AIMS:The objective of this study is to explore the regulatory role of DNA methylation in delayed encephalopathy after carbon monoxide poisoning (DEACMP) and to identify candidate epigenetic biomarkers. METHODS:In this study, multi-omics analyses such as methylomics, transcriptomics, pyrophosphate sequencing, qRT-PCR, immunohistochemistry, and western blotting were utilized to investigate the role of epigenetic regulation and altered gene expression in the pathogenesis of DEACMP. RESULTS:Using integrated analysis, we identified 168 differentially methylated CpGs sites, 334 differentially expressed genes, and two differentially methylated and differentially expressed genes (DAB2IP and SMYD3) in the DEACMP group. The pyrosequencing results further revealed hypomethylation of DAB2IP and hypermethylation of SMYD3. Moreover, we verified the upregulation of DAB2IP expression accompanied by the downregulation of SMYD3 expression in the DEACMP rats model. CONCLUSION:This study, based on dysregulated DNA methylation and gene expression profiles, identified and validated two DEACMP-related genes (DAB2IP and SMYD3) that could serve as epigenetic biomarkers and potential therapeutic targets for DEACMP.

Acute lung injury (ALI) is a life‐threatening condition with excessive immune activation and dysregulated inflammation. Dendritic cells (DCs) play a pivotal role in immune regulation; however, their exact contribution to ALI pathogenesis remains unclear. This study demonstrates that the upregulation of the glycolytic regulator 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 2 (PFKFB2) by hypoxia‐inducible factor‐1α (HIF‐1α) enhances glycolysis, drives DC maturation, and exacerbates inflammation, contributing to the pathogenesis of ALI. The findings reveal that HIF‐1α directly binds to the PFKFB2 promoter and drives its transcription, leading to increased glycolysis, accelerated DC maturation, and amplified immune activation. In paraquat (PQ)‐ALI and lipopolysaccharide (LPS)‐ALI mouse models, DC‐specific PFKFB2 knockout and DC‐targeted delivery of HIF‐1α inhibitor‐loaded nanoparticles each significantly suppressed DC maturation and alleviated ALI severity. Analyses of lung tissues from patients with PQ poisoning, secondary bacterial pneumonia (2°BP), and Coronavirus Disease 2019 (COVID‐19), as well as from normal controls, confirmed these findings, showing increased PFKFB2 expression and DC maturation during ALI. These findings highlight the HIF‐1α–PFKFB2 signaling pathway as a critical regulator of glycolysis‐driven DC maturation and immune activation, offering novel insights into immunometabolic regulation and a promising therapeutic target for ALI.

Background: Pneumocystis jirovecii pneumonia (PJP), caused by Pneumocystis jirovecii (PJ), is an opportunistic infection prevalent in clinical settings. However, large-scale studies on the efficacy of metagenomic next-generation sequencing (mNGS)-based diagnosis of PJP in patients without human immunodeficiency virus infection (HIV) are lacking. Methods: The study included 168 patients diagnosed with either PJP (84) or other pneumonia types (non-PJP patients; 84) who underwent mNGS-mediated bronchoalveolar lavage fluid (BALF) analysis, Gomori methenamine silver (GMS) staining and peripheral blood 1,3-beta-D-glucan (BDG) testing. Additionally, patients with PJP were categorized into survival (n = 55) and non-survival (n = 29) groups based on a 28-day in-hospital outcome to compare clinical characteristics, inflammatory markers, PJ sequence counts in BALF, and serum BDG levels. Results: Serum BDG levels, the proportion of patients with serum BDG of > 60 pg/mL and > 200 pg/mL were notably higher in the PJP group compared with that in the non-PJP group (all P< 0.05). The sensitivity and specificity of mNGS in diagnosing PJP were higher than those of serum BDG testing (sensitivity: 100 % vs. 63.0 %; specificity: 96.4 % vs. 90.4 %; both P< 0.05). The most common coinfection was viral (30.9 %), followed by bacterial–viral coinfections (13.0 %). Treatment regimens were altered for 83.3 % of patients based on the mNGS results. The patients in the non-survival group showed markedly higher serum BDG levels (142.5 [32.7, 277.7] vs. 123.0 [34.0, 164.0]) and a higher proportion of PJ sequence counts of > 1 × 105 (13.7 % vs. 0, P= 0.005) relative to those in the survival group. Conclusion: The mNGS showed superior performance over serum BDG testing and GMS staining in diagnosing PJP in non-HIV patients and identified a broader range of coinfections.

