A 3-month-old neonatal rhesus macaque HFMD model caused by coxsackievirus B1 infection and viral tissue tropism.

Coxsackievirus B1 (CVB1), an enterovirus with multiple clinical presentations, has been associated with potential long-term consequences, including hand, foot, and mouth disease (HFMD), in some patients. However, the related animal models, transmission dynamics, and long-term tissue tropism of CVB1 have not been systematically characterized. In this study, we established a model of CVB1 respiratory infection in rhesus macaques and evaluated the clinical symptoms, viral load, and immune levels during the acute phase (0-14 days) and long-term recovery phase (15-30 days). We also investigated the distribution, viral clearance, and pathology during the long-term recovery period using 35 postmortem rhesus macaque tissue samples collected at 30 days postinfection (d.p.i.). The results showed that the infected rhesus macaques were susceptible to CVB1 and exhibited HFMD symptoms, viral clearance, altered cytokine levels, and the presence of neutralizing antibodies. Autopsy revealed positive viral loads in the heart, spleen, pancreas, soft palate, and olfactory bulb tissues. HE staining demonstrated pathological damage to the liver, spleen, lung, soft palate, and tracheal epithelium. At 30 d.p.i., viral antigens were detected in visceral, immune, respiratory, and muscle tissues but not in intestinal or neural tissues. Brain tissue examination revealed viral meningitis-like changes, and CVB1 antigen expression was detected in occipital, pontine, cerebellar, and spinal cord tissues at 30 d.p.i. This study provides the first insights into CVB1 pathogenesis in a nonhuman primate model of HFMD and confirms that CVB1 exhibits tissue tropism following long-term infection.

Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the potential effect of ursodeoxycholic acid （UDCA） in the prevention and treatment of COVID-19 in patients with chronic hepatitis B. MethodsClinical data were collected from 324 patients with chronic hepatitis B who were treated in Beijing Ditan Hospital， Capital Medical University， from January to December 2022， and according to whether UDCA was administered， they were divided into UDCA group and control group. The propensity score matching （PSM） method was used to balance the confounding factors such as age， sex， and chronic complications， and the two groups were compared in terms of SARS-CoV-2 infection rate， symptoms， and recovery time after COVID-19. The two groups were also compared in terms of related laboratory markers （white blood cell count ［WBC］， hemoglobin ［Hb］， platelet count ［PLT］， alanine aminotransferase ［ALT］， aspartate aminotransferase ［AST］， albumin ［Alb］， alkaline phosphatase ［ALP］， total bilirubin ［TBil］， triglyceride ［TG］， and total cholesterol ［TC］）， vaccination， and the incidence rate of liver disease symptoms after COVID-19. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of data with skewed distribution between the two groups； the chi-square test and the continuously corrected chi-square test were used for comparison of categorical data between two groups. The binary Logistic regression model was used for univariate and multivariate analyses to investigate the influencing factors for COVID-19 after matching. ResultsThere were 87 patients in the UDCA group and 237 patients in the control group， and after PSM， there were 78 patients in the UDCA group and 137 patients in the control group， with good balance between the two groups. There was a significant difference in SARS-CoV-2 infection rate between the UDCA group and the control group ［82.1% （64/78） vs 95.6% （131/137）， χ2=10.847， P=0.001］. After COVID-19， compared with the control group， the UDCA group had a significantly lower proportion of the patients with chill （10.9% vs 38.9%， χ2=16.124， P<0.001） and cough （56.3% vs 74.8%， χ2=6.889， P=0.009）. There was a significant difference between the UDCA group and the control group in the proportion of the patients with a recovery time of ≤7 days after COVID-19 （79.7% vs 61.1%， χ2=6.760， P=0.009）. Both univariate and multivariate logistic regression analyses showed that UDCA was an independent influencing factor for COVID-19 （odds ratio=0.21 and 0.17， both P<0.05）. ConclusionUDCA is an protective factor against COVID-19 in patients with chronic hepatitis B and can alleviate related symptoms to some extent and shorten the recovery time， and therefore， it has an important value in the prevention and treatment of COVID-19.

