[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[Progress in omics research and preclinical models of gallbladder cancer].

Gallbladder cancer(GBC)is one common type of bile tract cancers with poor prognosis. This review summarizes the recent development of studies about somatic mutation, molecular subtype, microenvironment heterogeneity, organoid, orthotopic model, patient-derived xenograft and clinical translation on GBC in aspects of genomic,transcriptome,single cell omics and clinical translation. We expect this review will provide new ideas on dissecting molecular mechanisms underlying the development and emerging chemoresistance of GBC following therapy and promote GBC precision medicine.

Sleep disturbances among medical workers during the outbreak of COVID-2019.

BACKGROUND: The outbreak of Corona Virus Disease-2019 (COVID-19) has posed unprecedented pressure and threats to healthcare workers in Wuhan and the entire country. AIMS: To assess the effect of the COVID-19 outbreak on the sleep quality of healthcare workers in a children's healthcare centre in Wuhan. METHODS: A cross-sectional, anonymized, self-reported questionnaire survey was conducted at the Children's Healthcare Centre of Renmin Hospital, Wuhan University, Wuhan, China. The questionnaire consisted of three parts, including socio-demographic characteristics and COVID-19 epidemic-related factors, the Pittsburgh sleep quality index (PSQI), and Zung's self-rating anxiety scale (SAS) and self-rating depression scale (SDS). RESULTS: In total, 47 out of 123 (38%) participants with PSQI scores > 7 were identified as having sleep disturbance. A logistic regression analysis showed that sleep disturbance was independently associated with being an only child (adjusted odds ratio (OR) and 95% confidence interval (CI) 3.40 (1.21-9.57), P < 0.05), exposure to COVID-19 patients (adjusted OR and 95% CI 2.97 (1.08-8.18), P < 0.05) and depression (adjusted OR and 95% CI 2.83 (1.10-7.27), P < 0.05). CONCLUSIONS: We observed that, during the outbreak of COVID-19, sleep disturbance was highly prevalent among paediatric healthcare workers, and sleep disturbance was independently associated with being an only child, exposure to COVID-19 patients and depression. Therefore, more mental health services are required for front-line paediatric healthcare workers in Wuhan.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

A novel double-variant RHAG allele leads to Rhmod phenotype.

AIMS/OBJECTIVES: We aimed to analyse the molecular backgrounds and red blood cell (RBC) antigen expression of a male blood donor with Rhmod phenotype and his family members. BACKGROUND: Rh deficiency phenotypes are rarely found worldwide and are characterised by the lack of Rh antigen expression on RBCs. During routine screening, we found a blood donor who seemingly lacked Rh antigens. Therefore, we recruited the donor and his family for further investigation. METHODS: RBC serotyping and antibody screening/identification were performed for each sample. A routine blood examination was also conducted. RHD, RHCE and RHAG were sequenced at the genomic DNA or RNA level. Eleven antigens or proteins associated with Rh complex were tested using flow cytometry analysis. RESULTS: The proband and one of his brothers showed extremely weak D antigen and Rh expression levels but did not manifest anaemia. Most of the expressed RBC antigens of the two Rh-deficient individuals were similar to the previously reported cases but with some exceptions. Molecular analyses demonstrated homozygous expression of a novel RHAG allele, namely, c.[572G>A;707A>C], both in the proband and one of his brothers. CONCLUSIONS: To our knowledge, we identified the second double-variant RHAG allele and the first one related to Rhmod phenotype. The novel allele was also confirmed to be heritable by family analyses.

p.R180C mutation of glycosyltransferase B leads to B subgroup, an in vitro and in silico study.

BACKGROUND AND OBJECTIVES: Dysfunctional glycosyltransferase A or B may lead to incomplete glycosylation of H antigen and atypical ABO blood group with weak A or B phenotypes, posing challenges for blood typing for transfusion. MATERIALS AND METHODS: Serological studies and ABO gene analysis were performed. Flow cytometry was performed on HeLa cells transfected glycosyltransferase B expressing plasmids. Agglutination of transfected cells and total glycosyltransferase B transfer capacity were examined. Molecular dynamics simulations were used to explore possible dynamic conformational changes around the binding pocket. RESULTS: We identified a mutation c.538C>T (p. R180C) of B allele in a Chinese donor and his father with ABw phenotype. In vitro expression study showed that mutation p.R180C, although not affecting expression of glycosyltransferase B, impaired H to B antigen conversion. The in silico analyses found that the residue Arg180 on the internal loop next to the entry of the binding pocket may have its long side chain salt-bridged with the highly flexible C-terminal carboxyl and contribute to the catalysis of H to B antigen conversion. CONCLUSION: The p.R180C mutation impairs the conversion from H to B antigen and leads to weak B phenotype. Dynamic interaction between Arg180 and C-terminal of glycosyltransferase B may stabilize its binding with UDP-galactose and facilitate H/B antigen conversion.

