Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing,China

Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs’effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.

WAVE PROPAGATION IN PIEZOELECTRIC/PIEZOMAGNETIC LAYERED PERIODIC COMPOSITES

This paper is concerned with the dynamic behaviors of wave propagation in layered periodic composites consisting of piezoelectric and piezomagnetic phases. The dispersion relations of Lamb waves axe derived. Dispersion curves and displacement fields are calculated with different piezoelectric volume fractions. Numerical results for BaTiO3/CoFe2O4 composites show that the dispersion curves resemble the symmetric Lamb waves in a plate. Exchange between the longitudinal （i.e. thickness） mode and coupled mode takes place at the crossover point between dispersion curves of the first two branches. With the increase of BaTiO3 volume fraction, the crossover point appears at a lower wave number and wave velocity is higher. These findings are useful for magnetoelectric transducer applications.

High-PSRR High-Order Curvature-Compensated CMOS Bandgap Voltage Reference

A high-PSRR high-order curvature-compensated CMOS bandgap voltage reference( BGR),which has the performances of high power supply rejection ratio( PSRR) and low temperature coefficient,is designed in SMIC 0. 18 μm CMOS process. Compared to the conventional curvature-compensated BGR which adopted a piecewise-linear current,the temperature characterize of the proposed BGR is effectively improved by adopting two kinds of current including a piecewise-linear current and a current proportional 1. 5 party to the absolute temperature T. By adopting a low dropout( LDO) regulator whose output voltage is the operating supply voltage of the proposed BGR core circuit instead of power supply voltage VDD,the proposed BGR with LDO regulator achieves a well PSRR performance than the BGR without LDO regulator. Simulation results show that the proposed BGR with LDO regulator achieves a temperature coefficient of 2. 1 × 10-6/ ℃ with a 1. 8 V power supply voltage and a line regulation of 4. 9 μV / V at 27 ℃. The proposed BGR with LDO regulator at 10 Hz,100 Hz,1 k Hz,10 k Hz and 100 k Hz have the PSRR of- 106. 388,- 106. 388,- 106. 38,- 105. 93 and-88. 67 d B respectively.

Changes in intraocular pressure and central corneal thickness during pregnancy:a systematic review and Meta-analysis

AIM：To conduct a Meta-analysis for investigating the variations in intraocular pressure（IOP）and central corneal thickness（CCT）during normal pregnancy.METHODS：We searched for clinical trials published up to November 2015 without language or region restrictions in Pub Med,EMBASE,Web of Science,the Cochrane Central Register of Controlled Trials,Ovid,EBSCO,Elsevier,the Chinese Biomedicine Database,Wan Fang,CNKI,CQVIP and Google Scholar.Studies of the ocular changes observed in pregnant women were selected.The main outcomes were assessed by changes in IOP and CCT.RESULTS：Fifteen studies were included.In subgroup analyses,IOP was significantly decreased during the second MD=-1.53,95%CI（-2.19,-0.87）;P〈0.00001,and third MD=-2.91,95%CI（-3.74,-2.08）;P〈0.00001 trimesters of pregnancy.CCT was increased during the second MD=10.12,95%CI（2.01,18.22）;P=0.01,trimester of pregnancy;moreover,during the third trimester of pregnancy,the CCT displayed an increasing trend,but the difference was not significant MD=5.98,95%CI（-1.11,13.07）;P=0.1.CONCLUSION：A decrease in IOP is accompanied by an increase in CCT in the second and third trimesters of a normal pregnancy in women.

Resource allocation for sum-rate maximization in NOMA-based generalized spatial modulation

The Multiple-Input Multiple-Output(MIMO)Non-Orthogonal Multiple Access(NOMA)based on Spatial Modulation(SM-MIMO-NOMA)system has been proposed to achieve better spectral efficiency with reduced radio frequency chains comparing to the traditional MIMO-NOMA system.To improve the performance of SM-MIMO-NOMA systems,we extend them to generalized spatial modulation scenarios while maintaining moderate complexity and fairness.In this paper,system spectral efficiency and transmission quality improvements are proposed by investigating a sum-rate maximization resource allocation problem that is subject to the total transmitted power,user grouping,and resource block constraints.To solve this non-convex and difficult problem,a graph-based user grouping strategy is proposed initially to maximize the mutual gains of intragroup users.An auxiliary-variable approach is then adopted to transform the power allocation subproblem into a convex one.Simulation results demonstrate that the proposed algorithm has better performance in terms of bit error rate and sum rates.

