Advances in the application of three-dimensional visualization technique in hepatic alveolar echinococcosis / 临床肝胆病杂志

Hepatic alveolar echinococcosis (HAE) is a parasitic disease caused by Echinococcus multilocularis infection and has wide distribution and great harm in China. At present, ultrasound, CT, and MRI are the main radiological examination methods for HAE, with certain limitations in preoperative diagnosis and evaluation. This article introduces the guiding effect of three-dimensional visualization technique and its derivative technologies in the accurate diagnosis and preoperative evaluation of HAE, so as to provide help for the clinical diagnosis and treatment of HAE in the future.

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants, including BQ.1, BQ. 1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants, as well as their ancestral BA.4/5, BA.2.75 and D614G variants, against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation, and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing, resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.

Determinants and Mechanisms of the Low Fusogenicity and Endosomal Entry of Omicron Subvariants

The rapid spread and strong immune evasion of the SARS-CoV-2 Omicron subvariants has raised serious concerns for the global COVID-19 pandemic. These new variants exhibit reduced fusogenicity and increased endosomal entry pathway utilization compared to the ancestral D614G variant, the underlying mechanisms of which remain elusive. Here we show that the C-terminal S1 mutations of the BA.1.1 subvariant, H655Y and T547K, critically govern the low fusogenicity of Omicron. Notably, H655Y also dictates the enhanced endosome entry pathway utilization. Mechanistically, T547K and H655Y likely stabilize the spike trimer conformation, as shown by increased molecular interactions in structural modeling as well as reduced S1 shedding. Importantly, the H655Y mutation also determines the low fusogenicity and high dependence on the endosomal entry pathway of other Omicron subvariants, including BA.2, BA.2.12.1, BA.4/5 and BA.2.75. These results uncover mechanisms governing Omicron subvariant entry and provide insights into altered Omicron tissue tropism and pathogenesis.

Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant

The newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.

The Correlation Between Brain Performance Capacity and COVID-19: A Cross-sectional Survey and Canonical Correlation Analysis

ObjectiveTo generate a concept of brain performance capacity (BPC) with sleep, fatigue and mental workload as evaluation indicators and to analyze the correlation between BPC and the impact of COVID-19. MethodsA cluster sampling method was adopted to randomly select 259 civil air crew members. The measurements of sleep quality, fatigue and mental workload (MWL) were assessed using the Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI-20) and NASA Task Load Index. The impact of COVID-19 included 7 dimensions scored on a Likert scale. Canonical correlation analysis (CCA) was conducted to examine the relationship between BPC and COVID-19. ResultsA total of 259 air crew members participated in the survey. Participants average PSQI score was 7.826 (SD = 3.796), with 49.8% reporting incidents of insomnia, mostly of a minor degree. Participants MFI was an average 56.112 (SD = 10.040), with 100% reporting some incidence of fatigue, mainly severe. The weighted mental workload (MWL) score was an average of 43.084 (SD = 17.543), with reports of mostly a mid-level degree. There was a significant relationship between BPC and COVID-19, with a canonical correlation coefficient of 0.507 (P=0.000), an eigenvalue of 0.364 and a contribution rate of 69.1%. All components of the BPC variable set: PSQI, MFI and MWL contributed greatly to BPC, with absolute canonical loadings of 0.790, 0.606 and 0.667, respectively; the same was true for the COVID-19 variable set, with absolute canonical loadings ranging from 0.608 to 0.951. ConclusionMultiple indicators to measure BPC and the interrelationship of BPC and COVID-19 should be used in future research to gain a comprehensive understanding of anti-epidemic measures to ensure victory in the battle against the spread of the disease.

Identification of a thermostable cellobiose 2-epimerase from Caldicellulosiruptor sp. Rt8.B8 and production of epilactose using Bacillus subtilis.

BACKGROUND: Epilactose, a potential prebiotics, was derived from lactose through enzymatic catalysis. However, production and purification of epilactose are currently difficult due to powerless enzymes and inefficient downstream processing steps. RESULTS: The encoding gene of cellobiose 2-epimerase (CE) from Caldicellulosiruptor sp. Rt8.B8 was cloned and expressed in Escherichia coli BL21(DE3). The enzyme was purified and it was suitable for industrial production of epilactose from lactose without by-products, because of high kcat (197.6 s-1 ) and preferable thermostability. The Rt8-CE gene was further expressed in the Bacillus subtilis strain. We successfully produced epilactose from 700 g L-1 lactose in 30.4% yield by using the recombinant Bacillus subtilis whole cells. By screening of a ß-galactosidase from Bacillus stearothermophilus (BsGal), a process for separating epilactose and lactose was established, which showed a purity of over 95% in a total yield of 69.2%. In addition, a mixed rare sugar syrup composed of epilactose and d-tagatose was successfully produced from lactose through the co-expression of l-arabinose isomerase and ß-galactosidase. CONCLUSION: Our study shed light on the efficient production of epilactose using a food-grade host expressing a novel CE enzyme. Moreover, an efficient and low-cost process was attempted to obtain high purity epilactose. In order to improve the utilization of raw materials, the production process of mixed syrup containing epilactose and d-tagatose with prebiotic properties produced from lactose was also established for the first time. © 2021 Society of Chemical Industry.