miR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene / 生物工程学报

This study aimed to explore the effect of miR-23b-3p on the differentiation of goat intramuscular preadipocytes, and to confirm whether miR-23b-3p plays its roles via targeting the PDE4B gene. Based on the pre-transcriptome sequencing data obtained previously, the miR-23b-3p, which was differentially expressed in goat intramuscular adipocytes before and after differentiation, was used as an entry point. real-time quantitative-polymerase chain reaction (qPCR) was used to detect the expression pattern of miR-23b-3p during the differentiation of goat intramuscular preadipocytes. The effects of miR-23b-3p on adipose differentiation and adipose differentiation marker genes were determined at the morphological and molecular levels. The downstream target genes of miR-23b-3p were determined using bioinformatics prediction as well as dual luciferase reporter assay to clarify the targeting relationship between miR-23b-3p and the predicted target genes. The results indicated that overexpression of miR-23b-3p reduced lipid droplet accumulation in goat intramuscular adipocytes, significantly down-regulated the expression levels of adipogenic marker genes AP2, C/EBPα, FASN, and LPL (P < 0.01). In addition, the expressions of C/EBPβ, DGAT2, GLUT4 and PPARγ were significantly downregulated (P < 0.05). After interfering with the expression of miR-23b-3p, lipid droplet accumulation was increased in goat intramuscular adipocytes. The expression levels of ACC, ATGL, AP2, DGAT2, GLUT4, FASN and SREBP1 were extremely significantly up-regulated (P < 0.01), and the expression levels of C/EBPβ, LPL and PPARγ were significantly up-regulated (P < 0.05). It was predicted that PDE4B might be a target gene of miR-23b-3p. The mRNA expression level of PDE4B was significantly decreased after overexpression of miR-23b-3p (P < 0.01), and the interference with miR-23b-3p significantly increased the mRNA level of PDE4B (P < 0.05). The dual luciferase reporter assay indicated that miR-23b-3p had a targeting relationship with PDE4B gene. MiR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene.

Research progress on the relationship between pediatric epilepsy and vitamin D / 中国临床药理学与治疗学

Epilepsy is a long-term, chronic, recurrent, multi-factorial, multi-symptomatic nervous system disease, and was caused by abnormal discharge of brain neurons. Etiology can cause irreversible brain dysfunction and even death. There are about 6.5 million children with epilepsy in China, with incidence rate twice that of adult, presenting serious threaten to children's growth and development. Vitamin D has been well-known for crucial importance to development of nervous, skeletal, and immune system. Studies have found that pediatric epilepsy as well as other neurological diseases were closely related with vitamin D deficiency. First, a large number of studies have shown that vitamin D in children with epilepsy is affected by epilepsy itself; second, the use of anti-seizure medicines can alter metabolism of vitamin D by inducing cytochrome oxidases; third, the inducement was concerned to varieties, combination and duration of anti-seizure medicines; fourth, it was expected that supplement of vitamin D during antiepileptic treatment would guarantee an improvement of treating given that anti-seizure medicines may lead to deficiency of vitamin D. Large numbers of researches have reported on the correlation ship between pediatric epilepsy and vitamin D. However, there is still a lack of systematic review. This article aims to retrospect the research progress of relationship between pediatric epilepsy and vitamin D, and provide valuable feedbacks on further treatment of pediatric epilepsy.

Gene cloning and sequence analysis of the RPL29 gene and its effect on lipogenesis in goat intramuscular adipocytes / 生物工程学报

The aim of this study was to clone the goat RPL29 gene and analyze its effect on lipogenesis in intramuscular adipocytes. Using Jianzhou big-eared goats as the object, the goat RPL29 gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR), the gene structure and expressed protein sequence were analyzed by bioinformatics, and the mRNA expression levels of RPL29 in various tissues and different differentiation stages of intramuscular adipocytes of goats were detected by quantitative real-time PCR (qRT-PCR). The RPL29 overexpression vector pEGFP-N1-RPL29 constructed by gene recombination was used to transfect into goat intramuscular preadipocytes and induce differentiation. Subsequently, the effect of overexpression of RPL29 on fat droplet accumulation was revealed morphologically by oil red O and Bodipy staining, and changes in the expression levels of genes related to lipid metabolism were detected by qRT-PCR. The results showed that the length of the goat RPL29 was 507 bp, including a coding sequence (CDS) region of 471 bp which encodes 156 amino acid residues. It is a positively charged and stable hydrophilic protein mainly distributed in the nucleus of cells. Tissue expression profiling showed that the expression level of this gene was much higher in subcutaneous adipose tissue and inter-abdominal adipose tissue of goats than in other tissues (P < 0.05). The temporal expression profile showed that the gene was expressed at the highest level at 84 h of differentiation in goat intramuscular adipocytes, which was highly significantly higher than that in the undifferentiated period (P < 0.01). Overexpression of RPL29 promoted lipid accumulation in intramuscular adipocytes, and the optical density values of oil red O staining were significantly increased (P < 0.05). In addition, overexpression of RPL29 was followed by a highly significant increase in ATGL and ACC gene expression (P < 0.01) and a significant increase in FASN gene expression (P < 0.05). In conclusion, the goat RPL29 may promote intra-muscular adipocyte deposition in goats by up-regulating FASN, ACC and ATGL.