Molecular characterization of the rpoB gene mutations of Mycobacterium tuberculosis isolated from China

Objective: To analyze characterization of the rpoBgene mutations of Mycobacterium tuber- culosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Beijing genotype strains. Methods: Genotypic analysis of 3479M. tuberculosis isolatesincluding 402 RIF-resistantand 3077 RIF-susceptible isolated from the na- tional drug-resistant tuberculosis baseline survey was performed. Results: DNA sequencing analysis of the 81-bp RIF resistance determining region (RRDR) of the ropB gene revealed that 98.01% of RIF-resistant strains showedrpoBgene mutation, isolates with mutations at codon rpoB531, rpoB 526 and rpoB 516 were the most frequently. Analysis of the rpoB gene of 3077 RIF-susceptible strains revealed that 98.96% of the strains had no mutation. The distribution of mutation frequency at differentcritical codons in different regions of China was statistically significant (p = 0.001). There was no significant difference in the occurrence of mutations at critical codons between the rifampicin-resistant Bei-jing and non-Beijing isolates.Conclusion: About 98% of RIF-resistant strains isolated from China carry mutations in RRDR ofrpoB gene.Mutation profiles in RIF-resistantM. tuberculosis clinical isolates are variable depending on the different geographical regionsof China. The results provide valuable information in adopting new molecular methods for diagnosis of TB in China.

One-pot synthesis of a giant twisted double-layer chiral macrocycle via [4+8] imine condensation and its X-ray structure

Trifluoroacetic acid(TFA)catalyzed condensation reaction between tetraaminooxacalix[4]arene and N-alkylcarbazole-3,6-dicarbaldehyde in CH_(2)Cl2afforded a single product in 87%–89%yield.Well-defined yet undissolvable1H NMR spectra suggested formation of robust and discrete structures in solution.X-ray single crystal analysis further revealed a giant twisted double-layer chiral macrocycle in the solid state,which was formed from[4+8]condensation of the two reactants via 16 imine bonds.DFT calculations discovered that only the[4+8]twisted product is thermodynamically favorable,which accounts for its highly selective and efficient formation out of a library of many other combinations.

相对定量分析异烟肼、链霉素单耐药与多耐药结核分枝杆菌临床分离株的蛋白质组差异

【目的】探讨异烟肼(isoniazid,INH)、链霉素(streptomycin,SM)单耐药结核分枝杆菌(Mycobacterium tuberculosis,MTB)与INH/SM多耐药MTB蛋白质组差异。【方法】应用i TRAQ结合Nano LC-MS/MS定量蛋白质组学技术,分析临床分离INH、SM或INH/SM耐药MTB与H37Rv标准株间均表达差异蛋白;并以INH/SM耐药MTB与H37Rv比值为对照,相对定量分析单耐药与多耐药MTB蛋白表达差异倍数;运用DAVID 6.7分析差异蛋白生物功能;STITCH 5.0分析差异蛋白与INH和SM相互作用。【结果】与H37Rv标准株比较,58个蛋白在INH、SM耐药与INH/SM耐药MTB间均有表达差异,共同差异蛋白生物功能主要为氧化还原酶活性和转移酶活性;主要参与丙酸代谢信号通路。共同差异蛋白中,与INH/SM耐药MTB比较,Rv2986c和Rv1908c在INH、SM耐药MTB均表达上调>1.25倍;Rv3133c和Rv0577则均表达下调<0.7倍;生物信息学预测发现以上4种蛋白可直接或间接与INH、SM进行相互作用。【结论】INH、SM单耐药和INH/SM多耐药MTB蛋白表达谱有较大差异,蛋白Rv2986c、Rv1908c、Rv3133c和Rv0577表达水平及相互作用可能与INH和SM耐药有关。

New incompatible pair of TCM:Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions

Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions.

