Age effect on the shared etiology of glycemic traits and serum lipids: evidence from a Chinese twin study.

PURPOSE: Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS: This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS: All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION: Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.

[Advances in the co-signal molecular function of Mtb-specific T lymphocytes].

Costimulatory and co-inhibitory receptors on T lymphocytes play an essential role in the immune response. There is increasing evidence that the expression of co-signal molecules on T cells is altered in infection, tumor, autoimmunity, and other diseases, and that intervention of co-signal molecules can be used in the immunotherapy. This paper reviewed the costimulatory and coinhibitory receptors on Mtb-specific T lymphocytes and further explained the mechanism of co-signal molecules in the progression of tuberculosis, to provide a reference for future research and clinical application.

[Evaluation of the efficacy of urine-based lipoarabinomannan antigen test in the diagnosis of pulmonary tuberculosis].

Objective: To analyze the diagnostic efficacy of urinary lipoarabinomannan (LAM) antigen detection method in tuberculosis patients, and to provide an experimental basis for the clinical application of urinary LAM kit in China. Methods: From March to May 2023, 228 patients with lung diseases [134 male, 94 female, age 20-82 (44.8±16.7) years] were prospectively collected in Beijing Chest Hospital, Capital Medical University, including 143 pulmonary tuberculosis patients and 85 non-tuberculosis patients. Urine and sputum samples from patients were collected for traditional etiological detection and urinary LAM antigen detection. The screening results of each positive detection combination were analyzed, and the difference analysis and regression analysis were performed. Results: The detection sensitivity and specificity of the urinary LAM kit were 46.2% (95%CI: 37.9%-54.7%) and 96.5% (95%CI: 89.3%-99.1%), respectively, with an overall coincidence rate of 64.9%. The detection rate of LAM antigen detection and GeneXpert MTB/RIF (Xpert) combined (60.8%, 87/143) was significantly higher than that of Xpert alone (49.7%, 71/143), and the difference was statistically significant (P<0.05). The results of risk factor analysis showed that the risk of negative urinary LAM antigen test results increased significantly as the bacterial load decreased. Conclusions: Urine LAM antigen detection method has a high specificity and can be combined with traditional methods to effectively improve the detection rate. Urinary LAM antigen detection method still has limitations, such as the influence of bacterial load and the inability to distinguish nontuberculosis mycobacteria samples, which needs further experimental verification.

Comparison of Aortobifemoral Bypass and Endovascular Treatment for Chronic Infrarenal Abdominal Aortic Occlusion From the CHAOS (CHronic Abdominal Aortic Occlusion, ASian Multicenter) Registry.

PURPOSE: To directly compare the clinical outcomes of aortobifemoral bypass surgery (ABF) and endovascular treatment (EVT) for chronic total occlusion (CTO) of the infrarenal abdominal aorta (IAA). MATERIALS AND METHODS: In this retrospective, multicenter study, we used an international database of 436 patients who underwent revascularization for CTO of the IAA between 2007 and 2017 at 30 Asian cardiovascular centers. After excluding 52 patients who underwent axillobifemoral bypass surgery, 384 patients (139 ABFs and 245 EVTs) were included in the analysis. Propensity score-matched analysis was performed to compare clinical results in the periprocedural period and the long-term. RESULTS: Propensity score matching extracted 88 pairs. Procedure time (ABF; 288 [240-345] minutes vs EVT; 159 [100-205] minutes, p<0.001) and length of hospital stay (17 [12-23] days vs 5 [4-13] days, p<0.001) were significantly shorter in the EVT group than in the ABF group, while the proportions of procedural success (98.9% versus 96.6%, p=0.620), complications (9.1% versus 12.3%, p=0.550), and mortality (2.3% versus 3.8%, p=1.000) were not different between the groups. At 1 months, ABI significantly increased more in the ABF group for both in a limb with the lower (0.56 versus 0.50, p=0.018) and the higher (0.49 versus 0.34, p=0.001) baseline ABI, while the change of the Rutherford category was not significantly different between the groups (p=0.590). At 5 years, compared with the EVT group, the ABF group had significantly better primary patency (89.4±4.3% versus 74.8±4.3%, p=0.035) and survival rates (86.9±4.5% versus 66.2±7.5%, p=0.007). However, there was no significant difference between the groups for secondary patency (100.0%±0.0% versus 93.5%±3.9%, p=0.160) and freedom from target lesion revascularization (TLR) (89.3±4.3% vs 77.3±7.3%, p=0.096). CONCLUSION: Even with recent advancements in EVT, primary patency was still significantly better for ABF in CTO of the IAA. However, there was no difference between the groups in terms of secondary patency and freedom from TLR at 5 years. Furthermore, there was no difference in procedural success, complications, mortality, and improvement in the Rutherford classification during the periprocedural period, with significantly shorter procedure time and hospital stay in the EVT group.

