Arctic Sea Ice Variations in the First Half of the 20th Century:A New Reconstruction Based on Hydrometeorological Data

The shrinking Arctic sea-ice area(SIA) in recent decades is a striking manifestation of the ongoing climate change.Variations of the Arctic sea ice have been continuously observed by satellites since 1979, relatively well monitored since the 1950s, but are highly uncertain in the earlier period due to a lack of observations. Several reconstructions of the historical gridded sea-ice concentration(SIC) data were recently presented based on synthesized regional sea-ice observations or by applying a hybrid model–empirical approach. Here, we present an SIC reconstruction for the period1901–2019 based on established co-variability between SIC and surface air temperature, sea surface temperature, and sea level pressure patterns. The reconstructed sea-ice data for March and September are compared to the frequently used Had ISST1.1 and SIBT1850 datasets. Our reconstruction shows a large decrease in SIA from the 1920 to 1940 concurrent with the Early 20th Century Warming event in the Arctic. Such a negative SIA anomaly is absent in Had ISST1.1 data. The amplitude of the SIA anomaly reaches about 0.8 mln km^(2) in March and 1.5 mln km^(2) in September. The anomaly is about three times stronger than that in the SIBT1850 dataset. The larger decrease in SIA in September is largely due to the stronger SIC reduction in the western sector of the Arctic Ocean in the 70°–80°N latitudinal zone. Our reconstruction provides gridded monthly data that can be used as boundary conditions for atmospheric reanalyses and model experiments to study the Arctic climate for the first half of the 20th century.

Relative Impacts of Sea Ice Loss and Atmospheric Internal Variability on the Winter Arctic to East Asian Surface Air Temperature Based on Large-Ensemble Simulations with NorESM2

To quantify the relative contributions of Arctic sea ice and unforced atmospheric internal variability to the “warm Arctic, cold East Asia”(WACE) teleconnection, this study analyses three sets of large-ensemble simulations carried out by the Norwegian Earth System Model with a coupled atmosphere–land surface model, forced by seasonal sea ice conditions from preindustrial, present-day, and future periods. Each ensemble member within the same set uses the same forcing but with small perturbations to the atmospheric initial state. Hence, the difference between the present-day(or future) ensemble mean and the preindustrial ensemble mean provides the ice-loss-induced response, while the difference of the individual members within the present-day(or future) set is the effect of atmospheric internal variability. Results indicate that both present-day and future sea ice loss can force a negative phase of the Arctic Oscillation with a WACE pattern in winter. The magnitude of ice-induced Arctic warming is over four(ten) times larger than the ice-induced East Asian cooling in the present-day(future) experiment;the latter having a magnitude that is about 30% of the observed cooling. Sea ice loss contributes about 60%(80%) to the Arctic winter warming in the present-day(future) experiment. Atmospheric internal variability can also induce a WACE pattern with comparable magnitudes between the Arctic and East Asia. Ice-lossinduced East Asian cooling can easily be masked by atmospheric internal variability effects because random atmospheric internal variability may induce a larger magnitude warming. The observed WACE pattern occurs as a result of both Arctic sea ice loss and atmospheric internal variability, with the former dominating Arctic warming and the latter dominating East Asian cooling.

Preface to the Special Topic on Ocean, Sea Ice and Northern Hemisphere Climate:In Remembrance of Professor Yongqi GAO's Key Contributions

This special issue commemorates the life work of Prof. Yongqi GAO who passed away in July 2021, his time cut short by illness. He had many great achievements, but still much more to contribute. The seven articles in this special issue are from research areas where he contributed, and they illustrate how his close colleagues are continuing his work.

