Prognostic value of cardiac magnetic resonance imaging feature tracking technology in patients with light chain amyloidosis.

AIM: To undertake a meta-analysis of the prognostic value of cardiac magnetic resonance imaging feature tracking (CMR-FT) in patients with light-chain cardiac amyloidosis (LCA). MATERIALS AND METHODS: A systematic search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library. All analyses were conducted using RevMan 5.3 software. RESULTS: Eight studies were included with 663 patients. For the left ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired global circumferential (GCS), radial (GRS) and longitudinal (GLS) strain in survivors of LCA (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.09-1.25; 0.95, 0.93-0.96; 1.12, 1.05-1.20, all p<0.001). For ejection fraction (EF) and mass index, surviving patients had higher EFs and mass index (OR 0.96, 95% CI 0.96-0.97; 1.01, 1.01-1.02). For the right ventricle, the results showed that CMR-FT was statistically significant in predicting death, with less impaired GLS and GRS in survivors of LCA (OR 1.11, 95% CI 1.08-1.15; 0.93, 0.90-0.96, all p<0.001). Surviving patients had higher EFs (OR 0.97, 95% CI 0.96-0.98, p<0.001). Upon removing the studies one by one, there was no significant change in the results of the study. Both analyses showed no apparent publication deviation on funnel plots. CONCLUSION: Parameters derived from CMR-FT technology are promising new predictors for LCA, and are easily available and reliable. Patients with poor myocardial deformability are at highest risk of death.

Socioeconomic inequalities in cervical cancer mortality in Canada, 1990 and 2019: a trend analysis.

OBJECTIVE: It is increasingly recognized that those of lower socioeconomic status (SES) are disproportionately affected by cancer mortality. The association between cervical cancer mortality and SES have been reported; however, it remains poorly understood in the Canadian population. Thus, this study investigates trends in income and education inequalities in cervical cancer mortality in Canada over the last three decades. STUDY DESIGN: Trend analysis. METHODS: A dataset constructed at the census division level (n = 280), comprising the Canadian Vital Statistics Death Database, the Canadian Census of Population, and the National Household Survey was used to measure cervical cancer mortality in Canada. Income and education inequalities in cervical cancer mortality were measured using age-standardized Concentration index (C). RESULTS: Crude cervical cancer mortality rates decreased significantly during the study period. Age-standardized C values were negative for the majority of years for income and education inequalities, reaching significance in some years. Trend analyses indicated an increasing concentration of cervical cancer mortality amongst those with lower education levels. CONCLUSION: Despite recent decreases in cervical cancer mortality rates, socioeconomic inequalities in cervical cancer mortality in Canada are persistent. Notably, those of lower income and education levels are disproportionately affected, underscoring an opportunity to improve clinical outcomes by addressing these inequalities.

Association between gestational cardiovascular health in the first trimester and pregnancy outcomes in the China birth cohort.

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.

[Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer].

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

[Clinical efficacy of intraarticular vancomycin in preventing early periprosthetic joint infection after primary knee arthroplasty].

Objective: To investigate the clinical effect of intraarticular vancomycin on early periprosthetic joint infection (PJI) in knee arthroplasty and the incidence of postoperative complications. Methods: This is a retrospective cohort study. The clinical data of 1 867 patients who underwent primary knee arthroplasty at Department of Joint Surgery, the Affiliated Hospital of Qingdao University from April 2022 to June 2023 were retrospectively analysed, including total knee arthroplasty (TKA), robotic-assisted total knee arthroplasty (RA-TKA) and unicondylar knee arthroplasty (UKA). There were 687 males and 1 180 females, aged (68.0±11.2)years(range:45 to 87 years). Patients were divided into the vancomycin group and the control group according to whether or not intra-articular injection of 1 g of vancomycin powder dissolved in 30 ml of saline was performed after intraoperative joint capsule closure. In the vancomycin group, 925 patients were included, including 782 TKA, 27 RA-TKA and 116 UKA.In the control group, 942 patients were included, including 767 TKA, 99 RA-TKA and 76 UKA. Early PJI, wound complications, and vancomycin-related toxicity including acute renal collapse, ototoxicity, and allergic reactions were assessed within 3 months postoperatively. The data were compared using the independent sample t test, χ² test, and Fisher's exact probability method, as appropriate. Major Extremity Trauma Research Consortium (METRC). Results: No PJI was found in all patients in the vancomycin group.Five cases (0.7%,5/767) of early PJI were found in TKA patients in the control group, with a statistically significant difference (P=0.030); 1 case of early PJI was found in each RA-TKA and UKA patients, with non-significant difference compared with vancomycin group (all P>0.05). Two cases (0.3%,2/782) of incisional complications were found in TKA patients in the vancomycin group, and 4 cases (0.5%, 4/767) of incisional complications were found in TKA patients in the control group, with non-significant difference(P=0.449); no incisional complication was found in RA-TKA patients in the vancomycin group, and 1 case (1.0%,1/99) of incisional complications were found in RA-TKA patients in the control group, the difference was not statistically significant (P>0.05); no incisional complication was found in both groups of UKA patients.No vancomycin-related acute kidney injury, ototoxicity, or allergic reactions was observed in all patients. Conclusion: Intra-articular injection of 1 g of vancomycin suspension after arthrotomy closure during TKA maybe lower the risk of early PJI without increasing the risk of wound complication and vancomycin-associated systemic toxicity.

