%) caused by the third passage virus of the classical GPV, reflecting the higher pathogenicity of the classical GPV for its original host. These findings are likely to reinforce the importance of surveillance for parvoviruses in different waterfowl species and stimulate further study to elucidate the impact of mutations in the GPV genome on its pathogenicity to goslings and ducks.

Genetic characterization of a novel calicivirus from a goose.

A novel calicivirus (strain H146) was detected in a goose and sequenced. The H146 genome consisted of two open reading frames (ORFs) with an 8-nucleotide (nt) overlap between the two ORFs, similar to what has been found in the bat sapovirus TLC58. The virus was most closely related to nacoviruses when comparing the complete genome sequence (49% identity), non-structural region (NS; 31-34% amino acid [aa] sequence identity), and major structural VP1 region (28-30% aa identity), whereas both goose calicivirus N and feline calicivirus were the closest relatives of H146 in the VP2 region (20% aa sequence identity). The levels of divergence between H146 and its closest relatives in different genomic regions are comparable to those between some members of different genera. Phylogenetic analysis based on the NS and VP1 amino acid sequences clearly demonstrated that H146 formed a separate clade. Thus, calicivirus H146 was identified as a founding member of a novel genus for which we propose the name "Sanovirus".

Isolation and detection of duck astrovirus CPH: implications for epidemiology and pathogenicity.

The transmission routes of duck astrovirus CPH (DAstV/CPH) and its pathogenicity in duck embryos were investigated. Using a reverse transcription-polymerase chain reaction (RT-PCR) developed in this study, DAstV/CPH was detected in 23/50 fresh droppings of breeder ducks, 39/65 breeding eggs, 26/31 dead embryos, and 6/10 newly hatched ducklings, which were taken from a Pekin duck farm where DAstV/CPH had previously been identified. This finding, and the detection of DAstV/CPH in 36/130 dead-in-shell duck embryo samples collected from different hatcheries located in six provinces, suggests that the virus may be horizontally and vertically transmitted and associated with hatchability problems. Inoculation and repeated passages in embryonating duck eggs resulted in isolation of DAstV/CPH. The virus caused severe chorioallantoic membrane lesions as well as growth retardation and embryo mortality, indicating that DAstV/CPH is pathogenic for duck embryos. The effect of DAstV/CPH on hatching was confirmed by an embryo infection experiment in which 8/10 9-day-old duck embryos inoculated with the third passage of DAstV/CPH were unable to hatch, with most embryos succumbing in the final stage of incubation. The use of RT-PCR on the hatched ducklings provided evidence that the embryos could develop into infected ducklings.

Bufei Yishen granule combined with acupoint sticking improves pulmonary function and morphormetry in chronic obstructive pulmonary disease rats.

BACKGROUND: The integrated therapy of Bufei Yishen granule and acupoint sticking has been used in the treatment of stable chronic obstructive pulmonary disease (COPD) clinically, with remarkable benefits. This study was initiated to observe the effects of the combination of Bufei Yishen granule and acupoint sticking on pulmonary function and morphormetry in a COPD rat model. METHODS: Rats were randomized into Control, Model, Bufei Yishen (BY), Acupoint sticking (AS), Bufei Yishen + Acupoint sticking (BY + AS) and aminophyline (APL) groups. COPD rats were duplicated by repeated cigarette smoke and bacterial exposures. The rats were treated with normal saline, Bufei Yishen granule, acupoint sticking, Bufei Yishen + Acupoint sticking and aminophylline, respectively, from week 9 through 20. Pulmonary function was measured by using a whole body plethysmograph every 4 weeks. The rats were sacrificed at the end of week 20, and lung tissue histology and ultrastructure was observed under light and electron microscopes. RESULTS: The pulmonary function, including tidal volume (VT), peak expiratory flow (PEF) and expiratory flow at 50 % tidal volume (EF50), was markedly decreased from week 8 in COPD rats (P < 0.05). At week 20, VT, PEF and EF50 were significantly lower in Model group (P < 0.05). Compared with Model group, VT, PEF and EF50 were higher in BY and BY + AS groups (P < 0.05), and EF50 was higher in AS group, while VT was higher in APL group (P < 0.05). Markedly histological and ultrastructural changes, including respiratory membrane thickening, volume density of lamellar corpuscle decreasing, mitochondria reducing in type II alveolar cell, were found in COPD rats and were alleviated in the treated groups, especially in BY and BY + AS groups. CONCLUSION: Bufei Yishen granule and acupoint sticking can improve pulmonary function and lung pathological impairment in COPD rats, the curative effect of the combination is better than acupoint sticking or aminophylline only.

