Discovery andsynthesis of novel benzoylhydrazone neuraminidase inhibitors.

Neuraminidase (NA) serves as a promising target for the exploration and development of anti-influenza drugs. In this work, lead compound 5 was discovered through pharmacophore-based virtual screening and molecular dynamics simulation, and 14 new compounds were obtained by modifying the lead compound 5 based on pharmacophore features. The biological activity test shows that 5n (IC50 = 0.13 µM) has a better inhibitory effect on wild-type NA (H5N1), while 5i (IC50 = 0.44 µM) has a prominent inhibitory effect on mutant NA (H5N1-H274Y), both of them are better than the positive control oseltamivir carboxylate (OSC). The analysis of docking results indicate that the good activities of compounds 5n and 5i may be attributed to the thiophene ring in 5n can stretch into the 150-cavity of NA, whereas the thiophene moiety in 5i can extend to the 430-cavity of NA. The findings of this study may be helpful for the discovery of new NA inhibitors.

Performance of the MeltPro TB assay as initial test for diagnosis of pulmonary tuberculosis with drug-resistance detection.

BACKGROUND: The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). METHODS: A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. RESULTS: For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P < 0.001). The specificity of MeltPro was 97.1%, similar to Xpert (98.0%; P > 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P < 0.001). Based on Xpert and/or MYCOTB results, MeltPro exhibited a sensitivity and specificity of 98.3% and 99.2%, respectively, for detecting RIF resistance. Based on MYCOTB results, MeltPro's sensitivity for detecting resistance to INH, EMB, STR, and FQ was 96.4%, 89.1%, 97.5%, and 90.3%, respectively, with specificities of 96.0%, 96.0%, 95.2%, and 99.4%, respectively. CONCLUSION: The MeltPro TB assay could potentially be an effective alternative as the initial test for rapid diagnosis of PTB with drug-resistance detection in clinical practice.

Diagnostic performance of metagenomic next-generation sequencing in non-tuberculous mycobacterial pulmonary disease when applied to clinical practice.

OBJECTIVE: To compare non-tuberculous mycobacterial pulmonary disease (NTMPD) diagnosis by metagenomic next-generation sequencing (mNGS) with Bactec mycobacterial growth indicator tube (MGIT) 960. METHODS: A total of 422 patients with suspected NTMPD in Shanghai Pulmonary Hospital between January 2020 and May 2021 were retrospectively analyzed; 194 were diagnosed with NTMPD. The diagnostic performance of mNGS and MGIT 960 for NTMPD was assessed. Receiver operating characteristic (ROC) curves and areas under curve (AUCs) were compared. RESULTS: The sensitivity of mNGS in NTMPD diagnosis was 81.4% and higher than that of MGIT 960 (53.6%). The specificity of mNGS in NTMPD diagnosis was 97.8%, similar to that of MGIT 960 (100%). The sensitivity of combined mNGS and MGIT 960 in NTMPD diagnosis was 91.8%. The sensitivity of mNGS for bronchoalveolar lavage fluid (BALF), pulmonary puncture tissue fluid, and sputum was 84.8%, 80.6%, and 77.5%, respectively; all were higher than that of MGIT 960 (P < 0.05). The AUC of mNGS and MGIT 960 was 0.897 and 0.768, respectively. The AUC of mNGS were BALF (0.916), pulmonary puncture tissue fluid (0.903), and sputum (0.870). CONCLUSION: The sensitivity of mNGS was superior to that of Bactec MGIT 960; the specificity in NTMPD diagnosis was similar. mNGS shows effective performance in NTMPD diagnosis.

Effectiveness and safety of regimens containing linezolid for treatment of Mycobacterium abscessus pulmonary Disease.

OBJECTIVE: To evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease. METHODS: The records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups. RESULTS: The two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0-17.0] vs. 18.0 months [IQR: 16.0-18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01). CONCLUSIONS: The linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy.