Expression of APOB, ADFP and FATP1 and their correlation with fat deposition in Yunnan's top six famous chicken breeds.

1. Adipose differentiation related protein (ADFP), fatty acid transport protein 1 (FATP1) and apolipoprotein B (APOB) are suspected to play an important role in determining intramuscular fat and in overall meat quality. 2. Yunnan's top six famous chicken breeds (the Daweishan Mini, Yanjin Black-bone, Chahua, Wuding, Wuliangshan Black-bone and Piao chicken) are known for the high quality of their meat, but little is known about their expression of these three genes. 3. The present study aimed to examine the ADFP, FATP1 and APOB genes in different tissues of these six breeds at different development stages. The subcutaneous fat from the back midline and front, abdominal fat, liver and muscle tissue was sampled at 28, 49, 70, 91 and 112 days. The expression of ADFP, FATP1 and APOB was measured by real-time PCR. 4. The results showed that the expression of the three genes differed depending on age, tissue types and breeds. However, the expression of the three genes correlated with fat traits. In conclusion, the expression of the ADFP, FATP1 and APOB genes is associated with the fat traits of Yunnan's top six chicken breeds. These results could help with molecular marker screening and marker-assisted breeding to improve the quality of poultry for meat production.

The parthenogenetic development of porcine in vitro matured oocytes vitrified before or after electric activation.

　　BACKGROUND: The highly efficient production of parthenogenetic embryos from vitrified porcine in vitro matured oocytes has become essential for biotechnology and biomedicine research. OBJECTIVE: To investigate the survival and parthenogenetic development of oocytes vitrified before or after electric activation. MATERIALS AND METHODS: The vitrified oocytes were parthenogenetically activated at 0, 0.5, 1, 2 and 4 h post warming (h.p.w.), and fresh oocytes were vitrified at 0, 0.5, 1, 2 and 4 h post electric activation (h.p.a.). RESULTS: In comparison with non-vitrified oocytes, the rates of survival and activation of oocytes vitrified at 0.5, 1, 2 and 4 h.p.a. were similar, but the parameters in other vitrified groups significantly decreased. Parthenogenetic development in vitrified 0.5, 1, 2 and 4 h.p.a. groups was also significantly higher than that in other vitrified groups. Moreover, the total cell numbers of blastocysts were similar among all groups. CONCLUSION: Porcine oocytes vitrified at 0.5-4 h h.p.a. showed acceptable survival and pronuclear formation, and a higher blastocyst yield could be obtained from these oocytes.

[The observation of tacrolimus eye drops preventing the early immunological rejection after penetrating keratoplasty for fungal keratitis].

Objective: To observe the early immunological rejection prevention effect of tacrolimus eye drops combined with glucocorticoids on fungal keratitis patients who received penetrating keratoplasty (PKP). Methods: In a retrospective case series study, medical records of fungal keratitis patients who received PKP in Shandong Eye Institute from March 2013 to December 2015 were reviewed. Twenty-six patients (26 eyes) were given tacrolimus eye drops, and 24 patients (24 eyes) were given 1% cyclosporine A eye drops immediately after PKP. Two weeks after PKP, these patients were given low concentration of glucocorticoids if no fungal recurrence was found. Immune rejection, fungal recurrence, intraocular pressure, and drug irritation symptoms were monitored. Data were analyzed by chi-square test and independent t-test. Results: The average follow-up was 7 months (range, 3 to 12 months) postoperatively. The rejection rate was 15.3% in the tacrolimus group and 47.8% in the cyclosporine A group (χ(2)=5.510, P<0.05). One patient in the tacrolimus group and two patients in the cyclosporine A group suffered fungal recurrence. Two patients in the tacrolimus group and four patients in the cyclosporine A group had secondary glaucoma. The intraocular pressure was controlled. Three patients receiving tacrolimus eye drops and 13 patients receiving cyclosporine A eye drops had mild irritation symptoms. Conclusions: Tacrolimus eye drops combined with low concentration of glucocorticoids can prevent the early immunological rejection after PKP for fungalkeratitis effectively and safely. (Chin J Ophthalmol, 2017, 53:305-310).

Role of E3 ubiquitin ligases in insulin resistance.

E3 ubiquitin ligases are a large family of proteins that catalyse the ubiquitination of many proteins for degradation by the 26S proteasome. E3 ubiquitin ligases play pivotal roles in the process of insulin resistance and diabetes. In this review, we summarize the currently available studies to analyse the potential role of E3 ubiquitin ligases in the development of insulin resistance. We propose two mechanisms by which E3 ubiquitin ligases can affect the process of insulin resistance. First, E3 ubiquitin ligases directly degrade the insulin receptor, insulin receptor substrate and other key insulin signalling molecules via the UPS. Second, E3 ubiquitin ligases indirectly regulate insulin signalling by regulating pro-inflammatory mediators that are involved in the regulation of insulin signalling molecules, such as tumour necrosis factor-α, interleukin (IL)-6, IL-4, IL-13, IL-1ß, monocyte chemoattractant protein-1 and hypoxia-inducible factor 1α. Determining the mechanism by which E3 ubiquitin ligases affect the development of insulin resistance can identify a novel strategy to protect against insulin resistance and diabetes.