Development and validation of a novel nomogram predicting pseudohypoxia type pheochromocytomas and paragangliomas.

PURPOSE: Pseudohypoxia type (PHT) pheochromocytomas and paragangliomas (PPGLs) are more likely to metastasize and have a poor prognosis. However, application of genetic tests has many restrictions. The study aims to establish a novel nomogram for predicting the risk of PHT PPGLs. METHODS: This retrospective cross-sectional study included 242 patients with pathology confirmed PPGLs in one tertiary care center in China in 2010-2021. Clinical and biochemical characteristics were collected. Next-generation sequencing was performed in all PPGLs patients for detection of mutation. Univariate and multivariable logistic regression analyses were used to select risk factors for constructing the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the nomogram and the calibration curve was performed. RESULTS: Four variables including age ≤ 35 years, hypertension, 24 h urinary output of urinary vanillylmandelic acid (VMA) ≥ 100 umol/24 h and urinary 17-ketosteroide (17 KS) ≤ 50 umol/24 h levels were independently associated with PHT PPGLs in the logistic regression analysis and were included in the nomogram. The nomogram showed a good discrimination performance with AUC of 0.829 [95% confidence interval (CI), 0.767-0.891] in the training set and 0.797 (95%CI, 0.659-0.935) in the validation set, respectively. The calibration curve showed a bias-corrected AUC of 0.809 vs. 0.795, and a Hosmer-Lemeshow (H-L) test yielded a p value of 0.801 vs. 0.885, indicating the nomogram's good ability to distinguish PHT PPGLs from non-PHT PPGLs. CONCLUSION: Our study has proposed a novel nomogram for individualized prediction of the PHT PPGLs, which may make contributions to guide the patients' personalized management, follow-up, and treatment.

[Effect of Mycobacterium tuberculosis protein Rv0309 on intracellular survival of Mycobacterium smegmatis by inhibiting macrophage autophagy via protein STUB1].

Objective: To investigate the molecular regulatory mechanism of Mycobacterium tuberculosis (MTB) protein Rv0309 to promote the survival of Mycobacterium smegmatis (Ms) in macrophages. Methods: Using Ms as a model to study Mycobacterium tuberculosis, recombinant Ms transfected with pMV261 and PMV261-RV0309 in the control group and RAW264.7 cells were constructed. The effect of Rv0309 protein on intracellular survival of Ms was investigated by counting colony forming units (CFUs). Mass spectrometry was used to screen proteins interacting with host protein Rv0309, and immunocoprecipitate (Co-IP) was used to verify that host protein STUB1 could interact with host protein Rv0309. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and CFUs were counted to explore the effect of protein Rv0309 on intracellular survival of Ms after STUB1 gene knock-out. STUB1 gene knock-out RAW264.7 cells were infected with Ms, and after obtaining samples, Western blotting assay was performed to explore the effect of protein Rv0309 on autophagy function of macrophages after STUB1 gene knock-out. Statistical analysis was performed using GraphPad Prism 8 software. T-test was selected for analysis in this experiment, with P<0.05 was considered statistically significant. Results: Western blotting showed that Rv0309 was expressed in M. smegmatis and secreted extracellularly. The CFUs of the Ms-Rv0309 group was higher than that of Ms-pMV261 group at 24 h after THP-1 macrophage infection, and the difference was statistically significant (P<0.05). The trend of infected RAW264.7 macrophages was the same as that of infected THP-1 macrophages. The Co-IP results showed that the corresponding Flag and HA bands appeared in the results of immunoprecipitation (IP):Flag and IP: HA. The level of CFUs in the experimental group with STUB1 deletion was significantly higher than that in the control group without STUB1 deletion. Compared with Ms-pMV261, the CFUs in the Ms-Rv0309 group was significantly higher than that in the Ms-pMV261 group. The gray scale of LC3Ⅱ bands of Ms-Rv0309 in experimental group was lighter than that of Ms-pMV261 in the control group at the corresponding time point, and the result was most significant at 8 h (LC3Ⅱ/ß-actin: 0.76±0.05 vs 0.47±0.07), the difference being statistically significant (P<0.05). After STUB1 genome knock-out, the gray level of LC3Ⅱ bands at the corresponding time was lighter than that without STUB1 genome knock-out. Comparison of the results of Ms-pMV261 and Ms-Rv0309 strains revealed that LC3Ⅱ band gray Rv0309 group was lighter at the corresponding time compared with pMV261 group. Conclusions: MTB protein Rv0309 can be successfully expressed in M. smegmatis and secreted extracellularly, which can inhibit the autophagy process of macrophages. Protein Rv0309 interacts with host protein STUB1 to inhibit macrophage autophagy and promote intracellular survival of Ms.

