Study on the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.

Objective: To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A. Methods: According to a random sequence generated by computer software, 200 patients with confirmed influenza A were divided into a study group and a control group with 100 cases in each group. Group allocation was concealed using sealed envelopes. The study group was treated with oral administration of baloxavir marboxil tablets, 40 mg once. The control group was given oral oseltamivir capsules, 75 mg twice a day, for five consecutive days. The therapeutic effects, symptom disappearance time and adverse drug reactions of the two groups after 5 days of treatment were compared. Results: There was no significant difference in the total effective rate between the two groups (99% vs. 98%, p > 0.05). There was no significant difference in fever subsidence time (1.54 ± 0.66 d vs. 1.67 ± 0.71 d, p > 0.05), cough improvement time (2.26 ± 0.91 d vs. 2.30 ± 0.90 d, p > 0.05) and sore throat improvement time (2.06 ± 0.86 d vs. 2.09 ± 0.83 d, p > 0.05) between the two groups. There was no significant difference in the incidence of adverse drug reactions between the two groups (8% vs. 13%, p > 0.05). Conclusion: Baloxavir marboxil tablets can be effectively used in the treatment of patients with influenza A and have a similar efficacy and safety profile as oseltamivir capsules.

Relevance of NAT2 genotype and clinical factors to risk for antituberculosis drug-induced liver injury.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

N-acetyltransferase 2 genetic polymorphisms and anti-tuberculosis-drug-induced liver injury: a correlation study.

Background: Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Conclusion: Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.

Strain Identification and Drug Resistance Analysis of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Nontuberculous Mycobacterial Lung Disease.

Objective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM). Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations. Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P<0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P<0.001, kappa=0.781). Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.

Incidence, causes, and risk factors for unplanned readmission in patients admitted with pulmonary tuberculosis in China.

INTRODUCTION: To investigate the incidence, causes, and risk factors for unplanned readmission within 30 days of discharge in patients with pulmonary tuberculosis (TB). METHODOLOGY: The clinical data of 1,062 patients with confirmed pulmonary TB who were admitted to our hospital from October 2018 to October 2021 were analysed retrospectively. The subjects were divided into a readmission group (354 cases) and a non-readmission group (708 cases) according to whether there was an unplanned admission within 30 days of discharge. We analysed the risk factors for unplanned readmission within 30 days after discharge with pulmonary TB. RESULTS: The incidence of unplanned readmission in patients with pulmonary TB was 5.2%. Being female (OR = 0.63, 95% CI: 0.434-0.942) and living in cities (OR = 0.218, 95% CI: 0.151-0.315) were protective factors for the readmission of patients with TB (p < 0.05). However, being ≥ 65 years old (OR = 2.574, 95% CI: 1.709-3.870), being a smoker (OR = 2.773, 95% CI: 1.751-4.390), having chronic obstructive pulmonary disease (COPD) (OR = 3.373, 95% CI: 1.708-6.660), having viral hepatitis (OR= 2.079, 95% CI: 1.067-4.052), receiving non-standard treatment (OR = 15.620, 95% CI: 10.413-23.431), having medical side effects (OR = 6.138, 95% CI: 3.798-9.922) and l unauthorised discharge (OR = 2.570, 95% CI: 1.509-4.376) were risk factors for the readmission to hospital of patients with TB (p < 0.05). CONCLUSIONS: Gender, age, place of residence, smoking, COPD, hepatitis, non-standard treatment, adverse drug reactions and unauthorised discharge were risk factors of TB for unplanned readmission.

Efficacy and safety of Nirmatrelvir/Ritonavir for treating the Omicron variant of COVID-19.

