A Targeted Deep Sequencing Method to Quantify Endogenous Retrovirus Gag Sequence Variants and Open Reading Frames Expressed in Nonobese Diabetic Mice.

Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.

Multi-locus sequence typing and phylogenetics of Cryptococcus neoformans AD hybrids.

Hybrid AD strains of the human pathogenic Cryptococcus neoformans species complex have been reported from many parts of the world. However, their origin, diversity, and evolution are incompletely understood. In this study, we analyzed 102 AD hybrid strains representing 21 countries on five continents. For each strain, we obtained its mating type and its allelic sequences at each of the seven loci that have been used for genotyping haploid serotypes A and D strains of the species complex by the Cryptococcus research community. Our results showed that most AD hybrids exhibited loss of heterozygosity at one or more of the seven analyzed loci. Phylogenetic and population genetic analyses of the allelic sequences revealed multiple origins of the hybrids within each continent, dating back to one million years ago in Africa and up to the present in other continents. We found evidence for clonal reproduction and long-distance dispersal of these hybrids in nature. Comparisons with the global haploid serotypes A and D strains identified new alleles and new haploid multi-locus genotypes in AD hybrids, consistent with the presence of yet-to-be discovered genetic diversity in haploid populations of this species complex in nature. Together, our results indicate that AD hybrids can be effectively genotyped using the same multi-locus sequencing type approach as that established for serotypes A and D strains. Our comparisons of the AD hybrids among each other as well as with the global haploid serotypes A and D strains revealed novel genetic diversity as well as evidence for multiple origins and dynamic evolution of these hybrids in nature.

Emergency department presentations during the COVID-19 pandemic in Queensland (to June 2021): interrupted time series analysis.

OBJECTIVES: To assess emergency department (ED) presentation numbers in Queensland during the coronavirus disease 2019 (COVID-19) pandemic to mid-2021, a period of relatively low COVID-19 case numbers. DESIGN: Interrupted time series analysis. SETTING: All 105 Queensland public hospital EDs. MAIN OUTCOME MEASURES: Numbers of ED presentations during the COVID-19 lockdown period (11 March 2020 - 30 June 2020) and the period of easing restrictions (1 July 2020 - 30 June 2021), compared with pre-pandemic period (1 January 2018 - 10 March 2020), overall (daily numbers) and by Australasian Triage Scale (ATS; daily numbers) and selected diagnostic categories (cardiac, respiratory, mental health, injury-related conditions) and conditions (stroke, sepsis) (weekly numbers). RESULTS: During the lockdown period, the mean number of ED presentations was 19.4% lower (95% confidence interval, -20.9% to -17.9%) than during the pre-pandemic period (predicted mean number: 5935; actual number: 4786 presentations). The magnitudes of the decline and the time to return to predicted levels varied by ATS category and diagnostic group; changes in presentation numbers were least marked for ATS 1 and 2 (most urgent) presentations, and for presentations with cardiac conditions or stroke. Numbers remained below predicted levels during the 12-month post-lockdown period for ATS 5 (least urgent) presentations and presentations with mental health problems, respiratory conditions, or sepsis. CONCLUSIONS: The COVID-19 pandemic and related public restrictions were associated with profound changes in health care use. Pandemic plans should include advice about continuing to seek care for serious health conditions and health emergencies, and support alternative sources of care for less urgent health care needs.

Identification of risk factors for ewe mortality during the pregnancy and lambing period in extensively managed flocks.