[Surgical treatment strategy of pulmonary artery sling: a series of 110 cases].

Objective: To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy. Methods: Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging (M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results: Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time. Conclusions: Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

[Treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations].

Objective: To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations. Methods: This is a retrospective case series. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged (M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results: There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection (Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 patient in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn't have obvious respiratory symptoms. Conclusions: The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Gut dysbiosis in cutaneous T-cell lymphoma is characterized by shifts in relative abundances of specific bacterial taxa and decreased diversity in more advanced disease.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) patients often suffer from recurrent skin infections and profound immune dysregulation in advanced disease. The gut microbiome has been recognized to influence cancers and cutaneous conditions; however, it has not yet been studied in CTCL. OBJECTIVES: To investigate the gut microbiome in patients with CTCL and in healthy controls. METHODS: A case-control study was conducted between January 2019 and November 2020 at Northwestern's busy multidisciplinary CTCL clinic (Chicago, Illinois, USA) utilizing 16S ribosomal RNA gene amplicon sequencing and bioinformatics analyses to characterize the microbiota present in fecal samples of CTCL patients (n = 38) and age-matched healthy controls (n = 13) from the same geographical region. RESULTS: Gut microbial α-diversity trended lower in patients with CTCL and was significantly lower in patients with advanced CTCL relative to controls (P = 0.015). No differences in ß-diversity were identified. Specific taxa were significantly reduced in patient samples; significance was determined using adjusted P-values (q-values) that accounted for a false discovery rate threshold of 0.05. Significantly reduced taxa in patient samples included the phylum Actinobacteria (q = 0.0002), classes Coriobacteriia (q = 0.002) and Actinobacteria (q = 0.03), order Coriobacteriales (q = 0.003), and genus Anaerotruncus (q = 0.01). The families Eggerthellaceae (q = 0.0007) and Lactobacillaceae (q = 0.02) were significantly reduced in patients with high skin disease burden. CONCLUSIONS: Gut dysbiosis can be seen in patients with CTCL compared to healthy controls and is pronounced in more advanced CTCL. The taxonomic shifts associated with CTCL are similar to those previously reported in atopic dermatitis and opposite those of psoriasis, suggesting microbial parallels to the immune profile and skin barrier differences between these conditions. These findings may suggest new microbial disease biomarkers and reveal a new angle for intervention.

Cloning, genome structure and expression analysis of MHC class I gene in Korean quail.

