Alzheimer's disease(AD)is a typical neurodegenerative disease.β-amyloid(AβÞplaque is the most prominent pathological biomarker associated with the progression of AD.Conventional Aβprobes,including commerci...Alzheimer's disease(AD)is a typical neurodegenerative disease.β-amyloid(AβÞplaque is the most prominent pathological biomarker associated with the progression of AD.Conventional Aβprobes,including commercial probe ThT,usually suffer from tedious washing procedures.Herein,novel AIE-active Aβprobes with excellent water solubility,named DE-V1-PYC3 and DE-V1-PYOH,were developed for the detection and image of Aβwithout tedious washing procedures.Compared with commercial probe ThT,the AIE-active Aβprobes exhibited better sensitivity and a±nity to Aβaggregates.Moreover,for ThT,the washing procedures are essential to obtain high signal-to-noise ratio(SNR)images of Aβplaques in AD brain tissue slices.DE-V1-PYC3 and DE-V1-PYOH can label Aβplaques in AD brain tissue slices with high SNR even without tedious washing procedures.展开更多
AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were d...AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.展开更多
AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 pa...AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.展开更多
BACKGROUND:Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa.This study aimed to investigate the effects of periplaneta americana extract on immune function,nutrition sta...BACKGROUND:Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa.This study aimed to investigate the effects of periplaneta americana extract on immune function,nutrition status and gastrointestinal complications of early enteral nutrition patients with systemic inflammatory response syndrome(SIRS).METHODS:Patients with SIRS were randomly divided into two groups:treatment and control groups.All patients in the two groups received conventional therapy including enteral nutrition,but periplaneta americana extract,an additional Chinese medicine,was given to the patients in the treatment group.At the beginning of treatment(0 day)and 1,3,and 7 days after treatment,the levels of immunoglobulin(Ig A),total lymphocyte count(TLC),total protein(TP)and prealbumin(PA)were respectively tested in patients'venous blood.The incidences of bloating,diarrhea,aspiration pneumonia and high blood sugar at 7 days after treatment were recorded.The mortality of the patients in 28 days was recorded.RESULTS:At 3 and 7 days after treatment,the levels of Ig A and TLC in the treatment group were higher than those in the control group(P<0.05).At 7 days after treatment,the levels of TP and PA in the treatment group were higher than those in the control group(P<0.05).The incidences of bloating and diarrhea in the treatment group were lower than those in the control group,the differences were significant(P<0.05).The mortality of treatment group was lower than that of the control group(P>0.05).CONCLUSION:Periplaneta americana extract could reduce gastrointestinal complications and improve immune function and nutritional status in patients with systemic inflammatory response syndrome.展开更多
AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar...AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats.The rats were randomly divided into four groups: normal,autograft, allograft, and allograft treated with tocilizumab.Kaplan-Meier was performed to draw the survival curve.The protein levels of interleukin-17A(IL-17A), vascular endothelial growth factor(VEGF), and forkhead box protein3(Foxp3) were measured by immunohistochemistry.The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat(RORγt), interleukin-6(IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction(RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. RESULTS: The survival time of tocilizumab group was(24±1.27 d) longer than that of allograft group(10±0.55 d).Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group(P<0.01),while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group(P<0.001).Flow cytometry showed that the number of Th17 cellsin allograft group was significantly higher than that in tocilizumab group(P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group(P<0.001). Simultaneously, Foxp3 m RNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups(P<0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.展开更多
This paper presents a new silicon-on-insulator(SOI) lateral-double-diffused metal-oxide-semiconductor transistor(LDMOST) device with alternated high-k dielectric and step doped silicon pillars(HKSD device). Due to the...This paper presents a new silicon-on-insulator(SOI) lateral-double-diffused metal-oxide-semiconductor transistor(LDMOST) device with alternated high-k dielectric and step doped silicon pillars(HKSD device). Due to the modulation of step doping technology and high-k dielectric on the electric field and doped profile of each zone, the HKSD device shows a greater performance. The analytical models of the potential, electric field, optimal breakdown voltage, and optimal doped profile are derived. The analytical results and the simulated results are basically consistent, which confirms the proposed model suitable for the HKSD device. The potential and electric field modulation mechanism are investigated based on the simulation and analytical models. Furthermore, the influence of the parameters on the breakdown voltage(BV) and specific on-resistance(R_(on,sp)) are obtained. The results indicate that the HKSD device has a higher BV and lower R_(on,sp) compared to the SD device and HK device.展开更多
Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acu...Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.展开更多