[Research progress in the diagnosis and treatment of childhood glaucoma].

Childhood glaucoma is a disease that seriously endangers children's visual health. It will accompany the patients throughout their lives and bring a heavy burden to families and society. Most childhood blindness caused by glaucoma is preventable or treatable. Relevant research has made progress in recent years. Based on the new consensus reached by the World Glaucoma Association and the latest medical evidence at home and abroad, this article summarizes the definition, classification, diagnosis, molecular genetics, pathogenesis and comprehensive treatments including drugs and surgery of childhood glaucoma, with a focus on the application of various surgical methods, so as to provide reference for clinical and scientific research and improve the clinical diagnosis and treatment of childhood glaucoma.

[Legal regulation of clinical application of artificial intelligence].

With the wide application of artificial intelligence (AI) technology in clinical practice, more and more legal problems need to be solved. At present, although the legal status of AI is still controversial in academic and practical circles, its infringement risk in clinical diagnosis and surgery cannot be avoided. On the basis of the distinction between strong and weak AI liability subjects, those who meet the requirements of infringement, damage consequence, causal relationship, subjective fault, etc., can constitute tort liability, but the existence of exemption causes can also exempt liability. In addition to the ex post accountability of tort liability, it is also necessary to establish a complete administrative legal regulation system. At present, China needs to explore and establish the classification registration system, compulsory insurance system and reserve system of AI as soon as possible, so as to strengthen the legal regulation of the whole process of AI clinical application before, during and after the event.

[Short-term efficacy of posterior ankle arthroscopy and tendoscope on ankle-derived flexor hallucis longus ganglion].

Objective: To investigate the short-term clinical efficacy of posterior ankle arthroscopy combined with tendoscope on ankle-origin flexor hallucis longus tendon ganglion. Methods: A follow-up study. Clinical data of 10 patients with hallux ganglion underwent posterior ankle arthroscopy combined with flexor hallucis longus tendoscope in the Tianjin First Central Hospital from January to June 2021 were analyzed retrospectively. There were 5 males and 5 females with a mean age of 42.7 (22-54) years. Disease distribution: 6 patients were on the right side and 4 cases were on the left side. The mean preoperative course of disease was 19.4 months (2-48 months). The patients were followed-up for a mean time of 12.4 months (8-20 months). The relationship between the origin of hallux ganglion and ankle joint was confirmed by ankle MRI and arthrography of ankle joint before the operation. During the operation, the joint capsule was explored, cleared and opened under the posterior ankle arthroscopy firstly, and then part of the tendon sheath of the forefoot was cleared and cut under the flexor hallucis longus tendoscope. American Orthopedic Foot and Ankle Society (AOFAS) forefoot rating scale and visual analogue scale (VAS) of pain were used to evaluate the clinical outcome before and after operation. Postoperative recurrence, perioperative and long-term complications were recorded spontaneously. Results: The cystic fluid signal of all patients could be traced from flexor hallucis longus tendon to the back of ankle joint by MRI before the operation. Intraoperative radiography showed that contrast media flowed from the back of ankle joint to the end of the hallux. The AOFAS score [M(Q1, Q3)] of the patients increased from 70.5(69.0, 87.8) before the operation to 100.0(85.8, 100.0) at the follow-up (P=0.002), and at the mean time, the VAS score decreased from 5.0(3.5, 6.0)to 0.5(0.0, 1.3) (P<0.001). No complications such as infection and recurrence occurred in all patients until the last follow-up. Conclusion: Posterior ankle arthroscopy combined with minimally invasive technique of tendoscope can treat ankle-origin flexor hallucis longus tendon ganglion effectively.