BACKGROUND: Ewe mortality during pregnancy and lambing is an issue for sheep producers globally, resulting in reduced productivity and profitability, compromised ewe welfare, and poor consumer perception. Despite these negative consequences, there was little investigation into factors associated with ewe death during this time. Therefore, this study aimed to assess associations between ewe body condition score (BCS), weight, reproductive parameters, and risk of mortality during pregnancy and lambing. METHODS: Four cohorts from three commercial New Zealand farms participated, with 13,142 ewe lambs enrolled and followed over time. Data were collected for five consecutive lambings. Visits aligned with key on-farm management times, specifically: prior to breeding, at pregnancy diagnosis (PD), prior to lambing (set-stocking), and, at weaning of their lambs. At each visit, ewes were weighed, BCS assessed and reproductive status was recorded when relevant (litter size at PD and lactation status after lambing). Ewes that died or were culled were recorded, and any ewes that were absent from consecutive visits were presumed dead. Logistic regressions were developed to assess the relationship between weight and BCS at each visit, PD result (single or multiple-bearing) and lactation status (wet or dry) in each year, and, risk of mortality during the pregnancy and lambing period in each year. RESULTS: In the PD to weaning period, mortality incidence ranged from 6.3 to 6.9% for two-tooth (18-months-old at breeding) to mixed-age (54-months-old at breeding) ewes. For ewe lambs (7 to 8-months-old at breeding), mortality was 7.3% from set-stocking to weaning. Heavier ewe lambs at PD were less likely to die during lambing (OR: 0.978, p = 0.013), as were those with greater set-stocking BCS. In subsequent years, BCS was a predictor of ewe death, with odds of mortality greatest for ewes < BCS 2.5. Additionally, for poorer BCS ewes, increasing weight reduced risk of mortality, but there was no impact of increasing weight in greater BCS ewes. CONCLUSIONS: This study identified risk factors associated with ewe mortality during the pregnancy and lambing period. Flock owners can use these to either cull at-risk ewes or proactively intervene to reduce likelihood of mortality, thereby improving flock productivity, profitability and welfare.

Using CT imaging features to predict visceral pleural invasion of non-small-cell lung cancer.

AIM: To examine the diagnostic performance of different models based on computed tomography (CT) imaging features in differentiating the invasiveness of non-small-cell lung cancer (NSCLC) with multiple pleural contact types. MATERIALS AND METHODS: A total of 1,573 patients with NSCLC (tumour size ≤3 cm) were included retrospectively. The clinical and pathological data and preoperative imaging features of these patients were investigated and their relationships with visceral pleural invasion (VPI) were compared statistically. Multivariate logistic regression was used to eliminate confounding factors and establish different predictive models. RESULTS: By univariate analysis and multivariable adjustment, surgical history, tumour marker (TM), number of pleural tags, length of solid contact and obstructive inflammation were identified as independent risk predictors of pleural invasiveness (p=0.014, 0.003, <0.001, <0.001, and 0.017, respectively). In the training group, comparison of the diagnostic efficacy between the combined model including these five independent predictors and the image feature model involving the latter three imaging predictors were as follows: sensitivity of 88.9% versus 77% and specificity of 73.5% versus 84.1%, with AUC of 0.868 (95% CI: 0.848-0.886) versus 0.862 (95% CI: 0.842-0.880; p=0.377). In the validation group, the sensitivity and specificity of these two models were as follow: the combined model, 93.5% and 74.3%, the imaging feature model, 77.4% and 81.3%, and their areas under the curve (AUCs) were both 0.884 (95% CI: 0.842-0.919). The best cut-off value of length of solid contact was 7.5 mm (sensitivity 68.9%, specificity 75.5%). CONCLUSIONS: The image feature model showed great potential in predicting pleural invasiveness, and had comparable diagnostic efficacy compared with the combined model containing clinical data.

[Efficacy and safety of allogeneic hematopoietic stem cell transplantation for the treatment of primary myelofibrosis].

Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients. Methods: A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [M(Q1, Q3)]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months. Results: All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. Ⅱ-Ⅳ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection. Conclusion: Allo-HSCT can be used as a safe and effective approach to treat PMF.

[Antimicrobial resistance and plasmid-mediated colistin resistance mechanism of diarrheagenic Escherichia coli recovered from foods in parts of China in 2020].

Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.

[Antimicrobial resistance and genomic characterization of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces of China in 2020].

