[Diagnosis and treatment procedures and health management for patients with hereditary angioedema].

As a recognized rare and highly fatal disease, hereditary angioedema (HAE) is difficult to diagnose and characterized by recurrent edema involving the head, limbs, genitals and larynx, etc. Diagnosis of HAE is not difficult. However, low incidence and lack of clinical characteristics lead to difficulty of doctors on timely diagnosis and correct intervention for HAE patients. Therefore, it is crucial to improve the awareness of this disease and prevent its recurrence. for HAE patients. In view of absent cognition of doctors and the general public on HAE, patients often suffer from sudden death or become disabled due to laryngeal edema which cannot be treated in time. Thus, based on the Internet mobile terminal platform, the team set up an all-day rapid emergency response system which is provided for HAE patients by setting up "one-click help". The aim is to offer optimization on overall management of HAE and designed the intelligent follow-up management to provide timely assistance and specialized suggestion for patients with acute attacks.

[Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen].

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

[Preliminary insights into the practice of hypoallergenic home visiting program].

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.

[Mechanism of nerve growth factor promotes angiogenesis and skeletal muscle fiber remodeling in a mouse hindlimb ischemic model].

Objective: To explore the mechanism of nerve growth factor (NGF) in the skeletal muscle fiber remodeling in ischemic limbs during therapeutic angiogenesis. Methods: Eighteen female mice with SPF grade, 6 weeks old and 25-30 g weighed were randomly allocated to sham-operated group (n=6), blank control group (n=6) and NGF gene transfection group (n=6). The left hindlimb ischemia models were established by ligating the femoral artery in blank control group and NGF gene transfection group. Seven days after the operation, mice in the three groups were separately injected with normal saline, empty plasmids, and NGF plasmids. Gastrocnemius of left hindlimbs was harvested after the blood perfusion assessment of the ischemic limb on the 21st postoperative day. The gastrocnemius muscle specimens were stained with HE, CD31 and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining, the mRNA expressions of myosin heavy chain-Ⅰ(MHC-Ⅰ), MHC-Ⅱa and MHC-Ⅱb were measured by real-time PCR, and the protein level of NGF and peroxisome proliferator-activated receptors-ß/δ (PPAR ß/δ) were detected by Western blot. The expression of cytochrome C oxidase (COX), isocitrate dehydrogenase (IDH) and adenosine triphosphate (ATP) were examined by enzyme-linked immunosorbent assay (ELISA). Results: On the 21st day after operation, the blood perfusion of the ischemic limb in NGF gene transfection group was (195.70±9.99)PU, which was lower than that in sham-operated group (312.15±17.32)PU (P=0.001), while it was higher than that in blank control group (82.11±8.55)PU (P=0.001). The degree of muscle atrophy in the NGF gene transfection group was lower than that in the blank control group. The capillary density of NGF gene transfection group (0.34±0.05) was higher than that of sham-operated group (0.11±0.03) and blank control group (0.27±0.04) (P<0.05). The endothelial cell proliferation index in NGF gene transfection group (0.39±0.19) was significantly higher than that in sham-operated group (0.18±0.01) and blank control group (0.25±0.14) (P<0.05). The expression of NGF, PPAR ß/δ, COX, IDH, ATP, and MHC-Ⅰ mRNA in NGF gene transfection group were significantly higher than those in sham-operated group and blank control group (P<0.05). Conclusions: NGF gene transfection can promote angiogenesis in the ischemic limbs of mice, increase the blood perfusion, and thus induce the remodeling of skeletal muscle fibers to type Ⅰ. This process may be related to NGF-induced PPAR ß/δ expression and promote the cellular aerobic metabolism in skeletal muscle.

Nomogram to predict haemorrhagic transformation after stroke thrombolysis: a combined brain imaging and clinical study.