1. The major histocompatibility complex (MHC) is a highly polymorphic region of the genome essential to immune responses and animal health. However, avian MHC genetic structure is different from that of mammals. In this study, the structure and expression of Korean quail MHC class I gene was analysed.2. The quail MHC gene consisted of eight exons and seven introns. The open reading frame of the cDNA was 353 amino acids, and the molecular weight was about 38.91 kDa. Exons 1 and 2 coded for leading peptides and alpha 1 regions, respectively. Exons 3 and 4 encoded alpha 2 and alpha 3 regions. Exons 5 to 8 coded for connecting peptides and transmembrane regions/cytoplasmic regions (TM/CY). The Korean quail MHC class I amino acid sequence shared 87% to 99% homology with Japanese quail and 71% to 75% with chicken. The amino acid shared 40% and 43% homology with humans and mice, respectively.3. Real-time quantitative PCR showed that MHC-I was highly expressed in immune tissues such as the bursa of Fabricius. Moreover, the constructed evolutionary tree was consistent with accepted evolutionary pathways.4. MHC-I is closely related to the host's immune system, and these findings may help to better understand the role of Korean quail MHC-I in the immune system.

[Trend analysis of influenza vaccination among hospitalized elderly people in Beijing, 2013-2019].

OBJECTIVE: To analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. METHODS: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. RESULTS: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). CONCLUSION: The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.

[Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins].

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

[Exploratory study on detection of drug resistance of Mycobacterium tuberculosis in sputum specimens by next-generation sequencing].

Objective: To compare the diagnostic performance of next-generation sequencing (NGS) detection methods in sputum samples and Mycobacterium tuberculosis strains, in order to explore the feasibility of the NGS method to detect drug resistance in sputum specimens. Methods: In this retrospective study, the sputum specimens and corresponding clinical isolates of 50 pulmonary tuberculosis patients admitted to Beijing Chest Hospital from January 2017 to December 2017 were collected. The gene mutations of katG, inhA, rpoB, embA, embB, rpsL, rrs, gyrA, gyrB and tlyA in sputum specimens and corresponding clinical isolates were detected by NGS method. The phenotypic drug susceptibility test (DST) of the strains was carried out by the proportion method. Using DST results as a reference, the sensitivity, specificity, positive predictive value and negative predictive value of the NGS method for clinical strains and sputum specimens, as well as the consistency statistic (Kappa) with phenotype DST were calculated respectively. The Chi-square test was used to compare the accuracy of the NGS testing in sputum samples and strain samples. Results: The results showed that rpoB(63.83%, 30/47) and rrs(57.45%, 27/47) were the most common mutated genes, followed by katG(46.81%, 22/47), rpsL(29.79%, 14/47), gyrA(27.66%, 13/47), embB(21.28%, 10/47), tlyA(12.77%, 6/47), gyrB(8.51%, 4/47), and inhA promoter(19.15%, 9/47), embA promoter region (12.77%, 6/47) mutation. when the NGS method was compared with the resistance phenotype of isoniazid, rifampicin, ethambutol, second-line injectable drugs (streptomycin, capreomycin, kanamycin, amikacin), levofloxacin, the sensitivity were 85.71%, 91.67%, 77.78%, 81.82%, 100.00%, 87.50%, 100.00%, 69.23%, and the specificity were 100.00%, 94.12, 87.50%, 89.47%, 97.06%, 96.97%, 94.29%, 89.29% in sputum samples, while in strain samples, the sensitivity were 92.86%, 100.00%, 81.82%, 86.96%, 88.89%, 80.00%, 100.00%, 85.71%. The specificity were 100.00%, 92.86%, 87.10%, 94.74%, 100.00%, 100.00%, 97.14%, 92.86%. Compared with the phenotypic drug susceptibility results, the NGS method has better detection performance for isoniazid, rifampicin, capreomycin, kanamycin, and amikacin in sputum specimens (Kappa≥0.75); while among the strains, the NGS method had a good detection performance for isoniazid, rifampicin, streptomycin, capreomycin, kanamycin, amikacin and levofloxacin (Kappa≥0.75). With the accuracy of the NGS method for detecting strains as a reference, there was no statistically significant difference in the accuracy of all drug resistance detected between strains and sputum specimens. Conclusions: This study showed that the NGS technology was effective in predicting the resistance of isoniazid, rifampicin, and second-line injectable drugs (capreomycin, kanamycin and amikacin) by detecting sputum samples and strain genotypes, suggesting the feasibility and potential of direct detection of sputum samples by the NGS method as an early detection method for drug resistance.

[Serum LAPTM4B-35 protein as a novel diagnostic marker for hepatocellular carcinoma].