Objective: To understand the antimicrobial resistance and genome characteristics of Campylobacter isolates recovered from retailed poultry meat samples in 20 provinces in China in 2020. Methods: In 2020, 265 Campylobacter strains including 244 Campylobacter jejuni and 21 Campylobacter coli collected from retailed poultry meat samples in China were tested for antimicrobial resistance to 9 antimicrobial compounds by using the agar dilution method. Forty-two selected isolates were sent for whole genome sequencing and 38 high-quality genomes were analyzed for their antimicrobial resistance genes, virulence genes, sequence types and genetic diversity. Results: The resistance rates of Campylobacter isolates from poultry meats to tetracycline, nalidixic acid and ciprofloxacin were the highest (84%-100%), with 53.2% of the isolates showing multidrug resistance in this study. The resistance rates of C. coli to erythromycin, azithromycin, telithromycin, gentamicin and clindamycin were significantly higher than those of C. jejuni (P<0.05). The resistance genes conferring resistance to ß-lactams (100%, 38/38), quinolones (94.7%, 36/38), tetracycline (81.6%, 31/38) and aminoglycosides (50%, 19/38) were the most frequently detected among 38 Campylobacter genomes. C. jejuni carried more virulence genes than C. coli. In total, 19 and 17 sequence types (ST) were obtained from 20 sequenced C. jejuni and 18 C. coli isolates, respectively, including 5 novel STs. The isolates showed a high genetic diversity based on their sequence types. Conclusion: The phenomenon of antimicrobial resistance in Campylobacter from poultry meat sources in China is relatively serious, and resistance and virulence genes are widely distributed in Campylobacter. There is genetic diversity in Campylobacter.

[Hereditary pulmonary hypertension family with BMPR2 gene variation: a case report and literature review].

Objective: To describe the clinical characteristics, diagnosis, genetic features and treatment of hereditary pulmonary hypertension complicated with suspected hereditary hemorrhagic telangiectasia (HHT). Methods: Firstly, we summarized and analyzed the clinical data of two cases of suspected HHT admitted to the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University. Secondly, the genes of peripheral blood of patients and their families were completely sequenced and sanger sequencing was performed to verify the variation sites, and then the mRNA deletion caused by the variation was further verified. Thirdly, "HHT" "FPAH" and "BMPR2 gene variation" were used as keywords,and the related literatures of Wanfang database and PubMed database from January 2000 to November 2021 were searched and reviewed. Results: We found two patients in a family from Yiyang, Hunan province, who had symptoms of hemoptysis or pulmonary hypertension without epistaxis or other clinical features of HHT. However, both patients had pulmonary vascular abnormalities and pulmonary hypertension in their lungs. We found that BMPR2 gene variation (NM_001204.7:c.1128+1G>T) was positive and ENG, ACVRL1 and SMAD4 genes were negative. Family analysis and Sanger verification were carried out on 16 individuals in 4 generations of the family (7 of whom were found to carry the mutant gene), and then transcriptional level mRNA sequencing further confirmed that the variation resulted in the deletion of exon 8 and exon 9, and amino acid sequence estimation revealed that the amino acids of the protein from 323 to 425 were deleted. We thought that the incomplete translation of BMPR2 gene could lead to BMPRⅡ dysfunction. Therefore, it was diagnosed as hereditary pulmonary hypertension with suspected HHT. Both patients were suggested to reduce the pulmonary artery pressure, and at the same time, the whole-body imaging examination should be performed to screen other arteriovenous malformations, and the annual cardiac color Doppler ultrasound should be reviewed to evaluate the changes of pulmonary artery pressure. Conclusions: Hereditary pulmonary hypertension (HPAH) is a group of diseases with increasing pulmonary vascular resistance caused by genetic factors, including familial PAH and simple PAH. Variation in the BMPR2 gene is an important pathogenic factor of HPAH. Therefore, we should pay attention to the inquiry of family history when we clinically encounter young patients with pulmonary hypertension. If the cause is unknown, genetic testing is recommended. HHT is a rare autosomal dominant genetic disease. The possibility of this disease should be considered in clinical manifestations such as familial pulmonary vascular abnormality, pulmonary hypertension and recurrent epistaxis. There is no effective specific treatment for HPAH and HHT, which are treated symptomatically (including blood pressure reduction and hemostasis, etc.). It is suggested for these patients that pulmonary artery pressure should be dynamically monitored and have genetic counseling before giving birth.