Cloning and expression profile of ZFP36L1 gene in goat / 生物工程学报

The purpose of this study was to clone and characterize the ZFP36L1 (zinc finger protein 36-like 1) gene, clarify its expression characteristics, and elucidate its expression patterns in different tissues of goats. Samples of 15 tissues from Jianzhou big-eared goats, including heart, liver, spleen, lung and kidney were collected. Goat ZFP36L1 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR), then the gene and protein sequence were analyzed by online tools. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of ZFP36L1 in intramuscular preadipocytes in different tissues and adipocytes of goat at different differentiation stages. The results showed that the length of ZFR36L1 gene was 1 224 bp, and the coding sequence (CDS) region was 1 017 bp, encoding 338 amino acids, which was a non-secretory unstable protein mainly located in nucleus and cytoplasm. Tissue expression profile showed that ZFP36L1 gene was expressed in all selected tissues. In visceral tissues, the small intestine showed the highest expression level (P < 0.01). In muscle tissue, the highest expression level was presented in longissimus dorsi muscle (P < 0.01), whereas the expression level in subcutaneous adipose tissue was significantly higher than that in other tissues (P < 0.01). The results of induced differentiation showed that the expression of this gene was up-regulated during adipogenic differentiation of intramuscular precursor adipocytes (P < 0.01). These data may help to clarify the biological function of the ZFP36L1 gene in goat.

Cloning, identification and functional analysis of the goat transcription factor c-fos / 生物工程学报

C-fos is a transcription factor that plays an important role in cell proliferation, differentiation and tumor formation. The aim of this study was to clone the goat c-fos gene, clarify its biological characteristics, and further reveal its regulatory role in the differentiation of goat subcutaneous adipocytes. We cloned the c-fos gene from subcutaneous adipose tissue of Jianzhou big-eared goats by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed its biological characteristics. Using real-time quantitative PCR (qPCR), we detected the expression of c-fos gene in the heart, liver, spleen, lung, kidney, subcutaneous fat, longissimus dorsi and subcutaneous adipocytes of goat upon induced differentiation for 0 h to 120 h. The goat overexpression vector pEGFP-c-fos was constructed and transfected into the subcutaneous preadipocytes for induced differentiation. The morphological changes of lipid droplet accumulation were observed by oil red O staining and bodipy staining. Furthermore, qPCR was used to test the relative mRNA level of the c-fos overexpression on adipogenic differentiation marker genes. The results showed that the cloned goat c-fos gene was 1 477 bp in length, in which the coding sequence was 1 143 bp, encoding a protein of 380 amino acids. Protein structure analysis showed that goat FOS protein has a basic leucine zipper structure, and subcellular localization prediction suggested that it was mainly distributed in the nucleus. The relative expression level of c-fos was higher in the subcutaneous adipose tissue of goats (P < 0.05), and the expression level of c-fos was significantly increased upon induced differentiation of subcutaneous preadipocyte for 48 h (P < 0.01). Overexpression of c-fos significantly inhibited the lipid droplets formation in goat subcutaneous adipocytes, significantly decreased the relative expression levels of the AP2 and C/EBPβ lipogenic marker genes (P < 0.01). Moreover, AP2 and C/EBPβ promoter are predicted to have multiple binding sites. In conclusion, the results indicated that c-fos gene was a negative regulatory factor of subcutaneous adipocyte differentiation in goats, and it might regulate the expression of AP2 and C/EBPβ gene expression.