Colorless to black switching with high contrast ratio via the electrochemical process of a hybrid organic-inorganic perovskite

Colorless‐to‐black switching has attracted widespread attention for smart windows and multifunctional displays because they are more useful to control solar energy.However,it still remains a challenge owing to the tremendous difficulties in the design of completely reverse absorptions in transmissive and colored states.Herein,we report on an electrochemical device that can switch between colorless and black by using the electrochemical process of hybrid organic–inorganic perovskite MAPbBr_(3),which shows a high integrated contrast ratio of up to 73%from 400 to 800 nm.The perovskite solution can be used as the active layer to assemble the device,showing superior transmittance over the entire visible region in neutral states.By applying an appropriate voltage,the device undergoes reversible switching between colorless and black,which is attributed to the formation of lead and Br_(2)in the redox reaction induced by the electron transfer process in MAPbBr_(3).In addition,the contrast ratio can be modulated over the entire visible region by changing the concentration and the applied voltage.These results contribute toward gaining an insightful understanding of the electrochemical process of perovskites and greatly promoting the development of switchable devices.

Impacts of the extratropical North Pacific on boreal summer Arctic circulation

北极夏季大气环流的一个显着特征是以北冰洋为中心的异常反气旋环流,与北极增暖存在紧密的联系.先前的研究已将其形成的潜在机制与早春欧亚融雪,热带太平洋海表温度异常联系起来.本研究发现北极夏季反气旋环流异常与春季副热带北太平洋海表温度异常(SSTA)存在显着联系,表明副热带北太平洋与北极之间存在遥相关.该SSTA的特点是北太平洋中纬度地区有暖的SSTA,,周围有明显的冷SSTA,类似于太平洋年代际振荡(PDO)的负位相,但热带地区没有明显的信号(本研究称之为类负位相PDO),5月份,这种类负位相PDO可以激发从白令海传播到北极的罗斯贝波,导致北极出现反气旋环流异常.这种反气旋环流异常可以持续到夏季.同时,这种类负位相PDO的SSTA可以持续到夏季,并在夏季引起白令海上空的低压异常.这种低层的低压异常会导致异常的上升运动,并引起高层的辐散异常,从而进一步加剧夏季北极对流层上层的反气旋环流异常。这种反气旋环流异常可迫使北极上空出现异常绝热下沉运动,导致北极出现显著的绝热加热.于是,北极上空出现显著的暖异常,其暖中心位于北极对流层中部。数值模拟试验证实了5月份类负位相PDO的SSTA与夏季北极反气旋环流异常之间的联系.

Projecting Spring Consecutive Rainfall Events in the Three Gorges Reservoir Based on Triple-Nested Dynamical Downscaling

Spring consecutive rainfall events(CREs) are key triggers of geological hazards in the Three Gorges Reservoir area(TGR), China. However, previous projections of CREs based on the direct outputs of global climate models(GCMs) are subject to considerable uncertainties, largely caused by their coarse resolution. This study applies a triple-nested WRF(Weather Research and Forecasting) model dynamical downscaling, driven by a GCM, MIROC6(Model for Interdisciplinary Research on Climate, version 6), to improve the historical simulation and reduce the uncertainties in the future projection of CREs in the TGR. Results indicate that WRF has better performances in reproducing the observed rainfall in terms of the daily probability distribution, monthly evolution and duration of rainfall events, demonstrating the ability of WRF in simulating CREs. Thus, the triple-nested WRF is applied to project the future changes of CREs under the middle-of-the-road and fossil-fueled development scenarios. It is indicated that light and moderate rainfall and the duration of continuous rainfall spells will decrease in the TGR, leading to a decrease in the frequency of CREs. Meanwhile, the duration, rainfall amount, and intensity of CREs is projected to regional increase in the central-west TGR. These results are inconsistent with the raw projection of MIROC6. Observational diagnosis implies that CREs are mainly contributed by the vertical moisture advection. Such a synoptic contribution is captured well by WRF, which is not the case in MIROC6,indicating larger uncertainties in the CREs projected by MIROC6.

Background removal from global auroral images:Data-driven dayglow modeling

Global images of auroras obtained by cameras on spacecraft are a key tool for studying the near-Earth environment.However,the cameras are sensitive not only to auroral emissions produced by precipitating particles,but also to dayglow emissions produced by photoelectrons induced by sunlight.Nightglow emissions and scattered sunlight can contribute to the background signal.To fully utilize such images in space science,background contamination must be removed to isolate the auroral signal.Here we outline a data-driven approach to modeling the background intensity in multiple images by formulating linear inverse problems based on B-splines and spherical harmonics.The approach is robust,flexible,and iteratively deselects outliers,such as auroral emissions.The final model is smooth across the terminator and accounts for slow temporal variations and large-scale asymmetries in the dayglow.We demonstrate the model by using the three far ultraviolet cameras on the Imager for Magnetopause-to-Aurora Global Exploration(IMAGE)mission.The method can be applied to historical missions and is relevant for upcoming missions,such as the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.

