[Research Progress of Bispecific Antibodies in Treatment of Multiple Myeloma--Review].

Multiple myeloma (MM) is an incurable malignant plasma cell diseases, the incidence of which is increasing year by year. The application of immunomodulators drugs, proteasome inhibitors, anti-CD38 antibodies, CAR-T, and HSCT have significantly improved the prognosis of patients with MM, however new therapeutic tools need to be developed to improve the prognosis of patients with relapsed/refractory after conventional regimens treatment. Bispecific antibodies are a novel immunotherapeutic approach that generates immune synapses by binding to targets on malignant plasma cells and cytotoxic immune effector cells (T cells/natural killer cells), leading to T/NK cells activation and malignant plasma cell lysis. Several preclinical and phase I clinical studies have shown good efficacy, bringing new possibilities for patients with relapsed/refractory MM to improve their prognosis in the future in combination with the rest of the treatment options. This article summarizes the classification of bispecific antibodies developed in recent years, and the results of preclinical and clinical trials, which will provide some reference for treating MM.

[Research Progress of NK Cell Therapy in Multiple Myeloma Treatment --Review].

Multiple myeloma (MM) is a hematologic neoplasm characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. NK cells, a class of innate lymphocytes with potent natural killer activity, are capable of recognizing and destroying tumor cells and virally infected cells, and have attracted attention as a potential anticancer therapy. In patients with MM, NK cells are suppressed in number and function, resulting in reduced immune surveillance and clearance of myeloma cells. Restoring or enhancing the killing effect of NK cells on myeloma cells is an important strategy for MM immunotherapy, and some progress has been made in clinical trials targeting NK cellrelated therapies. This article reviews the research progress on the applications prospects of NK cell in MM immunotherapy.

Predictive significance of joint plasma fibrinogen and urinary alpha-1 microglobulin-creatinine ratio in patients with diabetic kidney disease.

BACKGROUND: Although many biomarkers have high diagnostic and predictive power for diabetic kidney disease (DKD), less studies were performed for the predictive assessment in DKD and its progression with combined blood and urinary biomarkers. This study aims to explore the predictive significance of joint plasma fibrinogen (FIB) concentration and urinary alpha-1 microglobulin-creatinine (α1-MG/CR) ratio in DKD. METHODS: A total of 234 patients with type 2 diabetes were enrolled, and their clinical and laboratory data were retrospectively assessed. A ROC curve analysis was performed to evaluate the power of plasma FIB and urinary α1-MG/CR ratio for identifying DKD and advanced DKD, respectively. The predictive power for DKD and advanced DKD was analyzed by regression analysis. RESULTS: Plasma FIB and urinary α1-MG/CR levels were higher in patients with DKD than with pure T2D (p<0.001). The multivariate-adjusted odds ratios (ORs) were 5.047 (95%CI: 2.276-10.720) and 2.192 (95%CI: 1.539-3.122) (p<0.001) for FIB and α1-MG/CR as continuous variables for DKD prediction, respectively. The optimal cut-off values were 3.21 g/L and 2.11mg/mmol for identifying DKD, and 5.58 g/L and 11.07 mg/mmol for advanced DKD from ROC curves. At these cut-off values, the sensitivity and specificity of joint FIB and α1-MG/CR were 0.95 and 0.92 for identifying DKD, and 0.62 and 0.67 for identifying advanced DKD, respectively. The area under curve was 0.972 (95%CI: 0.948-0.995) (p<0.001) and 0.611, 95%CI: 0.488-0.734) (p>0.05). The multivariate-adjusted ORs for joint FIB and α1-MG/CR at the cut-off values were 214.500 (95%CI: 58.054-792.536) and 3.252 (95%CI: 1.040-10.175) (p<0.05), respectively. CONCLUSION: The present study suggests that joint plasma FIB concentration and urinary α1-MG/CR ratio can be used as a powerful predictor for general DKD, but it is less predictive for advanced DKD.

Does the "obesity paradox" exist after transcatheter aortic valve implantation?