Patients with type 2 diabetes mellitus and psoriasis re-infected with measles: one case report and literature analysis / 中国基层医药

Objective:To analyze the rash characteristics and diagnosis and treatment process of measles infection in patients with diabetes mellitus and psoriasis, to reduce the clinical diagnosis and treatment delay of such patients.Methods:The clinical data of a patient with diabetes combined with psoriasis and measles infection who was diagnosed and treated in The First Hospital of Yulin in April 2015 were analyzed.Results:The patient was admitted to hospital due to polydipsia and polyuria for 3 years and fever for 3 days. Hypoglycemic and anti-inflammatory treatment after admission was not good. On the third day after hospitalization, rash on the trunk and the extremities was seen. The patient had a history of measles infection. Based on clinical practice, Measles morbillivirus infection was not excluded, and Measles morbillivirus infection was confirmed by pathogen inspection. Measles reinfection was considered to be caused by variation of Measles morbillivirus. The atypical rash formed because of the patient's need for long-term treatment with Acitretin capsule and capotriol for psoriasis. After adjusting the antibiotic treatment, hypoglycemia and antiviral therapy were given, the body temperature was normal and the rash gradually subsided.Conclusion:For patients with type 2 diabetes mellitus and psoriasis, if they have a fever, they should be considered comprehensively to guard against re-infection caused by measles virus mutation. Timely etiological diagnosis is performed to avoid missed diagnosis and delayed treatment.

Evaluation of health warning labels for commercial locations vending sugar-sweetened beverages / 环境与职业医学

Background Long-term excessive consuming sugar-sweetened beverages have a negative impact on health. In order to decrease the consumption of sugar-sweetened beverages and create a healthy food environment, the Health Commission of Shenzhen Municipality pioneered to enforce health warning labels presented in commercial locations vending sugar-sweetened beverages based on relevant provisions of the Health Regulations of Shenzhen Special Economic Zone，but its effect has not yet been evaluated. Objective To evaluate the impact of presenting health warning labels in commercial locations vending sugar-sweetened beverages in Shenzhen. Methods A multi-stage stratified sampling method was used to randomly select one street in each of the 10 districts (excluding the Shenzhen Shantou Special Cooperation Zone) of Shenzhen followed by a convenience sampling to select sampling sites to conduct an undercover investigation on the presentation of health warning labels for sugar-sweetened beverages in six different types of venues (n=232) such as shopping malls, ordinary supermarkets/convenience stores, self-service vending machines, catering service places, medical institutions, and venues serving minors' education and activities. At the same time, 238 site managers, 1002 adult consumers, and 7396 child and adolescent consumers were interviewed. Results Among 213 commercial locations vending sugar-sweetened beverages, the rate of health warning label installation was 26.3%, with the highest installation rate in shopping malls (55.0%). Among site managers, 47.8% were aware that commercial locations were required to install health warning labels, and 50.0% were aware of the standards for setting up health warning labels. The higher the awareness of relevant regulations, the higher the rate of installation of health warning labels. More than half of site managers (55.3%) believed that after installing health warning labels, the sales of sugar-sweetened beverages and sugar-sweetened beverages in large-volume packages had decreased compared to the same period in previous years. Most of the interviewed consumers indicated that if they saw the health warning labels for sugar-sweetened beverages, they would buy less, give up purchasing, or choose low-sugar or sugar-free beverages, and also discourage their family members or friends from drinking such beverages. Compared with participants without awareness of the health warning labels, both adult and child and adolescent consumers with awareness of the health warning labels believed that the installation is beneficial to their good eating habits and reported a higher proportion of discouraging family members or friends from drinking such beverages, with a lower frequency of consuming sugar-sweetened beverages. Conclusion Health warning labels for sugar-sweetened beverages have a significant effect on promoting behavior changes, and both site managers and citizens have a high level of support for them. However, in view of the low voluntary compliance rate of commercial locations and the installation rate of health warning labels, the publicity and enforcement of the Health Regulations of Shenzhen Special Economic Zone should be enhanced.

Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). @*Materials and Methods@#An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. @*Results@#Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. @*Conclusion@#Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

The effects of sacubitril/valsartan on heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: Compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, Sacubitril/Valsartan has been reported to have superior results. However, the effects of sacubitril/valsartan on heart failure with preserved ejection fraction (HFpEF) are still in dispute. OBJECTIVES: This study aims to evaluate the effects of sacubitril/valsartan on the treatment of HFpEF patients. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrials.gov were used to search for randomised controlled trials of sacubitril/valsartan in HFpEF patients from inception to 7 December 2020. RESULTS: Four studies, with a total of 7739 participants, met the inclusion criteria. The present meta-analysis results showed that compared with the control group, sacubitril/valsartan reduced the hospitalisation rate of HF in HFpEF patients [Risk Ratio(RR): 0.85; 95% confidence interval (CI): 0.79-0.93; p = 0.0002). Regarding all-cause mortality, cardiovascular mortality, and the improvement in NYHA class, sacubitril/valsartan did not show apparent advantages. Although sacubitril/valsartan was linked to increasing the risk of symptomatic hypotension (RR: 1.44; 95% CI: 1.25-1.66; p﹤0.00001), there was no evidence supporting the incidence of renal function worsening and hyperkalemia. CONCLUSION: Our study shows that compared with valsartan or individualised medical therapy (IMT), there were not different between the two groups except for the hospitalisation rate which was favoured by Sacubitril/Valsartan treatment group for HFpEF patients.

circZNF124 regulates the proliferation, migration and invasion of colorectal cancer SW620 cells by targeting miR-4262 / 中国临床药理学与治疗学

AIM: To explore the effect and mechanism of circZNF124 on the proliferation, migration and invasion of colorectal cancer SW620 cells. METHODS: The expression levels of circZNF124 and miR-4262 in colorectal cancer tissues were measured by qRT-PCR method. Human colorectal cancer cells SW620 were cultured in vitro, and were randomly grouped into si-NC group, si-circZNF124 group, miR-NC group, miR-4262 group, si-circZNF124 j anti-miR-NC group, si-circZNF124 j antimiR-4262 groups. CCK-8 method, plate clone formation test, scratch test and Transwell test respectively were used to detect cell proliferation, clone formation, migration and invasion of SW620 cells. The dual luciferase reporter experiment analyzed the targeted binding of circZNF124 to miR-4262. Western blot was used to detect the expression of E-cadherin and N-cadherin protein. RESULTS: The expression of circZNF124 in colorectal cancer tissue was increased by about 3.75 times compared with that in the adjacent tissue (P i 0.05), and the expression of miR-4262 was decreased by about 0.73 times compared with the adjacent tissue (P i 0.05). Compared with the si-NC group, the cell viability, scratch healing rate and the protein level of N-cadherin in the si-circZNF124 group were decreased (P i 0.05), the number of cell clone formation and the number of invasive cells were decreased (P i 0.05), while the protein level of E-cadherin was increased (P i 0.05). circZNF124 could negatively regulate the expression of miR-4262. Compared with the miR-NC group, the cell viability, scratch healing rate and the protein level of N-cadherin in the miR-4262 group were reduced (P i 0.05), the number of cell clones and the number of invasive cells were reduced (P i 0.05), while the protein level of E-cadherin was increased (P i 0.05). Inhibition of miR-4262 expression reversed the effect of interfering circZNF124 expression on the proliferation, migration and invasion of SW620 cells.CONCLUSION: Interference with the expression of circZNF124 can attenuate the proliferation, migration and invasion of colorectal cancer cells by targeting miR-4262.

Spine curvature and the cardiopulmonary exercise endurance of adolescents with idiopathic scoliosis / 中华物理医学与康复杂志

Objective:To quantify any correlation between the severity of spinal curvature of an adolescent with idiopathic scoliosis and their cardiopulmonary exercise endurance.Methods:The cardiopulmonary exercise test (CPET) results and the full-length spinal X-rays in a standing position of 64 adolescents with idiopathic scoliosis were reviewed retrospectively. Independent t-tests were used to compare the two datasets obtained from those with left or right thoracic scoliosis. The correlation between the Cobb angle and cardiopulmonary exercise endurance was analyzed using Pearson correlation coefficients, multiple factor linear regression and two-stage linear regression.Results:After adjusting for gender, age, height and weight, the multiple linear regression analysis showed that the Cobb angle was significantly negatively correlated with maximum tidal volume (β=-0.013) and significantly positively correlated with the rate of respiration (β=0.421). The relationship between the Cobb angle and cardiopulmonary exercise endurance was non-linear. With a Cobb angle > 34°, a 1° increase reduces cardiopulmonary exercise endurance by a factor of 1.4 on average. At smaller Cobb angles the corresponding increase is about 0.87 times.Conclusions:The Cobb angle is a negative predictor of ventilation during exercise among adolescents with idiopathic scoliosis. The more severe a patient′s spinal curvature, the lower the cardiopulmonary exercise endurance is likely to be.