Design, synthesis and biological evaluation of 1,3,4-triazole-3-acetamide derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an ideal target for the development of anti-influenza drugs. In this paper, ZINC06057848 was screened out as a hit compound by docking-based virtual screening and molecular dynamics (MD) simulation. The modification and optimization of hit ZINC06057848 resulted in the discovery of a series of novel 1,3,4-triazole-containing NA inhibitors (5a-5j). Compound 5c exerts the best inhibitory activity (IC50 = 0.11 µM) against NA, which is comparable to the positive control oseltamivir carboxylate (OSC) (IC50 = 0.10 µM). Molecular docking analysis indicates that the good efficacy of inhibitor 5c may be attributed to the furan and triazole rings extending into 430-cavity and the ethylbenzene part occupying the active site. The results of this work may help in the development of new NA inhibitors.

Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is a promising target for development of anti-influenza drugs. In this study a dihydrofurocoumarin derivative ZINC05577497 was discovered as a lead NA inhibitor based on docking-based virtual screening technique. The optimization of lead ZINC05577497 led to the discovery of a series of novel NA inhibitors 5a-5j. Compound 5b has the most potent activity against NA with IC50 = 0.02 µM, which is lower than those of the reference oseltamivir carboxylate (OSC) (IC50 = 0.04 µM) and ZINC05577497 (IC50 = 0.11 µM). Other target compounds also show potential inhibition of NA activity. Molecular docking results indicate that the good potency of 5b may be attributed to the elongation of the dihydrofurocoumarin ring to the 150-cavity. The results of this paper will be useful to discover more potent NA inhibitors.

The Difference Se Makes: A Bio-Inspired Dppf-Supported Nickel Selenolate Complex Boosts Dihydrogen Evolution with High Oxygen Tolerance.

Inspired by the metal active sites of [NiFeSe]-hydrogenases, a dppf-supported nickel(II) selenolate complex (dppf=1,1'-bis(diphenylphosphino)ferrocene) shows high catalytic activity for electrochemical proton reduction with a remarkable enzyme-like H2 evolution turnover frequency (TOF) of 7838 s-1 under an Ar atmosphere, which markedly surpasses the activity of a dppf-supported nickel(II) thiolate analogue with a low TOF of 600 s-1 . A combined study of electrochemical experiments and DFT calculations shed light on the catalytic process, suggesting that selenium atom as a bio-inspired proton relay plays a key role in proton exchange and enhancing catalytic activity of H2 production. For the first time, this type of Ni selenolate-containing electrocatalyst displays a high degree of O2 and H2 tolerance. Our results should encourage the development of the design of highly efficient oxygen-tolerant Ni selenolate molecular catalysts.

Design, synthesis and biological evaluation of novel zanamivir derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an important antiviral drug target. Zanamivir is one of the most potent NA inhibitors. In this paper, a series of zanamivir derivatives as potential NA inhibitors were studied by combination of molecular modeling techniques including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The results show that the best CoMFA (comparative molecular field analysis) model has q2 = 0.728 and r2 = 0.988, and the best CoMSIA (comparative molecular similarity indices analysis) model has q2 = 0.750 and r2 = 0.981, respectively. The built 3D-QSAR models show significant statistical quality and excellent predictive ability. Seven new NA inhibitors were designed and predicted. 20 ns of MD simulations were carried out and their binding free energies were calculated. Two designed compounds were selected to be synthesized and biologically evaluated by NA inhibition and virus inhibition assays. One compound (IC50 = 0.670 µM, SI > 149) exhibits excellent antiviral activity against A/WSN/33 H1N1, which is superior to the reference drug zanamivir (IC50 = 0.873 µM, SI > 115). The theoretical and experimental results may provide reference for development of new anti-influenza drugs.

Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6 µM against NA, while IC50 value for oseltamivir is 61.1 µM. This compound may be further investigated for the treatment of infection by the new type influenza virus.

Discovery of novel polyheterocyclic neuraminidase inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone.

