Pulmonary manifestations of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered inthe case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.

Polysubstituted Isoflavonoids from Spatholobus suberectus,Flemingia macrophylla,and Cudrania cochinchinensis

Four hitherto unknown polysubstituted isofiavonoids,including three isofiavans:7,4'-dihydroxy-8,2',3'-trimethoxyisofiavan(1),7,2',4'-trihydroxy-8,3'-dimethoxyisofiavan(2),and 7,2',4'-trihydroxy-5-methoxyisofiavan(3),and one prenylated isofiavone cudraisofiavone M(4)were isolated from the ethanol extracts of Spatholobus suberectus(for 1 and 2),Flemingia macrophylla(for 3),and Cudrania cochinchinensis(for 4),respectively.Their structures were estab­lished on the basis of extensive spectroscopic analysis.Compounds 1 and 4 exhibited weak cytotoxic activity against five human cancer cell lines(HL-60,A-549,SMMC-7721,MCF-7,and SW-480).

Aristolane‑type Sesquiterpenoids from Nardostachys chinensis and Revised Structure of Aristolanhydride

Four hitherto unknown aristolane-type sesquiterpenes,including one novel 8,9-secoaristolane,namely secoaristolenedioic acid(1),two aristolone derivatives,namely 1α,2β-dihydroxyaristolone(2),9-epidebilon(3),and one rare aristolane-chalcone hybrid,namely 3′-hydroxynardoaristolone A(4)were isolated from the ethanol extract of the roots and rhizomes of Nardostachys chinensis.Their structures were elucidated on the basis of extensive spectroscopic analysis.In addition,the structure of aristolanhydride,recently isolated from the same species,was corrected by reanalysis of the published NMR data.

Prenylated Coumarins from Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata

Four hitherto unknown prenylated coumarins,namely 600-O-b-D-apiofuranosylapterin(1),40-O-isobutyroylpeguangxienin(2),6-(3-methyl-2-oxobutyroyl)-7-methoxycoumarin(3),and 6-hydroxycoumurrayin(4),were isolated from the ethanol extract of Heracleum stenopterum,Peucedanum praeruptorum,Clausena lansium,and Murraya paniculata,respectively.Their chemical structures were established on the basis of extensive spectroscopic analysis.Compound 2 exhibited in vitro cytotoxic activity against five human cancer cell lines(HL-60,A-549,SMMC-7721,MCF-7,and SW-480)with IC50 values ranging from 15.9 to 23.2μM.

Lanostane-Type Triterpenoids from Scilla scilloides and Structure Revision of Drimiopsin D

Two hitherto unknown lanostane-type triterpenoids,namely scillascillol(1)and scillascillone(2),and a hitherto unknown norlanostane-triterpene glycoside,namely scillascilloside B-1(3),were isolated from the ethanol extract of the whole plants of Scilla scilloides.Their structures were elucidated on the basis of extensive spectroscopic studies.In addition,the structure of drimiopsin D(6a)has been revised as 2,5-dimethoxy-8-methyl-1,3,6-trihydroxyxanthone(6)by reanalysis of the spectroscopic data.

New Iboga‑Type Indole Alkaloids from Tabernaemontana divaricata

Two hitherto unknown iboga-type indole alkaloids,namely(3R)-7,19-di-epi-3-methoxytabernoxidine(1)and(3R,19R)-19-hydroxy-3-(2-oxopropyl)voacangine(2),together with eight known alkaloids(3-10),were isolated from the twigs and leaves of Tabernaemontana divaricata.Their structures were established on the basis of spectroscopic data interpretation,single crystal X-ray diffraction analysis and circular dichroism spectrum.

Inhibition of Ubiquitin-specific Protease 4 Attenuates Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via Transforming Growth Factor Beta Receptor Type Ⅰ

Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.

Bilateral coronary-pulmonary artery fistula with paroxysmal atrial arrhythmia:a case report

Coronary-pulmonary artery fistula(CPAF)is a relatively rare type of congenital coronary artery variation,which is mostly asymptomatic and is discovered incidentally by coronary artery CT imaging or angiography.However,CPAF can cause a phenomenon of inter-artery steal and hemodynamic disorders,leading to myocardial ischemia,arrhythmia,heart failure,syncope and even cardiac sudden death in severe cases.Here we reported a case of a 53-year-old female who complained of intermittent palpitations and had a history of paroxysmal atrial fibrillation.The coronary angiography revealed bilateral coronary artery fistulae to pulmonary artery.In this case,the multiple fistulas were very rare and significant.Multidisciplinary treatment should be considered,including cardiologists,surgeons,anesthesiologists and nurses,etc.Regular follow-up is essential for long-term disease management after diagnosis or surgery.