[Study on the related factors of antiviral treatment in previously reported hepatitis C patients based on the Andersen model].

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.

[Influencing factors of poor treatment adherence in uncontrolled asthma patients in China].

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.

[A preliminary study on the efficacy and safety of a new type of trabeculotome tunnelling trabeculoplasty for open-angle glaucoma].

Objective: To compare the efficacy and safety of trabeculotome tunnelling trabeculoplasty and gonioscopy-assisted transluminal trabeculotomy (GATT) in the treatment of open-angle glaucoma. Methods: A prospective randomized controlled study. The patients with open-angle glaucoma diagnosed in the ophthalmology center of Beijing Tongren Hospital affiliated to Capital Medical University from January to July 2022 were collected and divided into GATT group (undergoing GATT) and 3T group (undergoing 3T operation) using a random number table. Intraocular pressure (IOP) was recorded for both groups at 1 day, 1 week, 1 month, and 3 months after the operation, and the types and quantities of anti-glaucoma drugs used, postoperative complications, and surgical success rate were compared. Normal distribution measurement data were analyzed using independent sample t-tests, non-normal distribution measurement data were analyzed using non-parametric tests, and counting data were analyzed using chi-square tests. Results: This study included 35 patients (43 eyes), consisting of 27 males and 8 females, with an average age of (43.0±14.3) years. There were 21 patients (23 eyes) in the GATT group and 19 patients (20 eyes) in the 3T group. The maximum IOP without anti-glaucoma drugs before surgery, the highest IOP with the maximum number of anti-glaucoma drugs, and the IOP at 3 months after surgery in the GATT group were (33.5±9.1), (22.2±6.1), and (16.0±3.1) mmHg (1 mmHg=0.133 kPa), respectively. The corresponding values for the 3T group were (35.2±7.8), (21.5±6.8), and (16.1±2.0) mmHg. After surgery, the IOP in both groups was lower than before surgery, with a statistically significant difference (P<0.05) and no significant difference between the two groups (P>0.05). In the 3 months following surgery, 13 eyes in the GATT group and 11 eyes in the 3T group received more than two types of anti-glaucoma drugs, with no significant difference between the two groups (P>0.05). Three months after surgery, the complete and conditional success rates of the GATT group were 14/18 and 16/18, respectively, and those of the 3T group were 12/15 and 13/15, respectively, with no significant difference between the two groups (P>0.05). The incidence of hyphema, ciliary detachment, and shallow anterior chamber 1 day after surgery was 91%(21/23), 35%(8/23), and 30%(7/23), respectively, in the GATT group and 55%(11/20), 5%(1/20), and 0 in the 3T group, with a statistically significant difference between the two groups (P<0.05). Conclusion: 3T and GATT have similar success rates in the treatment of open-angle glaucoma. However, compared with GATT, 3T has fewer complications and is considered to be safer. (This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on February 28, 2023).

[A prospective study on the safety and efficacy of excimer laser coronary angioplasty for the treatment of degenerated great saphenous vein graft].

