Generation of attosecond electron bunches of tunable duration and density by relativistic vortex lasers in near-critical density plasma.

Attosecond electron bunches have wide application prospects in free-electron laser injection, attosecond X/γ-ray generation, ultrafast physics, etc. Nowadays, there is one notable challenge in the generation of high-quality attosecond electron bunch, i.e., how to enhance the electron bunch density. Using theoretical analysis and three-dimensional particle-in-cell simulations, we discovered that a relativistic vortex laser pulse interacting with near-critical density plasma can not only effectively concentrate the attosecond electron bunches to over critical density, but also control the duration and density of the electron bunches by tuning the intensity and carrier-envelope phase of the drive laser. It is demonstrated that this method can efficiently produce attosecond electron bunches with a density up to 300 times of the original plasma density, peak divergence angle of less than 0.5 ∘, and duration of less than 67 attoseconds. Furthermore, by using near-critical density plasma instead of solid targets, our scheme is potential for the generation of high-repetition-frequency attosecond electron bunches, thus reducing the requirements for experiments, such as the beam alignment or target supporter.

The influence of respiratory movement on preoperative CT-guided localization of lung nodules.

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

Disturbance of mitochondrial dynamics in myocardium of broilers with pulmonary hypertension syndrome.

1. The following study investigated the relationship between pulmonary hypertension syndrome (PHS) and mitochondrial dynamics in broiler cardiomyocytes.2. An animal model for PHS was established by injecting broiler chickens with CM-32 cellulose particles. Broiler myocardial cells were cultured under hypoxic conditions to establish an in vitro model. The ascites heart index, histomorphology, mitochondrial ultrastructure, and mitochondrial dynamic-related gene and protein expression were evaluated.3. The myocardial fibres from PHS broilers had wider spaces and were wavy and twisted and the number of mitochondria increased. Compared with the control group, the gene and protein expression levels were decreased for Opa1, Mfn1, and Mfn2 in the myocardium of PHS broilers. The gene and protein expression was significantly increased for Drp1 and Mff.4. This study showed that PHS in broilers may cause myocardial mitochondrial dysfunction, specifically by diminishing mitochondrial fusion and enhancing fission, causing disturbances in the mitochondrial dynamics of the heart.

[The pathological characteristics and prognostic analysis of medullary thyroid microcarcinoma].

Objectives: To analyze the clinical characteristics and prognosis of medullary thyroid microcarcinoma (MTMC). Methods: A case series studies. The clinical data of patients with medullary thyroid carcinoma (MTC) diagnosed by postoperative pathology and with complete follow-up data who were initially treated in Tianjin Medical University Cancer Hospital from January 2013 to December 2019 were retrospectively analyzed. There were a total of 170 cases, including 70 males and 100 females, aged (49.7±12.3) years old. Among them, there were 61 patients with MTMC. They were divided into group A (with a maximum tumor idameter of ≤0.5 cm, n=13) and group B (with a maximum tumor diameter >0.5~≤1.0 cm, n=48) based on whether the maximum diameter of the tumor was >0.5 cm. Analysis was conducted on their pathological results and prognosis. Results: Among the MTC, MTMC accounted for 26.4% (61/231) with 26 males and 35 females aged Mï¼»Q1，Q3ï¼½51.0 (41.0, 59.0) years. Among the MTMC patients, 57.4% (35/61) were in stage Ⅰ, 16.4% (10/61) were in stage Ⅲ, and 26.2% (16/61) were in stage Ⅳ. For MTMC with a maximum diameter of≤0.5 cm and a maximum diameter of >0.5-≤1.0 cm, there was no statistically significant difference between the two groups in terms of gender, age, mixed cancer, invasion of glandular lobes, multifocal, central lymph node metastasis, lateral neck lymph node metastasis rate and other pathological characteristics(both P>0.05). In terms of prognosis, the recurrence free survival time of MTMC patients was 83.1 (68.0, 97.0) months. Among them, structural tumor recurrence occurred in 5 patients (8.2%) after surgery, and 1 patient (1.6%) died. The expected 5-year and 10-year survival rates were 93.4% and 89.0%, respectively. There was no statistically significant difference in recurrence free survival time among MTMC patients, MTC patients with a maximum diameter of >1.0-≤2.0 cm, and MTC patients with a maximum diameter of >2.0 cm (all P>0.05). Conclusion: MTMC has strong invasiveness, and although the prognosis of most MTMCs is relatively good, the risk of long-term recurrence and death is still high.

[Arterial spin labeling in assessment of interstitial fibrosis in renal allografts].

Objective: To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation. Methods: This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC). Results: A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)-1·min-1; ci1 group: (181.7±29.3) ml·(100 g)-1·min-1; ci2 group: (158.8±39.2) ml·(100 g)-1·min-1; ci3 group: (123.1±27.2) ml·(100 g)-1·min-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively. Conclusion: ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

[Relationship between sleep status and occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China].