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis is considered a minimally invasive procedure. Body mass index (BMI) has been rarely evaluated for pulmonary complications after TAVI. This study aimed to assess the influence of BMI on pulmonary complications and other related outcomes after TAVI. METHODS: The clinical data of 109 patients who underwent TAVI in our hospital from May 2018 to April 2021 were retrospectively analyzed. Patients were divided into three groups according to BMI: low weight (BMI < 21.9 kg/m2, n = 27), middle weight (BMI 21.9-27.0 kg/m2, n = 55), and high weight (BMI > 27.0 kg/m2, n = 27); and two groups according to vascular access: through the femoral artery (TF-TAVI, n = 94) and through the transapical route (TA-TAVI, n = 15). Procedure endpoints, procedure success, and adverse outcomes were evaluated according to the Valve Academic Research Consortium (VARC)-2 definitions. RESULTS: High-weight patients had a higher proportion of older (p < 0.001) and previous percutaneous coronary interventions (p = 0.026), a higher percentage of diabetes mellitus (p = 0.026) and frailty (p = 0.032), and lower glomerular filtration rate (p = 0.024). Procedure success was similar among the three groups. The 30-day all-cause mortality of patients with low-, middle-, and high weights was 3.7% (1/27), 5.5% (3/55), and 3.7% (1/27), respectively. In the multivariable analysis, middle- and high-weight patients exhibited similar overall mortality (middle weight vs. low weight, p = 0.500; high weight vs. low weight, p = 0.738) and similar intubation time compared with low-weight patients (9.1 ± 7.3 h vs. 8.9 ± 6.0 h vs. 8.7 ± 4.2 h in high-, middle-, and low-weight patients, respectively, p = 0.872). Although high-weight patients had a lower PaO2/FiO2 ratio than low-weight patients at baseline, transitional extubation, and post extubation 12th hour (p = 0.038, 0.030, 0.043, respectively), there were no differences for post extubation 24th hour, post extubation 48th hour, and post extubation 72nd hour (p = 0.856, 0.896, 0.873, respectively). Chronic lung disease [odds ratio (OR) 8.038, p = 0.001] rather than high weight (OR 2.768, p = 0.235) or middle weight (OR 2.226, p = 0.157) affected postoperative PaO2/FiO2 after TAVI. CONCLUSIONS: We did not find the existence of an obesity paradox after TAVI. BMI had no effect on postoperative intubation time. Patients with a higher BMI should be treated similarly without the need to deliberately extend the intubation time for TAVI.

Effects of seasonal and climate variations on in-hospital mortality and length of stay in patients with type A aortic dissection.

OBJECTIVE: To investigate the effects of seasonal and climatic changes on postoperative in-hospital mortality and length of stay (LOS) in patients with type A acute aortic dissection (AAD). METHODS: Patients undergoing implantation of the modified triple-branched stent graft to replace the descending aorta in addition to aortic root reconstruction for type A AAD in our hospital from January 2016 to December 2019 were included. Relevant data were retrospectively collected and analyzed. RESULTS: A total of 404 patients were included in our analyses. The multivariate unconditional logistic regression analysis showed that patients admitted in autumn (OR 4.027, 95% CI 1.023-17.301, P = 0.039) or with coronary heart disease (OR 8.938, 95% CI 1.991-29.560, P = 0.049) were independently associated with an increased risk of postoperative in-hospital mortality. Furthermore, patients admitted in autumn (OR 5.956, 95% CI 2.719-7.921, P = 0.041) or with hypertension (OR 3.486, 95% CI 1.192-5.106, P = 0.035) were independently associated with an increased risk of longer LOS. CONCLUSION: Patients admitted in autumn or with coronary heart disease are at higher risk of in-hospital mortality following surgery for type A AAD. Also, patients admitted in autumn or with hypertension have a longer hospital LOS. In the autumn of the temperature transition, we may need to strengthen the management of medical quality after surgery for type A AAD.

Ecological adaptation in Atlantic herring is associated with large shifts in allele frequencies at hundreds of loci.

Atlantic herring is widespread in North Atlantic and adjacent waters and is one of the most abundant vertebrates on earth. This species is well suited to explore genetic adaptation due to minute genetic differentiation at selectively neutral loci. Here, we report hundreds of loci underlying ecological adaptation to different geographic areas and spawning conditions. Four of these represent megabase inversions confirmed by long read sequencing. The genetic architecture underlying ecological adaptation in herring deviates from expectation under a classical infinitesimal model for complex traits because of large shifts in allele frequencies at hundreds of loci under selection.

Reconstruction of the birth of a male sex chromosome present in Atlantic herring.

