Bufei Huoxue capsule attenuates COPD-related inflammation and regulates intestinal microflora, metabolites.

Background: Bufei Huoxue capsule (BFHX) is widely used for the clinical treatment of chronic obstructive pulmonary disease (COPD) in China. Objectives: The aim of this study is to explore the effects on COPD and the underlying mechanism of BFHX. The process and methods: In this study, we established a COPD mouse model through cigarette smoke (CS) exposure in combination with lipopolysaccharide (LPS) intratracheal instillation. Subsequently, BFHX was orally administrated to COPD mice, and their pulmonary function, lung pathology, and lung inflammation, including bronchoalveolar lavage fluid (BALF) cell count and classification and cytokines, were analyzed. In addition, the anti-oxidative stress ability of BFHX was detected by Western blotting, and the bacterial diversity, abundance, and fecal microbiome were examined using 16S rRNA sequencing technology. Outcome: BFHX was shown to improve pulmonary function, suppress lung inflammation, decrease emphysema, and increase anti-oxidative stress, whereas 16S rRNA sequencing indicated that BFHX can dynamically regulate the diversity, composition, and distribution of the intestinal flora microbiome and regulate the lysine degradation and phenylalanine metabolism of COPD mice. These results highlight another treatment option for COPD and provide insights into the mechanism of BFHX.

Mendelian randomization analysis identifies druggable genes and drugs repurposing for chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD. Methods: Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases. Results: A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1. Conclusions: Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.

Efficient Lead Removal by Assembly of Bio-Derived Ellagate Framework, Which Enables Electrocatalytic Reduction of CO2 to Formate.

Lead (Pb) poisoning and CO2-induced global warming represent two exemplary environmental and energy issues threatening humanity. Various biomass-derived materials are reported to take up Pb and convert CO2 electrochemically into low-valent carbon species, but these works address the problems separately rather than settle the issues simultaneously. In this work, cheap, natural ellagic acid (EA) extracted from common plants is adopted to assemble a stable metal-organic framework (MOF), EA-Pb, by effective capture of Pb2+ ions in an aqueous medium (removal rate close to 99%). EA-Pb represents the first structurally well-defined Pb-based MOF showing selective electrocatalytic CO2-to-HCOO- conversion with Faradaic efficiency (FE) of 95.37% at -1.08 V versus RHE. The catalytic mechanism is studied by 13CO2 labeling, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and theoretical calculation. The use of EA-Pb as an electrocatalyst for CO2 reduction represents a 2-in-1 solution of converting detrimental wastes (Pb2+) as well as natural resources (EA) into wealth (electrocatalytic EA-Pb) for addressing the global warming issue.

Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

Background: The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. Methods: This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. Results: The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Conclusion: Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.

Exploration of the minimal clinically important difference value of the 3-min simulated pedal motion in patients with chronic obstructive pulmonary disease: A self-controlled prospective clinical trial.

BACKGROUND: To help elderly patients with severe or very severe chronic obstructive pulmonary disease (COPD) with pulmonary rehabilitation, we have developed Zheng's supine rehabilitation exercise (ZSRE). Currently, none of the terminal or critically ill patients with severe exercise limitation can complete the 6-min walking distance (6MWD) and cardiopulmonary exercise testing (CPET). METHODS: In this study, we discuss the definition of the standardized 3-min simulated pedal motion (3MSPM) test and its operational specifications. Also, we evaluate the minimal clinically important difference (MCID) value of the 3MSPM. RESULTS: The results showed that the mMRC score of COPD patients with acute exacerbation of dyspnea was progressively reduced from the second day of respiratory rehabilitation, and the difference between the first and seventh days was statistically significant (p < 0.000, χ2 = 176.664). 6MWD increased progressively, and the difference between 6MWD on day 1-7 was statistically significant (p = 0.024, F = 2.443). The difference between 3MSPM on day 1-7 was also statistically significant (p < 0.000, F = 4.481). Further analysis showed that 6MWD was negatively correlated with mMRC (p < 0.000, OR = -0.524). 3MSPM was positively correlated with 6MWD (p < 0.000, OR = 0.640) but negatively correlated with mMRC (p < 0.000, OR = -0.413). There is a linear regression relationship between 6MWD and 3MSPM, that is, 6MWD = 14.151 + 0.301 * 3MSPM, adjusted R2 = 0.401. CONCLUSION: Based on the regression equation, 3MSPM can predict 6MWD, and it can be used as a simple exercise endurance method to evaluate patients with safety hazards in underground activities or who cannot complete the 6MWD test. The minimum clinically important difference value is increased by 23.