Tamoxifen does not d eteriorate cardiac function in female alphaMHC-MerCreMer transgenic mice

Cre-loxP recombination system is widely used in gene function research to realize specific gene knockout or knockin through DNA editing.TheαMHC-MerCreMer transgenic mouse line can achieve conditional cardiomyocyte-specific gene editing and make itself be of high value in cardiovascular research.However,there is an ongoing controversy on cardiomyopathy caused by unspecific Cre activity or related to tamoxifen overload,and the majority of studies only focused on male mice.Here,we investigated in femaleαMHC-MerCreMer mice the effect of tamoxifen on myocardia at a conventional dose of 20 mg/kg for five consecutive days by intraperitoneal injection.Our results confirmed that the conventional dose of tamoxifen administration effectively knock down myocardial MED1 expression within one week,without any changes in body weight or heart and liver mass after a 2-week washout period.Serological examination showed that tamoxifen did not deteriorate hepatic or renal function.Hematoxylin-eosin and Sirius red staining revealed no difference in the structure or fibrosis deposition in the heart upon tamoxifen treatment.F4/80 immunohistochemistry staining showed no signs of increased macrophage infiltration in myocardia.The results of RT-qPCR also confirmed the histological observations.Furthermore,differences in energy metabolism and inflammatory response were observed in femaleαMHC-MerCreMer mice,and the underlying mechanism still needs to be clarified.

Genetic Diversity of Soybean and the Establishment of a Core Collection Focused on Resistance to Soybean Cyst Nematode

Soybean cyst nematode （SCN; Heterodera glycines） Is one of the most Important pests affecting soybean production. The best method of control of SCN is through the development of resistant cultlvars. However, limited progress has been made in soybean breeding In China because most modern cultlvars have no resistance to SCN. The distribution and phenotype of 432 immune or highly resistant Chinese accessions were surveyed and a primary core collection was selected as a representative sample for further analyses. Using evenly distributed simple sequence repeat markers, five selection methods were applied to the primary core collection and the optimal method was chosen to establish a core collection, which consisted of 28 accessions. These encompassed 70.8% of the ailelic variation present in the overall resistant collection. The 28 accessions differed from the reference resistant accessions at the genomlc level, Indicating that Chinese resistant accessions are distinct from known resistant accessions. This applied core collection provides a rational framework for undertaking diversity surveys, using genetic variation for the investigation of complex traits and for the discovery of novel traits.

Incidence and risk factors of tuberculosis among the elderly population in China:a prospective cohort study

Background:China is facing challenges of the shifting presentation of tuberculosis(TB)from younger to elderly due to an ageing population,longer life expectancy and reactivation disease.However,the burden of elderly TB and influence factors are not yet clear.To fill the gap,we generated a cohort study to measure the magnitude of TB incidence and associated factors among the elderly population aged 65 years and above in China.Methods:In this cohort established in 2013 through a prevalence survey conducted in selected sites,a total of 34076 elderlies without TB were enrolled into two-year follow-up.We used both active and passive case findings to find out all TB patients among them.The person-year(PY)incidence rates for both bacteriologically positive TB and active TB were calculated.Cox proportional regression model was performed to test effect of risk factors,and the population attributable fraction(PAF)of each risk factor contributing to incident TB among elderlies was calculated.Results:Over the two-year follow-up period,a total of 215 incident active TB were identified,62 of which were bacteriologically positive.The incidence rates for active TB and bacteriologically positive TB were 481.8 per 100000 PY(95%CI:417.4–546.2 per 100000 PY)and 138.9 per 100000 PY(95%CI:104.4–173.5 per 100000 PY),respectively.Incident cases detected by active case finding were significantly higher(P<0.001).Male,non-Han nationality,previously treated TB,ex/current smoker and body mass index(BMI)<18.5 presented as independent predictors for developing TB disease.For developing bacteriologically positive TB,the biggest contribution was from self-reported ex or current smoker(18.06%).And,for developing active TB,the biggest contribution was from non-Han nationality(35.40%),followed by male(26.80%)and age at 75 years and above(10.85%).Conclusions:Ageing population in China had a high TB incidence rate and risk to develop TB disease,implying that National TB Program(NTP)needs to prioritize for elderly.Active case finding should be applied capture more active TB cases among this particular population,especially for male,non-Han nationality,and those with identified risk factors.