Synthesis of polyvinylethylene glycols (PVEGs) via polyetherification of vinylethylene carbonate by synergistic catalysis.

An efficient and controllable polyetherification of vinylethylene carbonate (VEC) using diols as initiators is developed. By using a synergistic catalysis with palladium and boron reagents under mild conditions, the polymerization process enables the regioselective production of a series of polyvinylethylene glycols (PVEGs) bearing pendent vinyl groups in high yields with accurate molecular weight control and narrow molecular weight distribution. The utility of PVEGs is demonstrated by the production of functional polyurethanes and post-polymerization modification via thiol-ene photo-click chemistry.

Effectiveness of telerehabilitation in patients with post-COVID-19: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the effects of telerehabilitation on clinical symptoms, physical function, psychological function and quality of life (QoL) in patients with post-COVID-19. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: PubMed, Web of Science, Embase and Cochrane Library were searched for publications from 1 January 2020 to 17 April 2024. ELIGIBILITY CRITERIA: RCTs investigating the effects of telerehabilitation in patients with post-COVID-19 were included. The outcomes of interest encompassed clinical symptoms, physical function, psychological function and QoL. Only studies reported in English were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and evaluated the risk of bias. Statistical analysis was conducted using Review Manager V.5.3, employing mean difference (MD) with a 95% CI, and the corresponding P value was used to ascertain the treatment effect between groups. Heterogeneity was quantified using the I2 statistic. The quality of evidence was assessed by GRADE. RESULTS: 16 RCTs (n=1129) were included in this systematic review, 15 of which (n=1095, 16 comparisons) were included in the meta-analysis. The primary pooled analysis demonstrated that, compared with no rehabilitation or usual care, telerehabilitation can improve physical function (measured by 30 s sit-to-stand test [6 RCTs, n=310, MD=1.58 stands, 95% CI 0.50 to 2.66; p=0.004]; 6 min walking distance [6 RCTs, n=324, MD=76.90 m, 95% CI 49.47 to 104.33; p<0.00001]; and physical function from the 36-item short-form health survey [5 RCTs, n=380, MD=6.12 units, 95% CI 2.85 to 9.38; p=0.0002]). However, the pooled results did not indicate significant improvements in clinical symptoms, pulmonary function, psychological function or QoL. The quality of the evidence was graded as low for physical function and Hospital Anxiety and Depression Scale-anxiety and very low for other assessed outcomes. The overall treatment completion rate was 78.26%, with no reports of severe adverse events in any included trials. CONCLUSIONS: Despite the lack of significant improvements in certain variables, telerehabilitation could be an effective and safe option for enhancing physical function in patients with post-COVID-19. It is advisable to conduct further well-designed trials to continue in-depth exploration of this topic. STUDY REGISTRATION: PROSPERO, CRD42023404647.

[International research progress of risk factors, diagnosis and management in early chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) has a high global morbidity and mortality and a severe disease burden, yet progress in treatment and prevention has been slow in recent decades. Early COPD has few symptoms and is severely underdiagnosed and undertreated; it is crucial to search for effective clues of early COPD and provide management interventions. By reviewing the definition, risk factors, diagnosis and management interventions, this study explores the disease evolution of early-stage COPD, which can help clinical practice to develop more effective preventive and therapeutic strategies for stopping or slowing down the natural progression of the disease, improving the long-term prognosis, and reducing the disease burden.

The efficacy of traditional Chinese medicine in the treatment of the COVID-19 pandemic in Henan Province: a retrospective study.