Anthropogenic Influence on Decadal Changes in Concurrent Hot and Dry Events over China around the Mid-1990s

The frequency and duration of observed concurrent hot and dry events(HDEs) over China during the growing season(April–September) exhibit significant decadal changes across the mid-1990s. These changes are characterized by increases in HDE frequency and duration over most of China, with relatively large increases over southeastern China(SEC), northern China(NC), and northeastern China(NEC). The frequency of HDEs averaged over China in the present day(PD,1994–2011) is double that in the early period(EP, 1964–81);the duration of HDEs increases by 60%. Climate experiments with the Met Office Unified Model(MetUM-GOML2) are used to estimate the contributions of anthropogenic forcing to HDE decadal changes over China. Anthropogenic forcing changes can explain 60%–70% of the observed decadal changes,suggesting an important anthropogenic influence on HDE changes over China across the mid-1990s. Single-forcing experiments indicate that the increase in greenhouse gas(GHG) concentrations dominates the simulated decadal changes,increasing the frequency and duration of HDEs throughout China. The change in anthropogenic aerosol(AA) emissions significantly decreases the frequency and duration of HDEs over SEC and NC, but the magnitude of the decrease is much smaller than the increase induced by GHGs. The changes in HDEs in response to anthropogenic forcing are mainly due to the response of climatological mean surface air temperatures. The contributions from changes in variability and changes in climatological mean soil moisture and evapotranspiration are relatively small. The physical processes associated with the response of HDEs to GHG and AA changes are also revealed.

Projecting Wintertime Newly Formed Arctic Sea Ice through Weighting CMIP6 Model Performance and Independence

Precipitous Arctic sea-ice decline and the corresponding increase in Arctic open-water areas in summer months give more space for sea-ice growth in the subsequent cold seasons. Compared to the decline of the entire Arctic multiyear sea ice,changes in newly formed sea ice indicate more thermodynamic and dynamic information on Arctic atmosphere–ocean–ice interaction and northern mid–high latitude atmospheric teleconnections. Here, we use a large multimodel ensemble from phase 6 of the Coupled Model Intercomparison Project(CMIP6) to investigate future changes in wintertime newly formed Arctic sea ice. The commonly used model-democracy approach that gives equal weight to each model essentially assumes that all models are independent and equally plausible, which contradicts with the fact that there are large interdependencies in the ensemble and discrepancies in models' performances in reproducing observations. Therefore, instead of using the arithmetic mean of well-performing models or all available models for projections like in previous studies, we employ a newly developed model weighting scheme that weights all models in the ensemble with consideration of their performance and independence to provide more reliable projections. Model democracy leads to evident bias and large intermodel spread in CMIP6 projections of newly formed Arctic sea ice. However, we show that both the bias and the intermodel spread can be effectively reduced by the weighting scheme. Projections from the weighted models indicate that wintertime newly formed Arctic sea ice is likely to increase dramatically until the middle of this century regardless of the emissions scenario.Thereafter, it may decrease(or remain stable) if the Arctic warming crosses a threshold(or is extensively constrained).

Recent Ventures in Interdisciplinary Arctic Research:The ARCPATH Project

This paper celebrates Professor Yongqi GAO's significant achievement in the field of interdisciplinary studies within the context of his final research project Arctic Climate Predictions: Pathways to Resilient Sustainable Societies-ARCPATH(https://www.svs.is/en/projects/finished-projects/arcpath). The disciplines represented in the project are related to climatology, anthropology, marine biology, economics, and the broad spectrum of social-ecological studies. Team members were drawn from the Nordic countries, Russia, China, the United States, and Canada. The project was transdisciplinary as well as interdisciplinary as it included collaboration with local knowledge holders. ARCPATH made significant contributions to Arctic research through an improved understanding of the mechanisms that drive climate variability in the Arctic. In tandem with this research, a combination of historical investigations and social, economic, and marine biological fieldwork was carried out for the project study areas of Iceland, Greenland, Norway, and the surrounding seas, with a focus on the joint use of ocean and sea-ice data as well as social-ecological drivers. ARCPATH was able to provide an improved framework for predicting the near-term variation of Arctic climate on spatial scales relevant to society, as well as evaluating possible related changes in socioeconomic realms. In summary, through the integration of information from several different disciplines and research approaches, ARCPATH served to create new and valuable knowledge on crucial issues, thus providing new pathways to action for Arctic communities.