[Global liver cancer incidence and mortality and future trends from 2000 to 2020: GLOBOCAN data analysis].

Objective: To compare the geographical differences and time trends of liver cancer incidence and mortality in different regions around the world so as to predict the future burden of liver cancer. Methods: The incidence and mortality data of liver cancer in different Human Development Index (HDI) countries from 2000 to 2020 were collected from the GLOBOCAN 2020 database. The joinpoint model and annual percent change (APC) were used to analyze the liver cancer global incidence and mortality as well as future epidemic trends from 2000 to 2020. Results: ASMR for male liver cancer was increased from 8.0/100, 000 in 2000 to 7.1/100,000 in 2015 (APC = -0.7, 95%CI: -1.2 ~ -0.3, P = 0.002), while ASMR for female liver cancer was increased from 3.0/100, 000 in 2000 to 2.8/100, 000 in 2015 (APC = -0.5, 95%CI: -0.8 ~ -0.2, P < 0.001). The ratio of male to female ASMR was 2.67:1 in 2000 and 2.51:1 in 2015, indicating a slight narrowing of the difference in mortality between men and women. In 2020, the global ASIR and ASMR for liver cancer were 9.5/100 000 and 8.7/100 000, respectively. Male ASIR and ASMR (14.1/100, 000 and 12.9/100, 000, respectively) were 2 ~ 3 times higher than females (5.2/100, 000 and 4.8/100, 000, respectively). There were significant differences between ASIR and ASMR in different HDI countries and regions (P(ASIR) = 0.008, P(ASMR) < 0.001), and the distributions of ASMR and ASIR were very similar. New cases and deaths were expected to increase by 58.6% (143,6744) and 60.9% (133, 5 375) in 2040, with the number of cases and deaths increasing by 39,7003 and 37,4208 in Asia, respectively. Conclusion: ASMR due to liver cancer worldwide has had a downward trend between 2000 and 2015. However, the latest epidemiological status and predictions of liver cancer in 2020 indicate that prevention and control will still be a major challenge globally in the next 20 years.

[Scimitar syndrome with pulmonary sequestration containing carcinoma: a case report].

We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment.

Definition of large niche after Cesarean section based on prediction of postmenstrual spotting: Chinese cohort study in non-pregnant women.

OBJECTIVE: A large niche after Cesarean section (CS) is associated with long-term complications, of which postmenstrual spotting is associated positively with the size of the niche. However, the diagnosis of a large niche in the literature is inconsistent and the definition is largely subjective. The aim of this study was to generate a definition for a large niche in non-pregnant women based on the presence of postmenstrual spotting. METHODS: Women who had undergone CS in our hospital between January 2012 and June 2017 were selected randomly from our database, contacted by telephone and subsequently examined between January 2016 and June 2020. Eligible for inclusion were non-pregnant women who had their last CS more than 1 year earlier and agreed to undergo transvaginal sonography (TVS). All participants underwent examination of their CS scar by TVS (two-dimensional color Doppler) during the midfollicular phase. Niche depth, length, width, residual myometrial thickness (RMT), adjacent myometrial thickness (AMT) and ratio of niche depth/AMT were recorded. Women diagnosed with a niche, defined as an indentation at the site of the CS with a depth of at least 2 mm, were classified into two groups (symptomatic or asymptomatic) according to whether they experienced postmenstrual spotting. Logistic regression analysis was used to establish the best cut-off values for the niche parameters to predict postmenstrual spotting. A new definition was generated based on the niche parameters with the highest area under the receiver-operating-characteristics (ROC) curve (AUC) for the prediction of postmenstrual spotting. RESULTS: A total of 727 women who had a CS > 1 year earlier underwent TVS examination, of whom 263 were diagnosed with a niche (prevalence of 36.2%). Of these, 160 women experienced postmenstrual spotting and 103 were asymptomatic. The three variables with the highest AUC for prediction of postmenstrual spotting were niche depth/AMT ratio (AUC, 0.798; 95% CI, 0.745-0.852), niche depth (AUC, 0.731; 95% CI, 0.668-0.795) and RMT (AUC, 0.683; 95% CI, 0.618-0.748). Based on the best cut-offs according to ROC-curve analysis, a large niche was defined as: niche depth ≥ 0.50 cm, RMT ≤ 0.21 cm or niche depth/AMT ratio ≥ 0.56. The prevalence of a large niche according to this definition was 22.4% (163/727). The new definition had a specificity of 61.17% (95% CI, 52.34-70.41%) and sensitivity of 76.87% (95% CI, 70.28-84.16%) for a large niche. CONCLUSION: This study has provided a new definition for a large niche after CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Genome-wide re-sequencing reveals population structure and genetic diversity of Bohai Black cattle.