Prevalence and risk factors of active pulmonary tuberculosis among elderly people in China:a population based cross-sectional study

Background:The problem of population aging is a critical public health concern in modern China,and more tuberculosis(TB)control efforts are needed to reach elderly people at high priority.In this study,we aim to determine the prevalence and identify the risk factors of TB among elderly people in China.Methods:A multistage cluster-sampled cross-sectional survey was conducted in 2013,and 27 clusters were selected from 10 counties of 10 provinces in China.All consenting participants greater than or equal to 65 years of age were screened for pulmonary TB with a chest X-ray(CXR)and a symptom questionnaire.Three sputum specimens for bacteriological examination by microscopy and culture were collected from those whose screening was positive.Prevalence was calculated,a multiple logistic regression model was performed to confirm the risk factors,and population attributable fraction(PAF)of each risk factor was calculated to indicate the public health significance.Results:Of 38888 eligible people from 27 clusters,34269 participants finished both questionnaire and physical examination.There were 193 active pulmonary TB cases,62 of which were bacteriologically confirmed.The estimated prevalence of active pulmonary TB and bacteriologically confirmed TB in those 65 years of age and older was 563.19 per 100000(95%CI:483.73-642.65)and 180.92 per 100000(95%CI:135.89-225.96),respectively.Male sex,older age,living in rural areas,underweight,diabetes,close contact of pulmonary TB(PTB)and previous TB history are all risk factors for TB.The risk of TB increased with increasing age and decreasing body mass index(BMI)after adjusting for other factors,and there is a positive dose-response relationship.Conclusions:In China,active case finding(ACF)could be implemented among elderly people aged 65 and above with underweight,diabetes,close contact history and previous TB history as a priority,which will get significant yields and be cost-effective.

Inequity in catastrophic costs among tuberculosis-affected households in China

Background:There are limited nationally representative studies globally in the post-2015 END tuberculosis(TB)era regarding wealth related inequity in the distribution of catastrophic costs due to TB care.Under the Chinese national tuberculosis programme setting,we aimed to assess extent of equity in distribution of total TB care costs(pre-treatment,treatment and overall)and costs as a proportion of annual household income(AHI),and describe and compare equity in distribution of catastrophic costs(pre-treatment,treatment and overall)across population sub-groups.Methods:Analytical cross-seaional study using data from national TB patient cost survey carried out in 22 counties from six provinces in China in 2017.Drug-susceptible pulmonary TB registered under programme,who had received at least 2 weeks of intensive phase therapy were included.Equity was depiaed using concentration curves and concentration indices were compared using dominance test.Results:Of 1147 patients,the median cost of pre-treatment,treatment and overall care,were USD 283.5,USD 413.1 and USD 965.5,respectively.Richer quintiles incurred significantly higher pre-treatment and treatment costs compared to poorer quintiles.The distribution of costs as a proportion of AHI and catastrophic costs were significantly pro-poor overall as well as during pre-treatment and treatment phase.All the concentration curves for catastrophic costs(due to pre-treatment,treatment and overall care)stratified by region(east,middle and west),area of residence(urban,rural)and type of insurance new rural co-operative medical system[NCMS],non-NCMSalso exhibited a pro-poor pattern with statistically significant(P<0.01)concentration indices.The pro-poor distribution of the catastrophic costs due to TB treatment was significantly more inequitable among rural,compared to urban patients,and NCMS compared to non-NCMS beneficiaries.Conclusions:There is inequity in the distribution of catastrophic costs due to TB care.Universal health coverage,social protection strategies complemented by quality TB care is vital to reduce inequitable distribution of catastrophic costs due to TB care in China.

Chevrier＇s Field Mouse(Apodemus chevrieri) and Père David＇s Vole(Eothenomys melanogaster) in China Carry Orthohepeviruses that form Two Putative Novel Genotypes Within the Species Orthohepevirus C

