An artificial intelligence-based bone age assessment model for Han and Tibetan children.

Background: Manual bone age assessment (BAA) is associated with longer interpretation time and higher cost and variability, thus posing challenges in areas with restricted medical facilities, such as the high-altitude Tibetan Plateau. The application of artificial intelligence (AI) for automating BAA could facilitate resolving this issue. This study aimed to develop an AI-based BAA model for Han and Tibetan children. Methods: A model named "EVG-BANet" was trained using three datasets, including the Radiology Society of North America (RSNA) dataset (training set n = 12611, validation set n = 1425, and test set n = 200), the Radiological Hand Pose Estimation (RHPE) dataset (training set n = 5491, validation set n = 713, and test set n = 79), and a self-established local dataset [training set n = 825 and test set n = 351 (Han n = 216 and Tibetan n = 135)]. An open-access state-of-the-art model BoNet was used for comparison. The accuracy and generalizability of the two models were evaluated using the abovementioned three test sets and an external test set (n = 256, all were Tibetan). Mean absolute difference (MAD) and accuracy within 1 year were used as indicators. Bias was evaluated by comparing the MAD between the demographic groups. Results: EVG-BANet outperformed BoNet in the MAD on the RHPE test set (0.52 vs. 0.63 years, p < 0.001), the local test set (0.47 vs. 0.62 years, p < 0.001), and the external test set (0.53 vs. 0.66 years, p < 0.001) and exhibited a comparable MAD on the RSNA test set (0.34 vs. 0.35 years, p = 0.934). EVG-BANet achieved accuracy within 1 year of 97.7% on the local test set (BoNet 90%, p < 0.001) and 89.5% on the external test set (BoNet 85.5%, p = 0.066). EVG-BANet showed no bias in the local test set but exhibited a bias related to chronological age in the external test set. Conclusion: EVG-BANet can accurately predict the bone age (BA) for both Han children and Tibetan children living in the Tibetan Plateau with limited healthcare facilities.

Assessment of eIF2α phosphorylation during immunogenic cell death.

Immunogenic cell death (ICD) is a modality of cellular demise that when it is induced by certain anticancer treatments can ignite an adaptive anticancer immune response. ICD is characterized by the emission of a specific set of danger-associated molecular patterns (DAMPs) including calreticulin exposure at the plasma membrane, ATP liberation, HMGB1 exodus and type-I IFN release. The apical signaling triggering the appearance of these hallmarks involves the phosphorylation on serine 51 of the α-subunit of eukaryotic initiation factor 2 (EIF2), a key protein in the orchestration of endoplasmic reticulum (ER) stress responses. EIF2α can be phosphorylated by a family of four EIF2A kinases: EIF2AK1-4 (best known as heme regulated inhibitor, HRI, protein kinase R, PKR, protein kinase R-like endoplasmic reticulum kinase, PERK, and general control non-derepressible 2, GCN2), that each respond to a specific type of cellular stress. Here, we describe different techniques to investigate the biochemical pathways leading to eIF2α phosphorylation in the context of ICD.

A nationwide survey exploring physicians' and pharmacists' knowledge, awareness and perceptions regarding generic medicines in China.

BACKGROUND: Generic medicines substitution is an important means to control rapid growth of pharmaceutical expenditures for the healthcare system in China. Acceptance and utilization of generic medicines is highly influenced by healthcare providers' perceptions. This study aimed to compare the knowledge, awareness and perceptions of generic medicines between physicians and pharmacists in China. METHODS: We used an online, cross-sectional survey across China. The questionnaire explored four sections: demographic characteristics, assessment of the participants' knowledge and awareness of generic medicines, perceptions of generic medicines and generic substitution practices. Chi-square or Mann-Whitney-U tests were applied to compare differences between physicians and pharmacists. P-values < 0.05 were considered significant. RESULTS: A total of 1644 physicians and 4187 pharmacists participated. Most physicians (82.8%, n = 1362) and pharmacists (89.8%, n = 3760) correctly identified the definition of generic medicines. A similar percentage of physicians and pharmacists agreed that approved generic medicines are as effective (64.1% vs 68.2%) or safe (63.8% vs 69.1%) as brand-name medicines. Most physicians and pharmacists (67.6% vs 71.0%) supported the policy of generic substitution. In practice, 79.4% (n = 1305) of physicians reported that they had prescribed generic medicines. More than 78% of respondents reported an obvious increase in the number of generic medicines prescribed in their medical institutions. The majority of physicians and pharmacists identified lack of trust regarding efficacy and safety of generic medicines and the difficulty of changing patients' preference as top challenges in generic substitution. CONCLUSIONS: Both physicians and pharmacists surveyed had adequate knowledge of generic medicines, and hold positive attitude towards generics and generic substitution. Efficacy and safety are key factors related to prescribing or dispensing generic medicines. Various policies and regulations should be taken to encourage successful generic substitution.