Objective: To explore the safety and efficacy of excimer laser coronary angioplasty (ELCA) for the treatment of degenerated great saphenous vein graft (SVG). Methods: This is a single-center, prospective, single-arm study. Patients, who were admitted to the Geriatric Cardiovascular Center of Beijing Anzhen Hospital from January 2022 to June 2022, were consecutively enrolled. Inclusion criteria were recurrent chest pain after coronary artery bypass surgery (CABG), and coronary angiography confirmed that the SVG stenosis was more than 70% but not completely occluded, and interventional treatment for SVG lesions was planned. Before balloon dilation and stent placement, ELCA was used to pretreat the lesions. Optical coherence tomography (OCT) examination was performed and postoperative index of microcirculation resistance (IMR) were assessed after stent implantation. The technique success rate and operation success rate were calculated. The technique success was defined as the successful passage of the ELCA system through the lesion. Operation success was defined as the successful placement of a stent at the lesion. The primary evaluation index of the study was IMR immediately after PCI. Secondary evaluation indexes included thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), minimal stent area and stent expansion measured by OCT after PCI, and procedural complications (Ⅳa myocardial infarction, no reflow, perforation). Results: A total of 19 patients aged (66.0±5.6) years were enrolled, including 18 males (94.7%). The age of SVG was 8 (6, 11) years. The length of the lesions was greater than 20 mm, and they were all SVG body lesions. The median stenosis degree was 95% (80%, 99%), and the length of the implanted stent was (41.7±16.3)mm. The operation time was 119 (101, 166) minutes, and the cumulative dose was 2 089 (1 378, 3 011)mGy. The diameter of the laser catheter was 1.4 mm, the maximum energy was 60 mJ, and the maximum frequency was 40 Hz. The technique success and the operation success rate were both 100% (19/19). The IMR after stent implantation was 29.22±5.95. The TIMI flow grade of patients after ELCA and stent implantation was significantly improved (all P>0.05), and the TIMI flow grade of all patients after stent implantation was Grade Ⅲ. The cTFC decreased significantly after ELCA (33.2±7.8) and after stent placement (22.8±7.1) than preoperative level (49.7±13.0) (both P<0.001). The minimum stent area was (5.53±1.36)mm2, and the stent expansion rate was (90.0±4.3)%. Perforation, no reflow, type Ⅳa myocardial infarction and other complications were not observed. However, postoperative high-sensitivity troponin level was significantly increased ((67.937±33.839)ng/L vs. (5.316±3.105)ng/L, P<0.001). Conclusion: ELCA is safe and effective in the treatment of SVG lesions and could improve microcirculation and ensure full expansion of stent.

[Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province].

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

[Expression analysis of inflammatory factors in artificial quartz stone plate processing silicosis patients].

Objective: To investigate the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1ß) in the plasma and bronchoalveolar lavage fluid of silicosis patients with artificial quartz stone plate processing. Methods: In January 2022, 10 patients with artificial quartz stone plate processing silicosis and 20 patients with common silicosis who were hospitalized and diagnosed in a hospital at Zhejiang Province from June 2019 to December 2021 were retrospectively selected as the research objects, and 30 healthy people were selected as the control group during the same period. Plasma of all subjects and bronchoalveolar lavage fluid of all patients were collected. The levels of TNF-α, IL-6 and IL-1ß in plasma and bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay and were analyzed. Results: The levels of TNF-α, IL-6 and IL-1ß in the plasma of patients with silicosis were higher than those of the control group (P<0.05), and the levels of TNF-α and IL-1ß in the plasma of silicosis patients with artificial quartz stone plate processing were higher than those of common silicosis patients (P<0.05). The levels of TNF-α and IL-1ß in plasma of artificial quartz stone plate processing silicosis patients were higher than those of common silicosis patients at the same silicon stage (P<0.05). The levels of IL-1ß in bronchoalveolar lavage fluid of silicosis patients with artificial quartz stone plate processing was higher than that of patients with common silicosis (P<0.05) . Conclusion: The levels of TNF-α, IL-6 and IL-1ß in silicosis patients with artificial quartz stone plate processing are higher than those in patients with common silicosis, which may be related to dust components they are exposed to.

[Analysis of factors influencing lung function in patients with pneumoconiosis].