Hepatitis E virus(HEV)is the prototype of the family Hepeviridae and the causative agent of common acute viral hepatitis.Genetically diverse HEV-related viruses have been detected in a variety of mammals and some of them may have zoonotic potential.In this study,we tested 278 specimens collected from seven wild small mammal species in Yunnan province,China,for the presence and prevalence of orthohepevirus by broad-spectrum reverse transcription(RT)-PCR.HEV-related sequences were detected in two rodent species,including Chevrier’s field mouse(Apodemus chevrieri,family Muridae)and Père David’s vole(Eothenomys melanogaster,family Cricetidae),with the infection rates of 29.20%(59/202)and 7.27%(4/55),respectively.Further four representative full-length genomes were generated:two each from Chevrier’s field mouse(named Rd HEVAc14 and Rd HEVAc86)and Père David’s vole(Rd HEVEm40 and Rd HEVEm67).Phylogenetic analyses and pairwise distance comparisons of whole genome sequences and amino acid sequences of the gene coding regions showed that orthohepeviruses identified in Chinese Chevrier’s field mouse and Père David’s vole belonged to the species Orthohepevirus C but were highly divergent from the two assigned genotypes:HEV-C1 derived from rat and shrew,and HEV-C2 derived from ferret and possibly mink.Quantitative real-time RT-PCR demonstrated that these newly discovered orthohepeviruses had hepatic tropism.In summary,our work discovered two putative novel genotypes orthohepeviruses preliminarily named HEVC3 and HEV-C4 within the species Orthohepevirus C,which expands our understanding of orthohepevirus infection in the order Rodentia and gives new insights into the origin,evolution,and host range of orthohepevirus.

Improving tuberculosis case detection in underdeveloped multi-ethnic regions with high disease burden:a case study of integrated control program in China

Background:In the underdeveloped multi-ethnic regions of China,high tuberculosis(TB)burden and regional inequity in access to healthcare service increase the challenge of achieving the End TB goals.Among all the provinces,the highest TB burden is reported in Xinjiang,where ethnic minorities and older people have suffered most.However,current case-finding strategy is inadequate given the complex social determinants and suboptimal case detection rates.Thus,we developed an integrated TB control program to improve case detection and conducted a pilot in Xinjiang from 2014 to 2015.In this case study,we summarized the activities and key findings.We also shared the experiences and challenges of implementing interventions and provided recommendations to inform the TB control program in the future.Case presentation:The pilot interventions were implemented in one selected town in Yining based on local TB control programs.By applying tailor-made educational materials,outreach TB educational activities were conducted in diverse ways.In 22 Masjids,the trained imams promoted TB education to the Muslims,covering 20,440 persontimes in 88 delivered preaching sessions.In seven schools,1944 students were educated by the teachers and contributed to educating 6929 family members.In the village communities,13,073 residents participated in household education and screening.Among them,12,292 people aged under 65 years were investigated for suspicious pulmonary TB symptoms,where six TB patients were diagnosed out of 89 TB suspects;781 older people were mobilized for screening directly by chest X-ray,where 10 patients were diagnosed out of 692 participants.Supportive healthcare system,multi-sectoral cooperation and multi-channel financing mechanism were the successful experiences of implementation.The interventions were proved to be more effective than the previous performance:the number of TB suspects consulting doctors and patients detected increased by 50%and 26%,respectively.The potential challenges,implications and recommendations should been taken into account for further program improvement.Conclusions:In underdeveloped multi-ethnic regions with high TB burden,improving case detection is necessary and the interventions can be feasible and effective within a supportive system.More intensive educational and training approaches,a high index of TB suspicion and prioritization of older people in screening are recommended.To sustain and scale up the program,the impacts,cost-effectiveness,feasibility and acceptability of interventions warrant further research and evaluation in each specific context.

Profiling B and T cell immune responses to co-infection of Mycobacterium tuberculosis and hookworm in humans

Background:Humoral and cellular immune responses play protective roles against Mycobacterium tuberculosis(MTB)infection.However,hookworm infection decreases the immune response to hookworm and bystander antigens.Currently,immune responses to co-infection of MTB and hookworm are still unknown,although co-infection has been one of the public health problems in co-endemic areas of pulmonary tuberculosis(PTB)and hookworm disease.Therefore,it is essential to evaluate B and T cell immune responses to the co-infection.Methods:Seventeen PTB cases co-infected with hookworm,26 PTB cases,15 patients with hookworm infection,and 24 healthy controls without PTB or hookworm infection were enrolled in the study.Expressions of CD3,CD4,CD8,CD10,CD19,CD20,CD21,CD25,CD27,CD38,FoxP3,and PD-1 were assessed on B and T cell subsets using multicolor flow cytometry.Results:For the B cell(CD19+)subsets,naïve B cells(CD10−CD27−CD21+CD20+),plasma cells(CD10−CD27+CD21−CD20−),and tissue-like memory B cells(CD10−CD27−CD21−CD20+)had higher proportions,whilst resting memory B cells(CD10−CD27+CD21+CD20+)had lower proportions in the group co-infected with MTB and hookworm as compared to other groups.Frequencies of activated memory B cells(CD10−CD27+CD21−CD20+)did not differ among the four groups.For the T cell(CD3+)subsets,frequencies of regulatory T cells(CD4+CD25+Foxp3+)and exhausted CD4+and CD8+T cells(CD4+PD-1+and CD8+PD-1+)were higher,and frequencies of activated CD4+and CD8+T cells(CD4+CD38+and CD8+CD38+)were lower in the co-infected group as compared to the other groups.Conclusion:The change patterns of the cell profile of circulating lymphocytes were indentified in human co-infection of MTB and hookworm,which might indicate that the humoral and cellular immune responses are more suppressed.