OBJECTIVE: LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B. This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro, as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients. METHODS: Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells. RESULTS: LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients (n=43) were both significantly higher than that in the blood of normal donors (n=33) through sandwich ELISA. CONCLUSION: It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.

[Effect of long non-coding RNA MBNL1-AS1 expression on prognosis of acute myeloid leukemia patients].

Objective: To explore the prognosis effect of the expression of long-chain non-coding RNA (lncRNA) MBNL1-AS1 on acute myeloid leukemia (AML) patients. Methods: One hundred and twenty-five AML patients of the Cancer Genome Atlas (TCGA) from November 2001 to March 2010 were involved, including 70 patients who received chemotherapy only and other 55 patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in addition to chemotherapy. According to the median expression of lncRNA MBNL1-AS1, patients of chemotherapy group were divided into high expression sub-group(n=35) and low expression sub-group (n=35), and patients of allo-HSCT group were also divided into high expression sub-group (n=28) and low expression sub-group (n=27) for prognosis analysis. Clinical characteristics at diagnosis, including peripheral white blood cell counts (WBC), blast percentages in peripheral blood and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations in AML were described. The event-free survival (EFS) rate and overall survival (OS) rate of patients in different groups were analyzed, and the influence of the clinical characteristics of patients on the prognosis of AML was analyzed by COX multivariate analysis. Results: In the chemotherapy group, patients with low lncRNA-MBNL1-AS1 expression had significantly lower EFS and OS (60.0%, 8.6%) than patients with high lncRNA-MBNL1-AS1 expression (68.6%, 34.3%) (χ²=7.817, 10.880, all P<0.01). However, in the alloHSCT group, no significant differences were observed in EFS and OS of patients between high and low expression groups of lncRNA-MBNL1-AS1 (all P>0.05). COX multivariate analysis confirmed that age≥60 years old (EFS: HR (95%CI): 6.934 (1.918-25.075),P=0.003;OS: HR (95%CI): 4.119 (1.812-9.364), P=0.001), and low expression of lncRNA MBNL1-AS1 (EFS: HR (95%CI): 0.354 (0.126-0.941), P=0.038; OS: HR (95%CI): 0.424 (0.231-0.778), P=0.006)were independent risk factors for EFS and OS in the chemotherapy group. Conclusion: The long-chain non-coding RNA MBNL1-AS1 is related to the prognosis of AML, and its low expression is an independent poor prognostic factor in AML patients.

Depressive symptoms, professional quality of life and turnover intention in Korean nurses.

AIM: The purpose of this study was to identify the effects of depressive symptoms and professional quality of life on turnover intention. BACKGROUND: The high turnover rate of nurses is a critical healthcare issue globally. INTRODUCTION: Nurses often experience depressive symptoms and compassion fatigue due to the efforts of patient care. The impact of such psychological health issues on turnover intention needs to be confirmed. METHODS: Participants were 10 163 female nurses who completed an online or mobile survey using the Korea Nurses' Health Study. To identify the influencing factors on the turnover intention of nurses, descriptive statistics, spearman's correlation coefficients and multivariable ordinal logistic regression were performed. RESULTS: The turnover intention increased by about 2.81-4.60 times when depressive symptom was moderate or more, 1.14 times when secondary traumatic stress disorder was moderate or more, and 1.54 times when burnout was moderate or more. When compassion satisfaction was moderate or high, the turnover intention decreased by 0.72 and 0.52 times. DISCUSSION: Korean nurses demonstrated high levels of depressive symptoms, secondary traumatic stress and burnout, while demonstrating lower levels of compassion satisfaction. The results of this study demonstrate that depressive symptoms, secondary traumatic stress, burnout and compassion satisfaction affect turnover intention. CONCLUSIONS: To reduce nurses' turnover intention, it is necessary to reduce depressive symptoms and enhance the quality of professional life. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Hospital managers need to maintain adequate nurse-to-patient ratios and provide nurses with a supportive work environment. Also, health policymakers need to identify factors affecting hospital nurses' turnover intention and provide strategies to address them. These conditions may reduce the excessive workload placed on nurses, thereby preventing depression and burnout and improving nurses' quality of work-life.

[Nutritional risk screening and related factors of cancer patients in community of Shanghai, 2018-2019].