Objective To retrospectively investigate the distribution in kidney transplantation for fifteen years in Peking Union Medical College Hospital.Methods We conducted a descriptive research counting up the number of pati...Objective To retrospectively investigate the distribution in kidney transplantation for fifteen years in Peking Union Medical College Hospital.Methods We conducted a descriptive research counting up the number of patients who received kidney transplantation each year in our hospital during 1995 and 2010.Results The first kidney transplantation in our hospital occurred in the 1960s.The number of kidney transplantation increased until reaching a maximum of 47 grafts in 2001;since then the number fell.Conclusions With the decreased number of kidney transplantation,we have realized the shortage of transplantable organs is very serious.The continuing transplant shortage requires major efforts to expand the donor pool.Donation after cardiac death offers the potential to enlarge the donor pool,but we need to strictly control the criteria for potential donors.展开更多
BACKGROUND Intraoperative methylene blue testing(IMBT),air leak testing,or endoscopy is used to assess the anastomotic integrity of esophagojejunostomy during open total gastrectomy for gastric cancer.Totally laparosc...BACKGROUND Intraoperative methylene blue testing(IMBT),air leak testing,or endoscopy is used to assess the anastomotic integrity of esophagojejunostomy during open total gastrectomy for gastric cancer.Totally laparoscopic radical gastrectomy has been widely used to treat gastric cancer in the last few decades.However,reports on testing anastomotic integrity in totally laparoscopic radical gastrectomy are limited.AIM To explore the effects of IMBT on the incidence of postoperative anastomotic leaks(PALs)and identify the risk factors for PALs in totally laparoscopic radical gastrectomy.METHODS From January 2017 to December 2019,patients who underwent totally laparoscopic radical gastrectomy at the Shaanxi Provincial People's Hospital were retrospectively analyzed.According to whether or not they experienced an IMBT,the patients were divided into an IMBT group and a control group.If the IMBT was positive,an intraoperative suture was required to reinforce the anastomosis.The difference in the incidence of PALs was compared,and the risk factors were investigated.RESULTS This study consisted of 513 patients,211 in the IMBT group and 302 in the control group.Positive IMBT was shown in seven patients(3.3%)in the IMBT group,and no PAL occurred in these patients after suture reinforcement.Multivariate analysis showed that risk factors for predicting positive IMBT were body mass index(BMI)>25 kg/m2(hazard ratio[HR]=8.357,P=0.009),operation time>4 h(HR=55.881,P=0.002),and insufficient surgical experience(HR=15.286,P=0.010).Moreover,15 patients(2.9%)developed PALs in 513 patients,and the rates of PALs were significantly lower in the IMBT group than in the control group[2 of 211 patients(0.9%)vs 13 of 302 patients(4.3%),P=0.0026].Further analysis demonstrated that preoperative complications(HR=13.128,P=0.017),totally laparoscopic total gastrectomy(HR=9.075,P=0.043),and neoadjuvant chemotherapy(HR=7.150,P=0.008)were independent risk factors for PALs.CONCLUSION IMBT is an effective method to evaluate the integrity of anastomosis during totally laparoscopic radical gastrectomy,thus preventing technical defect-related anastomotic leaks.Preoperative complications,totally laparoscopic total gastrectomy,and neoadjuvant chemotherapy are independent risk factors for PALs.展开更多
DRIMARY benign ureteral tumors are rare and they arise from the mesodermal tissue of the ureteral wall. Less than 200 cases have been docu- mented in published reports.1 Bilateral ureteralfibroepithelial polyps are ex...DRIMARY benign ureteral tumors are rare and they arise from the mesodermal tissue of the ureteral wall. Less than 200 cases have been docu- mented in published reports.1 Bilateral ureteralfibroepithelial polyps are extremely rare and commonly occur in the proximal ureter, causing complete ureteral obstruction. Pyeloplasty is an effective treatment for im- proving renal function. Here we report a case with se- quential bilateral ureteral fibroepithelial polyps causing obstructive hydronephrosis.展开更多
Solar-driven photo-thermal catalytic CO_(2)methanation reaction is a promising technology to alleviate the problems posed by greenhouse gases emissions.However,designing advanced photo-thermal catalysts remains a rese...Solar-driven photo-thermal catalytic CO_(2)methanation reaction is a promising technology to alleviate the problems posed by greenhouse gases emissions.However,designing advanced photo-thermal catalysts remains a research challenge for CO_(2)methanation reaction.In this work,a series of ABO3(A=lanthanide,B=transition metal)perovskite catalysts with Ce-substituted LaNiO3(La_(1-x)Ce_(x)NiO_(3),x=0,0.2,0.5,0.8,1)were synthesized for CO_(2)methanation.The La_(0.2)Ce_(0.8)NiO_(3) exhibited the highest CH_(4) formation rate of 258.9 mmol·g^(-1)·hcat-1,CO_(2)conversion of 55.4%and 97.2%CH_(4) selectivity at 300℃with the light intensity of 2.9 W·cm^(-2).Then the catalysts were thoroughly analyzed by physicochemical structure and optical properties characterizations.The partial substitution of the A-site provided more active sites for the adsorption and activation of CO_(2)/H_(2).The sources of the active sites were considered to be the oxygen vacancies(O_(v))created by lattice distortions due to different species of ions(La^(3+),Ce^(4+),Ce^(3+))and exsolved Ni0 by H_(2)reduction.The catalysts have excellent light absorption absorbance and low electron-hole(e^(-)/h^(+))recombination rate,which greatly contribute to the excellent performance in photo-thermal synergistic catalysis(PTC)CO_(2)methanation.The results of in situ irradiated electron paramagnetic resonance spectrometer(ISI-EPR)and ISI-X-ray photoelectron spectroscopy(XPS)indicated that the aggregation of unpaired electrons near the defects and Ni metal(from La and Ce ions to Ov and Ni0)accelerated adsorption and activation of CO_(2)/H_(2).At last,the catalyst properties and structure were correlated with the proposed reaction mechanism from the in situ diffuse reflection infrared Fourier transform spectrum(DRIFTS)measurements.The in situ precipitation of the B-site enhanced the dispersion of Ni,while its enriched photoelectrons upon illumination further promote hydrogen dissociation.More H^(*)spillover accelerated the rate-determining step(RDS)of HCOO*hydrogenation.This work provides the theoretical basis for the development of catalysts and industrial application.展开更多