Atypical magnetic resonance imaging findings, misdiagnosis analysis and functional imaging value of primary central nervous system lymphoma / 中国医师杂志

Objective:To observe and analyze the atypical magnetic resonance imaging (MRI) findings and misdiagnosis reasons of primary central nervous system lymphoma (PCNSL), and to explore the value of conventional MRI signs combined with minimum apparent diffusion coefficient value (ADCmin) and imaging features of magnetic resonance spectroscopy (MRS) in the diagnosis and differentiation of atypical PCNSL.Methods:The clinical and imaging data of 15 patients with atypical PCNSL confirmed by clinical and pathological findings from Lianyungang Second People′s Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2020 was collected. All cases were examined by plain MRI, enhanced and diffusion weighted imaging (DWI), and 3 cases were examined by MRS. The conventional MRI features, DWI signal features and MRS imaging features of 15 cases of atypical PCNSL were observed and analyzed, and the MRI findings of atypical PCNSL and the causes of misdiagnosis were summarized and analyzed. The ADCmin of tumor parenchyma, the mean ADC values of proximal peritumor, distal peritumor and contralateral white matter were detected and compared to explore the variation rules of ADC values in different regions.Results:Of the 15 cases of PCNSL, 14 cases were single and 1 case was multiple, with a total of 21 lesions. (1) Single lesions in rare sites: 4 cases in the superficial part of the brain, 1 case in the bridge arm, 1 case in the cerebellar hemisphere, 1 case in the suprasellar saddle, and 1 case in the third ventricle. (2) Atypical MRI findings: cystic degeneration or necrosis in 5 lesions (5/21), accompanied by hemorrhage in 1 lesion (1/21); There were 3 isosensitive lesions on DWI, and isosensitive lesions on ADC false color images. There were 5 ring enhancement lesions and 3 sheet enhancement lesions. (3) Multi-center growth pattern: 1 case with a total of 7 lesions, located in the right thalamus, basal ganglia and corona radiata, showing multiple nodules and ring enhancement. 1H-MRS examination showed that choline (Cho) peak increased, creatine (Cr) peak decreased, N-acetyl aspartate (NAA) peak decreased, and obvious Lip peak appeared in all the 3 cases with single lesions. 2 cases showed high Lip peak as the first peak. The ADCmin values of tumor parenchyma, proximal peritumor, distal peritumor and contralateral white matter showed a parabola pattern of first rise and then decline, as follows: (0.54±0.06)×10 -3 mm 2/s, (1.55±0.10)×10 -3 mm 2/s, (1.45±0.09)×10 -3 mm 2/s, (0.85±0.03)×10 -3 mm 2/s, overall difference was statistically significant ( F=630.570, P<0.001). The pairwise comparison was statistically significant (all P<0.05). Conclusions:Atypical PCNSL is easy to be misdiagnosed. Conventional MRI feature analysis combined with DWI and MRS imaging features and comparison of ADC values in different tumor areas are helpful for the diagnosis and differentiation of PCNSL and are expected to improve diagnostic accuracy.

Research progress on the prognostic value of the ratio of lymphocytes to C-reactive protein in digestive system neoplasms / 国际肿瘤学杂志

Tumor-associated inflammation is closely related to the development of tumors. The ratio of lymphocytes to C-reactive protein (LCR) is a new marker reflecting the inflammatory state of the body, which plays an important role in predicting the prognosis of digestive system neoplasms. Compared with the detection of lymphocytes or C-reactive protein alone, this marker has higher sensitivity and accuracy, and can provide a new direction for clinical diagnosis and treatment of digestive system neoplasms.

Hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis: one case report / 中国血吸虫病防治杂志

Hepatic cystic echinococcosis is a chronic parasitic disease caused by the infection with the larvae of Echinococcus granulosus in human or animal liver tissues. As a chronic active infectious disease, tuberculous empyema mainly invades the pleural space and then causes visceral and parietal pleura thickening. It is rare to present comorbidity for hepatic cystic echinococcosis and tuberculous empyema. This case report presents a case of hepatic cystic echinococcosis complicated with tuberculous empyema misdiagnosed as hepatic and pulmonary cystic echinococcosis, aiming to improve clinicians’ ability to distinguish this disorder.