The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed to stabilize genetic sex determination. However, because sex chromosomes are notoriously cluttered with repetitive DNA and pseudogenes, the study of their evolution is hampered. Here we reconstruct the birth of a Y chromosome present in the Atlantic herring. The region is tiny (230 kb) and contains only three intact genes. The candidate male-determining gene BMPR1BBY encodes a truncated form of a BMP1B receptor, which originated by gene duplication and translocation and underwent rapid protein evolution. BMPR1BBY phosphorylates SMADs in the absence of ligand and thus has the potential to induce testis formation. The Y region also contains two genes encoding subunits of the sperm-specific Ca2+ channel CatSper required for male fertility. The herring Y chromosome conforms with a characteristic feature of many sex chromosomes, namely, suppressed recombination between a sex-determining factor and genes that are beneficial for the given sex. However, the herring Y differs from other sex chromosomes in that suppression of recombination is restricted to an ∼500-kb region harboring the male-specific and sex-associated regions. As a consequence, any degeneration on the herring Y chromosome is restricted to those genes located in the small region affected by suppressed recombination.

The promotion effects of silicate mineral maifanite on the growth of submerged macrophytes Hydrilla verticillata.

The effects of maifanite on the physiological and phytochemical process of submerged macrophytes Hydrilla verticillate (H.verticillata) were investigated for the first time in the study. The growth index: plant biomass, root length, plant height and leaf spacing, and physiological and phytochemical indexes: chlorophyll, soluble protein, malondialdehyde (MDA), peroxidase (POD), superoxide dismutase (SOD) content and vitality of the roots of H.verticillata were tested. The results found that maifanite can significantly promote the growth of H.verticillata. The modified maifanite were more conducive to plant growth compared with the raw maifanite, and the MM1 group had the best growth promoting effect. The physiological and phytochemical indexes showed that maifanite can delay the aging process of H.verticillata (P < 0.05). The possible reasons for promoting H.verticillata growth were that maifanite can provide excellent propagation conditions for plant rhizosphere microorganisms, contains abundant major and microelements, and improve the sediment microenvironment. This study may provide a technique for the further application of maifanite in the field of ecological restoration.

Female-biased gene flow between two species of Darwin's finches.

The mosaic nature of hybrid genomes is well recognized, but little is known of how they are shaped initially by patterns of breeding, selection, recombination and differential incompatibilities. On the small Galápagos island of Daphne Major, two species of Darwin's finches, Geospiza fortis and G. scandens, hybridize rarely and back-cross bidirectionally with little or no loss of fitness under conditions of plentiful food. We used whole-genome sequences to compare genomes from periods before and after successful interbreeding followed by back-crossing. We inferred extensive introgression from G. fortis to G. scandens on autosomes and mitochondria but not on the Z chromosome. The unique combination of long-term field observations and genomic data shows that the reduction of gene flow for Z-linked loci primarily reflects female-biased gene flow, arising from a hybrid-male disadvantage in competition for high-quality territories and mates, rather than from genetic incompatibilities at Z-linked loci.

Effects of maifanite on growth, physiological and phytochemical process of submerged macrophytes Vallisneria spiralis.

The restoration of submerged plants is critical for the reconstruction of eutrophic lake ecosystems. The growth of submerged plants is influenced by many factors. For the first time in this study, the effects of silicate-mineral maifanite supplement on the growth, physiological and phytochemical process of Vallisneria spiralis (V. spiralis) were investigated by an outdoor PVC barrel experiment, to provide a technical reference for further applications in aquatic ecological restoration. The results show that the maifanite could significantly promote the growth of V. spiralis. Specifically, the biomass, height, number of leaves, leaf width, root length, and root activity of V. spiralis in the maifanite-supplemented group were better than those of the control (P < 0.05). Moreover, the modified maifanite group performed better than the raw maifanite group (P < 0.05). The photosynthetic pigment, root activity, and the malondialdehyde and peroxidase activity of the maifanite-treated V. spiralis were better than those of the control to some extent. It was found that maifanite contained abundant major and trace elements, which are required for the growth of V. spiralis. It is concluded that maifanite is beneficial to the growth of V. spiralis and can be further applied to the ecological restoration of eutrophic lakes.

[Effects of bundled straw mulching on water consumption characteristics and grain yield of winter wheat in rain-fed semiarid region]. / ç§¸ç§†å¸¦çŠ¶è¦†ç›–å¯¹åŠå¹²æ—±é›¨å »åŒºå†¬å°éº¦è€—æ°´ç‰¹å¾å’Œäº§é‡çš„å½±å“.