We operated a p-type point contact high purity germanium(PPCGe)detector(CDEX-1B,1.008 kg)in the China Jinping Underground Laboratory(CJPL)for 500.3 days to search for neutrinoless double beta(0νββ)decay of^(76)Ge.A...We operated a p-type point contact high purity germanium(PPCGe)detector(CDEX-1B,1.008 kg)in the China Jinping Underground Laboratory(CJPL)for 500.3 days to search for neutrinoless double beta(0νββ)decay of^(76)Ge.A total of 504.3 kg⋅day effective exposure data was accumulated.The anti-coincidence and the multi/single-site event(MSE/SSE)discrimination methods were used to suppress the background in the energy region of interest(ROI,1989–2089 keV for this work)with a factor of 23.A background level of 0.33 counts/(keV⋅kg⋅yr)was realized.The lower limit on the half life of^(76)Ge 0νββdecay was constrained as T_(1/2)^(0ν)>1.0×10^(23)yr(90%C.L.),corresponding to the upper limits on the effective Majorana neutrino mass:<mββ><3.2–7.5 eV.展开更多
A hydrothermal deposition method was utilized to fabricate Ca-P composite coating induced by the layer-by-layer(LbL)assembled polyvinylpyrrolidone/deoxyribonucleic acid(PVP/DNA)_(20) multilayer on AZ31 alloy.The surfa...A hydrothermal deposition method was utilized to fabricate Ca-P composite coating induced by the layer-by-layer(LbL)assembled polyvinylpyrrolidone/deoxyribonucleic acid(PVP/DNA)_(20) multilayer on AZ31 alloy.The surface morphology and compositions were characterized by SEM,EDS,FTIR and XRD.Besides,the corrosion resistance and degradation behavior of the coating were tested via electrochemical polarization,impedance spectroscopy and immersion measurements.Results show that the main components of Ca-P coatings are hydroxyapatite,Ca_(3)(PO_(4))_(2) and Mg_(3)(PO_(4))_(2)·nH_(2)O.The LbL-assembled DNA and PVP promote the adsorption of Ca-P deposits on the sample surface,and structures and functional groups of the polyelectrolyte in the outermost layer are the primary influencing factor for the induction of the Ca-P coating.Carboxyl groups have the best biomineralization effect among all related functional groups.The enhanced corrosion resistance and adhesion highlight a promising use of(PVP/DNA)_(20)-induced Ca-P coatings in the field of biomedical magnesium alloys.展开更多
Background:The molecular mechanisms underlying the endometriosis are still not completely understood.In order to test the hypothesis that the approaches in phosphoproteomics might contribute to the identification of ...Background:The molecular mechanisms underlying the endometriosis are still not completely understood.In order to test the hypothesis that the approaches in phosphoproteomics might contribute to the identification of key biomarkers to assess disease pathogenesis and drug targets,we carried out a phosphoproteomics analysis of human endometrium.Methods:A large-scale differential phosphoproteome analysis,using peptide enrichment of titanium dioxide purify and sequential elution from immobilized metal affinity chromatography with linear trap quadrupole-tandem mass spectrometry,was performed in endometrium tissues from 8 women with or without endometriosis.Results:The phosphorylation profiling of endometrium from endometriosis patients had been obtained,and found that identified 516 proteins were modified at phosphorylation level during endometriosis.Gene ontology annotation analysis showed that these proteins were enriched in cellular processes of binding and catalytic activity.Further pathway analysis showed that ribosome pathway and focal adhesion pathway were the top two pathways,which might be deregulated during the development of endometriosis.Conclusions:That large-scale phosphoproteome quantification has been successfully identified in endometrium tissues of women with or without endometriosis will provide new insights to understand the molecular mechanisms of the development of endometriosis.展开更多
As relics of ancient ocean lithosphere,ophiolites are the most important petrological evidence for marking the sutures and also play a key role in reconstructing plate configuration.They also provide valuable windows ...As relics of ancient ocean lithosphere,ophiolites are the most important petrological evidence for marking the sutures and also play a key role in reconstructing plate configuration.They also provide valuable windows for studying crustal accretion and mantle processes occurring at modem ocean ridges.Abundant ophiolites are distributed along the Yarlung-Tsangpo suture and represent the relics of ocean lithosphere of the Neo-Tethys.They are characterized by an incomplete litho-stratigraphy,of which the mantle section is much thicker than the crustal section.Ocean crustal rocks outcropped in the Yarlung-Tsangpo ophiolites are much thinner than normal ocean crusts(~7 km)or even absent.Tectonic settings from which the Yarlung-Tsangpo ophiolites originated remain highly controversial,although an origin of the supra-subduction zone is prevailing.Moreover,their incomplete litho-stratigraphy has been commonly attributed to tectonic dismemberment during the late-stage emplacement after their formation.Nevertheless,such an incompleteness resembles the ocean lithosphere generated at modem ultraslow spreading ridges,such as the Southwest Indian Ridge(SWIR).In this paper,we present several lines of evidence that support the formation of the Yarlung-Tsangpo ophiolites at ultraslow spreading ridges,during which detachment faults were developed.This suggests that the Yarlung-Tsangpo ophiolites might represent the ocean core complexes(OCC)in the Neo-Tethys Ocean.The OCC with high topography in the seafloor were clogged in the trench and preserved as ophiolites through Indo-Eurasia collision.The clogging resulted in the demise of an old subduction and a new subduction was re-initiated beneath the clogged OCC.展开更多