Removing Perfluoro Pollutants PFOA and PFOS by Two-Pronged Design of a Ni8-Pyrazolate Porous Framework.

Inspired by the practical need to remove persistent perfluoro pollutants from the environment, we leverage cutting-edge crystal engineering approaches. For this, we set our eyes on a recent porous coordination framework system based on the Ni8-oxo cluster and pyrazolate linkers as it is known for its stability to bases and other harsh environmental conditions. Our designer linker molecule here features (1) pyrazole donors masked by t-butyloxycarbonyl and (2) ethynyl side units protected by triisopropylsilyl groups. The former solvothermally demasks to assemble the Ni8-pyrazolate framework, in which the triisopropylsilyl groups can be post-synthetically cleaved by guest fluoride ions to unveil the terminal alkyne group (-CCH). The ethynyl groups of the framework solid offer versatile reactions for functionalization, as with perfluorophenyl azide (via a click reaction) to afford the two prongs of the 1,2,3-triazole base unit and the perfluoro unit. Together, these two functions make for an effective adsorbent for the topical acid pollutants of perfluorooctanoic acid and perfluorooctanesulfonic acid, with a high apparent rate constant (kobs) of 0.99 g mg-1 h-1 and large maximum uptake capacity (qmax) of 268.5 mg g-1 for perfluorooctanoic acid and kobs of 0.77 g mg-1 h-1 and qmax of 142.1 mg g-1 for perfluorooctanesulfonic acid.

Effectiveness of a booster dose of COVID-19 vaccines during an outbreak of SARS-CoV-2 Omicron BA.2.2 in China: A case-control study.

Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2.2 variant remains scarce. A case-control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China (inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine). There were 414 cases infected with SARS-CoV-2 and 828 close contacts whose test results were consecutively negative as controls during the outbreak of the Omicron variant in Lu'an City, Anhui Province, China, in April 2022. The overall adjusted VE against Omicron BA.2.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: -9.1-61.3%), whereas the adjusted VE for booster vaccination was 51.6% (95% CI: 15.2-72.4%). Subgroup analysis showed that the overall adjusted VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8-86.6%) during the outbreak while any dose of inactivated vaccines and recombinant protein vaccine offered no protection. The adjusted VE of three-dose inactivated vaccines was 48.0% (95% CI: 8.0-70.6%), and the two-dose Ad5-nCoV vaccine was 62.9% (95% CI: 1.8-86%). There is no protection from a three-dose recombinant protein vaccine. COVID-19 vaccines offered 46.8% (95% CI: 9.5-68.7%) protection from infection within six months. There were statistically significant differences between the VEs of heterologous booster (VE = 76.4%, 95% CI: 14.3-93.5%) and homologous booster vaccination (VE = 51.8%, 95% CI: 9.6-74.3%) (P = .036). Booster vaccination of COVID-19 vaccines offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted.

Ni(II)-Pyrazolate Framework Bearing a Metalated Schiff-Base Moiety for Electrocatalytic Hydrogen Evolution.