BACKGROUND AND AIMS:Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. METHODS:We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. RESULTS:A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. CONCLUSIONS:The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.

Abstract Background Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. Methods Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. Results The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61–80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. Discussion In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

IntroductionPneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied.MethodsThis study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF. ResultsThe average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included Acinetobacter baumannii (19.6%), Klebsiella pneumoniae (17.9%), Pseudomonas aeruginosa (14.3%), Staphylococcus faecium (12.5%), Enterococcus faecium (12.5%), and Haemophilus parainfluenzae (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of Candida albicans (20.5%), 18 of Pneumocystis carinii (16.1%), and 10 of Aspergillus (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein–Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis). ConclusionSignificant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.

The purpose of this study was to explore the ability of metagenomic next-generation sequencing (mNGS) to detect pathogens in lower respiratory tract of patients with pulmonary infection. A retrospective study was conducted on 112 patients with pulmonary infection admitted to the First Affiliated Hospital of Zhengzhou University from April 30th 2018 to June 30th 2020. Sputum and pharyngeal swabs were collected from all patients, and bronchoalveolar lavage fluid (BALF) was collected during bronchoalveolar lavage. Respiratory tract pathogenic microorganisms were detected by routine methods (bacterial smear, PCR, culture, etc.), and BALF pathogenic microorganisms were detected by mNGS. The average age of the patients was 53.0 years old and 94.6% (106/112) of the patients obtained the results of pathogenic microorganisms. The overall detection rate of pathogenic microorganisms by mNGS was significantly higher than that of conventional methods (93.7% vs. 33.1%, P <0.05). mNGS detected bacteria in 75.0% (84/112) of patients, while conventional methods detected bacteria in only 28.6% (32/112) of all patients. The most commonly detected bacteria were Acinetobacter baumannii (19.6%), Klebsiella pneumoniae (17.9%), Pseudomonas aeruginosa (14.3%), Staphylococcus faecium (12.5%), Enterococcus faecium (12.5%) and Haemophilus parainfluenzae (11.6%). Fungi were detected by mNGS in 29.5% (33/112) of patients, including 23 cases of Candida albicans (20.5%), 18 cases of Pneumocystis carinii (16.1%), and 10 cases of Aspergillus (8.9%). Conventional methods detected fungi only in 7.1% (8/112) of patients. The detection rate of virus by mNGS was significantly higher than that by conventional methods (43.8% vs.0.9%, P <0.05). The most commonly detected viruses were EBV (15.2%), CMV (13.4%), circovirus (8.9%), human coronavirus (4.5%) and rhinovirus (4.5%). The results of Kappa analysis showed that the consistency of the two methods was poor ( P = 0.276), only 32.1% (36/112) of patients were positive for both methods, and 5.4% (6/112) of patients were negative for both methods. mNGS shows great advantages in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with poor therapeutic effect, mNGS detection can obtain etiological basis as far as possible, which is helpful to achieve accurate anti-infective treatment.

目的:分析自诉敌草快中毒患者的临床特征，为自诉敌草快中毒的患者提供诊疗思路。方法:采用回顾性临床研究方法，收集并总结2016—2021年郑州大学第一附属医院收治的自诉敌草快中毒患者的临床数据，并根据毒物检测结果是否含有百草枯，分为单纯敌草快中毒组及毒物检测到百草枯阳性组，分析比较两组脏器损伤、治疗、预后的差异，并研究分析了单纯敌草快中毒存活组与死亡组临床特征差异以及单纯敌草快中毒患者口服摄入量与脏器损伤、预后的关系。结果:2016—2021年自诉敌草快中毒的患者数量呈逐年增多趋势。150例自诉敌草快中毒的患者中，65例毒物检测含百草枯成分，占比43.33%。百草枯阳性组病死率高于单纯敌草快组（63.08% vs. 15.29%， P<0.001）。摄入量超过100 mL，单纯敌草快组中枢神经系统损伤发生率高于百草枯阳性组。摄入量超过50 mL，单纯敌草快中毒的病死率、肾损伤及心血管损伤的发生率均升高。和存活组相比，单纯敌草快中毒死亡组的初始血白细胞水平及多脏器损伤的发生率均升高，接受血液灌流、血液透析的比例显著性较高。 结论:敌草快中毒呈逐年增多趋势；敌草快中毒病死率低于百草枯；大剂量敌草快中毒的神经系统毒性强于百草枯；摄入量超过50 mL、入院初始血白细胞显著升高、出现多脏器损伤的敌草快中毒患者预后差。