Swarming behavior facilitates pair formation,and therefore mating,in many eusocial termites.However,the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightle...Swarming behavior facilitates pair formation,and therefore mating,in many eusocial termites.However,the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightless insect forms are still unclear.Here,we found that the dispersal flight of the eusocial termite Reticulitermes chinensis Snyder led to a gradual decrease in adenosine triphosphate supply from oxidative phospho・rylation,as well as a reduction in the activities of critical mitochondrial respiratory enzymes from preflight to dealation.Correspondingly,using three-dimensional reconstruction and transmission electron microscopy(TEM),the flight muscles were found to be gradually deteriorated during this process.In particular,two tergo-pleural muscles(IItpm5 and IIItpm5)necessary to adjust the rotation of wings for wing shedding behavior were present only in flying alates.These findings suggest that flight muscle systems vary in function and morphology to facilitate the swarming flight procedure,which sheds light on the important role of swarming in successful extension and fecundity of eusocial termites.展开更多
Surgical failures,caused by postoperative infections of bone implants,are commonly met,which cannot be treated precisely with intravenous antibiotics.Photothermal therapy(PTT)and photodynamic therapy(PDT)have attracte...Surgical failures,caused by postoperative infections of bone implants,are commonly met,which cannot be treated precisely with intravenous antibiotics.Photothermal therapy(PTT)and photodynamic therapy(PDT)have attracted widespread attention due to their non-invasive antibacterial effects on tissues and no bacterial resistance,which may be an excellent approach to solve infections related to bone implants for biodegradable magnesium alloys.Herein,a sodium copper chlorophyllin(SCC)with a porphyrin ring induced Ca-P coating was prepared on AZ31 magnesium alloy via layer-by-layer(LbL)assembly.The morphology and composition of the samples were characterized through field emission scanning electron microscope(FE-SEM)with affiliated energy dispersive spectrometer(EDS),X-ray diffractometer(XRD),and Fourier infrared spectrometer(FTIR)and X-ray photoelectron spectrometer(XPS)as well.Potentiodynamic polarization,electrochemical impedance spectroscopy(EIS)and hydrogen evolution experiments were employed to evaluate the corrosion behavior of the samples.Atomic absorption spectrophotometer was used to measure Cu elemental content of different immersion periods.Cytocompatibility and antibacterial performance of the coatings were probed using in vitro cytotoxicity tests(MTT assay),live/dead cell staining and plate counting method.The results showed that the obtained(Ca-P/SCC)10 coating exhibited good corrosion resistance,antimicrobial activity(especially under 808 nm irradiation)and biocompatibility.The antibacterial rates for E.coli and S.aureus were 99.9%and 99.8%,respectively;and the photothermal conversion efficiency was as high as 42.1%.Triple antibacterial mechanisms including photodynamic,photothermal reactions and copper-ions release were proposed.This coating exhibited a promising application for biodegradable magnesium alloys.展开更多
Unintended pregnancy is a global issue, with approximately 85,000,000 women around the world having unintended pregnancy annually. The contents of clinical application of women’s contraceptive methods are very wide, ...Unintended pregnancy is a global issue, with approximately 85,000,000 women around the world having unintended pregnancy annually. The contents of clinical application of women’s contraceptive methods are very wide, involving multiple areas. This consensus deeply discusses the specific contraceptive needs at different statuses, combined with gynecological diseases, postabortion contraception, and postpartum family planning, ensuring the correct use of contraceptive methods under the corresponding status. The top priority of the consensus is the specific contraception consensus section for women combined with gynecological diseases because medical treatment effect as well as side effects should be weighed carefully. The consensus is to make high-efficiency and individual contraceptive strategy for different groups based on multidisciplinary(gynecology, obstetrics, and family planning) and multidimensional aspects, which can provide uniform guidance for medical and health organizations under the condition as relevant global guidance or consensus is still lacking.展开更多
基金supported by the National Key R&D Program of China(2021ZD0201004)the National Natural Science Foundation of China(22165008,22077037,21474034,51673077 and 51603078)+1 种基金Hainan Provincial Natural Science Foundation of China(521RC506)the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2020WNLOKF018)。
文摘Alzheimer's disease(AD)is a typical neurodegenerative disease.β-amyloid(AβÞplaque is the most prominent pathological biomarker associated with the progression of AD.Conventional Aβprobes,including commercial probe ThT,usually suffer from tedious washing procedures.Herein,novel AIE-active Aβprobes with excellent water solubility,named DE-V1-PYC3 and DE-V1-PYOH,were developed for the detection and image of Aβwithout tedious washing procedures.Compared with commercial probe ThT,the AIE-active Aβprobes exhibited better sensitivity and a±nity to Aβaggregates.Moreover,for ThT,the washing procedures are essential to obtain high signal-to-noise ratio(SNR)images of Aβplaques in AD brain tissue slices.DE-V1-PYC3 and DE-V1-PYOH can label Aβplaques in AD brain tissue slices with high SNR even without tedious washing procedures.