Assessment of Osteoporosis in Lumbar Spine: In Vivo Quantitative MR Imaging of Collagen Bound Water in Trabecular Bone.

AIM: Bone collagen matrix makes a crucial contribution to the mechanical properties of bone by imparting tensile strength and elasticity. The collagen content of bone is accessible via quantification of collagen bound water (CBW) indirectly. We prospectively study the performance of the CBW proton density (CBWPD) measured by a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) magnetic resonance imaging (MRI) sequence in the diagnosis of osteoporosis in human lumbar spine. METHODS: A total of 189 participants with a mean age of 56 (ranged from 50 to 86) years old were underwent MRI, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DXA) in lumbar spine. Major fracture risk was also evaluated for all participants using Fracture Risk Assessment Tool (FRAX). Lumbar CBWPD, bone marrow fat fraction (BMFF), bone mineral density (BMD) and T score values were calculated in three vertebrae (L2-L4) for each subject. Both the CBWPD and BMFF were correlated with BMD, T score, and FRAX score for comparison. The abilities of the CBWPD and BMFF to discriminate between three different cohorts, which included normal subjects, patients with osteopenia, and patients with osteoporosis, were also evaluated and compared using receiver operator characteristic (ROC) analysis. RESULTS: The CBWPD showed strong correlation with standard BMD (R2 = 0.75, P < 0.001) and T score (R2 = 0.59, P < 0.001), as well as a moderate correlation with FRAX score (R2 = 0.48, P < 0.001). High area under the curve (AUC) values (≥ 0.84 using QCT as reference; ≥ 0.76 using DXA as reference) obtained from ROC analysis demonstrated that the CBWPD was capable of well differentiating between the three different subject cohorts. Moreover, the CBWPD had better correlations with BMD, T score, and FRAX score than BMFF, and also performed better in cohort discrimination. CONCLUSION: The STAIR-UTE-measured CBWPD is a promising biomarker in the assessment of bone quality and fracture risk.

Autophagic flux assessment by immunoblot.

Autophagy is one of the main adaptive mechanisms to maintain cellular homeostasis in response to multiple stresses. During autophagy diverse cellular components such as damaged organelles or superfluous proteins are targeted for lysosomal degradation. Importantly, during the initiation of autophagy MAP1LC3B (better known as LC3) lipidates into the membrane of the forming phagophore, which facilitates the formation and lengthening of autophagosomes. In addition, the autophagy receptor SQSTM1 (better known as p62) selectively recruits various cargos to autophagosomes for lysosomal degradation. Both, the conversion of LC3 as well as the degradation of p62 can be assessed as means of monitoring autophagy. Here we detail a protocol for assessing these key events of the autophagic flux via immunoblot.

Predictors for Surgeries With the Endoscope-Navigation System for Traumatic Optic Neuropathy and its Clinical Assessment.

BACKGROUND: To assess surgeries with the endoscope-navigation system (ENS) in patients who underwent traumatic optic neuropathy (TON) and find predictors for best corrected visual acuity (BCVA) outcomes. METHODS: The clinical data of 96 consecutive TON patients (96 eyes) who underwent decompression surgery with ENS in the Department of Ophthalmology, Shanghai Ninth People's Hospital, from January 2013 to December 2019 were retrospectively reviewed and analyzed. A binary logistic regression was performed to establish a predictive model for BCVA after treatment as TON outcome. RESULTS: By practicing ENS, 49/96 (51.0%) TON patients got improvement in BCVA, whereas the improvement rate of patients with BCVA of light perception or better was 72.5% (29/40). Hemorrhage within the postethmoid and/or sphenoid sinus, orbital fracture, time interval between trauma and treatment, and BCVA before treatment were predictors for BCVA improvement in TON patients by practicing ENS surgery. The area under raw current curves of the predictive model was 0.826. CONCLUSIONS: Surgeries with the ENS showed positive outcomes for TON patients, especially for those with better BCVA before treatment, shorter time interval between trauma and treatment, without orbital fracture or hemorrhage within the postethmoid and/or sphenoid sinus.

Performance of an artificial intelligence system for bone age assessment in Tibet.