Au-decorated porous structure graphene with enhanced sensing performance for low-concentration NO2 detection

A recent progress in new emerging two-dimensional(2 D)materials has provided promising opportunity for gas sensing in ultra-low detectable concentration.In this work,we have demonstrated a flexible NO2 gas sensor with porous structure graphene on polyethylene terephthalate substrates operating at room temperature.The gas sensor exhibited good performance with response of 1.2%and a fast response time within 30 s after exposure to50×10^-9 NO2 gas.As porous structure of graphene increased the surface area,the sensor showed high sensitivity of ppb level for NO2 detection.Au nanoparticles were decorated on the surface of the porous structure graphene skeleton,resulting in an incensement of response compared with pristine graphene.Au nanoparticles-decorated graphene exhibits not only better sensitivity(1.5-1.6 times larger than pristine graphene)for NO2 gas detection,but also fast response.The sensor was found to be robust and sensitive under the cycling bending test,which could also be ascribed to the merits of graphene.This porous structure graphene-based gas sensor is expected to enable a simple and inexpensive flexible gas sensing platform.

The Ca^(2+)-dependent DNases are Involved in Secondary Xylem Development in Eucommia ulmoides

Secondary xylem development has long been recognized as a typical case of programmed cell death （PCD） in plants. During PCD, the degradation of genomic DNA is catalyzed by endonucleases. However, to date, no endonuclease has been shown to participate in secondary xylem development. Two novel Ca^2＋-dependent DNase genes, EuCaN1 and EuCaN2, were identified from the differentiating secondary xylem of the tree Eucommia ulmoides Oliv., their functions were studied by DNase activity assay, in situ hybridization, protein immunolocalization and virus-induced gene silencing experiments. Full-length cDNAs of EuCaN1 and EuCaN2 contained an open reading frame of 987 bp, encoding two proteins of 328 amino acids with SNase-like functional domains. The genomic DNA sequence for EuCaN1 had no introns, while EuCaN2 had 8 introns. EuCaN1 and EuCaN2 digested ssDNA and dsDNA with Ca^2＋-dependence at neutral pH. Their expression was confined to differentiating secondary xylem cells and the proteins were localized in the nucleus. Their activity dynamics was closely correlated with secondary xylem development. Secondary xylem cell differentiation is influenced by RNAi of endonuclease genes. The results provide evidence that the Ca^2＋-dependent DNases are involved in secondary xylem development.

Prevalence of and risk factors for tuberculosis among healthcare workers in Chinese tuberculosis facilities

Background:China is one of 22 countries with a high tuberculosis(TB)burden in the world.Healthcare workers(HCWs)have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection control practices.We conducted a cross-sectional study to explore the prevalence of TB and its associated risk factors among HCWs in Chinese TB facilities.Methods:Two hundred and forty-one TB facilities employing a total of 9663 HCWs were selected from 12 provinces in China to represent healthcare settings at the provincial,prefectural,and county levels.Structured questionnaires were used to collect information on TB infection control practices and HCWs in those facilities.Data was double entered into EpiData 3.1;TB prevalence and associated risk factors were analyzed using SPSS 21.0 with bivariate and multivariate regression models.Results:The results showed that 71 HCWs had been diagnosed with TB,accounting for a prevalence of 760/100000.The multivariate analysis showed that associated risk factors included belonging to the age group of 51 years and above(aOR:6.17,95%CI:1.35-28.28),being a nurse(aOR=3.09,95%CI:1.15-8.32),implementation of 0-9 items of management measures(aOR=2.57,95%CI:1.37-4.80),and implementation of 0-1 items of ventilation measures(aOR=2.42,95%CI:1.31-4.47).Conclusion:This was the first national large sampling survey on TB prevalence among HCWs in China.It was found that the implementation of TB infection control practices in some facilities was poor.The TB prevalence in HCWs was higher than that in the general population.Therefore,TB infection control practices in Chinese medical facilities should be strengthened.