BACKGROUND: Since 2020, novel coronavirus disease (COVID-19) has posed serious threats to health systems and led to tremendous economic decline worldwide. Traditional Chinese medicine (TCM) is considered a promising treatment strategy for COVID-19 in China and is increasingly recognized as a key participant in the battle against COVID-19. Clinicians also need accurate evidence regarding the effectiveness of TCM treatments for COVID-19. METHODS: We retrospectively analyzed patients diagnosed with COVID-19 by collected from the electronic medical records of the hospitals in Henan Province from January 19, 2020, to March 2, 2020. Demographic characteristics, clinical data, frequency analysis of Chinese patent medicines (CPMs), Chinese medicine injections (CMIs), evaluation of baseline symptom scores, nucleic acid negative conversion, length of hospitalization, and mortality rates were studied. RESULTS: Between 15 January 2020 and 2 March 2020, 131 hospitals with 1245 patients were included. Survey response Chinese herbal decoction, CPMs, and CMIs combined with conventional Western medicine (CWM) used for the treatment of COVID-19. The top 8 CPMs were Lianhua Qingwen capsules, Shuanghuanglian oral liquid, Pudilan Xiaoyan oral liquid, Banlangen granules, Lanqin oral liquid, compound licorice tablets, Bailing capsules, montmorillonite powder. The most frequently used CMIs were Xuebijing, Tanreqing, Reduning, Xiyanping and Yanhuning. TCM combined with CWM improved the patients' symptom scores for fever, cough, chest tightness, shortness of breath, and fatigue. Nucleic acid negative conversion occurred at11.55 ± 5.91 d and the average length of hospitalization was 14.92 ± 6.15 d. The mortality rate was approximately 1.76%, which is a reduction in patient mortality. CONCLUSIONS: TCM combined with CWM improved clinical symptoms and reduced hospitalization and mortality rates.

Effects of comprehensive therapy based on traditional Chinese medicine patterns in stable chronic obstructive pulmonary disease: a four-center, open-label, randomized, controlled study.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat chronic obstructive pulmonary disease (COPD) for many years. This study aimed to evaluate the efficacy and safety of the comprehensive therapy based on the three common TCM patterns in stable COPD patients. METHODS: A four-center, open-label randomized controlled method was conducted. A total of 352 patients were divided into the trial group (n = 176, treated with conventional Western medicine and Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules, and Yi-Qi Zi-Shen granules based on the TCM patterns respectively) and the control group (n = 176, treated with conventional Western medicine). The frequency and duration of acute exacerbation, lung function, clinical symptoms, 6-minute walking distance (6MWD), dyspnea scale and quality of life were observed during a 6-month treatment period and at a further 12-month follow-up. RESULTS: A total of 306 patients completed the study fully. The full analysis set (FAS) population was 350 and the per-protocol analysis set (PPS) population was 306. After the 6-month treatment and 12-month follow-up, there were significant differences between the trial and control group in the following: frequency of acute exacerbation (FAS: P = 0.000; PPS: P = 0.000); duration of acute exacerbation (FAS: P = 0.000; PPS: P = 0.001); FEV1 (FAS: P = 0.007; PPS: P = 0.008); symptoms (FAS: P = 0.001; PPS: P = 0.001); 6MWD (FAS: P = 0.045; PPS: P = 0.042); dyspnea scale (FAS: P = 0.002; PPS: P = 0.004); and physical domain (FAS: P = 0.000; PPS: P = 0.000), psychological domain (FAS: P = 0.008; PPS: P = 0.011), social domain (FAS: P = 0.001; PPS: P = 0.000) and environment domain (FAS: P = 0.015; PPS: P = 0.009) of the WHOQOL-BREF questionnaire. There were no differences between the trial and control group in FVC, FEV1% and adverse events. CONCLUSIONS: Based on the TCM patterns, Bu-Fei Jian-Pi granules, Bu-Fei Yi-Shen granules and Yi-Qi Zi-Shen granules have beneficial effects on measured outcomes in stable COPD patients over the 6-month treatment and 12-month follow-up, with no relevant between-group differences in adverse events. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register Center, ChiCTR-TRC-11001406.