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial–mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-β1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-β1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.

目的:分析汞中毒患者的发病因素，探讨不同程度汞中毒患者的临床特征及其影响因素。方法:收集郑州大学第一附属医院2011年1月至2020年12月10年间收治的85例汞中毒患者临床资料，对其进行流行病学分析；进一步筛选出68例单纯汞中毒患者，按照病情严重程度分为轻度组与中重度组，并进行临床特征对比分析。结果:85例汞中毒患者以单纯汞中毒为主（85.9%），混合汞中毒仅占14.1%，常见于合并砷、铅中毒；中毒年龄高峰段为40~49岁，其中66.7%为使用偏方导致。纳入分析的68例单纯汞中毒患者，男性占比44.1%，平均年龄为29.3岁。主要中毒原因为自杀（25.0%）、使用偏方（23.5%）、误服（23.5%）；主要经消化道途径中毒（57.4%），慢性中毒占比一半左右（51.5%）。轻度组（ n=28）入院时多以无症状（42.9%）为主、中重度组（ n=40）以全身游走性疼痛（37.5%）为主；首诊科室分别以急诊内科（46.4%）和神经内科（35.0%）为主，病史不明确的单纯汞中毒患者有59.4%在初步诊断时被诊断为其他疾病，主要以肾病综合征（33.3%）、周围神经病变（22.2%）等诊断为主。实验室检查多见肾功能异常（29.4%），部分患者可见肝功能异常（10.3%）。中重度组与轻度组相比，中重度组的年龄更大（均数37.2岁 vs 18.1岁）、慢性中毒占比更高、工人职业占比更高、使用偏方和职业接触占比更高、皮肤及呼吸道中毒占比更高、住院时间更长、入院至确诊时间更长（中位数5.0 d vs. 1.0 d）、入院24 h内肾功能异常及肝功能异常的发生率更多见，差异均有统计学意义（ P<0.05）。 结论:近10年，汞中毒患者有逐年降低的趋势，轻度汞中毒以急性中毒为主，一般病情轻、预后好；中重度中毒以慢性中毒为主，往往病情更重、更隐匿，首发症状以神经系统为主，误诊率高，更易引起肝、肾功能异常。

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.

目的 分析总结非重症与重危症新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者早期临床特征和实验室检查等特点,以便临床及时评估与识别危重信号.方法 回顾性收集2020年1月16日至2020年3月1日郑州大学第一附属医院收治的COVID-19病例的临床特征、实验室检查等资料,分析非重症型与重危症型之间的差异.结果 共纳入67例确诊患者,其中非重症组22例,重危症组45例.重危症组患者年龄及基础病比例均高于非重症组(P<0.05).初发症状按发生率前五位依次为发热、咳嗽、胸闷、乏力、咳痰,重危症组胸闷症状及肺部啰音比例均高于非重症组,但差异无统计学意义(P>0.05),余症状体征均无统计学意义.入院时重危症组白细胞总数、中性粒细胞比例、D-二聚体及乳酸脱氢酶均高于非重症组,淋巴细胞计数低于非重症组,差异具有统计学意义(P<0.05);首诊于郑州大学第一附属医院的重危症组患者自发病至转为重危症的中位时间为10天,病情加重时较入院时白细胞总数、D-二聚体升高,淋巴细胞计数降低(P<0.05).结论 高龄、有无基础病、初始白细胞总数、中性粒细胞比例、D-二聚体、乳酸脱氢酶及淋巴细胞计数均与COVID-19病情程度有关.白细胞总数和D-二聚体逐渐升高、淋巴细胞绝对值逐渐降低等动态变化提示病情有转为重危症的风险;发病后第10天可能是病情转为重危症的重要时间点,建议及时复查.