Objective: To evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of coronavirus disease 2019 (COVID-19). Methods: Data from 58 patients who were infected with the Omicron variant of COVID-19 were retrospectively collected. The patients were divided into two groups according to the treatment regimen they received. Patients in both groups were given Lianhua Qingwen capsules orally, three times/day, 6 g/time. The study group was given Nirmatrelvir 300 mg/Ritonavir 100 mg orally, q12h, for 5 days, and the control group was not given any antiviral drugs. The two groups were compared in terms of the change in computed tomography (CT) values of COVID-19 nucleic acid, the negative conversion time of COVID-19 RNA, hospitalization time, adverse drug reactions and COVID-19 nucleic acid re-positive tests. Results: The time to increase the CT values in the study group was faster than that in the control group, and the CT values in the study group were significantly larger than in the control group on days four and seven (p < 0.05); The negative conversion time in the study group was shorter than the control group (Z = -2.424, p = 0.015), and the hospitalization time was also shorter (Z = -2.603, p = 0.009). There were no statistically significant adverse drug reactions during hospitalization in both groups (χ2 = 2.747, p = 0.097). None of the study group tested re-positive for SARS-CoV-2 nucleic acid after discharge. Conclusion: The efficacy of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of COVID-19 was positive and had good tolerance in patients.

Clinical characteristics and prognostic factors of 60 patients with acquired immune deficiency syndrome combined with Cryptococcus neoformans.

OBJECTIVE: Cryptococcal meningitis (CM) threatens people's health and is the main cause of opportunistic fungus-related death in acquired immune deficiency syndrome (AIDS) patients. Herein, we investigate the clinical characteristics and prognostic factors of AIDS patients with Cryptococcus neoformans in Wenzhou, Zhejiang Province, China. METHODS: Our study enrolled AIDS patients diagnosed with Cryptococcus neoformans infection who were hospitalised in our hospital. They were divided into Group A (32 patients with CM) and Group B (28 patients without CM) according to their diagnosis. The differences between the two groups of patients' clinical symptoms, imaging examinations and laboratory examinations were observed. Statistical methods were used to analyse the difference in prognosis between the two groups. RESULTS: Headache and fever were the most common clinical characteristics for patients with CM, while respiratory symptoms and fever were the most common clinical characteristics for patients without CM. The positive rate of cryptococcal capsular antigen, India ink staining and culture in the cerebrospinal fluid examination was higher in the CM patients than in the non-CM patients. The overall morbidity and mortality rate after systemic antifungal therapy was higher in the CM patients than in the non-CM patients. A higher incidence of headache, impaired consciousness, nuchal rigidity, first intracranial pressure > 200 mmH2O and mortality was observed in the CM patients than in the non-CM patients. Multifactorial logistic regression analysis showed that headache risk factors affecting the patient's prognosis at 12 weeks. CONCLUSION: Patients with AIDS diagnosed with Cryptococcus neoformans infection have insidious clinical symptoms in the early stage, and their manifestation is often non-specific, resulting in poor prognosis and high mortality among CM patients compared to patients without CM. Therefore, early identification and timely antifungal therapy before the disease progresses to meningitis are of great value in improving the survival rate of patients.

ZmGLP1, a Germin-like Protein from Maize, Plays an Important Role in the Regulation of Pathogen Resistance.

A gene encoding a protein similar to germin-like proteins (GLPs) was obtained from maize (Zea mays) and designated as ZmGLP1. Based on the ZmGLP1 conserved domain and phylogenetic status, ZmGLP1 was grouped into GLP subfamily b and has high similarity to OsGLP8-14 from Oryza sativa. ZmGLP1 is expressed in different maize tissues during different growth stages and is mainly expressed in the stems and leaves. The induced expression patterns confirmed that ZmGLP1 is differentially expressed under abiotic and hormone stress; it had an early response to jasmonic acid (JA) and ethephon (ET) but a late response to salicylic acid (SA) and was significantly upregulated under Bipolaris maydis infection. The overexpression of ZmGLP1 in Arabidopsis improved the resistance to biotrophic Pseudomonas syringae pv. tomato DC3000 (PstDC3000) and necrotrophic Sclerotinia sclerotiorum by inducing the expression of JA signaling-related genes. Moreover, the hydrogen peroxide (H2O2) content increased due to the overexpression of ZmGLP1 in Arabidopsis after pathogen infection. Compared to the wild-type control, the H2O2 content of ZmGLP1-overexpressing Arabidopsis infected by PstDC3000 increased significantly but was lower in transgenic plants infected with S. sclerotiorum. Furthermore, high-performance liquid chromatography-tandem mass (HPLC-MS/MS) spectrometry showed that the JA contents of ZmGLP1-overexpressing Arabidopsis markedly increased after pathogen infection. However, the improved resistance of ZmGLP1-overexpressing Arabidopsis pretreated with the JA biosynthetic inhibitor, sodium diethyldithiocarbamate trihydrate (DIECA), was suppressed. Based on these findings, we speculate that ZmGLP1 plays an important role in the regulation of Arabidopsis resistance to biotrophic PstDC3000 and necrotrophic S. sclerotiorum; the regulatory effects are achieved by inducing plant oxidative burst activity and activation of the JA signaling pathway.