Objective: To analyze the influencing factors of lung function in pneumoconiosis patients, and to provide reference for clinical treatment. Methods: From July 2020 to December 2020, a questionnaire survey was conducted on pneumoconiosis patients in the jurisdiction by using the "Guangdong Province Occupational Disease Prevention and Control Institute" questionnaire, and the relevant items of patients were examined. The rate of counting data is expressed, and the measurement data is expressed by mean and standard deviation. Chi-square test was used for comparison between groups, trend chi-square test was used for trend analysis of ordered classified data. Multivariate analysis was carried out with binary logistic regression model. Results: A total of 1409 pneumoconiosis patients were enrolled. The abnormal rate of lung function in pneumoconiosis patients was 68.77%. The results of trend Chi-square test showed that the abnormal rate of lung function increased with the age of exposure to dust in different age groups (Chi Sqnare Trend=64.12、8.49、24.20, P<0.05) . In univariate analysis, there were statistical significance in different dust exposure age, working age, pneumoconiosis stage, complications and occupational pneumoconiosis diseases (P<0.05) . Multiple logistic regression results showed that age of exposure to dust, years of service, stage of pneumoconiosis and complications were the main influencing factors of lung function in pneumoconiosis patients (P<0.05) . Compared with patients aged 0-30 years, patients aged 50-70 years and older had a higher rate of abnormal lung function (OR=2.16, 95%CI: 1.12~4.16; OR=4.82, 95%CI: 2.05~11.35, all P<0.05) ; Compared with patients with 0~20 years of service, patients with 20~30 years of service and more than 30 years of service had a higher rate of abnormal lung function (OR=1.58, 95%CI: 1.10~2.25; OR=1.63, 95%CI: 1.28~2.40, P<0.05) ; Compared with stage Ⅰ patients, Stage Ⅱ and Stage Ⅲ patients had a higher rate of abnormal lung function (OR=1.62, 95%CI: 1.20~2.17; OR=2.23, 95%CI: 1.40~3.55, all P<0.05) ; Compared with patients without comorbidities, patients with comorbidities had a higher rate of abnormal lung function (OR=1.68, 95%CI: 1.20~2.38, P<0.05) . Conclusion: The factors such as age of exposure to dust, working age, stage of pneumoconiosis and complications may be the influencing factors of lung function in pneumoconiosis patients.

Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain.

BACKGROUND: People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI. METHODS: Female Sprague-Dawley rats (230-250 g) with T10 compression or laminectomy were evaluated for physical conditions, coordinated hindlimb functions, neurological reflexes, and mechanical/thermal sensitivity thresholds at 1 day post-injury (p.i.) and weekly thereafter. Eight weeks p.i., central nervous system tissues were histochemically and immunohistochemically characterized for parameters/markers of histopathology and NIF/NTM/NML/NPL. Also analyzed was the correlative relationship between levels of selected biomarkers and thermosensitivity thresholds via statistical linear regression. RESULTS: SCI impaired sensorimotor functions, altered reflexes, and produced spontaneous pain signs and hypersensitivity to evoked nociceptive, mechanical, and thermal inputs. Only injured spinal cords exhibited neural lesion, microglia/astrocyte activation, and abnormal expression of proinflammatory cytokines, as well as NIF/NTM/NML/NPL markers. Brains of SCI animals displayed similar pathophysiological signs in the gracile and parabrachial nuclei (GrN and PBN: sensory relay), raphe magnus nucleus and periaqueduct gray (RMN and PAG: pain modulation), basolateral amygdala (BLA: emotional-affective dimension of pain), and hippocampus (HPC: memory/mood/neurogenesis). SCI augmented sensory NTM/NPL (GrN and PBN); increased GAD67 (PAG) level; reduced serotonin (RMN) and fear-off neuronal NTR2 (BLA) expressions; and perturbed neurogenesis (HPC). CONCLUSION: T10 compression caused chronic hyperalgesia that coexisted with NIF/NTM/NML/NPL responses at multilevel neuroaxis centers. The data have provided multidimensional biomarkers as new mechanistic leads to profile SCI NP for therapeutic/therapy development.

ATP and spontaneous calcium oscillations control neural stem cell fate determination in Huntington's disease: a novel approach for cell clock research.