It is noted that elevated serum amylase levels suggesting pancreatic damage has an association with prognosis in PQ patients. This study aimed to determine whether PQ can cause pancreatic damage. The two conventional models (intragastric infusion (iG) and intraperitoneal injection (iP)) may exhibit different effects on the pancreas depending on whether or not they pass through the digestive tract. In this study, the rats were divided into four groups: the intragastric infusion group (PQ-iG, n = 45), intraperitoneal injection group (PQ-iP, n = 53), normal control group 1 (NC-iG, n = 6) and normal control group 2 (NC-iP, n = 6). Pancreatic damage was compared between groups using serum amylase activity assay, hematoxylin and eosin (H&E) staining, TUNEL assay, and transmission electron microscopy (TEM). Serum amylase levels in group PQ-iG were significantly higher than in group PQ-iP (p < 0.05). Examination of the H&E sections showed damage to the pancreas. Both experimental groups were displayed inflammatory infiltration within 9 h of PQ treatment. After 9 h, patchy necrosis was observed in group PQ-iP, when inflammatory infiltration was still the dominant pathology. Necrosis appeared and gradually worsened in group PQ-iG, in which necrosis was the dominant pathology. The TUNEL assay showed significantly higher numbers of apoptotic cells in the pancreas of PQ-groups than in the control NC- groups (p < 0.05). TEM showed expansive endoplasmic reticulum lumens and mitochondria swelling in the pancreas of the PQ-groups. It is concluded that both methods of modeling could cause pancreatic damage and the type and degree of damage would change over time. Note that pancreatic damage in group PQ-iG was more severe than that in group PQ-iP. Therefore, clinical practitioners should pay close attention to pancreatic damage caused by PQ, especially when the route of PQ administration was oral.

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.

Objective:To investigate the clinical features of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis misdiagnosed as mental disorder, improve the early diagnosis rate and reduce misdiagnosis.Methods:The clinical data of patients with anti-NMDA receptor encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from 2012 to 2018 were collected. Patients misdiagnosed as mental disorders were screened out. Their psychiatric symptom characteristics, disease course characteristics, imaging and laboratory findings, treatment and prognosis were retrospectively analyzed.Results:A total of 121 cases of anti-NMDA receptor encephalitis were collected, and 43 cases of mental disorders were screened out. Sixteen of the 43 patients (37.2%) had prodromal symptoms, and all the patients had psychiatric behavioral abnormalities (100%), including 32 cases (74.4%) of seizures, 13 cases (30.2%) of decreased level of consciousness, 21 cases (48.8%) of involuntary movements, 15 cases (34.9%) of decreased memory, 8 cases (18.6%) of speech dysfunction, and 8 cases (18.6%) of other neurological symptoms (central hyperventilation, autonomic dysfunction). Memory loss was observed in 15 cases (34.9%), speech dysfunction in 8 cases (18.6%), other neurological symptoms (central hypoventilation, autonomic dysfunction) in 8 cases (18.6%), and various symptoms may appear simultaneously or successively in the same patient. Thirty-eight cases had complete resolution of symptoms or only minor physical impairment, and 5 cases had recurrent admissions with mental abnormalities and seizures. The recurrence rate accounted for 11.6% (5/43).Conclusions:The clinical manifestations of anti-NMDA receptor encephalitis are complex and varied. Most of them have mental behavior abnormalities as the first symptom, which is easily misdiagnosed as mental disorder and delayed treatment will lead to prolonged disease course and poor prognosis.