Analysis of risk factors of death after cardiopulmonary bypass in children with congenital heart disease less than 5 kg / 中国综合临床

Objective:To investigate the risk factors for surgical death in children with congenital heart disease (CHD) less than 5 kg undergoing cardiopulmonary bypass.Methods:The clinical data of 225 children with CHD who underwent open cardiopulmonary bypass in the First Affiliated Hospital of Air Force Military Medical University from February 2017 to February 2020 were collected for a retrospective case-control study. The independent sample T test was used for inter-group comparison of measurement data, Chi square test or chi squre correction test was used for the comparision between count data. Mann-Whitney rank-sum test was used for rank distribution data and multiple Logistic regression analysis was performed for factors affecting surgical death of children with CHD.Results:Among the 225 cases, 204 (90.67%, 204/225) survived surgery and 21 (9.33%, 21/225) died. Univariate analysis showed that age (2.48±0.68) months and body weight (2.28±0.56) kg in the death group were significantly lower than that in the survival group (4.92±0.65) months ( t=16.33, P<0.001) and body weight (4.26±0.52) kg ( t=16.38, P<0.001), while the proportion of female (66.67% (14/21)), malnutrition (none: 14.28% (3/21); Mild: 42.86% (9/21). Severity: 42.86%(9/21)), palliative surgery proportion (28.57%(6/21)), emergency surgery proportion (71.43%(15/21)), congenital heart surgery risk assessment (RACHS-1) grading ratio (<grade 3: 23.81%(5/21), ≥grade 3: 76.19% (16/21)), CPB time (135.24±11.19) min, aorta blocking time (78.24±8.20) min, operation time (178.43±13.82) min, heart malformation complex ratio (complex: 47.62% (10/21), simple: 52.38% (11/21)), ICU treatment days (4.76±0.77) d, postoperative mechanical ventilation time (121.33±12.66) h were significantly higher than the female survival group (41.67% (85/204), χ2=4.83, P=0.028), malnutrition rate (none: 38.24%(78/204); Mild: 42.15% (86/204)); Severe: 19.61% (40/204) ( z=2.72, P=0.007), palliative surgery proportion 8.82% (18/204), proportion of radicalsurgery91.18% (186/204) ( χ2=5.86, P=0.016), RACHS-1 grading ratio (<grade 3:77.45% (158/204); ≥grade 3: 22.55% (46/204), χ2=27.44, P<0.001), CPB time (106.87±11.12) min ( t=11.12, P<0.001), aorta occlusion time (58.68±9.26) min ( t=9.32, P<0.001), operation time (167.24±13.75) min ( t=3.55, P<0.001), heart malformation complex ratio (complex: 78.92%(161/204), simple: 21.08%(43/204) ( χ2=10.23, P<0.001)), ICU treatment time (3.67±0.87) d ( t=5.52, P<0.001), postoperative mechanical ventilation time (109.74±13.75) h ( t=3.70, P<0.001). Logistic regression analysis showed that operation time ( OR=1.064, 95% CI: 1.019-1.110, P=0.004), postoperative mechanical ventilation time ( OR=1.083, 95% CI: 1.031~1.138, P=0.002), ICU treatment time ( OR=5.317, 95% CI: 2.410-11.730, P<0.001) and malnutrition ( OR=2.974, 95% CI: 1.291-6.850, P=0.010) were independent risk factors for surgical death after cardiopulmonary bypass in children with CHD less than 5 kg. Conclusions:The mortality rate of CHD patients with low body weight less than 5 kg was relatively high. The increase of operation time, ICU treatment time, degree of malnutrition and postoperative mechanical ventilation time will increase the probability of death. Targeted measures should be taken to reduce the surgical mortality of children.

Phase 1 safety and pharmacokinetics studies of BRII-196 and BRII-198, SARS-CoV-2 spike-targeting monoclonal antibodies

BackgroundBRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults. MethodsSingle ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days. ResultsAll infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development. ConclusionsBRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.