Inspired by our earlier findings regarding neuraminidase (NA) inhibitors interacting with 150-cavity or 430-cavity of NA, sixteen novel polyheterocyclic NA inhibitors with 1,3,4-oxadiazole thioetheramide as core backbone were designed and synthesized based on the lead compound ZINC13401480. Of the synthesized compounds, compound N5 targeting 150-cavity exerts the best inhibitory activity against the wild-type H5N1 NA, with IC50 value of 0.14 µM, which is superior to oseltamivir carboxylate (OSC) (IC50 = 0.31 µM). Compound N10 targeting 430-cavity exhibits the best activity against the H5N1-H274Y mutant NA. Although the activity of N10 is comparable to that of OSC for wild-type H5N1 inhibition, it is approximately 60-fold more potent than OSC against the H274Y mutant, suggesting that it is not easy for the virus to develop drug resistance and is attractive for drug development. N10 (EC50 = 0.11 µM) also exhibits excellent antiviral activity against H5N1, which is superior to the positive control OSC (EC50 = 1.47 µM). Molecular docking study shows that the occupation of aromatic fused rings and oxadiazole moiety at the active site and the extension of the substituted phenyl to the 150-cavity or 430-cavity make great contributions to the good potency of this series of polyheterocyclic NA inhibitors. Some advancements in the discovery of effective target-specific NA inhibitors in this study may offer some assistance in the development of more potent anti-influenza drugs.

Design, synthesis and biological evaluation of sulfamethazine derivatives as potent neuraminidase inhibitors.

Aim: The purpose of this study is to design and synthesize a new series of sulfamethazine derivatives as potent neuraminidase inhibitors. Materials & methods: A sulfamethazine lead compound, ZINC670537, was first identified by structure-based virtual screening technique, then some novel inhibitors X1-X10 based on ZINC670537 were designed and synthesized. Results: Compound X3 exerts the most good potency in inhibiting the wild-type H5N1 NA (IC50 = 6.74 µM) and the H274Y mutant NA (IC50 = 21.09 µM). 150-cavity occupation is very important in determining activities of these inhibitors. The sulfamethazine moiety also plays an important role. Conclusion: Compound X3 maybe regard as a good anti-influenza candidate to preform further study.

[Box: see text].

EBUS-GS with the GeneXpert MTB/RIF assay for diagnosis of Mycobacterium tuberculosis infection of isolated pulmonary nodules.

OBJECTIVE: Investigate the use of endobronchial ultrasonography with a guide sheath (EBUS-GS) combined with Gene Xpert MTB/RIF (Xpert) for diagnosis of Mycobacterium tuberculosis (MTB) infection in isolated pulmonary nodules. METHODS: Patients who had isolated pulmonary nodules and unknown diagnoses at our institution from October 2020 to December 2021 were prospectively examined using EBUS-GS and Xpert. The diagnostic values of using EBUS-GS or bronchoalveolar lavage fluid (BALF) with acid-fast staining, MGIT 960 culture, pathological examination, and Xpert for isolated pulmonary nodules caused by MTB infection were compared using receiver operating characteristic (ROC) analysis. RESULTS: There were 135 patients, 64 with isolated pulmonary tuberculomas and 71 with non-tuberculous lesions. The sensitivity of EBUS-GS with Xpert was significantly higher than BALF with Xpert (57.81% vs. 34.78%, P = 0.017). Use of EBUS-GS with Xpert and MGIT 960 culture further increased the sensitivity to 62.50% (95%CI 50.64-74.36) and increased the specificity to 100%. The AUC values of BALF with MGIT 960 culture was 0.663(95%CI 0.543-0.783) and BALF with Xpert was 0.674 (95%CI 0.556-0.792). The AUC values of EBUS-GS with MGIT 960 culture was 0.680 (95%CI 0.554-0.743), with pathological examination was 0.713 (95%CI 0.573-0.760), and with Xpert was 0.789 (95%CI 0.655-0.829). CONCLUSION: Use of EBUS-GS with Xpert had high sensitivity and specificity in the diagnosis of isolated pulmonary tuberculoma. This method has significant potential for use in clinical practice.

Factors Associated with Treatment Outcome in Patients with Nontuberculous Mycobacterial Pulmonary Disease: A Large Population-Based Retrospective Cohort Study in Shanghai.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly common. This retrospective cohort study examined factors associated with outcomes in patients from Shanghai who had NTM pulmonary disease (NTMPD) from January 2014 to December 2018. The causative bacterial species, drug susceptibility test results, treatment outcomes, sputum culture conversion rate, and risk factors associated with treatment failure were determined. The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, p < 0.001) and M. abscessus (36.1%, p < 0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR = 9.355, p < 0.001; MAC: aOR = 2.970, p < 0.001), elevated ESR (>60 mm/h: aOR = 2.658, p < 0.001), receipt of retreatment (aOR = 2.074, p < 0.001), and being middle-aged or elderly (>60 years-old: aOR = 1.739, p = 0.021; 45-60 years-old: aOR = 1.661, p = 0.034). The main bacterial species responsible for NTMPD were MAC, M. abscessus, and M. kansasii. Patients who were infected by M. abscessus or MAC, with elevated ESR, received retreatment, and were middle-aged or elderly had an increased risk of treatment failure.