Treatment of coronavirus disease 2019 in Shandong,China:a cost and affordability analysis

Background:Coronavirus disease 2019(COVID-19)is now a global public threat.Given the pandemic of COVID-19,the economic impact of COVID-19 is essential to add value to the policy-making process.We retrospectively conducted a cost and affordability analysis to determine the medical costs of COVID-19 patients in China,and also assess the factors affecting their costs.Methods:This analysis was retrospectively conducted in Shandong Provincial Chest Hospital between 24 January and 16 March 2020.The total direct medical expenditures were analyzed by cost factors.We also assessed affordability by comparing the simulated out-of-pocket expenditure of COVID-19 cases relative to the per capita disposable income.Differences between groups were tested by student t test and Mann-Whitney test when appropriate.A multiple logistic regression model was built to determine the risk factors associated with high cost.Results:A total of 70 COVID-19 patients were included in the analysis.The overall mean cost was USD 6827 per treated episode.The highest mean cost was observed in drug acquisition,accounting for 45.1%of the overall cost.Total mean cost was significantly higher in patients with pre-existing diseases compared to those without preexisting diseases.Pre-existing diseases and the advanced disease severity were strongly associated with higher cost.Around USD 0.49 billion were expected for clinical manage of COVID-19 in China.Among rural households,the proportions of health insurance coverage should be increased to 70%for severe cases,and 80%for critically ill cases to avoid catastrophic health expenditure.Conclusions:Our data demonstrate that clinical management of COVID-19 patients incurs a great financial burden to national health insurance.The cost for drug acquisition is the major contributor to the medical cost,whereas the risk factors for higher cost are pre-existing diseases and severity of COVID-19.Improvement of insurance coverage will need to address the barriers of rural patients to avoid the occurrence of catastrophic health expenditure.

An improved noise reduction transformation for algorithm based on wavelet MEMS gyroscope

To solve the large noise problem for the low- precision gyroscopes in micro-electro mechanical systems （MEMS） of inertial navigation system, an improved noise reduction method, based on the analyses of the fast Fourier transformation （FFT） noise reduction principle and the simple wavelet noise reduction principle, was proposed. Furthermore, the FFT noise reduction method, the simple wavelet noise reduction method and the improved noise reduction method were comparatively analyzed and experimentally verified in the case of the constant rate and dynamic rate. The experimental analysis results showed that the improved noise reduction method had a very good result in the noise reduction of the gyroscope data at different fi：equencies, and its performance was superior to those of the FFT noise reduction method and the simple wavelet noise reduction method.

The optical and molecular signatures of DOM under the eutrophication status in a shallow,semi-enclosed coastal bay in southeast China

We applied stable carbon isotopes,ultraviolet-visible absorption(UV-Vis),fluorescence excitation-emission matrices spectroscopy(EEMs),and Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR-MS)to investigate the chemical composition and sources of the dissolved organic matter(DOM)in both the water column and pore water in Xiangshan Bay,a representative semi-enclosed and eutrophic bay in Zhejiang Province,China.One protein-like fluorescent component(C1)and two humic-like fluorescent components(C2 and C3)were identified by PARAFAC modeling.The concentration of dissolved organic carbon(DOC),the relative intensities of C2,C3,and black carbon-like compounds are all negatively correlated with salinity,indicating that there is a dilution effect of terrestrial signals by seawater in Xiangshan Bay.The differences in light penetration ability of Xiangshan Bay cause different degrees of photo-degradation,which may play an important role in the transformation of organic matter in Xiangshan Bay.The weak correlation between the C1 fluorescent component and salinity indicates that autochthonous sources cannot dominate the protein-like FDOM in the Xiangshan Bay drainage area.Multiple sources(such as anthropogenic inputs and release of pore water)also affect the distribution of the protein-like fluorescent component under eutrophication conditions.The relative proportion of the protein-like fluorescent component in Xiangshan Bay is on a medium level in China and anthropogenic inputs may be a significant source of DOM in coastal bays.