AIM: To construct a novel nomogram by integrating computed tomography perfusion (CTP) and clinical parameters for individualised prediction of haemorrhagic transformation (HT) in intravenous thrombolysis (IVT)-treated acute ischaemic stroke (AIS) patients. METHODS: Anterior circulation AIS patients who underwent IVT at a single centre from January 2018 to June 2020 were reviewed retrospectively. The CTP parameters of two regions of interest (ROI), the entire perfusion lesion areas, and the infract core areas, were assessed. HT was documented by follow-up CT 24 ± 2 h after IVT. Multivariable logistic regression was conducted by including clinical variables and CTP parameters to identify the independent predictors of HT. A nomogram was developed based on the independent predictors. The discriminative value and calibration of the nomogram were tested by concordance indexes (C-indexes) and calibration plots. Internal validation was performed using fivefold cross-validation. RESULTS: The nomogram was generated using the complete data from 341 patients. Seven variables were included in the final nomogram, including: the relative cerebral blood volume (rCBV), permeability surface (PS), and relative PS (rPS) in infract core areas, the relative time to maximum (rTmax) and rPS in entire perfusion lesion areas, the National Institutes of Health Stroke Scale (NIHSS), and atrial fibrillation (AF). The C-indexes were 0.815 and 0.817 for the nomogram and internal validation. The calibration plots showed excellent agreement. CONCLUSION: This is the first study establishing a nomogram based on CTP and clinical parameters to predict HT after stroke thrombolysis.

High Curie temperature and carrier mobility of novel Fe, Co and Ni carbide MXenes.

Two-dimensional (2D) magnets with room temperature ferromagnetism and semiconductors with moderate band gap and high carrier mobility are highly desired for applications in nanoscale electronics and spintronics. By performing the first-principles calculations, we investigate novel Fe, Co, Ni carbide based pristine (M2C) and functionalized (M2CT2, T: F, O, OH) MXenes. Our calculations show that Fe2C, Co2C, Ni2C, Fe2CF2, Fe2CO2, Fe2C(OH)2, Co2CF2, Co2C(OH)2 and Ni2CF2 are dynamically and mechanically stable. More importantly, Fe2C, Co2C, Fe2CF2 and Fe2C(OH)2 exhibit intrinsic ferromagnetism (magnetic moments 2-5µB per unit cell). Monte Carlo simulations suggest high Curie temperatures of 590 and 920 K for Fe2C and Fe2CF2, respectively, at the HSE06 level owing to the large spin magnetic moments and strong ferromagnetic coupling. Based on the deformation potential theory, we predict high and anisotropic hole mobility (0.2-1.4 × 104 cm2 V-1 s-1) for semiconducting Fe2CO2 and Co2C(OH)2. Additionally, Ni2CF2 demonstrates highly anisotropic electron mobility together with a direct band gap. Our results further show the effectiveness of surface functionalization in modulating the electronic and magnetic properties and broadening the properties of MXenes to achieve long-range intrinsic ferromagnetism well above room temperature and high carrier mobility.

Urinalysis in patients with neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Increasing evidence has demonstrated that aquaporin-4 (AQP4) immunoglobulin G causes damage to the kidney in neuromyelitis optica spectrum disorder (NMOSD). However, changes in urinalysis in NMOSD have not been investigated thus far. Our objective was to evaluate the changes in urinalysis in NMOSD patients. METHODS: Case data were collected from 44 patients with AQP4 antibody-positive NMOSD, 53 patients with multiple sclerosis (MS) and 79 age- and sex-matched healthy controls. Analyses of early morning urine and 24-h urine samples comparing NMOSD with MS patients were conducted. RESULTS: In the acute phase, urine pH levels (P < 0.001) and urine specific gravity levels (P < 0.001) from NMOSD patients were significantly higher and lower, respectively, than for MS patients. 24-h urine sodium and 24-h urine volume from NMOSD patients were significantly higher than for MS patients (both P = 0.001). A 24-h urine volume higher than 2500 ml (odds ratio 11.7, 95% confidence interval 1.863-73.066) and a 24-h urine sodium higher than 200 mmol (odds ratio 16.0, 95% confidence interval 2.122-120.648) are more likely to occur in NMOSD patients in the acute phase than in MS patients. CONCLUSIONS: The urinalysis results were significantly different between NMOSD patients and MS patients. The pathophysiological changes in AQP4 antibody-positive NMOSD patients were not limited to the central nervous system.