Analysis of surveillance results of brucellosis in Lushan County, Pingdingshan City, Henan Province from 2011 to 2019 / 中华地方病学杂志

Objective:The surveillance results of brucellosis in Lushan County, Pingdingshan City, Henan Province are analyzed to provide basis for formulating prevention and control strategies.Methods:Retrospective analysis method was used to collect the surveillance data from Lushan County Center for Disease Control and Prevention and Animal Husbandry Department from 2011 to 2019. Descriptive statistical analysis was made on the serological, pathogenic of brucellosis.Results:From 2011 to 2019, 15 943 high-risk people were investigated, and 10 834 were serologically tested, with a positive detection rate of 23.11% (2 504/10 834). Among them, the positive detection rate of brucellosis serum increased rapidly in 2013 and decreased after 2016. The positive detection rate was 25.87% (1 593/6 157) in men and 19.48% (911/4 677) in women. The age of positive detection was mainly 40-< 70 years old, accounting for 70.45% (1 764/2 504). The positive detection rate of farmers in all occupations was the highest, which was 25.97% (2 242/8 634). There were significant differences in the positive detection rates among different gender, age and occupation (χ 2=61.163, 27.855, 257.412, P < 0.01). A total of 578 blood samples from patients with acute brucellosis were isolated and cultured, 215 strains of Brucella were detected, and the positive detection rate was 37.20%. Conclusions:The high-risk group of human brucellosis in Lushan County, Pingdingshan City is middle-aged and elderly male farmers engaged in aquaculture. It is suggested that the joint prevention and control measures should be strengthened, the health education of high-risk groups should be strengthened, and comprehensive prevention and control measures should be taken to control the occurrence and prevalence of brucellosis.

Risk assessment of unintention injury among preschool children in Shunyi District of Beijing / 中国学校卫生

Objective@#To understand the current situation and associated factors of unintentional injury among preschool children in Shunyi District, and to provide reference for the development of unintentional injury intervention measures.@*Methods@#Three kindergartens in Shunyi district were selected through stratified cluster sampling method, and all the parents were surveyed online by self-designed questionnaire.@*Results@#The proportion of low, medium and high risk assessment of unintentional injury in preschool children were 59.5%, 37.5% and 3.0%, respectively. Risk of unintentional injury increased significantly with age and grade(χ 2=12.35, 12.70, P<0.05). The risk of unintentional injury in inter-generational care (3.7%) was higher than that in parental care(2.4%). The higher the education level of the primary caretaker and family income, the higher level of unintentional injury risk(χ 2=11.23, 14.10, P<0.05).There were significant differences in the risk for burning, poisoning, other accidental injury, prevention of accidental injury and total score of unintentional injury among children of different ages and classes(F=8.26，5.61，4.95，6.15，7.86；9.88，8.39，4.25，6.27，7.55，P<0.05). There was statistical significance in burning risk between boys and girls(t=-4.27, P<0.05). There was statistical significance in unintentional injury prevention between children of different residence(t=9.11, P<0.05). There were significant differences in behavior supervision among risk among children of different ages and grades(P<0.05). Multiple linear regression analysis showed that education level of primary caregivers (college:B=-2.66, 95%CI=-4.69--0.63; bachelor degree or higher:B=-3.80, 95%CI=-5.90--1.70), annual family income (B=-2.82, 95%CI=-4.80--0.84) were associated with unintentional injury risk of preschool children(P<0.05).@*Conclusion@#Health education of unintentional injury prevention among preschool children should focus on the primary caretaker with low education and low family income, which is crucial for prevention of children s injury.

An Antioxidant Enzyme Therapeutic for COVID-19

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. We report herein a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.