文摘AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.
基金Development Foundation from Nanjing Board of Health of Jiangsu Province,China,No.ZKX05008
文摘AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.
基金supported by Tangshan City Science and Technology Development Project(No.15130219a)
文摘BACKGROUND:Periplaneta americana extract is recognized to have a positive effect on gastrointestinal mucosa.This study aimed to investigate the effects of periplaneta americana extract on immune function,nutrition status and gastrointestinal complications of early enteral nutrition patients with systemic inflammatory response syndrome(SIRS).METHODS:Patients with SIRS were randomly divided into two groups:treatment and control groups.All patients in the two groups received conventional therapy including enteral nutrition,but periplaneta americana extract,an additional Chinese medicine,was given to the patients in the treatment group.At the beginning of treatment(0 day)and 1,3,and 7 days after treatment,the levels of immunoglobulin(Ig A),total lymphocyte count(TLC),total protein(TP)and prealbumin(PA)were respectively tested in patients'venous blood.The incidences of bloating,diarrhea,aspiration pneumonia and high blood sugar at 7 days after treatment were recorded.The mortality of the patients in 28 days was recorded.RESULTS:At 3 and 7 days after treatment,the levels of Ig A and TLC in the treatment group were higher than those in the control group(P<0.05).At 7 days after treatment,the levels of TP and PA in the treatment group were higher than those in the control group(P<0.05).The incidences of bloating and diarrhea in the treatment group were lower than those in the control group,the differences were significant(P<0.05).The mortality of treatment group was lower than that of the control group(P>0.05).CONCLUSION:Periplaneta americana extract could reduce gastrointestinal complications and improve immune function and nutritional status in patients with systemic inflammatory response syndrome.
基金Supported by Science and Technology Planning Project of Guangdong Province (No.2017A020211005)Science and Technology Programme of Guangzhou, China 2016 (No.201607010386)
文摘AIM: To examine the therapeutic effects of tocilizumab on experimental corneal transplantation and its effect on Treg/Th17 balance. METHODS: Allograft corneal graft was performed between host Sprague Dawley and Wistar donor rats.The rats were randomly divided into four groups: normal,autograft, allograft, and allograft treated with tocilizumab.Kaplan-Meier was performed to draw the survival curve.The protein levels of interleukin-17A(IL-17A), vascular endothelial growth factor(VEGF), and forkhead box protein3(Foxp3) were measured by immunohistochemistry.The mRNA levels of IL-17A, VEGF, retinoid-related orphan receptor gammat(RORγt), interleukin-6(IL-6) and Foxp3 were detected by reverse transcription real-time polymerase chain reaction(RT-PCR). The Treg and Th17 cells were investigated by flow cytometry. RESULTS: The survival time of tocilizumab group was(24±1.27 d) longer than that of allograft group(10±0.55 d).Moreover, immunohistochemical examination revealed that IL-17A and VEGF protein levels in the allograft group were significantly higher than that of tocilizumab group(P<0.01),while Foxp3 levels in the allograft group was significantly lower than that of the tocilizumab treated group(P<0.001).Flow cytometry showed that the number of Th17 cellsin allograft group was significantly higher than that in tocilizumab group(P<0.001). Meanwhile, the number of Tregs was significantly lower than in tocilizumab group(P<0.001). Simultaneously, Foxp3 m RNA expression level in corneal tissues of tocilizumab treated group was significantly higher than other groups(P<0.001). CONCLUSION: These findings suggest that tocilizumab may promote corneal allograft survival, possibly by modulating Treg-Th17 balance.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61704084 and 61874059)。
文摘This paper presents a new silicon-on-insulator(SOI) lateral-double-diffused metal-oxide-semiconductor transistor(LDMOST) device with alternated high-k dielectric and step doped silicon pillars(HKSD device). Due to the modulation of step doping technology and high-k dielectric on the electric field and doped profile of each zone, the HKSD device shows a greater performance. The analytical models of the potential, electric field, optimal breakdown voltage, and optimal doped profile are derived. The analytical results and the simulated results are basically consistent, which confirms the proposed model suitable for the HKSD device. The potential and electric field modulation mechanism are investigated based on the simulation and analytical models. Furthermore, the influence of the parameters on the breakdown voltage(BV) and specific on-resistance(R_(on,sp)) are obtained. The results indicate that the HKSD device has a higher BV and lower R_(on,sp) compared to the SD device and HK device.