[Network correlation of circRNA-miRNA and the possible regulatory mechanism in acute myocardial infarction].

Objective: Using microarray technology, to research characteristic circRNA and miRNA expression profile of acute myocardial infarction (AMI), and then explore the role of these circRNA and miRNA in gene regulation. The aim is to explore the mechanism of development of AMI. Methods: The patients hospitalized in the Cardiovascular Research Center of the First Affiliated Hospital of Xinxiang Medical University between November 2016 and January 2017 were included and divided into control group and AMI group according to diagnostic criteria. We collected their whole blood and extracted the total RNA, and the expression profiles of circRNA and microRNA genes in peripheral blood of AMI were analyzed by gene chip. We predicted circRNA which was possible to combine with miRNA, and drew a network diagram, and the differentially expressed circRNA was analyzed by GO and Pathway. Results: There was difference in circRNA expression profile between the control group and the AMI group. The results showed: (1) a total of 1 670 circRNA had differential expressions, and in the analysis of miRNA expression, 13 miRNA had differential expressions (P<0.05, fc≥2); (2) multiple circRNAs-miRNAs were involved in the occurrence of AMI; (3) the analysis of GO and Pathway for differentially expressed circRNAs showed that many pathways, disease and function participated in it. Conclusion: CircRNA, as an important post transcriptional regulator, is closely related to the development of AMI with miRNA.

[The analysis of risk factors and outcomes of carotid endarterectomy for carotid artery stenosis].

Objective: To evaluate the early and long-term outcomes of carotid endarterectomy for carotid artery stenosis and analyse the risk factors for the outcomes. Methods: A retrospective review of 369 patients underwent carotid endarterectomy(CEA) in Peking Union Medical College Hospital from Oct 2006 to Nov 2012 was conducted. Clinical data including general conditions, perioperative and follow-up outcomes were collected. Results: Three hundred sixty-nine patients underwent 407 CEAs. The long-term follow-up rate (≥30 d) was 89.9% and follow-up period was 11.8-48.3 months. Among 407 CEAs, patients with symptomatic carotid artery stenosis, carotid stenosis over 70% and contralateral severe carotid stenosis occupied 78.0%(317/407), 98.4%(400/407) and 12.04%(49/407) respectively. Total early complications (<30 d) of stroke, cardiac events and death was 3.93% (16/407). Univariate analysis showed no risk factor had significant effect on early complications (P>0.05). Total long-term complications of stroke, cardiac events and death was 8.7% (32/366). Univariate analysis showed that total long-term complication rate of smoking group was higher than non-smoking group (12.1% vs 5.1%, P<0.05), contralateral carotid artery stenosis group was higher than opposite one (28.6% vs 8.0%, P<0.05). Multivariate Logistic regression showed the HR of long-term complications rate in patients aged over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis were 2.59, 2.66, 2.48 and 6.06, respectively. Conclusions: CEA is safe method for the treatment of carotid stenosis. To CEA, age over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis are risk factors for long-term adverse outcomes.

[Study on the failure time of the vaccine vial monitor used for oral poliovirus vaccine at 25 ℃ and 37 ℃].