Ground-based and additional science support for SMILE

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere.Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission.Here,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these efforts.Preparations include constructing an online SMILE Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft conjunctions.We anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

Ophiolites of the Central Asian Orogenic Belt:Geochemical and petrological characterization and tectonic settings

We present a compilation of published data(field,petrography,ages and geochemistry)from 73 ophiolitic complexes of the Central Asian Orogenic Belt.The ophiolitic complexes,ranging in age from Neoproterozoic to Triassic.have been geochemically classified as subduction-related and subductionunrelated categories applying recent,well-established discrimination diagrams.The subductionunrelated category is further subdivided into Mid-Ocean Ridge type(MOR),a common rift-drift stage and Plume type,and the subduction-related category is subdivided into Backarc(BA),Forearc(FA).Backarc to Forearc(BA-FA)and Volcanic Arc(VA)types.The four subduction-related types define highly different geochemical features,with the BA and FA types defining end members showing subduction influence of 10%-100%and 90%-100%subduction influence,respectively,and the two other types(BAFA and VA)define values between the two end members.The subduction-related category comprises79%of the examined ophiolites,of which the BA type ophiolites is by far the dominant group,followed by the BA-FA type,and with FA and VA types as subordinate groups.The Neoproterozoic and Ordovician complexes exhibit the highest,whereas those of Silurian age exhibit the lowest subduction-influence.Of the remaining 21%subduction-unrelated ophiolites,the MOR type dominates.Both the subductionrelated and subduction-unrelated types,in particular the latter,are commonly associated with alkaline basalts taken to represent ocean island magmatism.Harzburgite,dunite,gabbro and basalt are the common lithologies in all ophiolite types,whereas the BA-FA,FA and VA types generally contain intermediate to felsic rocks,and in the FA type boninites occur.The subduction-related ophiolites types generally show low metamorphic grade,whereas greenschist.amphibolite and blueschist grades occur in the subduction-unrelated and BA types.The highly different subduction contribution(from 0 to 100%in the MOR and FA,respectively),attest to variable dips of the subducting slab,as well as variable flux of subduction-related elements into the mantle above subducting slabs,from where the ophiolite magmas got their geochemical fingerprints.As most MOR ophiolites get subducted to the deep mantle,the subduction-related ophiolites have become a dominant ophiolitic type on Earth’s surface through all times supporting the idea about the early start of Plate Tectonics.

Sonography of the small intestine

In the last two decades, there has been substantial development in the diagnostic possibilities for examining the small intestine. Compared with computerized tomography, magnetic resonance imaging, capsule endoscopy and double-balloon endoscopy, ultrasonography has the advantage of being cheap, portable, flexible and user-and patient-friendly, while at the same time providing the clinician with image data of high temporal and spatial resolution. The method has limitations with penetration in obesity and with intestinal air impairing image quality. The flexibility ultrasonography offers the examiner also implies that a systematic approach during scanning is needed. This paper reviews the basic scanning techniques and new modalities such as contrast-enhanced ultrasound, elastography, strain rate imaging, hydrosonography, allergosonography, endoscopic sonography and nutritional imaging, and the literature on disease-specific findings in the small intestine. Some of these methods have shown clinical benefit, while others are under research and development to establish their role in the diagnostic repertoire. However, along with improved overall image quality of new ultrasound scanners, these methodshave enabled more anatomical and physiological changes in the small intestine to be observed. Accordingly, ultrasound of the small intestine is an attractive clinical tool to study patients with a range of diseases.