Bohai Black (BHB) cattle, one of eight representative indigenous breeds in China, is well known for its high resistance to disease, endurance under unfavorable feeding conditions and excellent meat quality. Over recent, the number of BHB cattle has decreased sharply. To investigate the population structure and genetic diversity of this breed, the whole-genome data of 35 individuals from a conservation farm were obtained using the Illumina 150 bp paired-end platform. The results of the genetic structure and diversity analyses showed that BHB cattle had mixed Bos taurus and Bos indicus ancestry, close phylogenic relationships with Jiaxian Red and Luxi cattle and abundant genetic diversity. The bulls tested here could be divided into six families. This study presents a comprehensive evaluation of the genetic structure and diversity of the BHB cattle, and lays the theoretical basis for conservation and utilization of the valuable germplasm resource.

Isolation, identification and virulence gene characterization of Aeromonas dhakensis isolated from sea lion (Zalophus californianus).

Species of Aeromonas are ubiquitous pathogens of fish and aquatic animals and can infect humans and other animals through the food chain. However, there are few reports of marine mammalian infections. In 2020, a sea lion (Zalophus californianus) died acutely at an aquarium in Harbin, Heilongjiang Province, China. In order to explore the cause of death, we dissected the animal and observed pathological changes. Ogans were aseptically collected and used for bacterial isolation and culture. This revealed that the sea lion had died of sepsis caused by a bacterial infection. Isolated bacteria were investigated by morphology, biochemical phenotype and molecular identification, and this determined the pathogen as A. dhakensis. The isolate contained six virulence genes, hlyA, aerA, act, lafA, ela, fla, and was susceptible to most antibiotics. This is the first report of A. dhakensis associated with septicaemia in pinnipeds and a description of its virulence and resistance profiles. Its presence in aquatic environments poses a potential threat to marine mammals.

[Analysis and forecast of burden of pancreatic cancer along with attributable risk factors in Asia countries between 1990 and 2019].

Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.

[The association between bisphenol A exposure and obesity/overweight in children and adolescents: dose-response Meta analysis].

Objective: To explore the relationship between bisphenol A (BPA) exposure and obesity/overweight in children and adolescents through Dose-response Meta analysis. Methods: Articles published up to September 1st 2021 were systematically searched in PubMed, Web of science, Scopus, Embase, Cochrane library, CNKI, Wanfang databases and VIP Chinese Science and Technology Journal by using "bisphenol A" "BPA" "obesity" "weight" "fat""overweight" "body mass index" "BMI" "waist circumference" (both in English and in Chinese) as keywords. Use Stata 15.1 software to calculate the pooled OR (95%CI), perform heterogeneity test, subgroup analysis, sensitivity analysis, publication bias and the exposure-response relationship fitting. Results: A total of 9 English articles were included from 1 948 articles retrieved, including 8 articles from American and 1 article from China. 15 614 children/adolescents and 3 446 obese/overweight cases were further used for Meta-analysis of dose-response relationship. Meta-analysis results showed that there was heterogeneity among the highest dose groups in different studies(I2=52.1%, P=0.033). The random effect model-analysis found that compared with those in the lowest group, the OR(95%CI) for those in the highest group of urine BPA was 1.56(1.18-1.94)for the risk of obesity/overweight in children and adolescents, but there was no linear or nonlinear dose-response relationship. Sensitivity analyses showed that the results were robust, Egger's test(P=0.263) and Begg's test(P=0.348) showed that there was no publication bias. Conclusion: Bisphenol A exposure may increase the risk of obesity/overweight epidemics in children and adolescent.

[Correlation analysis between blood routine-derived inflammatory markers and respiratory function in pneumoconiosis patients].