Objective: To evaluate the failure time of vaccine vial monitor (VVM) used for oral poliovirus vaccine (OPV) at 25 ℃ and 37 ℃. Methods: 160 copies of VVM were produced by a company, the model was QM5D37A, samples were taken from different batches by using the method of random number table . 100 bottles of vaccine were produced by a domestic company, and samples were taken from different batches by using the method of random number table. 160 copies of labels were placed in the incubator at 25 ℃ and 37 ℃, which were used to measure the mutative color of the active region. When the values of color were equal to 40, the color of active region was the same with the reference color, and the VVM was failed. 100 bottles of vaccine were placed in the incubator at 25 ℃ and 37 ℃, which were used to measure the vaccine titer. When total vaccine titer was less than 6.12 CCID50 or vaccine titer of typeⅠ was less than 6.0 CCID50 or vaccine titer of type Ⅲ was less than 5.5 CCID50, the vaccine was failed. We drew the graph of mutative color to calculate the failure time range of VVM According to the graph , we can determine that whether the failure time of VVM was later than the time of vaccines by the data of OPV . Results: The earliest failure time of OPV was 21 days at 25 ℃, and the number of samples was one; The earliest Failure time of VVM was 12.5 days at 25 ℃, and it was less than the earliest failure time of OPV. The earliest failure time of OPV was 4.0 days at 37 ℃, and the number of samples was one; The earliest Failure time of VVM was 3.1 days at 37 ℃, and it was equal to the earliest failure time of OPV. Conclusion: We could know that the failure time of VVM was always earlier than the failure time of vaccines at the same temperatures . The latest failure time of VVM was equal to the earliest failure time of vaccines at 37 ℃. All of the failure times of samples were earlier than that of vaccines at 25 ℃.

Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis.

Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis. We demonstrate that LDHA is phosphorylated at tyrosine 10 by upstream kinases, HER2 and Src. Targeting HER2 or Src attenuated LDH activity as well as invasive potential in head and neck cancer and breast cancer cells. Inhibition of LDH activity by small hairpin ribonucleic acid or expression of phospho-deficient LDHA Y10F sensitized the cancer cells to anoikis induction and resulted in attenuated cell invasion and elevated reactive oxygen species, whereas such phenotypes were reversed by its product lactate or antioxidant N-acetylcysteine, suggesting that Y10 phosphorylation-mediated LDHA activity promotes cancer cell invasion and anoikis resistance through redox homeostasis. In addition, LDHA knockdown or LDHA Y10F rescue expression in human cancer cells resulted in decreased tumour metastasis in xenograft mice. Furthermore, LDHA phosphorylation at Y10 positively correlated with progression of metastatic breast cancer in clinical patient tumour samples. Our findings demonstrate that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers.

[Prognostic factors for inability to walk independently in patients with multiple system atrophy].

Objective: To explore the prognostic factors for inability to walk independently in patients with multiple system atrophy (MSA). Methods: A total of 123 patients with clinically confirmed MSA admitted to Navy General Hospital and Dongfang Hospital affiliated to the Second Clinical Medical College of Beijing University of Chinese Medicine, from February 2013 to February 2016, were retrospectively reviewed. Clinical data and all records were collected and all subjects were followed up by a telephone call in February 2016. The second milestone of activities of daily living scale (ADL), defined as inability to walk independently, was taken as the primary outcome. Eight possible prognostic factors were investigated and the survival analysis was performed with Cox proportional hazards model regression. Results: Of all the MSA patients, 74 subjects were men and 49 were women with a sex radio of 1.51∶1(M∶F). Seventy cases were diagnosed with MSA-cerebellar type (MSA-C) and 53 with MSA-Parkinson type (MSA-P) (C∶P=1.32∶1). Mean age at the onset of first symptom was (53±8) years old. All patients had severe autonomic nervous dysfunction. At the last follow-up, 56 cases (45.5%) were unable to walk independently. The median survival time from the onset of MSA to inability to walk independently was 73 months. The age of onset ≥ 55 years (HR=1.969, 95%CI 1.095-3.542, P=0.024) and the interval time from disease onset to combined motor and autonomic involvement≤3 years (HR=2.308, 95%CI 1.158-4.600, P=0.017) were independent prognostic factors for inability to walk independently, while gender, MSA clinical subtypes, initial symptoms, alcohol intake, smoking and toxic exposure were not indicators for independent walking (P>0.05). Conclusions: The prognostic factors for inability to walk independently in patients with MSA are the age of onset ≥55 years and the interval time from disease onset to combined motor and autonomic involvement≤3 years. Although factors including gender, MSA clinical subtypes, initial symptoms, alcohol intake, smoking and toxic exposure are not the predictive factors for inability to walk independently in our MSA patients, their roles in the prognosis of MSA still need further investigation.