A low-frequency multiple-band sound insulator without blocking ventilation along a pipe.

It is challenging to insulate sound transmission in low frequency-bands without blocking the air flow in a pipe. In this work, a small and light membrane-based cubic sound insulator is created to block acoustic waves in multiple low frequency-bands from 200 to 800 Hz in pipes. Due to distinct vibration modes of the membrane-type faces of the insulator and co-action of acoustic waves transmitting along different paths, large sound attenuation is achieved in multiple frequency-bands, and the maximum transmission loss reaches 25 dB. Furthermore, because the sound insulator with a deep subwavelength size is smaller than the cross-sectional area of the pipe, it does not block ventilation along the pipe.

Spectral target-detecting system using sine-wave modulation.

Target detection is one of the key technology of precision chemical application. Previously the digital coding modulation technique was commonly used to emit and receive the optical signal in the target detection systems previously in China. It was difficult to adjust the output power, and the anti-interference ability was weak in these systems. In order to resolve these problems, the target detection method based on analog sine-wave modulation was studied. The spectral detecting system was set up in the aspects of working principle, electric circuit, and optical path. Lab testing was performed. The results showed that the reflected signal from the target varied inversely with detection distances. It indicated that it was feasible to establish the target detection system using analog sine-wave modulation technology. Furthermore, quantitative measurement of the reflected optical signal for near-infrared and visible light could be achieved by using this system. The research laid the foundation for the future development of the corresponding instrument.

Clinical value of endobronchial ultrasound-guided aspiration and local isoniazid injection in the treatment of mediastinal tuberculous lymphadenitis.

BACKGROUND: This study aimed to investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) guided purulence aspiration and local isoniazid injection after lymph node puncture in the treatment of refractory mediastinal tuberculous lymphadenitis (MTLA) as compared to systemic anti-tuberculosis treatment. METHODS: This was a retrospective study. A total of 92 patients with MTLA and suppurative lymphadenitis who were treated in the Shanghai Pulmonary Hospital between January 2015 and December 2018 were included into present study and divided into systemic chemotherapy (CT) group and interventional therapy (IT) group. In the CT group, patients received systemic chemotherapy alone; in the IT group, patients received EBUS-TBNA guided lymph node aspiration and local isoniazid injection besides systemic chemotherapy. The recovery of lymphadenitis and adverse effects were observed. RESULTS: Seventy patients were included for final analysis, 35 patients in each group. In the IT group, aspiration and local injection were done 137 times; 4R (53.1%) and 7 groups of lymph nodes (30.6%) were the most common site of aspiration; the median number of local treatment was 3 times, and the median duration of local injection was 29 days. The recovery rate of lymphadenitis was 88.6% (31/35) in the IT group and 57.1% (20/35) in the CT group, showing marked difference (χ2=8.741, P<0.05). The most common symptoms of patients with MTLA were cough, fever, dyspnea and anorexia, and the time to recovery of these symptoms in the IT group was 0.83±0.32, 0.89±0.29, 1.00±0.18 and 1.07±0.15 months, respectively, which were markedly shorter than in the CT group 2.60±0.74, 2.46±0.73, 2.70±0.40 and 2.67±0.43 months (t=7.608, P<0.05; t=6.442, P<0.05; t=6.755, P<0.05; t=5.237, P<0.05). All the patients received EBUS-TBNA under local anesthesia, and evident adverse effects were not observed. They were followed up for 2 years, and recurrence was not noted. CONCLUSIONS: As compared to systemic chemotherapy, EBUS-TBNA guided lymph node aspiration and local isoniazid injection combined with systemic chemotherapy may significantly improve the therapeutic efficacy, which provides a new, safe and reliable management for the refractory MTLA.

Discovery of novel thiophene derivatives as potent neuraminidase inhibitors.