Objective: To analyze the correlation between blood routine-derived inflammation indicators and respiratory function in patients with pneumoconiosis. Methods: In January 2021, 492 male pneumoconiosis patients hospitalized in Hefei Institute of Occupational Disease Control and Prevention from 2012 to 2020 were randomly selected as the case group, 492 dust exposed non pneumoconiosis workers who underwent occupational health examination at the same time were taken as the control group. The occupational history and clinical examination data of the two groups of subjects were collected, the correlation between blood routine-derived inflammatory indexes and pulmonary function and blood gas analysis was analyzed retrospectively. Results: Compared with the control group, the lymphocyte monocyte ratio (LMR) in the case group was decreased, and the neutrophil lymphocyte ratio (NLR) was increased, and the difference was statistically significant (P<0.05) . There were significant differences in forced vital capacity as a percentage of the predicted value (FVC) , forced expiratory volume in the first second as a percentage of the predicted value (FEV(1)%) , one second rate (FEV(1)/FVC) , partial pressure of oxygen (PaO(2)) , partial pressure of carbon dioxide (PaCO(2)) , and pH among pneumoconiosis patients at different stages (P<0.05) . FVC%, FEV(1)%, FEV(1)/FVC, and PaO(2) decreased with the increase of the stage, the trend test was statistically significant (tau-b=-0.24, -0.34, -0.37, -0.17, P<0.05) , PaCO(2) and pH increased with the increase of the stage, and the trend test was statistically significant (tau-b=0.10, 0.08, P<0.05) . There were statistically significant differences in LYM, LMR, NLR, platelet lymphocyte ratio (PLR) in patients with pneumoconiosis at different stages (P<0.05) , and LYM and LMR decreased with the increase of stage, trend test showed that there was statistically significant (tau-b=-0.11, -0.13, P<0.05) . There were significant differences in FVC%, FEV(1)%, FEV(1)/FVC, PaO(2), pH, LMR, NLR, PLR among patients with different types of pneumoconiosis (P<0.05) . LMR in pneumoconiosis patients was significantly positively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=0.342, 0.324, 0.203, 0.207, P<0.05) , NLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.193, -0.202, -0.164, -0.177, P<0.05) , PLR was significantly negatively correlated with FVC%, FEV(1)%, FEV(1)/FVC and PaO(2) (r(s)=-0.194, -0.193, -0.106, -0.113, P<0.05) . Multiple linear regression analysis showed that LMR in pneumoconiosis patients was positively related with FVC%, FEV(1)% and PaO(2) (P<0.05) . Conclusion: LMR in patients with pneumoconiosis has a certain correlation with lung function and blood gas analysis, LMR is expected to become a sensitive indicator for evaluating pneumoconiosis.

Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations.

BACKGROUND: Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). It is critical to analyze RET mutants resistant to these drugs and unravel the molecular basis to improve patient outcomes. PATIENTS AND METHODS: Cell-free DNAs (cfDNAs) were analyzed in a RET-mutant medullary thyroid cancer (MTC) patient and a CCDC6-RET fusion NSCLC patient who had dramatic response to selpercatinib and later developed resistance. Selpercatinib-resistant RET mutants were identified and cross-profiled with pralsetinib in cell cultures. Crystal structures of RET-selpercatinib and RET-pralsetinib complexes were determined based on high-resolution diffraction data collected with synchrotron radiation. RESULTS: RETG810C/S mutations at the solvent front and RETY806C/N mutation at the hinge region were found in cfDNAs of an MTC patient with RETM918T/V804M/L, who initially responded to selpercatinib and developed resistance. RETG810C mutant was detected in cfDNAs of a CCDC6-RET-fusion NSCLC patient who developed acquired resistance to selpercatinib. Five RET kinase domain mutations at three non-gatekeeper residues were identified from 39 selpercatinib-resistant cell lines. All five selpercatinib-resistant RET mutants were cross-resistant to pralsetinib. X-ray crystal structures of the RET-selpercatinib and RET-pralsetinib complexes reveal that, unlike other TKIs, these two RET TKIs anchor one end in the front cleft and wrap around the gate wall to access the back cleft. CONCLUSIONS: RET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.

The association between overweight/obesity and vertebral fractures in older adults: a meta-analysis of observational studies.