Objective: To understand the prevalence of occasional hypertension in preschool children in three provinces in the middle and lower reaches of the Yangtze River in China, and analyze the relationship between their sleep status and occasional hypertension. Methods: From October to November 2017, a total of 24 842 preschool children from 109 kindergartens in 11 cities in Hubei, Anhui and Jiangsu provinces were selected by intentional sampling method. A self-made questionnaire was used to collect basic information about the subjects, and the sleep status data was collected by the Children's Sleep Habits Questionnaire. Physical examinations were performed on the subjects, and height, weight and blood pressure were measured on-site. The difference in occasional hypertension detection rate among preschool children with different characteristics was compared, and the correlation between sleep status and occasional hypertension detection rate was analyzed by the multivariate logistic regression model. Results: The age of the subjects was (4.4±1.0) years, including 12 729 boys (51.2%). The prevalence of occasional hypertension was 31.8% (7 907/24 842). The prevalence of occasional hypertension among preschool children in three provinces of the middle and lower reaches of the Yangtze River was 31.8%. There were statistically significant differences in the detection rate of occasional hypertension among preschool children of different genders, age groups, family residence, family economic status and parents' education level (all P values<0.05). The detection rate of occasional hypertension in children with less than 10 hours of sleep was higher than those with sufficient sleep, and the difference was statistically significant (P<0.05). The results of multivariate logistic regression analysis showed that after adjusting for factors such as gender, age, family residence, family economic status, parental education level, parental smoking history, and physical constitution, the ORs (95%CI) for less than 10 hours of sleep, turning on the lights while sleeping, and poor sleep quality were 1.09 (1.03-1.15), 1.17 (1.07-1.28) and 1.04 (0.91-1.18), respectively, compared with the corresponding reference group. Conclusion: The detection rate of occasional hypertension is high in preschool children in the middle and lower reaches of the Yangtze River and there is a positive correlation between insufficient sleep and turning on the light when sleeping and occasional hypertension in preschool children.

[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

Cost-effectiveness analysis of five drugs for treating postmenopausal women in the United States with osteoporosis and a very high fracture risk.

PURPOSE: Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US). METHODS: A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients. RESULTS: In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug. CONCLUSION AND RELEVANCE: Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

[A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease].

Objective: This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies. Methods: A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed. Results: Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 µg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis (r=0.547, P<0.001). Conclusions: The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

[Significance of preventing developmental origins of diseases in improving population quality].

More studies show that various diseases, especially chronic non-infectious diseases, have developmental origin. Developmental origins of diseases are mainly due to gametes and early life development stage being exposed to adverse environment, resulting in abnormal modification of epigenetic and stable inheritance to the adult stage, which could make the risk of various long-term diseases of individuals high. The theory of developmental origin provides a new perspective for the occurrence and development of diseases, and also provides a theoretical basis for disease prevention. Attaching importance to maternal and child health care and life-cycle management is conducive to the prevention of developmental diseases and is of great significance to the improvement of population quality.

[Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021].

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

[Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis].

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation].

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

[Clinical study of serum human-ßeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure].

Objective: To evaluate the diagnostic value of serum human-ßeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

[Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database].

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

[Effects of cadmium chloride on testicular autophagy and blood-testis barrier integrity in prepubertal male rats].

Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 µmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 µmol/L CdCl(2)), experimental group[10.0 µmol/L CdCl(2)+60.0 µmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 µmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 µmol/L, after exposure to 5.0, 10.0 µmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.

Experimental Evidence of Intrinsic Current Generation by Turbulence in Stationary Tokamak Plasmas.

High-ß_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-ß_{θe} regime.

Waves of Change: Brain Sensitivity to Differential, not Absolute, Stimulus Intensity is Conserved Across Humans and Rats.

Living in rapidly changing environments has shaped the mammalian brain toward high sensitivity to abrupt and intense sensory events-often signaling threats or affordances requiring swift reactions. Unsurprisingly, such events elicit a widespread electrocortical response (the vertex potential, VP), likely related to the preparation of appropriate behavioral reactions. Although the VP magnitude is largely determined by stimulus intensity, the relative contribution of the differential and absolute components of intensity remains unknown. Here, we dissociated the effects of these two components. We systematically varied the size of abrupt intensity increases embedded within continuous stimulation at different absolute intensities, while recording brain activity in humans (with scalp electroencephalography) and rats (with epidural electrocorticography). We obtained three main results. 1) VP magnitude largely depends on differential, and not absolute, stimulus intensity. This result held true, 2) for both auditory and somatosensory stimuli, indicating that sensitivity to differential intensity is supramodal, and 3) in both humans and rats, suggesting that sensitivity to abrupt intensity differentials is phylogenetically well-conserved. Altogether, the current results show that these large electrocortical responses are most sensitive to the detection of sensory changes that more likely signal the sudden appearance of novel objects or events in the environment.

Analgesic benefits of the quadratus lumborum block in total hip arthroplasty: a systematic review and meta-analysis.

The quadratus lumborum block (QLB) is reported to reduce pain and improve function following total hip arthroplasty; however, randomised controlled trials evaluating the benefits of adding this block to general or spinal anaesthesia in this population are conflicting. We performed a systematic review seeking randomised controlled trials investigating QLB benefits for total hip arthroplasty, stratifying comparisons regarding the addition of QLB to either general or spinal anaesthesia. The primary outcome was 24-h area under the curve (AUC) pain score. Pain scores were interpreted in the context of a population-specific minimal clinically important difference of 1.86 cm on a 10-cm visual analogue scale, or an AUC pain score of 5.58 cm.h. Secondary outcomes included analgesic consumption, functional recovery and opioid-related side-effects. In all, 18 trials (1318 patients) were included. Adding QLB to general or spinal anaesthesia improved 24-h AUC rest pain scores by a mean difference (95%CI) of -3.56 cm.h (-6.70 to -0.42; p = 0.034) and - 4.19 cm.h (-7.20 to -1.18; p = 0.014), respectively. These improvements failed to reach the pre-determined minimal clinically important difference, as did the reduction in analgesic consumption. Quadratus lumborum block improved functional recovery for general, but not spinal, anaesthesia. Opioid-related side-effects were reduced with QLB regardless of anaesthetic modality. Low-to-moderate quality evidence suggests that the extent to which adding QLB to either general or spinal anaesthesia reduces postoperative pain and opioid consumption after total hip arthroplasty is statistically significant but may be clinically unimportant for most patients. However, adding QLB to general anaesthesia might enhance functional recovery. Taken together, our findings do not support the routine use of QLB as part of multimodal analgesic regimens for total hip arthroplasty.