Objective: To study the risk of malnutrition and related factors of cancer patients in community of Shanghai. Methods: From October 2018 to January 2019, four communities, Pengpu New Village Street, Pengpu Town, Jiangning Road Street, and Caojiadu Street, from 14 communities in Jing 'an District, Shanghai City, were selected by using a random cluster sampling method based on the Shanghai Cancer Registration and reporting system. All cases of malignant tumors and benign tumors of the central nervous system were included. A total of 4 396 questionnaires were distributed. After the exclusion of 9 invalid questionnaires, 3 310 valid questionnaires were included with a rate of 99.73%. A self-designed questionnaire was used to collect data including basic demographic characteristics, history of malignant, physical and psychological pain, nutritional demands and cognitive status. Malnutrition Universal Screening Tools (MUST) was used to analyze the nutritional risk of cancer patients in the community. Multivariate logistic regression model was applied to analyze potential factors. Results: Among the 3 310 cancer patients who completed the survey, the average age of study participants was (64.05±13.02), and 1 467 cases (44.32%) were males. The incidence rate of nutritional risk was 12.84% (425/3 310). The result of logistic regression analysis showed that compared with male, other cancer patients and no physical pain, the risk factors of the occurrence of nutritional included: female (OR=1.53,95%CI:1.23-1.92), head and neck malignant tumors (OR=1.42,95%CI:1.07-1.90), bronchus/lung malignant tumors (OR=1.93,95%CI:1.43-2.61), liver, biliary/pancreatic malignant tumors (OR=2.11,95%CI:1.21-3.65) and upper gastrointestinal malignant tumors (OR=6.04,95%CI:4.31-8.46), patients with physical pain (OR=1.39,95%CI:1.02-1.89). Conclusion: Nutritional risk of cancer patients is higher in community of Shanghai. Gender, location of tumors and physical pain are associated with the occurrence of nutritional risk.

[Characteristics and analysis of corneal astigmatism in age-related cataract patients over 50 years old].

Objective: To investigate the relationship between corneal astigmatism and age, axial length (AL) in age-related cataract patients over 50 years old. Methods: In this retrospective study, 1 906 eyes of 953 patients with age-related cataract were diagnosed from February 2016 to August 2016 atPeking University People's Hospital, and their demographics, preoperative AL, magnitude and meridian of the corneal astigmatism measured by IOL Master were collected. Restricted cubic splines and Spearman rank correlation coefficients were used to investigate the relationship of the magnitude of cornea astigmatism to age. Chi-square test was used to assess the relationship of the meridian of astigmatism to age, AL and the magnitude of cornea astigmatism. Results: The patients were 410 men and 543 women. The corneal astigmatism was with-the-rule (WTR) in 570 eyes (29.91%), against-the-rule (ATR) in 1 005 eyes (52.73%) and oblique in 331 eyes (17.37%). The mean age was (72±9) years old. The medians (min, max) of AL and corneal astigmatism magnitude were 23.49 mm (19.83 mm to 33.89 mm) and 0.97 D (0.06 D to 4.65 D) in right eyes and 23.41 mm (17.54 mm to 32.09 mm) and 0.92 D (0.11 D to 4.88 D) in left eyes, respectively. The corneal astigmatism was ≥0.75 D in 64.95% (619/953) of the right eyes and 61.59% (587/953) of the left eyes. Among the elderly patients over 65 years old, when the AL was between 22.00-25.99 mm (r=0.186-0.279), the value of corneal astigmatism was positively correlated with age (all P<0.01) in both eyes. The value of ATR corneal astigmatism was positively correlated with age (right eyes, r=0.278, P<0.01; left eyes, r=0.225, P<0.01), while the value of WTR corneal astigmatism had no statistically significant correlation with age (right eyes, P=0.335; left eyes, P=0.633). The prevalence of WTR astigmatism decreased with age from 43.81% (46/105) to 20.73% (51/246) in right eyes and from 40.00% (42/105) to 24.80% (61/246) in left eyes, while the prevalence of ATR astigmatism increased with age from 38.10% (40/105) to 61.38% (151/246) in right eyes and from 33.33% (35/105) to 58.94% (145/246) in left eyes. The prevalence of oblique astigmatism was not significantly changed with age (right eyes, χ(2)=31.986, P<0.01; left eyes, χ(2)=27.686, P<0.01). There was no statistically significant difference in the distribution of corneal astigmatism meridians between different AL groups (right eyes, P=0.497; left eyes, P=0.897). With the increase of the magnitude of corneal astigmatism, the prevalence of oblique astigmatism significantly decreased from 25.45% (85/334) to 0 in right eyes and from 29.78% (109/366) to 1.35% (1/74) in left eyes, while the prevalence of ATR astigmatism significantly increased from 39.82% (133/334) to 79.27% (65/82) in right eyes and from 41.80% (153/366) to 59.46% (44/74) in left eyes (right eyes, χ(2)=72.229, P<0.01; left eyes, χ(2)=72.166, P<0.01). Conclusions: A majority of age-related cataract patients over 50 years old have astigmatism ≥0.75 D before cataract surgery. When the AL is between 22.00 mm and 25.99 mm, the magnitude of corneal astigmatism increases with age among people over 65 years old, especially the magnitude of ATR corneal astigmatism, while the magnitude of WTR corneal astigmatism has no obvious increase with age. The percentage of ATR astigmatism increases while the percentage of WTR astigmatism decreases with age. (Chin J Ophthalmol, 2020, 56: 349-355).