One-year follow-up results of atrial fibrillation patients who undergoing transcatheter aortic valve implantation / 中华心血管病杂志

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.

Effect of Echinococcus multilocularis secreted antigen on the phenotype and function of mouse bone marrow - derived dendritic cells induced by lipopolysaccharide / 临床肝胆病杂志

Objective To investigate the effect of different concentrations of Echinococcus multilocularis secretion antigen (Em-sAg) on the phenotype and function of mouse bone marrow-derived dendritic cells (BMDCs) induced by lipopolysaccharide (LPS). Methods The bone marrow precursor cells isolated from the mouse bone marrow cavity were stimulated by mouse recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to form BMDCs, and then cell morphology was observed under an inverted microscope. After the purity of BMDCs was identified by flow cytometry, BMDCs were divided into control group, positive control group (LPS 1 μg/ml), LPS+3 mg/ml Em-sAg group, LPS+1.5 mg/ml Em-sAg group, LPS+0.75 mg/ml Em-sAg group, and LPS+0.375 mg/ml Em-sAg group. Flow cytometry was used to measure the expression of BMDC surface molecules (CD80, CD86, and MHC-Ⅱ molecules) in each group, and ELISA was used to measure the expression level of the cytokine IL-12p70. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Observation under an inverted microscope showed that after 8-10 days of culture, the cells had burr-like protrusions and were in a state of complete suspension. Flow cytometry showed that the positive rate of CD11c was above 70% and most of the cultured cells were identified as BMDCs based on this. Flow cytometry further showed that compared with the control group, the LPS group had significant increases in the cell molecules CD80, CD86, and MHC-Ⅱ on surface (all P 0.05). ELISA showed that there was a significant difference in the level of IL-12 p70 between groups ( F =73.140, P < 0.05); compared with the control group, the LPS group had a significant increase in the expression level of IL-12p70 after stimulation ( P < 0.05); compared with the positive control group, the LPS+3 mg/ml Em-sAg group, the LPS+1.5 mg/ml Em-sAg group, the LPS+0.75 mg/ml Em-sAg group, and the LPS+0.375 mg/ml Em-sAg group had a significant reduction in the expression level of IL-12p70 ( P < 0.05), and the degree of reduction in the pro-inflammatory factor IL-12p70 increased with the increase in the concentration of Em-sAg. Conclusion Different concentrations of Em-sAg can inhibit LPS-induced maturity of BMDCs and the expression of the pro-inflammatory cytokine IL-12p70.

Transoral robotic surgery for treatment of lingual thyroglossal duct cyst / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility, safety and efficacy of transoral robotic surgery (TORS) in the treatment of lingual thyroglossal duct cyst (LTGDC). Methods: The clinical data of 10 patients with LTGDC treated with TORS in Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from May 2017 to November 2020 were analyzed retrospectively,including 6 males and 4 females, aged 5-44 years. The cysts were fully exposed, and resection usually started from the cephalic side of lesions. The range of resection was 3 to 5 mm away from the lesions, and partial hyoid bone was removed if necessary. Intra-operative robotic set-up time,operation time and estimated blood loss,and post-operative local bleeding, dyspnea and recovery time for oral intake were analyzed. SPSS 12.0 software was used for statistical analysis. Results: The cysts in all 10 patients were successfully resected by TORS with da Vinci Si surgical system. The mean robotic set-up and exposure time, operation time, estimated intraoperative blood loss and recovery time for oral intake were (15.5±7.1) min, (17.6±7.4) min, (8.9±6.4)ml and (2.3±2.2)days, respectively. No patient required tracheostomy intra-or post-operatively, and no symptoms of airway obstruction, postoperative bleeding, pharyngeal fistula, hoarseness and neurological impairment occurred after operation. The patients were followed up for 5 to 47 months, with median follow-up time of 17 months, and no recurrence was observed. Conclusion: TORS is safe and feasible for resection of LTGDC, with rapid recovery and low recurrence rate.