Background: Acute paraquat (PQ) poisoning is characterized by multi-organ failure and lacking effective therapies. Therefore, identifying risk factors and developing model that could predict early prognosis for patients with PQ poisoning is of great importance. Methods: This was a retrospective cohort study employed with patients suffered from acute PQ poisoning (n=1199). Patients (n=913) with PQ poisoning from 2011 to 2018 were randomly divided into 2 mutually exclusive groups: training (609 patients) and test (304 patients). Another 2 external cohorts containing 207 cases from Zhengzhou 2019 were used as validation from different time and 79 from Shenyang as validation from different site. Risk factors were identified by a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated by a latent class analysis. The prediction score of this model was developed based on the training sample and was further evaluated using the testing and validation samples. Results: Eight risk factors including age, ingestion volume, CK-MB, platelet (PLT), white blood cell (WBC), neutrophil counts (N), gamma-glutamyl transferase (GGT) and serum creatinine (Cr) were identified as in dependent risk indicators of in-hospital death events. The risk model had a C statistic of 0.895 (95% CI 0.855-0.928), 0.891 (95% CI 0.848-0.932) and 0.829 (95% CI 0.455-1.000) and a predictive range of 4.6%-98.2%, 2.3%-94.9% and 0%-12.5% for the test, validation_time and validation_site group, respectively. In the training group, the risk model classified 18.4%, 59.9% and 21.7% of patients into the high, average and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. Conclusion: Eight risk factors were identified in this study. And we developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This simple and reliable risk score system could be helpful in recognizing high-risk patients and reducing in-hospital death rate due to PQ poisoning.

Objective:To investigate therole of serum amylase elevation in the evaluation of diabetic ketoacidosis (DKA) patients and the related factors affecting serum amylase (AMS) levels in patients with diabetic ketoacidosis.Methods:A total of 249 patients with DKA who were admitted to the First Affiliated Hospital of Zhengzhou University from November 2011 to August 2018 were selected for this retrospective study. The patients were divided into the normal group ( n=176) and the elevated group ( n=73) according to the AMS level measured by fasting venous blood samples. The enumeration data such as sex, type of DM, diabetic vascular complications, number of deaths, number of ICU monitoring, and number of acute pancreatitis (AP) after discharge were analyzed by chi-square test or Fisher test, and the measurement data such as age, pH, HbA1c, CO 2CP, Ca 2+, BUN, and Scr were analyzed by independent sample t test to compare the difference between the two groups. Results:The intensive care unit (ICU) monitoring rate was 50.7%, the median length of stay in ICU was 4 days, the median length of hospital stay was 14 days, and the median treatment cost was 28 000 yuan, which were higher in the elevated group than those in the normal group ( P<0.05). There were no significant differences in mortality, AP during hospitalization, and the probability of AP after discharge between the elevated group and the normal group ( P>0.05). The duration of diabetes, the number of previous DKA, the incidence of diabetic vascular complications, HbA1c, pH, BUN, and Scr in the elevated group were all higher than those in the normal group ( P<0.01 or P<0.05). Conclusions:DKA patients with elevated AMS are more likely to be admitted to ICU, and the length of stay in ICU, total length of hospital stay and total cost of treatment are all increased. Where as the overall mortality rate during hospitalization and the likelihood of AP after discharge are not increased.

Objective:To explore the risk factors of prognosis and develop a nomogram to predict the risk of short-term mortality in patients with acute respiratory failure (ARF).Methods:The clinical data of 827 ARF patients in MIMIC-III database and 296 ARF patients in the Second Affiliated Hospital of Wenzhou Medical University from January 2010 to December 2019 were collected and analyzed by the univariate and multivariable logistic regression analysis. A nomogram was developed to predict 30-day mortality in ARF patients according to the risk factors.Results:Multivariate logistic regression analysis showed that the lowest systolic blood pressure, the highest respiratory rate, the lowest fingertip oxygen saturation, the highest bilirubin, the lowest albumin and 24 h urine volume were independent risk factors of ARF ( OR=0.988, 1.028, 0.980, 0.750, 1.059 and 0.999, all P<0.05). Combined with the clinical situation, mechanical ventilation, the highest heart rate and age were also included in the nomogram model. The AUC of ROC curve in this model was 0.752 (95% CI: 0.719-0.784), the AUC of ROC curve in external validation set was 0.666 (95% CI: 0.621-0.711). The calibration curves both in the primary cohort and validation cohort were close to the standard curve. Conclusions:This nomogram has good differentiation and generalization, which is helpful for clinicians to accurately evaluate the mortality risk of ARF.