Risk factors for delirium in intensive care unit and its duration / 中华危重病急救医学

Objective:To screen risk factors for delirium and its duration in intensive care unit (ICU)patients.Methods:1 200 patients admitted to ICU of the Second Hospital of Shanxi Medical University from May 2017 to May 2019 were enrolled. The gender, age, anesthesia mode, duration of mechanical ventilation and hypoxia, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sedative drug use, and length of ICU stay were recorded. The occurrence and duration of ICU delirium were recorded. Multivariate Logistic regression analysis and multiple linear regression analysis were used to analyze the factors with statistical significance differences between the groups for screening the risk factors for delirium and its duration in ICU patients.Results:397 of 1 200 patients developed delirium, the incidence of ICU delirium was 33.1%. The duration of delirium in 189 patients (47.6%) was 1.0 day, and the duration of delirium in 397 delirium patients was 2.0 (1.5, 2.5) days. ① Analysis of risk factors for delirium: univariate analysis showed that there was no significant difference in the incidence of ICU delirium among patients with different genders or ages. The incidence of ICU delirium in patients with duration of mechanical ventilation or hypoxia 4-9 days and ≥ 10 days was higher than that in patients with ≤ 3 days. The incidence of ICU delirium of general anesthesia and internal medicine patients was higher than that of patients with lumbar anesthesia. The incidence of ICU delirium in patients with APACHEⅡ score ≥ 20 was higher than that in patients with ≤ 10 and 11-19. The patients with length of ICU stay > 9 days had a higher ICU delirium incidence than those ≤ 8 days. Increased incidence of ICU delirium in sedative patients was found as compared with those who did not use sedatives. Multivariate Logistic regression analysis showed that APACHEⅡ score [odds ratio ( OR) = 5.491, 95% confidence interval (95% CI) was 4.361-6.913, P < 0.001], the length of ICU stay ( OR = 2.679, 95% CI was 1.822-3.941, P < 0.001) and the use of sedatives ( OR = 2.479, 95% CI was 1.821-3.374, P < 0.001) were risk factors for ICU delirium. ② Analysis of risk factors of ICU delirium duration: univariate analysis showed that there was no significant difference in ICU delirium duration in patients with different genders or ages. The duration of ICU delirium in patients with duration of mechanical ventilation or hypoxia ≥ 10 days was longer than that in patients with ≤ 3 days and 4-9 days. The duration of ICU delirium in general anesthesia and non-surgical patients was higher than that in patients with spinal anesthesia. The ICU delirium duration in patients with APACHEⅡ score ≥ 20 was longer than that in patients with ≤ 10 and 11-19. The duration of ICU delirium in patients with the length of ICU stay > 9 days was longer than that in patients with ≤ 8 days. The duration of ICU delirium in patients on sedatives was longer than those not taking sedatives. Multiple linear regression analysis showed that the duration of ICU delirium increased by an average of 0.061 days (β = 0.061, 95% CI was 0.032-0.090, P < 0.001) for each additional day of hypoxia (hypoxia duration was divided into three grades of ≤ 3, 4-9 and ≥ 10 days). For every one increase in APACHE Ⅱ score (APACHE Ⅱ score was divided into three grades of ≤ 10, 11-19 and ≥ 20), duration of ICU delirium extended an average of 0.058 days (β = 0.058, 95% CI was 0.048-0.068, P < 0.001). ICU delirium duration increased by an average of 0.065 days in patients with length of ICU stay > 9 days as compared with those ≤ 8 days (β = 0.065, 95% CI was 0.056-0.075, P < 0.001). On average, the duration of ICU delirium was prolonged by 0.362 days in patients on sedatives as compared with those who did not use sedatives (β = 0.362, 95% CI was 0.234-0.490, P < 0.001). Conclusions:APACHEⅡ score, the length of ICU stay and the use of sedatives were common risk factors for ICU delirium and its duration. The hypoxic duration was risk factors for ICU delirium duration.

Efficacy of apatinib combined with etoposide in the treatment of patients with platinum-resistant recurrent ovarian cancer / 中国基层医药

Objective:To investigate the efficacy and safety of apatinib combined with etoposide capsules in the treatment of patients with platinum-resistant recurrent ovarian cancer.Methods:The clinical data and follow-up data of 63 patients with platinum-resistant recurrent ovarian cancer treated in Cancer Hospital of Jilin Province from January 2017 to June 2018 were analyzed retrospectively.According to the different treatment methods, the patients were divided into single group( n=28) and combination group( n=35). The patients in the single group were treated with etoposide capsules, while the patients in the combination group were treated with apatinib and etoposide capsules.The short-term clinical efficacy, progression free survival and adverse reactions of the two groups were compared. Results:The main adverse reactions of the two groups were anemia and leukopenia.There was no statistically significant difference in adverse reactions between the two groups( P>0.05). The objective response rate(ORR) of the combined group was 54.3%(19/35), which was higher than that of the single group [25.0%(7/28)](χ 2=5.504, P<0.05). The PFS of the combined group was 8 months(95% CI: 7.4-8.6 months), which was significantly longer than that of the single group(4 months, 95% CI: 3.5-4.5 months), the difference was statistically significant(χ 2=52.400, P<0.01). Conclusion:Apatinib combined with etoposide capsules is effective in the treatment of platinum resistant recurrent ovarian cancer, which can significantly extend the median PFS, without increasing the incidence of serious adverse reactions.