Consensus of experts on the medical risk prevention for the patients with cardiovascular diseases during dental treatment (2022 edition) / 中华口腔医学杂志

With the aging process of population in the society, the prevalence of cardiovascular diseases (CVD) in China is increasing continuously and the number of dental patients with CVD is increasing gradually too. Due to the lack of guidelines for dental patients with CVD in our country, how to implement standardized preoperative evaluation and perioperative risk prevention remains a problem to be solved for dentists at present. The present expert consensus was reached by combining the clinical experiences of the expert group of the Fifth General Dentistry Special Committee, Chinese Stomatological Association and respiratory and cardiology experts in diagnosis and treatment for CVD patients, and by systematically summarizing the relevant international guidelines and literature regarding the relationship between CVD and oral diseases and the diagnosis and treatment of dental patients with heart failure, hypertension and antithrombotic therapy. The consensus aims to provide, for the dental clinicians, the criteria on diagnosis and treatment of CVD in dental patients in China so as to reduce the risk and complications, and finally to improve the treatment levels of dental patients with CVD in China.

Research on the doctors′ willingness of working at primary institutions and the economic incentive effect from the perspective of mental account / 中华医院管理杂志

Objective:To understand the incentive effect and influencing factors of the current economic incentive policy for medical alliances in Longhua District of Shenzhen(the alliance for short) on doctors′ willingness to work at primary medical institutions(the primary for short) from the perspective of mental account, and to explore the economic incentive effect of different economic incentive distribution methods on doctors′ willingness to work at the primary.Methods:The questionnaire was designed based on mental account theory. Random sampling was made in November 2019 for a questionnaire survey among doctors in two district-level medical institutions of the alliance in Longhua District of Shenzhen. The purpose was to analyze their inclination to work at the primary and their selection preferences for economic incentive distribution methods under the current economic incentive policy. The data were analyzed by descriptive analysis, and the influencing factors of doctors′ willingness to work at the primary were analyzed by χ2 test and binary logistic regression. Results:A total of 254 valid questionnaires were collected with an effective recovery rate of 90.7%. Among the respondents, 189(74.4%) were willing to work at the primary, 168(66.1%) chose to receive the economic incentives specifically for working at the primary, and 148 people(58.3%) hoped to receive such economic incentives immediately. Education background, self-rated economic income level of doctors and different payment methods of economic incentive for working at the primary had significant effects on their willingness to work at the primary( P<0.05). Conclusions:The current economic incentive policy of the alliance can meet the demands for economic incentives in terms of doctors′ material accounts, and doctors′ overall inclination to work at the primary was strong. If the amount of economic incentives is constant, doctors preferred to receive the economic incentives specifically, mainly affected by income accounts and additional income accounts. In addition, education and self-assessment of economic income level were important factors affecting the willingness of doctors to work at the primary, which may be affected by mental accounts other than material accounts.

Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Geranyl phenyl ethers from Illicium micranthum and their anti-HBV activity / 中国天然药物

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.

Neutralization and Stability of SARS-CoV-2 Omicron Variant

The SARS-CoV-2 B.1.1.529/Omicron variant was first characterized in South Africa and was swiftly designated a variant of concern1. Of great concern is its high number of mutations, including 30-40 mutations in the virus spike (S) protein compared to 7-10 for other variants. Some of these mutations have been shown to enhance escape from vaccine-induced immunity, while others remain uncharacterized. Additionally, reports of increasing frequencies of the Omicron variant may indicate a higher rate of transmission compared to other variants. However, the transmissibility of Omicron and its degree of resistance to vaccine-induced immunity remain unclear. Here we show that Omicron exhibits significant immune evasion compared to other variants, but antibody neutralization is largely restored by mRNA vaccine booster doses. Additionally, the Omicron spike exhibits reduced receptor binding, cell-cell fusion, S1 subunit shedding, but increased cell-to-cell transmission, and homology modeling indicates a more stable closed S structure. These findings suggest dual immune evasion strategies for Omicron, due to altered epitopes and reduced exposure of the S receptor binding domain, coupled with enhanced transmissibility due to enhanced S protein stability. These results highlight the importance of booster vaccine doses for maintaining protection against the Omicron variant, and provide mechanistic insight into the altered functionality of the Omicron spike protein.

Effects of steam-flaked grains on foals' growth and faecal microbiota.