A robust and porous Ni-based metal-organic framework (MOF), NiL1, was assembled from Ni(II) ions and a dipyrazolate linker (L12-). A Ni(II)-anchored MOF catalyst Ni@NiL1-Sal has been successfully prepared by post-synthetic modification (PSM) condensation between NiL1 with salicylaldehyde, followed by chelation of Ni(II) ions by salicylaldimine as a secondary active site. Ni@NiL1-Sal with carbon black was found to exhibit enhanced electrocatalytic hydrogen evolution reaction (HER) performance (the smallest overpotential, 384 mV, and Tafel slope, 87 mV dec-1) when compared with primitive NiL1 and NiL1-Sal. Such improvement in HER highlights the creation of unambiguous secondary active sites as an avenue to the rational design of a functional MOF-based electrocatalyst.

Screening and Validation of Odorants against Influenza A Virus Using Interpretable Regression Models.

Influenza is a respiratory infection caused by the influenza virus that is prevalent worldwide. One of the most contagious variants of influenza is influenza A virus (IAV), which usually spreads in closed spaces through aerosols. Preventive measures such as novel compounds are needed that can act on viral membranes and provide a safe environment against IAV infection. In this study, we screened compounds with common fragrances that are generally used to mask unpleasant odors but can also exhibit antiviral activity against a strain of IAV. Initially, a set of 188 structurally diverse odorants were collected, and their antiviral activity was measured in vapor phase against the IAV solution. Regression models were built for the prediction of antiviral activity using this set of odorants by taking into account their structural features along with vapor pressure and partition coefficient (n-octanol/water). The models were interpreted using a feature weighting approach and Shapley Additive exPlanations to rationalize the predictions as an additional validation for virtual screening. This model was used to screen odorants from an in-house odorant data set consisting of 2020 odorants, which were later evaluated using in vitro experiments. Out of 11 odorants proposed using the final model, 8 odorants were found to exhibit antiviral activity. The feature interpretation of screened odorants suggested that they contained hydrophilic substructures, such as hydroxyl group, which might contribute to denaturation of proteins on the surface of the virus. These odorants should be explored as a preventive measure in closed spaces to decrease the risk of infections of IAV.

Utilizing Metal-Thiocatecholate Functionalized UiO-66 Framework for Photocatalytic Hydrogen Evolution Reaction.

Exploiting clean energy is essential for sustainable development and sunlight-driven photocatalytic water splitting represents one of the most promising approaches toward this goal. Metal-organic frameworks (MOFs) are competent photocatalysts owing to their tailorable functionality, well-defined structure, and high porosity. Yet, the introduction of the unambiguous metal-centered active site into MOFs is still challenging since framework motifs capable of anchoring metal ions firmly are lacking. Herein, the assembly using 1,4-dicarboxylbenzene-2,3-dithiol (H2 dcbdt) and Zr-Oxo clusters to give a thiol-functionalized UiO-66 type framework, UiO-66-dcbdt, is reported. The thiocatechols on the struts are allowed to capture transition metal (TM) ions to generate UiO-66-dcbdt-M (M  = Fe, Ni, Cu) with unambiguous metal-thiocatecholate moieties for photocatalytic hydrogen evolution reaction (HER). UiO-66-dcbdt-Cu is found the best catalyst exhibiting an HER rate of 4.18 mmol g-1  h-1  upon irradiation with photosensitizing Ru-polypyridyl complex. To skip the use of the external sensitizer, UiO-66-dcbdt-Cu is heterojunctioned with titanium dioxide (TiO2 ) and achieves an HER rate of 12.63 mmol g-1  h-1  (32.3 times that of primitive TiO2 ). This work represents the first example of MOF assembly employing H2 dcbdt as the mere linker followed by chelation with TM ions and undoubtedly fuels the rational design of MOF photocatalysts bearing well-defined active sites.

Compliance and rehabilitation effects of Zheng's supine rehabilitation exercise performed at home among patients with chronic obstructive pulmonary disease: a retrospective study.