Epidemiology of perforated peptic ulcer:Age-and gender-adjusted analysis of incidence and mortality

AIM:To investigate the epidemiological trends in inci-dence and mortality of perforated peptic ulcer(PPU)in a well-defined Norwegian population. METHODS:A retrospective,population-based,single-center,consecutive cohort study of all patients diag-nosed with benign perforated peptic ulcer.Included were both gastric and duodenal ulcer patients admitted to Stavanger University Hospital between January 2001 and December 2010.Ulcers with a malignant neoplasia diagnosis,verified by histology after biopsy or resection,were excluded.Patients were identified from the hospitals administrative electronic database using pertinent ICD-9 and ICD-10 codes(K25.1,K25.2,K25.5, K25.6,K26.1,K26.2,K26.5,K26.6).Additional searches using appropriate codes for relevant laparoscopic and open surgical procedures(e.g.,JDA 60,JDA 61,JDH 70 and JDH 71)were performed to enable a complete identification of all patients.Patient demographics,presentation patterns and clinical data were retrieved from hospital records and surgical notes.Crude and adjusted incidence and mortality rates were estimated by using national population demographics data. RESULTS:In the study period,a total of 172 patients with PPU were identified.The adjusted incidence rate for the overall 10-year period was 6.5 per 100 000 per year(95%CI:5.6-7.6)and the adjusted mortality rate for the overall 10-year period was 1.1 per 100 000 per year(95%CI:0.7-1.6).A non-significant decline in ad-justed incidence rate from 9.7 to 5.6 occurred during the decade.The standardized mortality ratio for the whole study period was 5.7(95%CI:3.9-8.2),while the total 30-d mortality was 16.3%.No difference in in-cidence or mortality was found between genders.However,for patients≥60 years,the incidence increased over 10-fold,and mortality more than 50-fold,compared to younger ages.The admission rates outside office hours were high with almost two out of three(63%) admissions seen at evening/night time shifts and/or during weekends.The observed seasonal variations in admissions were not statistically significant. CONCLUSION:The adjusted incidence rate,seasonal distribution and mortality rate was stable.PPU fre-quently presents outside regular work-hours.Increase in incidence and mortality occurs with older age.

Recent developments in the pathophysiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.

Acute complications of spinal cord injuries

The aim of this paper is to give an overview of acute complications of spinal cord injury(SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperaturecontrol and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation.

Impacts of the Autumn Arctic Sea Ice on the Intraseasonal Reversal of the Winter Siberian High

During 1979–2015, the intensity of the Siberian high(SH) in November and December–January(DJ) is frequently shown to have an out-of-phase relationship, which is accompanied by opposite surface air temperature and circulation anomalies.Further analyses indicate that the autumn Arctic sea ice is important for the phase reversal of the SH. There is a significantly positive(negative) correlation between the November(DJ) SH and the September sea ice area(SIA) anomalies. It is suggested that the reduction of autumn SIA induces anomalous upward surface turbulent heat flux(SHF), which can persist into November, especially over the Barents Sea. Consequently, the enhanced eddy energy and wave activity flux are transported to mid and high latitudes. This will then benefit the development of the storm track in northeastern Europe. Conversely, when downward SHF anomalies prevail in DJ, the decreased heat flux and suppressed eddy energy hinder the growth of the storm track during DJ over the Barents Sea and Europe. Through the eddy–mean flow interaction, the strengthened(weakened)storm track activities induce decreased(increased) Ural blockings and accelerated(decelerated) westerlies, which makes the cold air from the Arctic inhibited(transported) over the Siberian area. Therefore, a weaker(stronger) SH in November(DJ) occurs downstream. Moreover, anomalously large snowfall may intensify the SH in DJ rather than in November. The ensemble-mean results from the CMIP5 historical simulations further confirm these connections. The different responses to Arctic sea ice anomalies in early and middle winter set this study apart from earlier ones.