基金supported by the National Natural Science Foundation of China,No.81272074the Scientific Research Foundation Project for Doctors in Liaoning Province of China,No.20121094+1 种基金Aohongboze Graduate Sci-tech Innovation Foundationthe President Fund of Liaoning Medical University of China,No.2013003
文摘Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.
文摘Objective To retrospectively investigate the distribution in kidney transplantation for fifteen years in Peking Union Medical College Hospital.Methods We conducted a descriptive research counting up the number of patients who received kidney transplantation each year in our hospital during 1995 and 2010.Results The first kidney transplantation in our hospital occurred in the 1960s.The number of kidney transplantation increased until reaching a maximum of 47 grafts in 2001;since then the number fell.Conclusions With the decreased number of kidney transplantation,we have realized the shortage of transplantable organs is very serious.The continuing transplant shortage requires major efforts to expand the donor pool.Donation after cardiac death offers the potential to enlarge the donor pool,but we need to strictly control the criteria for potential donors.
文摘BACKGROUND Intraoperative methylene blue testing(IMBT),air leak testing,or endoscopy is used to assess the anastomotic integrity of esophagojejunostomy during open total gastrectomy for gastric cancer.Totally laparoscopic radical gastrectomy has been widely used to treat gastric cancer in the last few decades.However,reports on testing anastomotic integrity in totally laparoscopic radical gastrectomy are limited.AIM To explore the effects of IMBT on the incidence of postoperative anastomotic leaks(PALs)and identify the risk factors for PALs in totally laparoscopic radical gastrectomy.METHODS From January 2017 to December 2019,patients who underwent totally laparoscopic radical gastrectomy at the Shaanxi Provincial People's Hospital were retrospectively analyzed.According to whether or not they experienced an IMBT,the patients were divided into an IMBT group and a control group.If the IMBT was positive,an intraoperative suture was required to reinforce the anastomosis.The difference in the incidence of PALs was compared,and the risk factors were investigated.RESULTS This study consisted of 513 patients,211 in the IMBT group and 302 in the control group.Positive IMBT was shown in seven patients(3.3%)in the IMBT group,and no PAL occurred in these patients after suture reinforcement.Multivariate analysis showed that risk factors for predicting positive IMBT were body mass index(BMI)>25 kg/m2(hazard ratio[HR]=8.357,P=0.009),operation time>4 h(HR=55.881,P=0.002),and insufficient surgical experience(HR=15.286,P=0.010).Moreover,15 patients(2.9%)developed PALs in 513 patients,and the rates of PALs were significantly lower in the IMBT group than in the control group[2 of 211 patients(0.9%)vs 13 of 302 patients(4.3%),P=0.0026].Further analysis demonstrated that preoperative complications(HR=13.128,P=0.017),totally laparoscopic total gastrectomy(HR=9.075,P=0.043),and neoadjuvant chemotherapy(HR=7.150,P=0.008)were independent risk factors for PALs.CONCLUSION IMBT is an effective method to evaluate the integrity of anastomosis during totally laparoscopic radical gastrectomy,thus preventing technical defect-related anastomotic leaks.Preoperative complications,totally laparoscopic total gastrectomy,and neoadjuvant chemotherapy are independent risk factors for PALs.
文摘DRIMARY benign ureteral tumors are rare and they arise from the mesodermal tissue of the ureteral wall. Less than 200 cases have been docu- mented in published reports.1 Bilateral ureteralfibroepithelial polyps are extremely rare and commonly occur in the proximal ureter, causing complete ureteral obstruction. Pyeloplasty is an effective treatment for im- proving renal function. Here we report a case with se- quential bilateral ureteral fibroepithelial polyps causing obstructive hydronephrosis.
基金supported by the National Natural Science Foundation of China(No.52076176)Fundamental Research Funds for the Central Universities(Nos.xzd012023037 and xzy022023034)Innovation Capability Support Program of Shaanxi(No.2023-CX-TD-26).