Background: Zheng's supine rehabilitation exercise (ZSRE) can be performed by elderly patients with the acute exacerbation of severe or extremely severe chronic obstructive pulmonary disease (COPD) with high safety and compliance and was helpful for their recovery. Investigation is warranted of the compliance and rehabilitation effects of ZSRE performed at home in patients with COPD. Methods: We performed telephone interviews with 157 patients with COPD who were hospitalized on the 26th floor of the National Clinical Research Center for Respiratory Disease and who received COPD education and ZSRE training from 1 September 2015 to 31 August 2016. We retrospectively analyzed the patients' compliance with performing ZSRE at home after discharge and the frequency of hospitalization for treatment of acute exacerbation in both the previous and subsequent years. Results: Among the 157 patients, 66 failed to complete home ZSRE after discharge (non-rehabilitation group), 41 performed home ZSRE once a day after discharge (one-session rehabilitation group), and 50 performed home ZSRE at least twice a day after discharge (multiple-session rehabilitation group). The home ZSRE compliance rate was 57.96% (91/157). There were no significant differences in the mean number of hospitalizations in the year prior to receiving COPD education and ZSRE training among the non-rehabilitation group (1.06±0.75), one-session rehabilitation group (1.27±0.78), and multiple-session rehabilitation group (1.16±0.91). However, there was a significant difference in the mean number of hospitalizations among the groups in the year following discharge (1.44±1.17, 0.78±0.82, and 0.66±0.75, respectively). The number of hospitalizations significantly increased in the non-rehabilitation group and significantly decreased in the one- and multiple-session rehabilitation groups. Conclusions: Home ZSRE can be performed with high compliance by elderly patients with severe or extremely severe COPD and can reduce the number of readmissions.

Microenvironment Regulation of Metal-Organic Frameworks to Anchor Transition Metal Ions for the Electrocatalytic Hydrogen Evolution Reaction.

Bearing triazine-centered linkers, three primitive metal-organic frameworks (MOFs) with a Zr6O4 cluster have been prepared as ZrL1 (without any branch), ZrL2 (with -F), and ZrL3 (with -SCH3). The electrocatalytic hydrogen evolution reaction (HER) by their pristine and transition metal-loaded (TM-loaded) forms was studied. It was found that the loading of TM ions could enhance the electrocatalytic power of these TM-loaded MOFs in HER, as reflected by their lower overpotentials and smaller Tafel slopes when compared with primitive MOFs. More importantly, the best electrocatalytic HER performance of ZrL3-TM among all TM-loaded MOFs studied in this work highlights the effective housing of TM ions for unambiguous active sites through cooperative coordination by triazinic N and thioether pendants. This work proposes microenvironment regulation of MOFs as an effective strategy to enhance the electrocatalytic activity of MOF materials.

An odorant receptor that senses four classes of musk compounds.

Musk was originally identified in male musk deer and other mammals to mark territories and attract females. In humans, musk compounds are widely used in perfumes and consumer products for their superior perceptual odor quality.1,2,3,4,5 Strikingly diverse natural and synthetic chemicals have exhibited a similar "musky" odor, which has resulted in diverse models of musk odor perception and raises questions regarding the simplistic associations between chemical features and odor quality. Scientists' lack of understanding of this principle has hampered the design of a novel musk compound. Here, we functionally identified the odorant receptor, OR5A2, as a receptor for the musky odor of diverse musk compounds. First, we discovered that engineered OR5A2 with enhanced expression in heterologous cells is sensitive to and selective of musk compounds in all four structural classes. Second, the clarified functional variation of OR5A2 accounts for the reported association between genetic variation and perception in a musk compound. Finally, the revealed ligand selectivity of OR5A2 provides insight into developing a trained model to use machine learning-based virtual screening on candidates for a new musk compound. We propose that OR5A2 contributes to the long-sought gateway of sensing musk compounds and generating their unique odor quality.

Carbazole-Equipped Metal-Organic Framework for Stability, Photocatalysis, and Fluorescence Detection.