To explore a new technique of planting wheat with high yield and efficiency by mulching technology in rain-fed semiarid regions in Northwest China, a two-year fixed-site trail was conducted during 2013-2015. There were five mulching modes: (1) three sowing rows by bundled straw mul-ching with alternating 30-cm-wide mulching belt and planting belt (SM1), (2) four sowing rows by bundled straw mulching with alternating 40-cm-wide mulching belt and planting belt with (SM2), (3) five sowing rows by bundled straw mulching with alternating 50-cm-wide mulching belt and planting belt (SM3), (4) whole plastic film mulching with dibbling (PMF), (5) bare field planting without any mulching (CK). We examined the effects of different mulching modes on water consumption, water use efficiency (WUE), and yield of winter wheat in rain-fed region in Northwest China. The results showed that bundled straw mulching significantly increased soil water storage. Soil water storage with bundled straw mulching was remarkably higher than that with the whole plastic mul-ching with SM1＞SM2＞SM3. Soil water storage at 0-200 cm soil layer in flowering period was increased by 15.4%-20.8%,11.2%-14.7%and 10.1%-14.5% respectively over that in the bare field. Bundled straw mulching significantly increased water consumption during the whole growing period while reduced water consumption from sowing and flowering periods. Further, it increased water consumption from flowering to maturity periods and the ratio of water consumption during this period to the total water consumption during the whole growing periods. The results showed that mulching could increase the consumption ratio of deep water storage from the soil layer below 120 cm. Compared with CK, PMF and SM significantly increased grain yield and water use efficiency by 11.9%-19.5%, 26.9%-27.1%, respectively, and increased water use efficiency by 9.8%-13.9%, 18.4%-22.0% respectively. In all, bundled straw mulching could reduce water consumption ratio in the early growing periods, improve moisture condition, increase grain yield and water use efficiency of winter wheat. Therefore, we concluded that bundled straw mulching is an environment-friendly cultivation technology suitable for the winter wheat in semi-arid region of the Loess Plateau in Northwest China.

A chromosome-level assembly of the Atlantic herring genome-detection of a supergene and other signals of selection.

The Atlantic herring is a model species for exploring the genetic basis for ecological adaptation, due to its huge population size and extremely low genetic differentiation at selectively neutral loci. However, such studies have so far been hampered because of a highly fragmented genome assembly. Here, we deliver a chromosome-level genome assembly based on a hybrid approach combining a de novo Pacific Biosciences (PacBio) assembly with Hi-C-supported scaffolding. The assembly comprises 26 autosomes with sizes ranging from 12.4 to 33.1 Mb and a total size, in chromosomes, of 726 Mb, which has been corroborated by a high-resolution linkage map. A comparison between the herring genome assembly with other high-quality assemblies from bony fishes revealed few inter-chromosomal but frequent intra-chromosomal rearrangements. The improved assembly facilitates analysis of previously intractable large-scale structural variation, allowing, for example, the detection of a 7.8-Mb inversion on Chromosome 12 underlying ecological adaptation. This supergene shows strong genetic differentiation between populations. The chromosome-based assembly also markedly improves the interpretation of previously detected signals of selection, allowing us to reveal hundreds of independent loci associated with ecological adaptation.

Transcatheter and intraoperative device closure and surgical repair for atrial septal defect.

BACKGROUND: Transcatheter and intraoperative device closure for atrial septal defect (ASD) are widely applied to reduce the incision size and the potential for injury during cardiopulmonary bypass (CPB) in conventional surgical repair. No studies had been conducted to compare the safety and efficiency of these three treatments. METHODS: From January 2018 to April 2018, 87 patients with an isolated ASD who had undergone transcatheter device closure (n = 45), intraoperative device closure (n = 22) and surgical repair (n = 20) were retrospectively reviewed and further analyzed to compare these three treatments. RESULTS: The successful closure rate was similar in the three groups. There was a significant difference in aortic cross-clamping time, CPB duration and operative time between the surgical group and the device groups. The length of intensive care unit stay, postoperative mechanical ventilation time and length of hospital stay were shorter in the two device groups than in the surgical group. The incision was the most extended in the surgical group. Regarding major adverse events, no significant differences were found among the three groups. CONCLUSIONS: Transcatheter and intraoperative device closure and surgical repair for ASD are all safe and effective. Considering their respective disadvantages and advantages, the transcatheter approach may be the first choice for an isolated secundum ASD, the intraoperative approach may be the second choice, and surgical repair may be the last resort.

Neonatal isolation modulates glucocorticoid-receptor function and synaptic plasticity of hippocampal and amygdala neurons in a rat model of single prolonged stress.