OBJECTIVE: To investigate whether bone age (BA) of children living in Tibet Highland could be accurately assessed using a fully automated artificial intelligence (AI) system. METHODS：: Left hand radiographs of 385 children (300 Tibetan and 85 immigrant Han) aged 4-18 years who presented to the largest medical center of Tibet between September 2013 and November 2019 were consecutively collected. From these radiographs, BA was determined using the Greulich and Pyle (GP) method by experts in a consensus manner; furthermore, BA was estimated by a previously reported artificial intelligence (AI) BA system based on Han children from southern China. The performance of the AI system was compared with that of experts by using statistical analysis. RESULTS: Compared with the experts' results, the accuracy of the AI system for Tibetan and Han children within 1 year was 84.67 and 89.41%, respectively, and its mean absolute difference (MAD) was 0.65 and 0.56 years, respectively. The discrepancy in hand-wrist bone maturation was the main cause of low accuracy of the system in the 4- to 6-year-old group. CONCLUSION: The AI BA system developed for Han Chinese children living in flat regions could enable to assess BA accurately in Tibet where medical resources are limited. ADVANCES IN KNOWLEDGE: AI-based BA system may serve as an effective and efficient solution to assess BA in Tibet.

Composition and risk assessment of perioperative patient safety incidents reported by anesthesiologists from 2009 to 2019: a single-center retrospective cohort study.

BACKGROUND: Patient safety incident (PSI) reporting has been an important means of improving patient safety and enhancing organizational quality control. Reports of anesthesia-related incidents are of great value for analysis to improve perioperative patient safety. However, the utilization of incident data is far from sufficient, especially in developing countries such as China. METHODS: All PSIs reported by anesthesiologists in a Chinese academic hospital between September 2009 and August 2019 were collected from the incident reporting system. We reviewed the freeform text reports, supplemented with information from the patient medical record system. Composition analysis and risk assessment were performed. RESULTS: In total, 847 PSIs were voluntarily reported by anesthesiologists during the study period among 452,974 anesthetic procedures, with a reported incidence of 0.17%. Patients with a worse ASA physical status were more likely to be involved in a PSI. The most common type of incident was related to the airway (N = 208, 27%), followed by the heart, brain and vascular system (N = 99, 13%) and pharmacological incidents (N = 79, 10%). Those preventable incidents with extreme or high risk were identified through risk assessment to serve as a reference for the implementation of more standard operating procedures by the department. CONCLUSIONS: This study describes the characteristics of 847 PSIs voluntarily reported by anesthesiologists within eleven years in a Chinese academic hospital. Airway incidents constitute the majority of incidents reported by anesthesiologists. Underreporting is common in China, and the importance of summarizing and utilizing anesthesia incident data should be scrutinized.

Comprehensive Assessment of Candidate Reference Genes for Gene Expression Studies Using RT-qPCR in Tamarixia radiata, a Predominant Parasitoid of Diaphorina citri.

Tamarixia radiata (Waterston) is a predominant parasitoid of the Asian citrus psyllid (ACP), a destructive citrus pest and vector of huanglongbing (HLB) disease in the fields of southern China. To explore the functioning of target genes in T. radiata, the screening of specific reference genes is critical for carrying out the reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) under different experimental conditions. However, no reference gene(s) for T. radiata has yet been reported. Here, we selected seven housekeeping genes of T. radiate and evaluated their stability under the six conditions (developmental stage, sex, tissue, population, temperature, diet) by using RefFinder software, which contains four different programs (geNorm, ΔCt, BestKeeper, and NormFinder). Pairwise variation was analyzed by geNorm software to determine the optimal number of reference genes during the RT-qPCR analysis. The results reveal better reference genes for differing research foci: 18S and EF1A for the developmental stage; PRS18 and EF1A for sex, PRS18 and RPL13 for different tissues (head, thorax, abdomen); EF1A and ArgK between two populations; ß-tubulin and EF1A for different temperatures (5, 15, 25, 35 °C); and ArgK and PRS18 for different feeding diets. Furthermore, when the two optimal and two most inappropriate reference genes were chosen in different temperatures and tissue treatments, respectively, the corresponding expression patterns of HSP70 (as the reporter gene) differed substantially. Our study provides, for the first time, a more comprehensive list of optimal reference genes from T. radiata for use in RT-qPCR analysis, which should prove beneficial for subsequent functional investigations of target gene(s) in this natural enemy of ACP.

The manufacturing procedure of 3D printed models for endoscopic endonasal transsphenoidal pituitary surgery.