BACKGROUND: There is little objective information concerning the effect of steam-flaked grains on foal's growth performance and faecal microbiota. To determine the effects of steam-flaked grains on foal's growth performance and faecal microbiota, faecal samples were collection from 18 foals which had been fed either corn, oat or barley diets over the 60 days of the experiment. Body weight and conformation measurements were collected. Next-generation sequencing of the V3 + V4 region of the 16 S rRNA gene was used to assess the microbial composition of faeces. Alpha diversity, Venn graph, Relative abundance and beta diversity are presented. RESULTS: There was a significantly higher larger increase in the body weight of those foals fed barley compared to either corn or oats. There were also significant changes in the Alpha diversity of the gut microbiota. The Shannon and Simpson indices were significantly higher in the barley fed group than those fed corn or oats. The Chao1 index was significantly higher in the oat fed group than the corn or barley fed groups. There were significant changes in the relative abundance of bacteria in the microbiota in terms of phylum, family and genus. The histogram of LDA value distribution showed that the 12 statistically different biomarkers of the bacteria were present. Tax4Fun function annotation clustering heat map showed that functional information was detected from 26 species of bacteria in faecal samples from the foals. CONCLUSIONS: Differences by starch sources were found in overall growth of the foals and in the faecal microbiota if either supplementary corn, oat or barley was fed. Further studies are required to determine the potential impact of the changes in the microbiota on the health and development of foals fed cereal starch of different sources.

Multimeric nanobodies from camelid engineered mice and llamas potently neutralize SARS-CoV-2 variants

Since the start of the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 2 million deaths worldwide. Multiple vaccines have been deployed to date, but the continual evolution of the viral receptor-binding domain (RBD) has recently challenged their efficacy. In particular, SARS-CoV-2 variants originating in the U.K. (B.1.1.7), South Africa (B.1.351) and New York (B.1.526) have reduced neutralization activity from convalescent sera and compromised the efficacy of antibody cocktails that received emergency use authorization. Whereas vaccines can be updated periodically to account for emerging variants, complementary strategies are urgently needed to avert viral escape. One potential alternative is the use of camelid VHHs (also known as nanobodies), which due to their small size can recognize protein crevices that are inaccessible to conventional antibodies. Here, we isolate anti-RBD nanobodies from llamas and "nanomice" we engineered to produce VHHs cloned from alpacas, dromedaries and camels. Through binding assays and cryo-electron microscopy, we identified two sets of highly neutralizing nanobodies. The first group expresses VHHs that circumvent RBD antigenic drift by recognizing a region outside the ACE2-binding site that is conserved in coronaviruses but is not typically targeted by monoclonal antibodies. The second group is almost exclusively focused to the RBD-ACE2 interface and fails to neutralize pseudoviruses carrying the E484K or N501Y substitutions. Notably however, they do neutralize the RBD variants when expressed as homotrimers, rivaling the most potent antibodies produced to date against SARS-CoV-2. These findings demonstrate that multivalent nanobodies overcome SARS-CoV-2 variant mutations through two separate mechanisms: enhanced avidity for the ACE2 binding domain, and recognition of conserved epitopes largely inaccessible to human antibodies. Therefore, while new SARS-CoV-2 mutants will continue to emerge, nanobodies represent promising tools to prevent COVID-19 mortality when vaccines are compromised.

Effect of hepatic volume change on clinical practice in patients with extensive hepatic vein occluded Budd-Chiari Syndrome treated with TIPS / 中华肝胆外科杂志

Objective:To investigate the changes of liver volume and liver function in patients with extensive hepatic vein occluded Budd-Chiari syndrome (BCS) treated with transjugular intrahepatic portosystem shunt (TIPS).Methods:The clinical data of 29 BCS patients from Affiliated Hospital of Xuzhou Medical University during March 2016 to June 2019 were retrospectively collected and analyzed. The BCS was caused by extensive hepatic vein occlusion and patients were treated with TIPS. Pre- and postoperative abdominal CT/MRI images were collected and analyzed, and hepatic volume was measured with 3D-reconstruction. The liver volume and liver function during before and post the surgery were also collected and analyzed with preoperative value.Results:Patients including 8 males and 21 females, aged (33.3±6.3) years, were enrolled in this study. TIPS was successfully performed in all patients, with a technical success rate 100%. No serious complications related to TIPS occurred. Patients were followed up for 12-33 months (median, 16 months). Compared with preoperative [(2 124.6±420.9) cm 3] , the hepatic volume of time points after operation [1 week: (1 926.3±372.3) cm 3; 3 months: (1 480.6±183.1) cm 3; 6 months: (1 461.9±153.0) cm 3; 12 months: (1 469.3±148.5) cm 3] were all significantly reduced, and the differences were statistically significant ( P<0.05). Compared with preoperative values, the hepatic function indexes at each time point after operation were significantly improved ( P<0.05). The complete remission rate of ascites was 96.4% (27/28), 100.0% (28/28) and 100.0% (28/28) at 3, 6 and 12 months, respectively. Conclusion:The extensive hepatic vein occlusive BCS patients were benefit from TIPS therapy. Six months after operation, the hepatic volume and the hepatic function returned to normal level.