The useful yet underutilized backfolded design is invoked here for functionalizing porous solids with the versatile carbazole function. Specifically, we attach carbazole groups as backfolded side arms onto the backbone of a linear dicarboxyl linker molecule. The bulky carbazole side arms point away from the carboxyl links and do not disrupt the Zr-carboxyl framework formation; namely, the resultant MOF solid ZrL1 features the same net as that of the unfunctionalized dicarboxyl linker, also known as the PCN-111 net or UiO-66 net. The ZrL1 structure features only half linker occupancy (about 6 out of the 12 linkers around the Zr6O8 cluster being missing) and partially collapses upon activation (acetone exchange and evacuation). Notably, the stability improves after heating in diphenyl oxide at 260 °C (POP-260 treatment; to form ZrL1-260), as indicated by the higher crystallinity and surface area of the activated ZrL1-260 sample. The ZrL1-260 samples achieve 72% yield in photocatalyzing reductive dehalogenation of phenacyl bromide; ZrL1 can detect nitro-aromatic compounds via fluorescence quenching, with selectivity and sensitivity toward 4-nitroaniline, featuring a limit of detection of 96 ppb.

Dense Dithiolene Units on Metal-Organic Frameworks for Mercury Removal and Superprotonic Conduction.

With 2-COOH and 4-SH donors all packed onto the benzene ring, tetrasulfanyl terephthalic acid (TST) is a simple yet fully equipped ligand to move the field of metal-coordination materials─it is now accomplished. The hard-soft carboxyl-thiol synergy is leveraged here in selectively bonding the carboxyl units to Zr(IV) ions to form the same cubic net of UiO-66 (this being based on the terephthalic linker)─with the free-standing dithiolene units equipping the grid of ZrTST. The 3D network of ZrTST averages about 7.6 connections [as in Zr6O4(OH)4(C8H4O4S4)3.8], with the other 4.4 sealed by acetate ions. The ZrTST solid is stable in boiling water (it is formed in water/acetic acid/ethane dithiol) and remains ordered even above 300 °C. The thiol-enabled ZrTST (powder) takes up mercury from water with a high distribution coefficient Kd (e.g., 1.2 × 106 mL·g-1); it also shows proton conductivity (1.9 × 10-3 S·cm-1 at 90 °C and 90% relative humidity), which, most notably, increases to a highest value of 3.7 × 10-1 S·cm-1 after oxidizing the -SH into the -SO3H groups.

A Ferrocene Metal-Organic Framework Solid for Fe-Loaded Carbon Matrices and Nanotubes: High-Yield Synthesis and Oxygen Reduction Electrocatalysis.

Using a carbon-rich designer metal-organic framework (MOF), we open a high-yield synthetic strategy for iron-nitrogen-doped carbon (Fe-N-C) nanotube materials that emulate the electrocatalysis performance of commercial Pt/C. The Zr(IV)-based MOF solid boasts multiple key functions: (1) a dense array of alkyne units over the backbone and the side arms, which are primed for extensive graphitization; (2) the open, branched structure helps maintain porosity for absorbing nitrogen dopants; and (3) ferrocene units on the side arms as atomically dispersed precursor catalyst for targeting micropores and for effective iron encapsulation in the carbonized product. As a result, upon pyrolysis, over 89% of the carbon component in the MOF scaffold is successfully converted into carbonized products, thereby contrasting the easily volatilized carbon of most MOFs. Moreover, over 97% of the iron ends up being encased as acid-resistant Fe/Fe3C nanoparticles in carbon nanotubes/carbon matrices.

[Clinical characteristics and therapeutic effect of TP53 variant in patients with acute leukemia].

OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION: The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.

Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial.