Cu(Ⅱ)-catalyzed domino reaction of 2-halobenzamide and arylmethanamine to construct 2-aryl quinazolinone

A novel method for achieving a copper（II）-catalyzed domino reaction for the construction of 2-aryl quinazolinones,without the addition of any ligand and additive,has been developed.The domino reaction achieved N-（a-substituted）benzylation,benzylic C–H amidation,and C–C（or C–H） bond cleavage.

A novel onlay urethroplasty for hypospadias with mild chordee after degloving:modified for complete removal of scar tissue underlying the urethral plate and for long-term outcomes

Urethral plate(UP)-preserving urethroplasty is simple and has few complications,but it may affect the development of penis in the long term and lead to recurrent chordee.In this study,we used obliquely cut UP to repair hypospadias with mild chordee after degloving(15°-30°)and compared the results with onlay urethroplasty to explore its rationality and feasibility.Between April 2018 and October 2020,108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty.Clinical data were prospectively collected,and medium-term outcomes were assessed at follow-up.The complications were compared between the two groups.Forty-four patients underwent the modified onlay procedure(GroupⅠ),with follow-up time(mean±standard deviation[s.d.])of 23.2±4.5(range:17-31)months.Sixty-four patients underwent a standard onlay procedure(GroupⅡ),with follow-up time(mean±s.d.)of 39.7±3.9(range:32-46)months.There was no difference in age at surgery.The urethral defect length and operative time were longer in GroupⅠ.Six cases of fistula and one case each of stricture and diverticulum were reported in GroupⅠ.In GroupⅡ,11 cases of fistula and one case each of stricture and diverticulum were reported.The complication rates were 18.2%and 20.3%in GroupⅠand GroupⅡ,respectively(P>0.05).These medium-term follow-up results demonstrate that the modified onlay procedure(oblique cut UP urethroplasty)is a safe and feasible technique for hypospadias with mild chordee after degloving.Compared with standard onlay urethroplasty,this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.

Evolution of microstructure and texture during cold rolling and high-temperature annealing in Ni-5 at% W substrate for coated conductor

The evolution of microstructure and texture at four strain levels was investigated in Ni-5 at%W alloy by means of electron backscatter diffraction(EBSD)technique.The deformation microstructure evolves gradually from microbands(MBs)to typical lamellar structures with strain increasing in cold-rolled materials,while only lamellar structures in heavily cold-rolled materials.Subsequently,quantitative analysis of microstructure and texture was performed.It indicates that the texture is a typical pure metal deformation texture,but a few cube and rolling direction(RD)-rotated cube orientations also can be observed in the deformed samples.The use of high-temperature annealing enables an area fraction of cube orientation>95%to be obtained for high strained substrate.In addition,it is worth noting that the point-to-point misorientation inside the band with various orientations is found to keep quite low.But the point-to-origin misorientation over the same distance is dependent on strain and orientation type in the band.The cube-oriented regions were characterized by a high accumulated orientation gradient,close to 28°,compared to the non-cube-oriented regions.This means that the accumulated orientation gradient only occurs in the cube band with the reduction of 98%,which partly explains the formation of strong cube texture after high-temperature annealing.

Recognizing parallel-stranded G-quadruplex by cyanine dye dimer based on dual-site binding mode

G-quadruplexes （G4s） play important roles in biological systems, such as telomere maintenance, replication, and transcription. Based on the DNA sequence, loop geometry, and the local environments, G4s can be classified into different conformations. It is important to detect different types of G4s to monitor the diseases related with G4s. Most ligands bind to G4s based on end-stacking modes, while rare ligands bind to G4s through groove binding modes. We have found that a cyanine dye DMSB interacts with parallel G4 by end-stacking and groove simultaneous binding mode. In this article, we found that DMSB could simply discriminate parallel G4s from other DNA motifs by using UV-vis spectrum. These results give some clues to develop high specificity G4 probes.