High densities of serotonin and peptide YY cells in the colon of patients with lymphocytic colitis

AIM： TO investigate colonic endocrine cells in lympho- cytic colitis （LC） patients. METHODS： Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 years （range 19-84 years）. Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleed- ing was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years （range 18-67 years）. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for se- rotonin, peptide YY （PYY）, pancreatic polypeptide （PP） enteroglucagon and somatostatin cells. The cell densi- ties were quantified by computerised image analysis using Olympus software. RESULTS： The colon of both the patient and the control subjects were macroscopically normal. Histo- pathological examination of colon biopsies from con- trols revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC： an increase in intraepithelial lymphocytes （〉 20 lymphocytes/100 epithelial cells） and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreac- tive cells were primarily located in the upper part of the crypts of Lieberk0hn. These cells were basket- or flask-shaped. There was no statistically significant dif- ference between the right and left colon in controls with regards to the densities of serotonin- and PYY- immunoreactive cells （P = 0.9 and 0.1, respectively）. Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6±2.6 （P = 0.008）. In the left colon, the corresponding figures were 28.5± 1.9 and 42.4± 2.9, respectively （P = 0.009）. PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 （P = 0.00006）. In the left colon, PYY cell density in controls was 6.6± 1.2 and in LC patients 53.3 ± 4.6 （P = 0.00007）. CONCLUSION： The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be sec- ondary.

Progress in the development of vaccines for hepatitis C virus infection

The hepatitis C virus(HCV), first described in 1989, is now a leading cause of liver cirrhosis and hepatocellular carcinoma. With more than 170 million people infected globally, this virus is a major public health issue. The current standard therapy is based on interferon in combination with ribavirin. This costly therapy often fails to completely clear the infection and is associated with adverse side effects. Recent anti-HCV therapies are interferon-free direct-acting antiviral(DAA) regimens for HCV, including simeprevir, sofosbuvir, and ledipasvir, which have effects on non-structural proteins. DAA regimens have several advantages, such as specifically targeting HCV viral replication, accompanied by very high sustained virological response rates and lower side effects like flu-like syndrome. These facts plus the fact that most HCV cases progress to chronic infection suggest the potential need for an efficient HCV vaccine. Different innovative methods, including methods based on peptide, recombinant protein, DNA, vector-based, and virus-like particles, have been introduced for the development of HCV vaccines. An extensive number of studies have been published on these vaccines, and some vaccines were even tested in clinical trials. In the current review, progress in the development of preventive and therapeutic vaccines against the HCV is reviewed in the context of peptide vaccines, recombinant protein vaccines, HCV-like particle, DNA vaccines and viral vectors expressing HCV genes.

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome(IBS).METHODS: Seventy-six patients with IBS were included in the study(62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome Ⅲ criteria for functional dyspepsia(FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom(IBS-D), 21 had a mixture of diarrhea and constipation(IBS-M), and 29 had constipation as the predominant symptom(IBS-C). Fortythree age and sex-matched healthy volunteers withoutany gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex(ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software(version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389(320, 771), 359(130, 966), 966(529, 1154), 358(120, 966) and 126(0, 262) cells/mm2, respectively. There was a significant difference between the tested groups(P < 0.0001). Dunn's multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls(P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489(130, 966), and in those with IBS only 490(130, 956). There was no statistical significant difference between these 2 groups of patients(P = 0.9). The immunoreactivity intensity did not differ between any of the groups(P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density(r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation(r = 90.69; P < 0.0001). The densities of the serotonin cells were 63(51, 82), 51(25, 115), 120(69, 128), 74(46, 123) and 40(0, 46) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups(P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls(P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls(P = 0.5 and 0.4, respectively). The serotonin cell densityin patients with both IBS and FDP was 62(25, 115)and in those with IBS only 65(25, 123). There was no statistically significant difference between these2 groups of patients(P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups(P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire(r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation(r = 0.51;P < 0.0001). The densities of the somatostatin cells were 97(72, 126), 72(0, 206), 29(0, 80), 46(0, 103)and 206(194, 314) cells/mm2 in the control, IBS-total,IBS-D, IBS-M and IBS-C groups, respectively(Figures7 and 8). There was a statistically significant difference between the controls and the IBS subgroups(P <0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls(P < 0.01, P =0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86(0-194), and in those with IBS only 110(0-206). There was no statistically significant difference between these 2 groups of patients(P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density(r =0.38; P = 0.0007) and was positively correlated with that of constipation(r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.