The Relevance of Host Gut Microbiome Signature Alterations on de novo Fatty Acids Synthesis in Patients with Multi-Drug Resistant Tuberculosis.

Background: Tuberculosis (TB) is still the single pathogen infectious disease with the largest number of deaths worldwide. The relationship that intestinal microbiota disorder and de novo fatty acid synthesis metabolism have with disease progression in multi-drug resistant TB (MDR-TB) has not yet been fully studied. Objective: To investigate the effects of long periods of MDR-TB, pre-extensively drug-resistant TB (pre-XDR-TB), or rifampicin-resistant TB (RR-TB) on gut microbiome dysbiosis and advanced disease. Methods: The sample was chosen between March 2019 and September 2019 in Wenzhou Central Hospital and comprised 11 patients with pre-XDR-TB, 23 patients with RR-TB, and 28 patients with MDR-TB. Healthy individuals were chosen as the control group (CK group). An overnight fast blood sample was drawn via venipuncture into tubes without anticoagulant. For analysis, 300 mg of faeces from patients from the same group was mixed and analysed using DNA extraction, NGS sequencing, and bioinformatics. A QIAamp Fecal DNA Mini Kit was used to isolate the DNA. The extracted DNA was stored at -20°C. Results: Advanced TB was concurrent with an elevated level of the proportions of acetyl-CoA carboxylase (ACC1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthase (FASN) to GAPDH in de novo fatty acids synthesis, and Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus were increased significantly in RR-TB patients compared to healthy individuals, whereas their abundance in the pre-XDR-TB and MDR-TB groups showed little change in comparison with the control group. Proteobacteria levels were greatly increased in the RR-TB and MDR-TB patient groups but not in the patients with pre-XDR-TB or the healthy subjects. The pre-XDR-TB group exhibited alterations of the intestinal microbiome: coliform flora showed the highest abundance of Verrucomicrobiales, Enterobacteriales, Bifidobacteriales and Lactobacillales. De novo fatty acids synthesis was enhanced in patients and was associated with the gut microbiome dysbiosis induced by the antimicrobials, with Bacteroidetes, Bacteroidales, and Bacteroidaceae displaying the most important correlations on a phylum, order, and family level, respectively. Conclusion: The progression to advanced TB was observed to be a result of the interaction between multiple interrelated pathways, with gut-lung crosstalk potentially playing a role in patients with drug-resistant TB.

Clinical Manifestation, Imaging Features and Treatment Follow-up of 29 Cases with Hepatic Tubercolosis.