BACKGROUND: Endoscopic endonasal transsphenoidal pituitary surgery is usually difficult and risky. With limited sources of cadaveric skulls, traditional methods of using virtual images to study the surgery are difficult for neurosurgeons and students because the surgery requires spatial imagination and good understanding of the patient's conditions as well as practical experience. The three-dimensional (3D) printing technique has played an important role in clinical medicine due to its advantages of low cost, high-efficiency and customization. OBJECTIVE: CT images are used as the source data of 3D printing. The data obtained directly from the CT machine has limited accuracy, which cannot be printed without processing. Some commercial platforms can help build an accurate model but the cost and customization are not satisfactory. In this situation, a tactile, precise and low-cost 3D model is highly desirable. METHODS: Five kinds of computer software are used in the manufacturing of medical 3D models and the processing procedure is easy to understand and operate. RESULTS: This study proposes a practical and cost-effective method to obtain the corrected digital model and produce the 3D printed skull with complete structures of nasal cavity, sellar region and different levels of pituitary tumors. The model is used for the endoscopic endonasal transsphenoidal pituitary surgery preparation. CONCLUSION: The 3D printed medical model can directly help neurosurgeons and medical students to practice their surgery skills on both general and special cases with customized structures and different levels of tumors.

Artificial intelligence system can achieve comparable results to experts for bone age assessment of Chinese children with abnormal growth and development.

OBJECTIVE: Bone age (BA) is a crucial indicator for revealing the growth and development of children. This study tested the performance of a fully automated artificial intelligence (AI) system for BA assessment of Chinese children with abnormal growth and development. MATERIALS AND METHODS: A fully automated AI system based on the Greulich and Pyle (GP) method was developed for Chinese children by using 8,000 BA radiographs from five medical centers nationwide in China. Then, a total of 745 cases (360 boys and 385 girls) with abnormal growth and development from another tertiary medical center of north China were consecutively collected between January and October 2018 to test the system. The reference standard was defined as the result interpreted by two experienced reviewers (a radiologist with 10 years and an endocrinologist with 15 years of experience in BA reading) through consensus using the GP atlas. BA accuracy within 1 year, root mean square error (RMSE), mean absolute difference (MAD), and 95% limits of agreement according to the Bland-Altman plot were statistically calculated. RESULTS: For Chinese pediatric patients with abnormal growth and development, the accuracy of this new automated AI system within 1 year was 84.60% as compared to the reference standard, with the highest percentage of 89.45% in the 12- to 18-year group. The RMSE, MAD, and 95% limits of agreement of the AI system were 0.76 years, 0.58 years, and -1.547 to 1.428, respectively, according to the Bland-Altman plot. The largest difference between the AI and experts' BA result was noted for patients of short stature with bone deformities, severe osteomalacia, or different rates of maturation of the carpals and phalanges. CONCLUSIONS: The developed automated AI system could achieve comparable BA results to experienced reviewers for Chinese children with abnormal growth and development.

Estrogens in municipal wastewater and receiving waters in the Beijing-Tianjin-Hebei region, China: Occurrence and risk assessment of mixtures.

The potentially high release of estrogens to surface waters due to high population density and local livestock production in the Beijing-Tianjin-Hebei region may pose adverse effects on reproductive systems of aquatic organisms. This study found that total measured concentrations of estrone (E1), 17ß-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2) and diethylstilbestrol (DES) were 468 ± 27 ng/L in treated wastewater and 219 ± 23 ng/L in river waters in this region. E2, E3 and EE2 were the predominant estrogens in river waters. The restriction of DES for human use should have been enforced, however concentrations of DES were relatively high compared to other studies. Haihe and Yongdingxin Rivers delivered approximately 1.8 tonnes of estrogens to the Bohai Bay annually. Concentrations of individual estrogens were significantly higher in river waters in the dry season, however, mass loadings were significantly higher in the wet season. The average E2-equivalent concentrations reached 1.2 ± 0.2 and 0.64 ± 0.08 µg-E2/L following long-term and short-term exposure estimates, respectively, in river waters with an EE2 contribution of over 90 %. This could give rise to high risks to fish. Estrogens in river waters largely derived from human excretion. Field studies on estrogenic effects on fish reproductive systems are required locally considering high estrogen contamination levels.

Standardized patient methodology in mainland China: a nationwide survey.