SUMOylation in Neurological Diseases.

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases.

Sumoylation in Lens Differentiation and Pathogenesis.

Sumoylation, a post-translational modification discovered over a decade ago, turns out to be a very important regulatory mechanism mediating multiple cellular processes. Recent studies from our laboratory and others also revealed that it plays a crucial role in regulating both differentiation and pathogenesis of the ocular lens. This review will summarize these progresses.

Molecular Cloning and Developmental Expression Patterns of the Striatin Gene Encoding A Member of the Regulatory Subunits for the Protein Serine/Threonine Phosphatase-2A in Fish.

PURPOSE: The protein phosphatase-2A (PP-2A) is one of the most important serine/threonine phosphatases in eukaryotes. The holoenzyme of PP-2A consists of three subunits: a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. While both A and C subunits are coded by two different genes, the B subunits exist in 26 or more isoforms which are encoded by at least 15 different genes. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the gene encoding goldfish striatin, a member of the B'" family regulatory subunits for PP-2A, and determined their tissue-specific and temporal expression patterns. METHODS: The cDNA cloning was conducted with RT-PCR-based RACE. The mRNA expression levels for the goldfish striatin were analyzed with RT-PCR. The expression levels of the striatin protein from goldfish were determined with Western blot analysis. The semi-quantitation of the mRNA and protein expression levels was conducted with the software of U-scanning. RESULTS: Our study revealed that the full length cDNA for striatin consists of 2965 bp coding for a deduced protein of 769 amino acids, which bears a very high level of amino acid sequence identity with the homolog protein from other species. The striatin mRNA is highly expressed in the kidney, to a less degree in brain, fin, muscle, liver, ovary and gill, and the lowest in testis and heart. Similar pattern of protein expression is detected in the above 9 tissues. During the development of goldfish, the striatin mRNA maintains a relatively high level at the 2-cell, multiple cell and blastula stages. Then, it drops down substantially at gastrula stage and fluctuates around this level in the next 8 different stages. At the protein level, the striatin maintained higher level from 2-cell to gastrula stages, then decreased at neurula and optic vesicle stages, and gradually increased again to peak at eye pigmentation stage, then slightly decreased in the next few stages of development. CONCLUSIONS: Our results suggest that the striatin may play an important role in regulating goldfish development and adult tissue homeostasis. While the former function may or may not occur through PP- 2A functions, the later function appears to occur via PP-2A activity.

Contrast Functions of αA- and αB-Crystallins in Cancer Development.

α-Crystallins, initially identified as the structural proteins of the ocular lens, belong to the small heat shock protein family. They play significant roles in maintaining the lens transparency and preventing protein aggregation. α-Crystallins exist in two isoforms: αA and αB, and they display differential tissue distribution. Their mutations are implicated in several human diseases including cardiac myopathies, neurodegenerative diseases, cataracts and various types of cancers. Increased αB expression was detected in retinoblastoma, breast cancer, glioblastoma, prostate and renal cell carcinomas, indicating its role in promoting tumor growth. A complex picture emerges for αA. Although earlier studies suggest that αA may promote cancer development, recent studies from our laboratory demonstrate that αA can act as a tumor suppressor inhibiting cell transformation and retarding cell migration through modulating MAP kinase activity. In this review, we summarize the recent progress about the functions of αA and αB in cancer development.