Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

Programmable Base Editing in Mycobacterium tuberculosis Using an Engineered CRISPR RNA-Guided Cytidine Deaminase.

Multidrug-resistant Mycobacterium tuberculosis (Mtb) infection seriously endangers global human health, creating an urgent need for new treatment strategies. Efficient genome editing tools can facilitate identification of key genes and pathways involved in bacterial physiology, pathogenesis, and drug resistance mechanisms, and thus contribute to the development of novel treatments for drug-resistant tuberculosis. Here, we report a two-plasmid system, MtbCBE, used to inactivate genes and introduce point mutations in Mtb. In this system, the assistant plasmid pRecX-NucSE107A expresses RecX and NucSE107A to repress RecA-dependent and NucS-dependent DNA repair systems, and the base editor plasmid pCBE expresses a fusion protein combining cytidine deaminase APOBEC1, Cas9 nickase (nCas9), and uracil DNA glycosylase inhibitor (UGI). Together, the two plasmids enabled efficient G:C to A:T base pair conversion at desired sites in the Mtb genome. The successful development of a base editing system will facilitate elucidation of the molecular mechanisms underlying Mtb pathogenesis and drug resistance and provide critical inspiration for the development of base editing tools in other microbes.

NLRP3 ablation enhances tolerance in heat stroke pathology by inhibiting IL-1ß-mediated neuroinflammation.

BACKGROUND: Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. METHODS: In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1ß neutralizing antibody was injected to test potential therapeutic effect on heat stroke. RESULTS: Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1ß in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1ß production with prior infection condition. Furthermore, IL-1ß neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. CONCLUSIONS: Based on the above results, NLRP3/IL-1ß induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1ß may serve as a biomarker for heat stroke severity and potential therapeutic method.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Synthesis and characterization of a series of transition metal oxychlorides: MBi(SeO3)2(H2O)Cl (M = Co, Ni, Cu).

Three new transition metal oxychlorides MBi(SeO3)2(H2O)Cl (M = Co, Ni, Cu) have been firstly synthesized through a hydrothermal reaction method at 200 °C. They were structurally determined to be isostructural with the Pbca space group of the orthorhombic system. They feature a 3D framework topology with two-dimensional tunnels intersected and filled with Cl anions parallel to the crystallographic bc-plane. Two neighboring MO5Cl octahedra are connected by a sharing edge into a M2O8Cl2 dimer which serves as the structural knots to knit the 2D [Bi(SeO3)2]∞ layers in the ab-plane together into the total 3D crystal architecture. The optical band gaps of CoBi(SeO3)2(H2O)Cl (1), NiBi(SeO3)2(H2O)Cl (2) and CuBi(SeO3)2(H2O)Cl (3) were evaluated to be 3.7 eV, 3.5 eV and 3.2 eV, respectively, through extrapolating the UV-vis-NIR optical absorption spectra. Besides, the spin-allowed d-d transition absorption spectra of the transition ion centers are observed in three compounds exhibiting different colors. Compounds 1, 2 and 3 can stay thermally stable below 370 °C, 400 °C and 300 °C, respectively, as found from the results of thermal analysis based on the simultaneous thermogravimetry and differential scanning calorimetry techniques. 1, 2 and 3 exhibit antiferromagnetic properties below Néel temperatures 6 K, 18 K and 52 K, respectively. Above the Néel temperatures, Curie-Weiss behavior dominates in the M-T process for the three compounds. The cell parameters are listed: a = 14.056 Å, b = 7.582 Å, c = 14.996 Å, and Z = 8 for 1, a = 14.083 Å, b = 7.575 Å, c = 14.860 Å, and Z = 8 for 2, and a = 14.576 Å, b = 7.371 Å, c = 14.656 Å, and Z = 8 for 3.

Imaging manifestations and pathological analysis of severe pneumonia caused by human infected avian influenza (H7N9).

OBJECTIVE: To investigate the imaging and pathological findings of severe pneumonia caused by human infected avian influenza (H7N9), and therefore to further understand and improve diagnostic accuracy of severe pneumonia caused by human infected avian influenza (H7N9). METHODS: The relevant clinical and imaging data of 19 cases, including 10 males and 9 females, with pneumonia caused by human infected avian influenza (H7N9) was retrospectively analyzed. One of the cases had received percutaneous lung biopsy, with the clinical, imaging and pathological changes possible to be analyzed. RESULTS: The lesions were mainly located at lower lobes and dorsal of lungs, involving multiple lobes and segments. Ground-glass opacities and/or pulmonary opacities were the more often imaging manifestations of severe pneumonia caused by human infected avian influenza (H7N9) in early and evolving phases (19/19,100%). By biopsy following percutaneous lung puncture, exudation of slurry, cellulose, RBC and neutrophils, formation of hyaline membrane, squamous metaplasia and organizing exudates were observable at the alveolar space. Some of alveoli collapsed, and some responded to show compensatory emphysema. CONCLUSION: The imaging features of severe pneumonia caused by human infected avian influenza (H7N9) include obvious ground-glass opacity and pulmonary consolidation, mainly at lower lobes and dorsal of lungs, with rapid changes. The cross-analysis of imaging and pathology preliminary can elucidate the pathological mechanisms of ground-glass opacities and pulmonary consolidation of severe pneumonia. Such an intensive study is beneficial to prompt clinicians to observe and evaluate the progress of the disease. In addition, it is also in favor of managing the symptoms and reducing the mortality rate.