BACKGROUND: Early life and stressful experiences affect hippocampal and amygdala structure and function. They also increase the incidence of mental and nervous system disorders in adults. However, prospective studies have yet to show if early-life experiences affect the risk/severity of post-traumatic stress disorder (PTSD). METHODS: We applied neonatal isolation (NI) alone, single prolonged stress (SPS) alone and NI + SPS to rats. We evaluated anxiety-like behavior and spatial memory of behavior using open field, elevated plus maze, and Morris water maze tests. Then, we measured expression of glucocorticoid receptors (GRs) and synaptic-related proteins by immunofluorescence, immunohistochemistry and western blotting in the hippocampus and amygdala. RESULTS: NI + SPS exacerbated the increased anxiety levels and impaired spatial memory induced by NI alone or SPS alone. NI alone or SPS alone induced varying degrees of change in expression of GRs and synaptic proteins (synapsin I and postsynaptic density protein-95) in the hippocampus and amygdala. There were opposite changes in GR expression in the hippocampal dentate gyrus and basolateral amygdala. The degree of such change was exacerbated considerably by NI + SPS. In addition, neuroligin (NLG)-1 and NLG-2 were distributed in postsynaptic sites of excitatory and inhibitory synapses, respectively. NI, SPS, and NI + SPS altered the patterns of NLG-1 and NLG-2 colocalization as well as their intensity. NI + SPS strengthened the increased ratio of NLG-1/NLG-2 in the hippocampus, but decreased this ratio in the amygdala. CONCLUSIONS: NI and SPS together induced greater degrees of change in anxiety and spatial memory, as well as GR and synaptic protein levels, in the hippocampus and amygdala than the changes induced by NI alone or SPS alone.

Intraoperative Device Closure of a Perimembranous Ventricular Septal Defect Using the Right Thoracic Ventricle Approach.

BACKGROUND: This study compared the safety and effectiveness of intraoperative device closure of a perimembranous ventricular septal defect (pmVSD) using the right thoracic minimal incision to right ventricle and lower midline sternotomy to right ventricle approaches. METHODS: We retrospectively analyzed the clinical data of 46 patients who underwent intraoperative device closure of a pmVSD through the right thoracic minimal incision to right ventricle route (group 1) and 52 patients who underwent intraoperative device closure of a pmVSD through a minimal incision in the lower sternum (group 2) at our hospital from March 2016 to March 2017. In group 1, a right thoracic minimal incision to the fourth intercostal space was used to establish a delivery system through the right ventricle to complete pmVSD closure. RESULTS: In group 1, intraoperative device closure of the pmVSD was successful in 44 patients and was converted to open surgery in 2 patients (a delivery system could not be established in the one, and a significant residual shunt was present in the other). In group 2, the corresponding numbers of patients were 50 and 2, respectively. Neither group exhibited serious adverse effects, including dislocation of the occluder, third-degree atrioventricular block, or new onset of aortic valve regurgitation during the perioperative period or during a median follow-up period of 1 to 2 years. CONCLUSIONS: Intraoperative device closure of a pmVSD through the right thoracic minimal incision to right ventricle approach is safe and effective. This procedure can avoid some of the shortcomings caused by sternotomy, uses an incision with an improved cosmetic appearance, and is worth recommendation.

[Effect of straw belt-mulching on soil temperature and yield of winter wheat in rain-fed semiarid region.] / ç§¸ç§†å¸¦çŠ¶è¦†ç›–å¯¹åŠå¹²æ—±é›¨å »åŒºå†¬å°éº¦ç”°åœ°æ¸©å’Œäº§é‡çš„å½±å“.

To evaluate the effects of straw belt-covering on soil temperature and yield of winter wheat in rain-fed semiarid region in Northwest China, five mulching modes, including flat field planting without any mulching (CK), whole plastic film mulching (PM), straw mulching by 30 cm covering belt with an interval of 30 cm planting belt with three-row sowing (SM1), straw mulching by 40 cm covering belt with an interval of 40 cm planting belt with four-row sowing (SM2), and straw mulching by 50 cm covering belt with an interval of 50 cm planting belt with five-row sowing (SM3), were set by two-year fixed-site trails in 2013-2015. The results showed that soil temperature significantly varied among different growth stages and soil layers in all treatments. SM1, SM2 and SM3 significantly decreased soil temperature by 1.0-1.3 ℃, 0.7-0.9 ℃ and 0.7-1.1 ℃ in the 0-25 cm soil layer, respectively. The mulching had double effects with increasing and decreasing soil temperatures. The straw mulching significantly increased soil temperature in the duration of seedling to overwintering stage, but greatly decreased soil temperature in the duration of reviving to mature stage. The temperature-increasing effect of film mulching was stronger than that of straw mulching, which was opposite to the temperature-decreasing effect. Straw mulching significantly reduced in the effective accumulated temperature and the daily temperature variations during the whole growth stages. The effective accumulated temperature under straw mulching decreased by 3.4-33.5 ℃·d, and the soil temperature difference decreased by 0.6-2.0 ℃. During over-wintering stage, the straw mulching showed a higher average soil temperature (0.2-0.3 ℃) and negative accumulated temperature (0.4-17.0 ℃·d) than those under the CK. The straw mulching significantly increased grain yield by 11.9%-19.5%. The variations of spikes per unit area were the main factor responsible for yield difference. The findings indicated that that straw mulching method is suitable for winter wheat production in rain-fed region of Northwest China.