Calcium, the most versatile second messenger, regulates essential biology including crucial cellular events in embryogenesis. We investigated impacts of calcium channels and purinoceptors on neuronal differentiation of normal mouse embryonic stem cells (ESCs), with outcomes being compared to those of in vitro models of Huntington's disease (HD). Intracellular calcium oscillations tracked via real-time fluorescence and luminescence microscopy revealed a significant correlation between calcium transient activity and rhythmic proneuronal transcription factor expression in ESCs stably expressing ASCL-1 or neurogenin-2 promoters fused to luciferase reporter genes. We uncovered that pharmacological manipulation of L-type voltage-gated calcium channels (VGCCs) and purinoceptors induced a two-step process of neuronal differentiation. Specifically, L-type calcium channel-mediated augmentation of spike-like calcium oscillations first promoted stable expression of ASCL-1 in differentiating ESCs, which following P2Y2 purinoceptor activation matured into GABAergic neurons. By contrast, there was neither spike-like calcium oscillations nor responsive P2Y2 receptors in HD-modeling stem cells in vitro. The data shed new light on mechanisms underlying neurogenesis of inhibitory neurons. Moreover, our approach may be tailored to identify pathogenic triggers of other developmental neurological disorders for devising targeted therapies.

Association between cerebral blood flow changes and blood-brain barrier compromise in spontaneous intracerebral haemorrhage.

AIM: To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the association between the alterations in cerebral blood flow and BBB permeability around the haematoma. MATERIALS AND METHODS: Spontaneous ICH patients underwent unenhanced computed tomography (CT) and CT perfusion (CTP) simultaneously. Haematoma volume was measured on CT. The values of cerebral haemodynamic parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and permeability-surface area product (PS) were measured in the perihaematomal region and the contralateral mirror region, and then relative values were calculated for statistical analysis. Linear regression was used to evaluate associations between BBB permeability and variables. RESULTS: A total of 87 ICH patients were included in this study. The focally elevated BBB permeability was observed in the perihaematomal region in ICH patients. Linear regression showed that reduced rCBF (ß = -0.379, p=0.001) and increased rCBV (ß = 0.412, p=0.000) correlated independently with increased relative PS (rPS) value in deep ICH, while only increased rCBV (ß = 0.423, p=0.071) correlated to increased rPS value in patients with lobar ICH. CONCLUSIONS: BBB permeability is focally elevated in the region around the haematoma. Cerebral haemodynamic alterations are associated with increased BBB permeability. Cerebral hypoperfusion may aggravate BBB compromise, and a compensatory increase in CBV may lead to reperfusion injury on BBB.

Diagnosing subclinical facial eczema in cattle: does combining liver enzyme tests increase the accuracy of diagnosis?

AIMS: To assess whether adding glutamate dehydrogenase (GDH) activity measurements to measurements of gamma-glutamyl transferase (GGT) activity appreciably increases the accuracy of diagnosis of subclinical facial eczema (FE) in cattle. METHODS: As part of a larger study on the impact of FE on productivity, GGT and GDH activities were measured in serum samples collected from 426 cattle from one dairy farm in the Taranaki region in April 2018. Bayesian latent class analysis was then used to estimate herd prevalence of subclinical FE as well as the specificity and sensitivity of the activity in serum of GGT or GDH alone, and of GGT and GDH activities combined, as diagnostic tests for subclinical FE. RESULTS: The latent class analysis estimated the true prevalence of subclinical FE in the study population as 47.5 (95% probability interval (PI) = 38.3-55.3)%. There was no evidence of any clinically relevant difference between GGT and GDH activities as predictors of subclinical FE; the difference between the areas under the receiver operating characteristic curves for the two measures was 0.005 (95% PI = -0.02 to -0.03). Using the two tests in parallel, with a threshold of 50 IU/L for GGT and 225 IU/L for GDH resulted in specificity and sensitivity of >95%, markedly increasing the accuracy of diagnosis of subclinical FE compared to using GGT or GDH alone at any threshold. CONCLUSIONS AND CLINICAL RELEVANCE: In this herd, combining the two tests resulted in a clinically relevant improvement in the accuracy of diagnosis of subclinical FE compared to using either test alone, which if used at the individual level will result in fewer cattle being assigned the wrong FE status. This will also apply at the herd level, with combined testing producing fewer false-positive herd test results than using one enzyme alone. This is particularly important for monitoring the efficacy of FE control measures when the expectation should be that the proportion of cattle with FE is very low.