文摘Solar-driven photo-thermal catalytic CO_(2)methanation reaction is a promising technology to alleviate the problems posed by greenhouse gases emissions.However,designing advanced photo-thermal catalysts remains a research challenge for CO_(2)methanation reaction.In this work,a series of ABO3(A=lanthanide,B=transition metal)perovskite catalysts with Ce-substituted LaNiO3(La_(1-x)Ce_(x)NiO_(3),x=0,0.2,0.5,0.8,1)were synthesized for CO_(2)methanation.The La_(0.2)Ce_(0.8)NiO_(3) exhibited the highest CH_(4) formation rate of 258.9 mmol·g^(-1)·hcat-1,CO_(2)conversion of 55.4%and 97.2%CH_(4) selectivity at 300℃with the light intensity of 2.9 W·cm^(-2).Then the catalysts were thoroughly analyzed by physicochemical structure and optical properties characterizations.The partial substitution of the A-site provided more active sites for the adsorption and activation of CO_(2)/H_(2).The sources of the active sites were considered to be the oxygen vacancies(O_(v))created by lattice distortions due to different species of ions(La^(3+),Ce^(4+),Ce^(3+))and exsolved Ni0 by H_(2)reduction.The catalysts have excellent light absorption absorbance and low electron-hole(e^(-)/h^(+))recombination rate,which greatly contribute to the excellent performance in photo-thermal synergistic catalysis(PTC)CO_(2)methanation.The results of in situ irradiated electron paramagnetic resonance spectrometer(ISI-EPR)and ISI-X-ray photoelectron spectroscopy(XPS)indicated that the aggregation of unpaired electrons near the defects and Ni metal(from La and Ce ions to Ov and Ni0)accelerated adsorption and activation of CO_(2)/H_(2).At last,the catalyst properties and structure were correlated with the proposed reaction mechanism from the in situ diffuse reflection infrared Fourier transform spectrum(DRIFTS)measurements.The in situ precipitation of the B-site enhanced the dispersion of Ni,while its enriched photoelectrons upon illumination further promote hydrogen dissociation.More H^(*)spillover accelerated the rate-determining step(RDS)of HCOO*hydrogenation.This work provides the theoretical basis for the development of catalysts and industrial application.
基金Supported by the National Key Research and Development Program of China(2017YFA0402201,2022YFA1604701,2022YFA1605000)the National Natural Science Foundation of China(12322511,12175112,12005111,11725522)。
文摘We operated a p-type point contact high purity germanium(PPCGe)detector(CDEX-1B,1.008 kg)in the China Jinping Underground Laboratory(CJPL)for 500.3 days to search for neutrinoless double beta(0νββ)decay of^(76)Ge.A total of 504.3 kg⋅day effective exposure data was accumulated.The anti-coincidence and the multi/single-site event(MSE/SSE)discrimination methods were used to suppress the background in the energy region of interest(ROI,1989–2089 keV for this work)with a factor of 23.A background level of 0.33 counts/(keV⋅kg⋅yr)was realized.The lower limit on the half life of^(76)Ge 0νββdecay was constrained as T_(1/2)^(0ν)>1.0×10^(23)yr(90%C.L.),corresponding to the upper limits on the effective Majorana neutrino mass:<mββ><3.2–7.5 eV.
基金This work was supported by the National Natural Science Foundation of China(Grant No.52071191)the Natural Science Foundation of Shandong Province(ZR2020QE009)+1 种基金the Research Start-up Fund of Shandong University of Science and Technology(01040125219)the“Elite Plan”Foundation of Shandong University of Science and Technology(0104060541112).
文摘A hydrothermal deposition method was utilized to fabricate Ca-P composite coating induced by the layer-by-layer(LbL)assembled polyvinylpyrrolidone/deoxyribonucleic acid(PVP/DNA)_(20) multilayer on AZ31 alloy.The surface morphology and compositions were characterized by SEM,EDS,FTIR and XRD.Besides,the corrosion resistance and degradation behavior of the coating were tested via electrochemical polarization,impedance spectroscopy and immersion measurements.Results show that the main components of Ca-P coatings are hydroxyapatite,Ca_(3)(PO_(4))_(2) and Mg_(3)(PO_(4))_(2)·nH_(2)O.The LbL-assembled DNA and PVP promote the adsorption of Ca-P deposits on the sample surface,and structures and functional groups of the polyelectrolyte in the outermost layer are the primary influencing factor for the induction of the Ca-P coating.Carboxyl groups have the best biomineralization effect among all related functional groups.The enhanced corrosion resistance and adhesion highlight a promising use of(PVP/DNA)_(20)-induced Ca-P coatings in the field of biomedical magnesium alloys.
文摘Background:The molecular mechanisms underlying the endometriosis are still not completely understood.In order to test the hypothesis that the approaches in phosphoproteomics might contribute to the identification of key biomarkers to assess disease pathogenesis and drug targets,we carried out a phosphoproteomics analysis of human endometrium.Methods:A large-scale differential phosphoproteome analysis,using peptide enrichment of titanium dioxide purify and sequential elution from immobilized metal affinity chromatography with linear trap quadrupole-tandem mass spectrometry,was performed in endometrium tissues from 8 women with or without endometriosis.Results:The phosphorylation profiling of endometrium from endometriosis patients had been obtained,and found that identified 516 proteins were modified at phosphorylation level during endometriosis.Gene ontology annotation analysis showed that these proteins were enriched in cellular processes of binding and catalytic activity.Further pathway analysis showed that ribosome pathway and focal adhesion pathway were the top two pathways,which might be deregulated during the development of endometriosis.Conclusions:That large-scale phosphoproteome quantification has been successfully identified in endometrium tissues of women with or without endometriosis will provide new insights to understand the molecular mechanisms of the development of endometriosis.