To understand the clinical and imaging manifestations and the treatment and follow-up of hepatic tuberculosis (HTB), we retrospectively analysed the clinical and imaging data of 29 patients with HTB who had been diagnosed clinically or by biopsy, and the clinical and imaging data had been summarised. Patient characteristics were followed up after anti-TB drug treatment. The median age of the 29 patients with HTB was 37 years, and most were male (58.6%). The patient's symptoms included fever (48.2%), respiratory symptoms (27.5%), abdominal pain (24.1%), and abdominal distension (10.3%). Elevated erythrocyte sedimentation rate (79.3%), elevated serum C-reactive protein (75.8%) and hypoalbuminemia (62.0%) were common features. Three patients were serologically positive for acquired human immunodeficiency syndrome, and two were serologically positive for hepatitis B surface antigen with normal tumour markers. The 29 patients with HTB included 17 with serous HTB, 9 with parenchymal HTB (8 with parenchymal nodular HTB and 1 with parenchymal miliary HTB), 1 with intrahepatic abscess type HTB, and 2 with hilar HTB. Approximately 86% of the patients also had pulmonary TB. Most of the serous HTB patients also had tuberculous peritonitis. Enhanced computerized tomography scans of the serous and parenchymal HTB cases showed the progressive development of lesions. Abnormal blood perfusion was observed in the hepatic artery, and the clearest evidence of TB was observed in the hepatic portal vein. Magnetic resonance imaging indicated that the lesions returned a high signal in the diffusion-weighted imaging sequence. However, the lesions' apparent diffusion coefficient values reflected high signals. The Xpert MTB/RIF test detected Mycobacterium TB complex in the liver biopsy fluid from 10 patients. Regarding histopathology, one patient showed granulomatous inflammation, and one patient's acid-fast bacillus (AFB) stain was positive. The treatment of two patients was stopped due to their adverse reactions to the drugs and the risk of creating drug-resistant TB. The remaining patients received anti-TB treatment, but one subsequently died, and two were unavailable for follow-up. The clinical symptoms of HTB are difficult to detect, and it has diverse manifestations by imaging, with no obvious specificity in terms of pathological results. Therefore, follow-up of liver lesions for checking anti-TB therapy is another method for diagnosing HTB. In addition, early active anti-TB treatment can achieve good curative results.

Macrophage migration inhibitory factor (MIF) acetylation protects neurons from ischemic injury.

Ischemia-induced neuronal death leads to serious lifelong neurological deficits in ischemic stroke patients. Histone deacetylase 6 (HDAC6) is a promising target for neuroprotection in many neurological disorders, including ischemic stroke. However, the mechanism by which HDAC6 inhibition protects neurons after ischemic stroke remains unclear. Here, we discovered that genetic ablation or pharmacological inhibition of HDAC6 reduced brain injury after ischemic stroke by increasing macrophage migration inhibitory factor (MIF) acetylation. Mass spectrum analysis and biochemical results revealed that HDAC6 inhibitor or aspirin treatment promoted MIF acetylation on the K78 residue. MIF K78 acetylation suppressed the interaction between MIF and AIF, which impaired MIF translocation to the nucleus in ischemic cortical neurons. Moreover, neuronal DNA fragmentation and neuronal death were impaired in the cortex after ischemia in MIF K78Q mutant mice. Our results indicate that the neuroprotective effect of HDAC6 inhibition and aspirin treatment results from MIF K78 acetylation; thus, MIF K78 acetylation may be a therapeutic target for ischemic stroke and other neurological diseases.

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the detection of drug resistance of Mycobacterium tuberculosis in re-treated patients.

OBJECTIVE: To evaluate the value of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the detection of drug resistance of Mycobacterium tuberculosis in re-treated patients. METHODS: MALDI-TOF MS was used to detect the resistance of 202 cases of retreatment pulmonary tuberculosis infection strains to isoniazid (INH), rifampin (RFP), ethambutol (EMB), streptomycin (SM), ofloxacin (Ofx), moxifloxacin (Mfx), amikacin (Am), Kanamycin (Km) and capreomycin (Cm), and the results were compared with those of BACTEC 960 liquid culture detection to compare the coincidence rate of the two methods. RESULTS: MALDI-TOF MS detected 60 copies of Mtb gene mutation, and drug-resistant gene mutation strains accounted for 34.68% (60/173) of positive strains. Rifampicin-related rpoB gene mutations accounted for 86.67% (52/60), isoniazid-related katG + inhA gene mutations accounted for 80.00% (48/60) and inhA-15 gene mutations accounted for 8.33% (5/60), streptomycin-related rpsL gene mutations accounted for 28.33% (17/60), ethambutol-related embB gene mutations accounted for 45.00% (27/60), quinolone-related gyrA basic mutation accounted for 26.67% (16/60), ethyl/propylthiamine-related embB gene mutation accounted for 36.67% (22/60) and inhA-15 gene mutation accounted for 10.00% (6/60), aminoglycoside-related rrs gene mutation accounted for 26.67% (16/60), clofazimine Fazimine, bedaquiline related Rv0678 193 gene mutations accounted for 3.33% (2/60), pyrazinamide, p-aminosalicylate, linezolid were not seen mutated genes. Multi-gene mutant strains accounted for 63.33% (38/60) of drug-resistant strains. CONCLUSION: MALDI-TOF MS assay has good agreement with BACTEC960 liquid culture drug sensitivity test, which can be a rapid and effective method to screen for drug resistance of Mycobacterium tuberculosis, and has some clinical application value in patients with relapse tuberculosis.