BACKGROUND: To investigate whether the administration of hydrogen/oxygen mixture was superior to oxygen in improving symptoms in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: This prospective, randomized, double-blind, controlled clinical trial in 10 centres enrolled patient with AECOPD and a Breathlessness, Cough, and Sputum Scale (BCSS) score of at least 6 points. Eligible patients were randomly assigned (in a 1:1 ratio) to receive either hydrogen/oxygen mixture or oxygen therapy. Primary endpoint was the change from baseline in BCSS score at day 7. Adverse events (AEs) were recorded to evaluate safety. RESULTS: Change of BCSS score in Hydrogen/oxygen group was larger than that in Oxygen group (- 5.3 vs. - 2.4 point; difference: - 2.75 [95% CI - 3.27 to - 2.22], meeting criteria for superiority). Similar results were observed in other time points from day 2 through day 6. There was a significant reduction of Cough Assessment Test score in Hydrogen/oxygen group compared to control (- 11.00 vs. - 6.00, p < 0.001). Changes in pulmonary function, arterial blood gas and noninvasive oxygen saturation did not differ significantly between groups as well as other endpoints. AEs were reported in 34 (63.0%) patients in Hydrogen/oxygen group and 42 (77.8%) in Oxygen group. No death and equipment defects were reported during study period. CONCLUSIONS: The trial demonstrated that hydrogen/oxygen therapy is superior to oxygen therapy in patient with AECOPD with acceptable safety and tolerability profile. TRIAL REGISTRATION: Name of the registry: U.S National Library of Medicine Clinical Trials; Trial registration number: NCT04000451; Date of registration: June 27, 2019-Retrospectively registered; URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/study/NCT04000451?term=04000451&draw=2&rank=1 .

In-Situ Intermolecular Interaction in Composite Polymer Electrolyte for Ultralong Life Quasi-Solid-State Lithium Metal Batteries.

Solid-state lithium metal batteries built with composite polymer electrolytes using cubic garnets as active fillers are particularly attractive owing to their high energy density, easy manufacturing and inherent safety. However, the uncontrollable formation of intractable contaminant on garnet surface usually aggravates poor interfacial contact with polymer matrix and deteriorates Li+ pathways. Here we report a rational designed intermolecular interaction in composite electrolytes that utilizing contaminants as reaction initiator to generate Li+ conducting ether oligomers, which further emerge as molecular cross-linkers between inorganic fillers and polymer matrix, creating dense and homogeneous interfacial Li+ immigration channels in the composite electrolytes. The delicate design results in a remarkable ionic conductivity of 1.43×10-3  S cm-1 and an unprecedented 1000 cycles with 90 % capacity retention at room temperature is achieved for the assembled solid-state batteries.

Invisible Silver Guests Boost Order in a Framework That Cyclizes and Deposits Ag3Sb Nanodots.

The infusion of metal guests into (i.e., metalating) the porous medium of metal-organic frameworks (MOFs) is a topical approach to wide-ranging functionalization purposes. We report the notable interactions of AgSbF6 guests with the designer MOF host ZrL1 [Zr6O4(OH)7(L1)4.5(H2O)4]. (1) The heavy-atom guests of AgSbF6 induce order in the MOF host to allow the movable alkyne side arm to be fully located by X-ray diffraction, but they themselves curiously remain highly disordered and absent in the strucutral model. The enhanced order of the framework can be generally ascribed to interaction of the silver guests with the host alkyne and thioether functions, while the invisible heavy-atom guest represents a new phenomenon in the metalation of open framework materials. (2) The AgSbF6 guests also participate in the thermocyclization of the vicinal alkyne units of the L1 linker (at 450 °C) and form the rare nanoparticle of Ag3Sb supported on the concomitantly formed nanographene network. The resulted composite exhibits high electrical conductivity (1.0 S/cm) as well as useful, mitigated catalytic activity for selectively converting nitroarenes into the industrially important azo compounds, i.e., without overshooting to form the amine side products. The heterogeneous/cyclable catalysis entails only the cheap reducing reagents of NaBH4, ethanol, and water, with yields being generally close to 90%.