Preparation of an inoculum of Gluconacetobacter xylinus without mutants in shaken culture.

AIMS: A high-quality inoculum of Gluconacetobacter xylinus is important to produce bacterial cellulose (BC), a versatile biomaterial. This work aims to develop a method of preparing an inoculum of this bacterium with high cell density and without mutants. METHODS AND RESULTS: Inocula of G. xylinus ACCC 10220 without and with cellulase or carboxymethyl cellulose (CMC) were prepared in shaken culture. BC pellets and BC-negative mutants were present in the inoculum without additives but absent in the inoculum with additives. Based on BC weights statically produced in fresh BC-producing media initiated by different seed culture, the 24-h-shaken inoculum with 1·50% (w/v) CMC was the best because of high biomass and absence of mutants. The BC weights in fresh media inoculated by the 96-h-static inoculum and 24-h-shaken CMC inoculum at 7% (v/v) were 0·70 and 1·05 g l(-1) , respectively, implying significant difference (P < 0·01) in BC weights. However, structure properties of the two BC samples, including the crystallinity index, mass fraction of cellulose Iα , degree of polymerization (DP) and micromorphology were slightly different. CONCLUSIONS: The 24-h-shaken CMC inoculum was the most suitable for a starter culture of BC. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel method of preparing G. xylinus inoculum in shaken culture was developed, featuring high biomass, absence of mutants and no BC entanglements. Cellulase or CMC added into the medium completely suppressed mutation of G. xylinus, and CMC facilitated to form colloidal BC with the low DP in shaken culture, indicating less BC stress to cells. These findings suggested the mutation could be induced by BC stress, and not by shear stress commonly accepted.

Identification of a novel HLA-A*24 variant allele, A*24:02:60.

HLA-A*24:02:60 allele differs from A*24:02:01:01 by one nucleotide substitution at nt 564 from C to T.

Identification of a novel HLA-B*40 allele, HLA-B*40:210, in a Chinese individual.

The newly detected HLA-B*40:210 allele has two nucleotide changes in exon 2 compared to B*40:49 allele.

Identification of a novel HLA-B*40 allele, HLA-B*40:229, in a Chinese individual.

The novel HLA-B*40:229 allele shows one nucleotide difference from B*40:02:01 in exon 2 at nucleotide position 97 (C → T).

The Diagnostic Value of FibroScan in Assessing Significant Liver Fibrosis in Patients with Chronic Hepatitis B.

OBJECTIVE: Significant liver fibrosis is recognized as the key link of therapy and prognosis in patients with chronic hepatitis B infection (CHB). The present study is designed to estimate the benefits of FibroScan (FS) in diagnosing significant fibrosis in patients with CHB. METHODS: Two hundred and eight consecutive CHB patients, who underwent liver biopsy, FS and laboratory tests, were recruited. The receiver operating characteristic (ROC) curves were generated to assess the performance of non-invasive models. RESULTS: Liver stiffness measurement (LSM) and aspartate transaminase (AST) to platelet (PLT) ratio index (APRI), but not age-platelet index (API) or AST to alanine aminotransferase (ALT) ratio (AAR), were closely correlated with significant fibrosis; areas under ROC curves (AUROC) were 0.817 (p < 0.001), 0.705 (p = 0.003), 0.626 (p = 0.065) and 0.631 (p = 0.055), respectively. When combining LSM with APRI, the AUROC was 0.813, p < 0.001. CONCLUSION: FibroScan can predict the presence of significant liver fibrosis, so as to avoid liver biopsy. It seems that the combination of FS and APRI does not significantly improve the ability to predict significant fibrosis.

Identification of a novel HLA-A*02 allele, HLA-A*02:06:13, in a Chinese individual.

The novel HLA-A*02:06:13 allele shows one nucleotide difference from A*02:06:01 in exon 4 at nucleotide position 657 (T→C).

A new human leukocyte antigen class I allele: HLA-A*11:125.

HLA-A*11:125 allele differs from A*11:01:01 by one nucleotide substitution at nt 140 from T to C.

Correlated energy-spread removal with space charge for high-harmonic generation.

We study the effect of longitudinal space charge on the correlated energy spread of a relativistic high-brightness electron beam that has been density modulated for the emission of coherent, high-harmonic radiation. We show that, in the case of electron bunching induced by a laser modulator followed by a dispersive chicane, longitudinal space charge forces can act to strongly reduce the induced energy modulation of the beam without a significant reduction in the harmonic bunching content. This effect may be optimized to enhance the output power and overall performance of free-electron lasers that produce coherent light through high-gain harmonic generation. It also increases the harmonic number achievable in these devices, which are otherwise gain-limited by the induced energy modulation from the laser.