Neuraminidase (NA) is an important target for the treatment of influenza. In this study, a new lead NA inhibitor, 4 (ZINC01121127), was discovered by pharmacophore-based virtual screening and molecular dynamic (MD) simulation. Some novel NA inhibitors containing thiophene ring were synthesized by optimizing the skeleton of the lead compound 4. Compound 4b had the most potent inhibitory activity against NA (IC50 = 0.03 µM), which was better than the positive control oseltamivir carboxylate (IC50 = 0.06 µM). 4b (EC50 = 1.59 µM) also exhibits excellent antiviral activity against A/chicken/Hubei/327/2004 (H5N1-DW), which is superior to the reference drug OSC (EC50 = 5.97 µM). Molecular docking study shows that the thiophene moiety plays an essential role in compound 4b, which can bind well to the active site of NA. The good activity of 4b may be also ascribed to the extending of quinoline ring into the 150-cavity. The results of this study may provide an insightful help for the development of new NA inhibitors.

Design, Synthesis, and Biological Evaluation of Novel Acylhydrazone Derivatives as Potent Neuraminidase Inhibitors.

Neuraminidase (NA) is an important target for current research on anti-influenza drugs. The acylhydrazone derivatives containing the -CONHN=CH- framework have been shown to have good NA inhibitory activity. In this paper, a series of novel acylhydrazone NA inhibitors (9a-9n) were designed and synthesized, and the inhibitory activities against NA were evaluated in vitro. The NA inhibition results showed that compound 9j has the most potent inhibitory activity (IC50 = 0.6 µM) against NA, which is significantly lower than that of the positive control oseltamivir carboxylic acid (OSC) (IC50 = 17.00 µM). Molecular docking analysis indicates that the acylhydrazone group plays an important role in compound 9j, which can bind well to the residues Arg371 and Arg292 in the S1 subsite of NA. The good potency of 9j may be also ascribed to the extending of morpholinyl ring into the 430-cavity. The results of this work may contribute to the development of more potent NA inhibitors to against mutant influenza viruses.

Diagnostic Value of Virtual Bronchoscopic Navigation in the Bronchial Tuberculosis Induced Central Airway Stenosis.

INTRODUCTION: Electronic bronchoscopy is invasive and may cause pain. This study aimed to explore the clinical value of virtual bronchoscopic navigation (VBN) in the diagnosis of benign central airway stenosis (CAS) secondary to tracheobronchial tuberculosis (TBT). METHODS: Sixty-eight patients with benign CAS caused by TBT were recruited between July 2015 and December 2017. The location, length and diameter of stenoses were independently determined by VBN and electronic bronchoscopy (EOB), and the sensitivity and specificity of VBN in identifying stenosis were assessed with EOB as the gold standard. RESULTS: In 68 patients with TBT, the overall coincidence between EOB and VBN in the identification of stenosis was 100%. A total of 188 sites were selected from the central airway, and the stenosis was graded into 0%, ≤ 25%, 26-50%, 51-75%, 76-90% and > 90%. The sensitivity of VBN in determining the degree of stenosis was 98.45%, 100.00%, 100.00%, 100.00%, 84.62% and 0.00%, respectively; the specificity was 91.53%, 96.07%, 97.09%, 97.08%, 97.14% and 97.30%, respectively; the accuracy rate was 96.28%, 96.28%, 97.34%, 97.34%, 96.28% and 95.7%, respectively. The length of airway stenosis on EOB was divided into < 10 mm, 10-30 mm, 30-50 mm and > 50 mm. There was no significant difference in the length of airway stenosis between VBN and EOB (t = 0.083, P = 0.936; t = 1.340, P = 0.199; t = 1.297, P = 0.216; t = 2.186, P = 0.081). In three patients who received stent placement, VBN was able to accurately assess the postoperative expansion. CONCLUSION: VBN is helpful for the diagnosis of TBT-induced CBS and may provide important information on the location, length, diameter and cross-sectional area of stenosis for further EOB examination and interventional therapy. VBN is recommended for patients with TBT and those with contradictions to bronchoscopy, as well as for regular follow-up of stable TBT, because it reduces the incidence of injury, avoids repeat operations and shortens treatment time.

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China.

Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 [52%]), and dry cough (11 [44%]). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.