基金the National Science Fund for Distinguished Young Scholars(Grant No.42025201)。
文摘As relics of ancient ocean lithosphere,ophiolites are the most important petrological evidence for marking the sutures and also play a key role in reconstructing plate configuration.They also provide valuable windows for studying crustal accretion and mantle processes occurring at modem ocean ridges.Abundant ophiolites are distributed along the Yarlung-Tsangpo suture and represent the relics of ocean lithosphere of the Neo-Tethys.They are characterized by an incomplete litho-stratigraphy,of which the mantle section is much thicker than the crustal section.Ocean crustal rocks outcropped in the Yarlung-Tsangpo ophiolites are much thinner than normal ocean crusts(~7 km)or even absent.Tectonic settings from which the Yarlung-Tsangpo ophiolites originated remain highly controversial,although an origin of the supra-subduction zone is prevailing.Moreover,their incomplete litho-stratigraphy has been commonly attributed to tectonic dismemberment during the late-stage emplacement after their formation.Nevertheless,such an incompleteness resembles the ocean lithosphere generated at modem ultraslow spreading ridges,such as the Southwest Indian Ridge(SWIR).In this paper,we present several lines of evidence that support the formation of the Yarlung-Tsangpo ophiolites at ultraslow spreading ridges,during which detachment faults were developed.This suggests that the Yarlung-Tsangpo ophiolites might represent the ocean core complexes(OCC)in the Neo-Tethys Ocean.The OCC with high topography in the seafloor were clogged in the trench and preserved as ophiolites through Indo-Eurasia collision.The clogging resulted in the demise of an old subduction and a new subduction was re-initiated beneath the clogged OCC.
基金by the National Natural Science Foundation of China(31772516 and 31501634)was funded by the Key Foreign Cooperation Projects of the Bureau of International Cooperation of Chinese Academy of Sciences(152111KYSB20160067).
文摘Swarming behavior facilitates pair formation,and therefore mating,in many eusocial termites.However,the physiological adjustments and morphological transformations of the flight muscles involved in flying and flightless insect forms are still unclear.Here,we found that the dispersal flight of the eusocial termite Reticulitermes chinensis Snyder led to a gradual decrease in adenosine triphosphate supply from oxidative phospho・rylation,as well as a reduction in the activities of critical mitochondrial respiratory enzymes from preflight to dealation.Correspondingly,using three-dimensional reconstruction and transmission electron microscopy(TEM),the flight muscles were found to be gradually deteriorated during this process.In particular,two tergo-pleural muscles(IItpm5 and IIItpm5)necessary to adjust the rotation of wings for wing shedding behavior were present only in flying alates.These findings suggest that flight muscle systems vary in function and morphology to facilitate the swarming flight procedure,which sheds light on the important role of swarming in successful extension and fecundity of eusocial termites.
基金the National Natural Science Foundation of China(No.52071191,52101288)Shandong Provincial Natural Science Foundation,China(ZR2020QE009).
文摘Surgical failures,caused by postoperative infections of bone implants,are commonly met,which cannot be treated precisely with intravenous antibiotics.Photothermal therapy(PTT)and photodynamic therapy(PDT)have attracted widespread attention due to their non-invasive antibacterial effects on tissues and no bacterial resistance,which may be an excellent approach to solve infections related to bone implants for biodegradable magnesium alloys.Herein,a sodium copper chlorophyllin(SCC)with a porphyrin ring induced Ca-P coating was prepared on AZ31 magnesium alloy via layer-by-layer(LbL)assembly.The morphology and composition of the samples were characterized through field emission scanning electron microscope(FE-SEM)with affiliated energy dispersive spectrometer(EDS),X-ray diffractometer(XRD),and Fourier infrared spectrometer(FTIR)and X-ray photoelectron spectrometer(XPS)as well.Potentiodynamic polarization,electrochemical impedance spectroscopy(EIS)and hydrogen evolution experiments were employed to evaluate the corrosion behavior of the samples.Atomic absorption spectrophotometer was used to measure Cu elemental content of different immersion periods.Cytocompatibility and antibacterial performance of the coatings were probed using in vitro cytotoxicity tests(MTT assay),live/dead cell staining and plate counting method.The results showed that the obtained(Ca-P/SCC)10 coating exhibited good corrosion resistance,antimicrobial activity(especially under 808 nm irradiation)and biocompatibility.The antibacterial rates for E.coli and S.aureus were 99.9%and 99.8%,respectively;and the photothermal conversion efficiency was as high as 42.1%.Triple antibacterial mechanisms including photodynamic,photothermal reactions and copper-ions release were proposed.This coating exhibited a promising application for biodegradable magnesium alloys.
文摘Unintended pregnancy is a global issue, with approximately 85,000,000 women around the world having unintended pregnancy annually. The contents of clinical application of women’s contraceptive methods are very wide, involving multiple areas. This consensus deeply discusses the specific contraceptive needs at different statuses, combined with gynecological diseases, postabortion contraception, and postpartum family planning, ensuring the correct use of contraceptive methods under the corresponding status. The top priority of the consensus is the specific contraception consensus section for women combined with gynecological diseases because medical treatment effect as well as side effects should be weighed carefully. The consensus is to make high-efficiency and individual contraceptive strategy for different groups based on multidisciplinary(gynecology, obstetrics, and family planning) and multidimensional aspects, which can provide uniform guidance for medical and health organizations under the condition as relevant global guidance or consensus is still lacking.