A meta-analysis of observational studies was conducted to assess the relationship between overweight/obesity and vertebral fractures in older adults. We found that overweight was related to a decreased risk of vertebral fractures in female and non-Asian populations, while obesity failed to be associated with vertebral fracture risks based on the present data. INTRODUCTION: Recent investigations suggest that the influence of overweight/obesity on fracture risks is site-specific, while conflicting data were reported related to vertebral fracture. This meta-analysis was performed to qualitatively assess the relationship between overweight/obesity and the risk of vertebral fracture. METHODS: MEDLINE, Web of Science, Embase, and Cochrane were searched for relevant observational articles assessing the vertebral fracture risk of the overweight or obese population compared to normal population. Two independent reviewers conducted data extraction and quality assessment. Relative risks (RR) and 95% confidence intervals (CI) were pooled using a random effect model. RESULTS: Eleven studies including 1,078,094 participants were extracted from 1645 records. Pooled RR showed that decreased risk of vertebral fractures was observed in the overweight older adults (RR: 1.16; 95% CI: 1.07-1.26; I2: 51.8%), but not in the obese populations (RR: 0.98; 95% CI: 0.82-1.17; I2: 92.1%). In the subgroup analysis, we found a significant inverse association between overweight and risk of vertebral fracture in women (RR: 0.92; 95% CI: 0.85-1.00; I2: 0.0%), non-Asian areas (RR: 0.89; 95% CI: 0.80-0.99; I2: 40.7%), sample size > 2000 (RR: 0.87; 95% CI: 0.80-0.94; I2: 4.9%), and quality score > 7 (RR: 0.87; 95% CI: 0.79-0.95; I2: 21.9%). Furthermore, pooled studies of sample size > 2000 (RR: 0.66; 95% CI: 0.76, 0.89; I2: 52.1%) and quality score > 7 (RR: 0.75; 95% CI: 0.62, 0.91; I2: 68.1%) showed that the people with obesity had a significantly lower prevalence of vertebral fracture. CONCLUSIONS: Overweight aged adults tend to have a lower vertebral fracture risk. When gender and ethnicity were taken into consideration, the inverse relationship between overweight and vertebral fracture risk were only observed in female and non-Asian populations. Besides, there is insufficient data to conclude the relationship between obesity and the risk of vertebral fractures, and thus, further studies are needed.

Inactivation of Bacillus anthracis and Bacillus atrophaeus spores on different surfaces with ultraviolet light produced with a low-pressure mercury vapor lamp or light emitting diodes.

AIMS: To obtain quantitative efficacy data of two ultraviolet light (UVC) technologies for surface inactivation of Bacillus anthracis Ames and Bacillus atrophaeus spores. METHODS AND RESULTS: Spores were deposited onto test coupons and controls of four different materials, via liquid suspension or aerosol deposition. The test coupons were then exposed to UVC light from either a low-pressure mercury vapor lamp or a system comprised of light emitting diodes, with a range of dosages. Positive controls were held at ambient conditions and not exposed to UVC light. Following exposure to UVC, spores were recovered from the coupons and efficacy was quantified in terms of log10 reduction (LR) in the number of viable spores compared to that from positive controls. CONCLUSIONS: Decontamination efficacy varied by material and UVC dosage (efficacy up to 5·7 LR was demonstrated). There was no statistical difference in efficacy between the two species or between inoculation methods. Efficacy improved for the LED lamp at lower relative humidity, but this effect was not observed with the mercury vapor lamp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study will be useful in determining whether UVC could be used for the inactivation of B. anthracis spores on different surface types.

CT-based radiomics model to distinguish necrotic hepatocellular carcinoma from pyogenic liver abscess.

AIM: To investigate the feasibility of a computed tomography (CT)-based radiomics model in distinguishing necrotic hepatocellular carcinoma (nHCC) from pyogenic liver abscess (PLA). MATERIAL AND METHODS: One hundred-four enrolled patients with nHCC (n=56) and PLA (n=48) were divided randomly into a training cohort (n=62) and validation cohort (n=42). ROI (region of interest) of the wall (ROI-wall) and ROI of the necrotic cavity (ROI-necrotic cavity) of the lesion were delineated from each arterial phase (AP) and portal venous phase (PP) image. The least absolute shrinkage and the selection operator logistic regression method was used to select radiomics features, and radiomics scores (R-scores) were calculated. Four radiomics models, including R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP and R-score (ROI-necrotic cavity) in the PP, were constructed and evaluated by area under the curve (AUC) of receiver operating characteristic curve. RESULTS: The AUCs of R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP, and R-score (ROI-necrotic cavity) in the PP were 0.935 and 0.917, 0.906 and 0.824, 0.985 and 0.928, 0.899 and 0.850, in the training and validation cohorts, respectively. In the training cohort, the AUC of R-score (ROI-wall) in the PP was higher than that of R-score (ROI-wall) in the AP (p=0.024) or R-score (ROI-necrotic cavity) in the AP (p=0.046) or R-score (ROI-necrotic cavity) in the PP (p=0.044). CONCLUSION: CT-based radiomics models can be used to distinguish nHCC from PLA.