Diagnostic value of computed tomography in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: Computed tomography (CT) has been approved for diagnosing chronic obstructive pulmonary disease (COPD). The diagnostic accuracy, however, has never been examined in a systematic review. Therefore, we conducted a meta-analysis to evaluate the accuracy of CT in diagnosing COPD. METHODS: Articles reporting diagnostic accuracy of CT for COPD were searched from seven electronic databases and hand searching. Two reviewers independently extracted data and assessed methodological quality. Sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (LR+ and LR-, respectively), and diagnostic odds ratios (DOR) were pooled using a bivariate model. The diagnostic performance of overall test also was assessed using the visual power of the ROC plot to present the bivariate model. Potential between-study heterogeneity was explored using subgroup analyses. RESULTS: Data were extracted from 8 studies that met the inclusion criteria. All summary measures were grossly heterogeneous and therefore would not be appropriately summarized. These studies were further stratified by type of imaging technique and test index. The summary estimates of CT for COPD were as follows: SEN, 0.83(95% CI, 0.73-0.89); SPE, 0.87(95% CI, 0.70-0.95); LR+, 6.2(95% CI, 2.5-15.5); LR-, 0.20(95% CI, 0.12-0.34); and DOR, 31(95% CI, 8-116). The five summary estimates of CT on the lung density were 0.80 (95% CI, 0.74-0.84), 0.77(95% CI, 0.58-0.89), 3.5(95% CI, 1.8-6.9), 0.26(95% CI, 0.20-0.34) and 13(95% CI, 6-32), respectively. CONCLUSIONS: The current meta-analyses suggest that quantitative measures of CT may be useful to diagnose COPD. Developed CT technology may improve the accuracy of diagnosis. Further studies assessed diagnostic performance of CT are needed.

Randomized controlled multicenter clinical trial for integrated treatment of community-acquired pneumonia based on traditional Chinese medicine syndrome differentiation.

OBJECTIVE: To evaluate the efficacy and safety of treatment based on syndrome differentiation of Traditional Chinese Medicine (TCM) for community-acquired pneumonia (CAP). METHODS: A total of 240 CAP patients were randomly divided into the following two groups: the control group was treated by anti-infection plus conventional medicine treatment; and the trial group was treated by TCM plus the above-mentioned treatment given to the controls. The course of treatment was 14 days, and the patients were followed up for 7 days. RESULTS: Of the 240 patients, 235 accomplished the whole process of treatment. The five patients who withdrew from the study were brought into an intent-to-treat analysis. The therapeutic effects of the trial group were superior to those of the control group (P < 0.01). The trial group took less time to become clinically stable, with a higher score in the quality of life (P < 0.01). There were no significant differences in mortality rate (P > 0.05), white blood cell count (P > 0.05), bacterial clearance rate (P > 0.05), and adverse reactions between the two integrated groups. CONCLUSION: Treatment based on TCM syndrome differentiation for CAP has the advantages of resulting in less time to achieve a stable clinical condition, improvement of clinical symptoms and quality of life, and is comparatively safe.

Prognostic factors for community-acquired pneumonia in middle-aged and elderly patients treated with integrated medicine.

OBJECTIVE: To identify prognostic factors in middle-aged and elderly patients with community-acquired pneumonia (CAP) who underwent integrated interventions involving traditional Chinese medicine (TCM) and modern medicine. METHODS: Patients aged > or =45 years and diagnosed with CAP were divided into a middle-aged cohort (45-59 years) and an elderly cohort (> or =60 years), and clinical data comprising 75 predictor variables in seven classes were collected. After replacing missing data, calibrating multicenter differences and classifYing quantitative data, univariate and multivariate analysis were performed. RESULTS: On multivariate analysis, eight independent risk factors--respiration rate, C reactive protein (CRP), cost of hospitalization, anemia, gasping, confusion, moist rales and pneumonia severity index (PSI)--were correlated with the outcome "not cured" in the elderly cohort. Nine factors--neutrophil percentage (Neu%), blood urea nitrogen (BUN), time to clinical stability, appetite, anemia, confusion, being retired or unemployed, Gram-negative bacterial infection and educational level were correlated with not cured in the middle-aged cohort. CONCLUSION: Independent predictive risk factors correlated with adverse outcomes in elderly patients were higher respiration rate, CRP > or = four times the mean or median for the patient's center, cost of hospitalization >11,323 RMB and PSI >11, plus anemia, gasping, confusion and moist rales; those in middle-aged patients were higher Neu%, BUN > or = mean or median, loss of appetite, anemia, confusion, being retired or unemployed and lower educational level. Gram-negative bacterial infection and time to clinical stability >9 days were protective factors.