[Relationship between SHP-1 gene methylation and STAT3 phosphorylation and prognosis in patients with myelodysplastic syndrome].

Objective: To assess the methylation level of SHP-1 promoter region and the effects on the phosphorylation of the Signal Transducers and Activators of Transcription 3 (STAT3) protein in bone marrow specimen of patients with myelodysplastic syndrome (MDS), and to explore the relationship of SHP-1 methylation and prognosis of the patients. Method: Bone marrow specimens of 93 patients with MDS were collected from the General Hospital of Tianjin Medical University from September 2010 to June 2014. The enrolled subjects included 54 males and 39 females and they were divided into the low-risk group (IPSS score:0-1.0, median: 0.5) and the high-risk group (IPSS score: 1.5-3.0, median: 2.5) according to the International Prognostic Score System (IPSS). The methylation level of SHP-1 was detected by methylation-specific polymerase chain reaction, and the level of p-STAT3 was detected using Western blot. Results: In the high-risk group, 64.44% (29/45) of the patients had methylation in the SHP-1 promoter region, which was significantly higher than the low-risk group 22.92% (11/48). Therefore, SHP-1 methylation was frequently presented in the patients of the high-risk group. Similarly, 66.67% (30/45) of the patients in the high-risk group had positive STAT3 phosphorylation status, whereas only 20.83% (10/48) were tested positive in the low-risk group. In addition, correlation analysis also revealed that the SHP-1 methylation rate was positively correlated with the positive rate of STAT3 phosphorylation (r=0.57,P<0.001). Conclusions: SHP-1 methylation is significantly correlated with the risk of MDS patients. It may be used as an independent predictor of shorter survival in patients of the high-risk group. The increased level of SHP-1 methylation will lead to the uncontrolled activation of the downstream JAK/STAT3 pathway, which in turn can cause further positive feedback to amplify the carcinogenic signal.

Evidence for Secondary Flux Rope Generated by the Electron Kelvin-Helmholtz Instability in a Magnetic Reconnection Diffusion Region.

Secondary flux ropes are suggested to play important roles in energy dissipation and particle acceleration during magnetic reconnection. However, their generation mechanism is not fully understood. In this Letter, we present the first direct evidence that a secondary flux rope was generated due to the evolution of an electron vortex, which was driven by the electron Kelvin-Helmholtz instability in an ion diffusion region as observed by the Magnetospheric Multiscale mission. The subion scale (less than the ion inertial length) flux rope was embedded within the electron vortex, which contained a secondary electron diffusion region at the trailing edge of the flux rope. We propose that intense electron shear flow produced by reconnection generated the electron Kelvin-Helmholtz vortex, which induced a secondary reconnection in the exhaust of the primary X line and then led to the formation of the flux rope. This result strongly suggests that secondary electron Kelvin-Helmholtz instability is important for reconnection dynamics.