Correlation Analysis Between Serum Uric Acid, Prealbumin Level, Lactate Dehydrogenase, and Severity of COVID-19.

Objective: To analyze the correlation between serum uric acid, prealbumin levels, lactate dehydrogenase (LDH), and the severity of COVID-19. Methods: The data from 135 patients with COVID-19 was collected, and the patients were divided into a non-severe group (110 cases) and a severe group (25 cases), according to the severity of illness. Sixty cases with normal physical examinations over the same period and 17 cases diagnosed with other viral pneumonia in the past five years were selected as the control group to analyze the correlation between the detection index and the severity of COVID-19. Results: Serum albumin and prealbumin in the severe group were significantly lower than those in the non-severe group (p < 0.01); serum uric acid in the severe group was lower than that in the non-severe group (p < 0.05). LDH and C-reaction protein (CRP) in the severe group were higher than those in non-severe group (p < 0.01); the levels of albumin, prealbumin, serum uric acid, and LDH in the severe group were significantly different from those in healthy control group (p < 0.01) and the levels of prealbumin, serum uric acid, LDH, and CRP in the severe group were significantly different from those in the other viral pneumonia group (p < 0.01). Serum albumin and prealbumin were positively correlated with the oxygenation index (p < 0.001), while LDH was negatively correlated with oxygenation index (p < 0.001). Conclusion: Serum albumin, prealbumin, the oxygenation index, and LDH are risk factors of COVID-19.

Methyltransferase-like 3 contributes to inflammatory pain by targeting TET1 in YTHDF2-dependent manner.

ABSTRACT: The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation. Although RNA m6A is enriched in mammalian neurons, its regulatory function in nociceptive information processing remains elusive. Here, we reported that Complete Freund's Adjuvant (CFA)-induced inflammatory pain significantly decreased global m6A level and m6A writer Mettl3 in the spinal cord. Mimicking this decease by knocking down or conditionally deleting spinal Mettl3 elevated the levels of m6A in ten-eleven translocation methylcytosine dioxygenases 1 (Tet1) mRNA and TET1 protein in the spinal cord, leading to production of pain hypersensitivity. By contrast, overexpressing Mettl3 reversed a loss of m6A in Tet1 mRNA and blocked the CFA-induced increase of TET1 in the spinal cord, resulting in the attenuation of pain behavior. Furthermore, the decreased level of spinal YT521-B homology domain family protein 2 (YTHDF2), an RNA m6A reader, stabilized upregulation of spinal TET1 because of the reduction of Tet1 mRNA decay by the binding to m6A in Tet1 mRNA in the spinal cord after CFA. This study reveals a novel mechanism for downregulated spinal cord METTL3 coordinating with YTHDF2 contributes to the modulation of inflammatory pain through stabilizing upregulation of TET1 in spinal neurons.

Clinical Characteristics of Patients With Re-admitted of Novel Coronavirus 2019 (nCOVID-19) in Wenzhou, China.