[Construction and verification of the risk prediction model for acute exacerbation within 6 months in patients with chronic obstructive pulmonary disease: a secondary analysis based on previous research data].

OBJECTIVE: To construct the risk prediction model of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and verify its effectiveness based on deep learning and back propagation algorithm neural network (BP neural network). METHODS: Based on the relevant data of 1 326 patients with chronic obstructive pulmonary disease (COPD) in the team's previous clinical study, the acute exacerbation, and its risk factors during the stable period and 6 months of follow-up were recorded and analyzed. Combined with previous clinical research data and expert questionnaire results, the independent risk factors of AECOPD after screening and optimization by multivariate Logistic regression including gender, body mass index (BMI) classification, number of acute exacerbation, duration of acute exacerbation and forced expiratory volume in one second (FEV1) were used to build the BP neural network by Python 3.6 programming language and Tensorflow 1.12 deep learning framework. The patients were randomly selected according to the ratio of 4:1 to generate the training group and the test group, of which, the training group had 1 061 sample data while the test group had 265 pieces of sample data. The training group was used to establish the prediction model of neural network, and the test group was used for back-substitution test. When using the training group data to construct the neural network model, the training group was randomly divided into training set and verification set according to the ratio of 4:1. There were 849 training samples in the training set and 212 verification samples in the verification set. The optimal model was screened by adjusting the parameters of the neural network and combining the area under the receiver operator characteristic curve (AUC), and the sample data of the test group was substituted into the model for verification. RESULTS: The independent risk factors including gender, BMI classification, number of acute exacerbation, duration of acute exacerbation and FEV1 were collected from the team's previous clinical research, and the AECOPD risk prediction model was constructed based on deep learning and BP neural network. After 10 000 training sessions, the accuracy of the AECOPD risk prediction model in the validation set of the training group was 83.09%. When the number of training times reached 8 000, the accuracy basically tended to be stable and the prediction ability reached the upper limit. The AECOPD risk prediction model trained for 10 000 times was used to predict the risk of the validation set data, and the receiver operator characteristic curve (ROC curve) analysis showed that the AUC was 0.803. When using this model to predict the risk of the data of the test group, the accuracy rate was 81.69%. CONCLUSION: The risk prediction model based on deep learning and BP neural network has a medium level of prediction efficiency for acute exacerbation within 6 months in COPD patients, which can evaluate the risk of AECOPD and assist the clinic in making accurate treatment decisions.

Prevalence of Pulmonary Embolism and Deep Venous Thromboembolism in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) increases the risk of pulmonary embolism (PE) and deep venous thrombosis (DVT). AECOPD combined with PE and DVT poses challenges for treatment and management. This necessitates prevention and management to estimate the overall prevalence of PE and DVT among patients with AECOPD and to identify the risk factors. Methods: We searched the PubMed, Embase, and Cochrane Library databases from their inception to January 9, 2021 and extracted the data from the included studies. The risk of bias was assessed for each study. We separately calculated the prevalence of PE and DVT in patients with AECOPD. Subgroup analysis and meta-regression analyses were performed to determine the sources of heterogeneity. Furthermore, we assessed the publication bias. Results: The meta-analysis included 20 studies involving 5,854 people. The overall prevalence of PE and DVT among patients with AECOPD was 11% (95% CI: 0.06-0.17) and 9% (95% CI: 0.06-0.12), respectively. Subgroup analysis demonstrated that the prevalence of PE among patients with AECOPD was 12, 2, 7, and 16% in the European, South-East Asia, Western Pacific, and Eastern Mediterranean regions, respectively, and the DVT was 10, 9, 9, and 4%, respectively. The prevalence of PE among patients with AECOPD aged ≥ 70 and <70 years old was 6 and 15%, respectively, and the DVT was 8 and 9%, respectively. The prevalence of PE among patients with AECOPD diagnosed within 48 h and other times (beyond 48 h or not mentioned) was 16 and 6%, respectively, and DVT was 10 and 7%, respectively. Conclusion: The pooled prevalence of PE and DVT among patients with AECOPD was insignificantly different between the different age groups and the WHO regions. However, the early diagnosis was associated with a higher prevalence of PE. Clinicians and the public need to further improve the awareness of prevention and management for PE and DVT among patients with AECOPD. Systematic Review Registration: PROSPERO, identifier CRD42021260827.