Investigation on the adsorption of phosphorus in all fractions from sediment by modified maifanite.

Sediment phosphorus (P) removal is crucial for the control of eutrophication, and the in-situ adsorption is an essential technique. In this study, modified maifanite (MMF) prepared by acidification, alkalization, salinization, calcination and combined modifications, respectively, were first applied to treat sediment P. The morphology and microstructure of MMF samples were characterized by X-ray fluorescence (XRF), Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and Brunauer-Emmett-Teller (BET). Various adsorption parameters were tested, such as dosage of maifanite, time, operation pH and temperature. The adsorption mechanisms were also investigated and discussed. Results showed that CMMF-H2.5-400 (2.5 mol/L H2SO4 and calcined at 400 °C) exhibited the highest P adsorption capacity. Thus, it was selected as the in-situ adsorbent material to control the internal P loading. Under the optimal conditions of dynamic experiments, the adsorption rates of TP, IP, OP, Fe/Al-P and Ca-P by CMMF-H2.5-400 were 37.22%, 44.41%, 25.54%, 26.09% and 60.34%, respectively. The adsorption mechanisms analysis revealed that the adsorption of P onto CMMF-H2.5-400 mainly by ligand exchange. Results of this work indicated that the modification treatment could improve the adsorption capacity of maifanite, and CMMF-H2.5-400 could be further applied to eutrophication treatment.

Electroacupuncture for patients with irritable bowel syndrome: A systematic review and meta-analysis protocol.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional intestinal disease characterized by chronic or recurrent abdominal pain, abdominal distension, constipation and diarrhea. Many IBS sufferers are usually present with poor quality of life for the abdominal discomfort, diarrhea, constipation, and other complaints. At present, the commonly used drug therapy for IBS in the Western clinic, such as antidiarrheal, laxative, gastrointestinal antispasmodic, often cannot get satisfying curative effect. Thus complementary therapies like electroacupuncture (EA) which may be effective to decrease patients' pain and fewer side-effects will be sought. EA, an innovative form of traditional acupuncture, is drawing more attention to the treatment of IBS due to its roles in symptom improvement. This systematic review protocol aims at describing a meta-analysis to critically evaluate the effectiveness and safety on EA for patients with IBS. METHODS: We search Ovid MEDLINE, Ovid Embase, PubMed, the Cochrane Central Register of Controlled Trials (Cochrane Library), the Allied and Complementary Medicine Databases (AMED), China National Knowledge Infrastructure (CNKI) for random controlled trials EA for IBS from their inception to April 1, 2018. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. RevManV5. 3 will be applied to data extraction. Risk of bias for each RCT will be assessed according to criteria by the Cochrane Handbook to evaluate the methodological quality. RESULTS: This study will provide a high-quality synthesis of current evidence of effectiveness and safety on EA for patients with IBS. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether EA is an effective intervention for patient with IBS. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018081610.

Rapid hybrid speciation in Darwin's finches.

Homoploid hybrid speciation in animals has been inferred frequently from patterns of variation, but few examples have withstood critical scrutiny. Here we report a directly documented example, from its origin to reproductive isolation. An immigrant Darwin's finch to Daphne Major in the Galápagos archipelago initiated a new genetic lineage by breeding with a resident finch (Geospiza fortis). Genome sequencing of the immigrant identified it as a G. conirostris male that originated on Española >100 kilometers from Daphne Major. From the second generation onward, the lineage bred endogamously and, despite intense inbreeding, was ecologically successful and showed transgressive segregation of bill morphology. This example shows that reproductive isolation, which typically develops over hundreds of generations, can be established in only three.