Background: During the COVID-19 pandemic, many patients admitted to hospital for treatment have recovered and been discharged; however, in some instances, these same patients are re-admitted due to a second fever or a positive COVID-19 PCR test result. To ascertain whether it is necessary to treat these patients in hospitals, especially in asymptomatic cases, we summarize and analyze the clinical and treatment characteristics of patients re-admitted to hospital with a second COVID-19 infection. Methods: Of the 141 COVID-19 cases admitted to the Wenzhou Central Hospital between January 17, 2020, to March 5, 2020, which were followed until March 30, 2020, 12 patients were re-admitted with a second COVID-19 infection. Data was collected and analyzed from their clinical records, lab indexes, commuted tomography (CT), and treatment strategies. Results: Most of the 141 patients had positive outcomes from treatment, with only 12 (8.5%) being re-admitted. In this sub-group: one (8.3%) had a fever, a high white blood cell count (WBC), and progressive CT changes; and one (8.3%) had increased transaminase. The PCR tests of these two patients returned negative results. Another 10 patients were admitted due to a positive PCR test result, seven of which were clinically asymptomatic. Compared to the CT imaging following their initial discharge, the CT imaging of all patients was significantly improved, and none required additional oxygen or mechanical ventilation during their second course of treatment. Conclusions: The prognoses of the re-admitted patients were good with no serious cases. We conclude that home treatment with concentrated medical observation is a safe and feasible course of treatment if the patient returns a positive PCR test result but does not display serious clinical symptoms. During medical observation, patients with underlying conditions should remain a primary focus, but most do not need to be re-admitted to the hospital.

Epidemiological Features of 105 Patients Infected with the COVID-19.

OBJECTIVE: To investigate and evaluate the clinical features of patients infected with the 2019 novel coronavirus (COVID-19) outside of Wuhan. METHODS: 105 patients admitted to our hospital with clinical- and laboratory-confirmed COVID-19 infection were studied. Data were collected from January 17, 2020 to March 5, 2020. RESULTS: 105 patients (57 male and 48 female) were confirmed to have COVID-19 infection. Among the 105 patients, 55 (52%) had made short trips to Wuhan during the two weeks before the onset of illness, and these were the first-generation confirmed cases. An exact date of close contact with someone in Wenzhou with confirmed or suspected COVID-19 infection from Wuhan (the second-generation confirmed cases) could be provided by 38 (36%) patients. Of the remaining patients, six (6%; the third-generation confirmed cases) were familial clusters of the second-generation confirmed cases, three (3%) had no definite epidemiological features, and 16 (15%) were from the same location as for the case report. CONCLUSION: Due to the infectiousness of COVID-19, patients with infections should be diagnosed and treated as early as possible after developing fever symptoms or showing other clinical characteristics or imaging features. With respect to high-risk cases, we must focus on any complications that arise and take effective measures to treat them immediately. This will significantly improve the prognosis of patients with severe infections.

Association of RAGE with acute ischemic stroke prognosis in type 2 diabetes.

BACKGROUND: In experimental models, the receptor for advanced glycation end products (RAGE) has been reported as a key mediator in cerebral ischemia. In this study, the clinical significance of serum RAGE levels in acute ischemic stroke patients with type 2 diabetes was determined. METHOD: Three hundred seven patients (165 patients without diabetes and 142 patients with diabetes) with acute cerebral infarction (ACI) were enrolled over 3 consecutive months. On admission, their National Institute of Health Stroke Scale (NIHSS) scores were recorded. The clinical laboratory data of all subjects were collected, and their serum levels of RAGE were assayed using enzyme-linked immunosorbent assay (ELISA). On admission and 3 months after stroke, the clinical outcomes were assessed using the Barthel index (BI) and modified Rankin scale (mRS). RESULTS: Patients with diabetes (PwD) had significantly higher levels of triglycerides (TGs), RAGE, fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), and worse stroke prognosis than patients without diabetes (p < 0.05). Hypertension history, RAGE, and FBG in patients without diabetes in ischemic stroke were increased, relative to stroke prognosis. Weight, RAGE, and FBG data showed significant correlation with stroke outcome in PwD (p < 0.05). Multiple logistic regression analysis indicated that the RAGE level was an independent risk factor for poor prognosis of stroke, especially in PwD with ACI (p < 0.05). CONCLUSION: Acute ischemic stroke is associated with elevated serum RAGE level, which, at admission, is an independent predictor of poor outcome for stroke in type 2 diabetes.

NOD1/RIP2 signalling enhances the microglia-driven inflammatory response and undergoes crosstalk with inflammatory cytokines to exacerbate brain damage following intracerebral haemorrhage in mice.