[The relationship between chest CT findings and viral load in patients with novel influenza A (H1N1)].

OBJECTIVE: To evaluate the value of chest CT findings and dynamic changes of viral load in patients with novel influenza A (H1N1) infection in clinical diagnosis, differential diagnosis and treatment. METHODS: Fifty-one patients with confirmed novel influenza A (H1N1) according to the diagnostic criteria of the Ministry of Health, received chest X-ray, CT scans (HRCT) and viral load tests in our hospital from May to December of 2009. Based on whether there were signs of pneumonia in CT imaging, the patients were divided into a pneumonia group (n = 31) and a non-pneumonia group (n = 20). The relationship between chest CT changes and viral load was observed and analyzed statistically using SPSS 10.5 software. RESULTS: Patchy consolidations of lungs were the main findings in pneumonia group with influenza A (H1N1) infection, and ground-glass opacities were the main CT findings at acute and convalescent phases. Lobular and segmental shadows of the lungs were diffusely distributed, mostly found in lower lungs, especially the left lung. In some cases, the lung diseases were accompanied with mediastinal lymphadenopathy. Co-existence of pulmonary parenchymal, interstitial and pleural diseases was observed. Peak viral load occurred at the early phase of illness, with the mean initial viral load being 7.7 copies/ml and 4.2 copies/ml in the pneumonia and the non-pneumonia groups respectively. The viral nucleic acid became negative 4 days after antiviral treatment (course of 6 days). Dynamic observation of 3 patients with novel influenza A (H1N1) pneumonia showed that, the viral clearance period preceded the absorption of lung lesions in 2 cases, but viral clearance period of a young patient was significantly prolonged. CONCLUSION: In patients with the novel influenza A (H1N1) infection, the viral load in the pneumonia group was significantly higher than that in the group with normal chest imaging. Dynamic observation on chest imaging and viral load may be beneficial for clinicians to start prompt and effective treatment.

[Determination of trace manganese by catalytic kinetic spectrophotometry method with CTMAB as the sensitizer].

A new catalytic spectrophotometric method for the determination of trace amount of Mn(II) was developed. The method is based on the oxidation of 7-(2-nitryl-4-methyl phenylazo)-8-hydroxy-qinolin-5-slfonic acid by potassium periodate in the presence of nitrilo triacec acid as an activator and CTMAB as a sensitizer. The wavelengths for the determination was 509 nm. The linear range of determination is 0-3. 2 x 10(-9) g x mL(-1) for Mn(II). The determination limit is 3.8 x 10(-11) g x mL(-1). The interference of foreign ions was studied. The method can be used for the determination of Mn(II) in mung bean, rice, cereal and soil samples.

Bis(ethylenediammonium) decaaquadisodium decavanadate, (C2H10N2)2[Na2(H2O)10][V10O28].

In the title compound, the decavanadate anion, [V(10)O(28)](6-), and the bridged [Na(2)(H(2)O)(10)](2+) dication lie across inversion centers. The charge balance is achieved by ethylenediammonium cations, H(3)NCH(2)CH(2)NH(3)(2+), which are disordered. The decavanadate anions are surrounded by the [Na(2)(H(2)O)(10)](2+) dications, thus forming layers, and the ethylenediammonium cations are located between these layers.

A new hydrated ammonium hydroxyborate, (NH(4))(2)[B(10)O(14)(OH)(4)].H(2)O.

The structure of a new synthetic compound, diammonium tetrahydroxydecaborate monohydrate, has been determined by single-crystal X-ray diffraction. It crystallizes in triclinic space group P-1 and all atoms occupy general sites. The title compound is composed of [B(10)O(15)(OH)(4)](4-) ions as the fundamental building blocks, and these are linked end-to-end by sharing two common O atoms, thus producing infinite chains of composition [B(10)O(14)(OH)(4)](n)(2n-). These chains are linked by hydrogen bonds, thus forming borate sheets. Water molecules and ammonium ions between these sheets connect adjacent sheets via hydrogen bonds.