[CCERW: a new rule to predict treatment failure in patients with community-acquired pneumonia in middle aged and elderly people].

OBJECTIVE: To develop and validate a clinical rule to predict treatment failure in middle-aged and elderly patients suffering from community-acquired pneumonia (CAP) in China, and to compare it with other prognostic rules. METHODS: Data of 58 variables affiliated to 6 aspects, including demographics, underlaying diseases, previous status, complications, symptoms, signs and laboratory examination results from the CAP patients aged≥45 years admitted to the respiratory departments in three university affiliated hospitals between December 17, 2006 and December 22, 2008 were enrolled prospectively and then validated in two groups to create a derivation cohort with 75% of the patients for rule development and an internal validation cohort with the other 25% for internal test. An external validation cohort was formed at the same time with patients admitted to the other university affiliated hospital for external test. The single outcome was treatment failure at the time of 14 days after admitted or at discharge from hospital. Univariate analysis, multivariate analysis and receiver operating characteristics (ROC) curve were used for the rule establishment, assessment and comparison among the pneumonia severity index (PSI), CURB65 [confusion, blood urea nitrogen>6.8 mmol/L, respiratory rate (RR)≥30 breaths per minute, systolic blood pressure (SBP)<90 mm Hg (1 mm Hg=0.133 kPa) or diastolic blood pressure (DBP)≤60 mm Hg, age≥65 years] and CRB65 (confusion, RR≥30 breaths per minute, SBP<90 mm Hg or DBP ≤60 mm Hg, age≥65 years). RESULTS: The data of a total of 539 patients in three hospitals were enrolled for analysis. Of those, 400 and 139 patients were randomly allocated into the derivation cohort or internal validation cohort respectively. Meanwhile, 159 patients were enrolled in the external validation cohort. Analyzing the data from 400 patients in the derivation cohort, 33 variables of 6 aspects had significant difference between cure and treatment failure outcome in the univariate analysis. Then, in the multivariate analyses, five independent predictive factors showed significant difference, including confusion (C), creatinine<60 µmol/L, electrolyte disturbances (E), respiratory failure (R), white blood cell (WBC)>7.5×10(9)/L. A clinical prediction rule CCERW based on these variables showed that the treatment failure outcome increased directly with increasing scores: 5.5%-9.1%, 12.8%-20.0% and 31.0%-40.5% for scores of 0-1, 2 and 3-6, respectively. ROC curve analysis yielded an area under the curve (AUC) for CCERW of 0.709 [95% confidence intervals (95%CI) 0.638-0.780], 0.725 (95%CI 0.613-0.838) and 0.686 (95%CI 0.590-0.782) in the derivation, internal and external validation cohorts respectively; and in the same manner, of 0.710 (95%CI 0.659-0.761) for total 698 patients, which was better than PSI, CURB65 and CRB65, at 0.667 (95%CI 0.614-0.719), 0.648 (95%CI 0.592-0.705), and 0.584 (95%CI 0.530-0.638), respectively. CONCLUSION: CCERW can help physicians to distinguish high and low risk leading to treatment failure in middle-aged and elder patients with CAP, and has better predictable capability than PSI, CURB65 and CRB65. We prudent recommend the simple rule can be used in the middle-aged and elder patients with CAP of Han race people in China.

Mechanisms of Hepatocellular Injury in Hepatitis A.

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8+ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.

[Application progress of metabonomics evaluation methods in bronchial asthma].

Bronchial asthma (asthma) is a complex heterogeneous disease, with a high rate of missed diagnosis and misdiagnosis. Repeated attacks of bronchial asthma can cause complications such as chronic obstructive pulmonary disease, emphysema, and pulmonary heart disease. In recent years, mass-spectrometry-based metabolomics has developed rapidly. It can sensitively identify metabolic fluctuations and pathological changes in patients with asthma. By analyzing the molecules produced by various metabolic pathways,it can help us to find relevant biomarkers and provide a better method for early diagnosis and severity assessment of asthma. We reviewed and analyzed the literature of metabolomics technology in disease progression, early diagnosis and severity assessment, so as to provide reference for asthma research.