BACKGROUND: Secondary brain damage caused by the innate immune response and subsequent proinflammatory factor production is a major factor contributing to the high mortality of intracerebral haemorrhage (ICH). Nucleotide-binding oligomerization domain 1 (NOD1)/receptor-interacting protein 2 (RIP2) signalling has been reported to participate in the innate immune response and inflammatory response. Therefore, we investigated the role of NOD1/RIP2 signalling in mice with collagenase-induced ICH and in cultured primary microglia challenged with hemin. METHODS: Adult male C57BL/6 mice were subjected to collagenase for induction of ICH model in vivo. Cultured primary microglia and BV2 microglial cells (microglial cell line) challenged with hemin aimed to simulate the ICH model in vitro. We first defined the expression of NOD1 and RIP2 in vivo and in vitro using an ICH model by western blotting. The effect of NOD1/RIP2 signalling on ICH-induced brain injury volume, neurological deficits, brain oedema, and microglial activation were assessed following intraventricular injection of either ML130 (a NOD1 inhibitor) or GSK583 (a RIP2 inhibitor). In addition, levels of JNK/P38 MAPK, IκBα, and inflammatory factors, including tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, and inducible nitric oxide synthase (iNOS) expression, were analysed in ICH-challenged brain and hemin-exposed cultured primary microglia by western blotting. Finally, we investigated whether the inflammatory factors could undergo crosstalk with NOD1 and RIP2. RESULTS: The levels of NOD1 and its adaptor RIP2 were significantly elevated in the brains of mice in response to ICH and in cultured primary microglia, BV2 cells challenged with hemin. Administration of either a NOD1 or RIP2 inhibitor in mice with ICH prevented microglial activation and neuroinflammation, followed by alleviation of ICH-induced brain damage. Interestingly, the inflammatory factors interleukin (IL)-1ß and tumour necrosis factor-α (TNF-α), which were enhanced by NOD1/RIP2 signalling, were found to contribute to the NOD1 and RIP2 upregulation in our study. CONCLUSION: NOD1/RIP2 signalling played an important role in the regulation of the inflammatory response during ICH. In addition, a vicious feedback cycle was observed between NOD1/RIP2 and IL-1ß/TNF-α, which could to some extent result in sustained brain damage during ICH. Hence, our study highlights NOD1/RIP2 signalling as a potential therapeutic target to protect the brain against secondary brain damage during ICH.

Application Value of SAT-TB Combined with Acid-Fast Staining in the Diagnosis and Treatment of Pulmonary Tuberculosis.

OBJECTIVES: This study is aimed at evaluating the clinical application value of RNA simultaneous amplification and testing method for Mycobacterium tuberculosis (SAT-TB) combined with acid-fast staining in the diagnosis and treatment of pulmonary tuberculosis (PTB). METHODS: This paper included 168 suspected and confirmed PTB sufferers admitted to The Sixth People's Hospital of Wenzhou from December 2018 to December 2019, whose sputum was collected and tested using SAT-TB, smear acid-fast staining method, and the BACTEC MGIT 960 system. With the MGIT 960 culture test method as the gold standard, the application value of SAT-TB, acid-fast staining, or SAT-TB combined with acid-fast staining in the diagnosis and treatment of PTB was assessed. RESULTS: With the MGIT 960 culture as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB for the diagnosis of PTB were 57.3%, 92.5%, 84.3%, and 73.5%, respectively. The conformity was 76.8%, and the Kappa value was 0.515, suggesting a statistically significant difference (χ 2 = 7.314, p < 0.05) and a general consistency degree. Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value of SAT-TB combined with sputum smear acid-fast staining were 81.3%, 86.0%, 88.4%, and 80.8%, respectively, with the MGIT 960 culture still the gold standard. The conformity and Kappa value were 83.9% and 0.672, respectively, showing no statistically significant difference (χ 2 = 0.438, p > 0.05) and a relatively high consistency degree. CONCLUSION: SAT-TB combined with acid-fast staining had a similar detection rate to that of the MGIT 960 culture test with a high consistency degree, which could be applied in the diagnosis of PTB efficiently and accurately.