BACKGROUND: To describe the current status of standardized patient (SP) practice in mainland China. METHODS: We conducted a nationwide survey in 2016. One hundred and eighty-three SP educators (SPEs) responded to the questionnaire, representing 80 medical centers from 25 provinces in mainland China. All of these centers were affiliated with China Standardized Patients Practice Teaching Guidance. In the survey, we assessed the methods of SPs' recruitment, hourly wage, how SPs were used and challenges of SP role. We also compared these data among the 4 different regions in China. RESULTS: In mainland China, the most frequent range of SPs' age was between 30 and 40 years (24.8%). The SPs were usually recruited by recommendations from the SPEs or a current SP (43.8%), as well as advertising in the hospitals (43.8%). The mean hourly wage was US$12.60 for teaching activities and US$18.82 for medical examinations. The median frequency for training SPs was 12.9 times per year. The SPs were used in areas such as internal medicine (89.6%), surgery (79.2%) and pediatrics (56.3%). The most challenging parts for the SPs were to remember all of the key points of the cases (51.9%) and portraying the emotions of the case (51.9%). Almost half of the SPs reported that, when interacting with medical students, they had difficulty in providing feedback in consistent with students' learning objectives. SPs' gender, age, rewards and scenarios playing were different significantly among the 4 geographic regions in China (P < 0.05). CONCLUSIONS: This survey provided the reliable data on the current situation of SP application in China. SP activities have had an encouraging progress but regional development imbalance.

Spatial and seasonal variations of antibiotics in river waters in the Haihe River Catchment in China and ecotoxicological risk assessment.

Concentrations of widely used antibiotics were predicted to be the highest in the Haihe River Catchment across China previously, potentially resulting in high ecotoxicological risks in this region. As a result of growing usage and regulation of antibiotic use in animals, the pattern of use may have altered temporally for different antibiotics. It is important to monitor the occurrence of antibiotics within different categories for understanding their mass loading to the catchment and the potential ecotoxicological risks involved. This study investigated the seasonal occurrence and spatial variation of 15 antibiotics in the Haihe River Catchment during 2016-2017. The investigated compounds included veterinary antibiotics, human-use antibiotics, and those intended for both human and animal use. Measurements reported from previous studies were compared with the results of this study and indicated that the use of veterinary antibiotics is probably increasing around the catchment. The ∑antibiotics concentration (i.e. the summed concentration of the 15 target antibiotics) ranged from 414 to 1951 ng/L, with an average of 821 ng/L. Discharges from wastewater treatment plants were the main sources of these compounds. The mass loading of antibiotics to the river waters was higher during wet seasons than during dry seasons. The mass fluxes of the antibiotics continuously increased towards the lower reaches of the rivers. The total annual input of the antibiotics from the Haihe River and Yongdingxin River into the Bohai Bay was 5008 kg/yr. Ofloxacin, trimethoprim, leucomycin, anhydro erythromycin and florfenicol were the predominant antibiotics, whilst amoxicillin, anhydro erythromycin, ofloxacin, norfloxacin and enrofloxacin may pose high ecotoxicological risks to the investigated aquatic ecosystem. Several antibiotics selected in this study were reported for the first time in this catchment. This study provides important information for chemical management and indicates that further monitoring is needed on the more harmful and veterinary antibiotics in the catchment.

[Spatial Distribution Study and Pollution Assessment of Pb in Soils in the Xijiang River Drainage of Guangxi].

To obtain data for the accumulation of Pb and its risk in soils in the Xijiang River drainage of Guangxi, 2594 samples were collected from nonferrous metal mining soils, farmland soils (paddy soils and dryland soils), and the background soils in the drainage area. Geostatistical analysis combined with GIS was used to study the soil spatial distribution characteristics and pollution distribution of the soil Pb content. The results showed that the Pb background value of the soil was 51.84 mg ·kg-1 in the Xijiang River Basin, and the results of the single sample T test showed that the soil background value was significantly higher than that of a previous study (22.08 mg ·kg-1) and the soil background value (20.50 mg ·kg-1) in Guangxi province. The geometric mean concentration of Pb in the mining soils, dryland soils, and paddy soils were 655.9, 116.7, and 40.63mg ·kg-1, respectively, significantly higher than that in other soils. Using GB 15618-1995 and the baseline as the limiting value, the corresponding exceedance rate of the mining soils, dryland soils, and paddy soils were 57.69%, 16.40%, and 8.92% and 54.95%, 8.09%, and 2.03%. The mining soils and farmland soils had an obvious lead accumulation trend. There was an obvious spatial autocorrelation of Pb in the soil, and the structural variation was dominant. The content of Pb in the upper reaches of the Xijiang River reached the middle and lower reaches of the Xijiang River, and the soil Pb was characterized by an obvious decrease. The accumulation of high Pb content in the upper reaches of Diaojiang River is much larger than that in the lower reaches of Diaojiang River. The content of Pb in soil samples in the Xijiang River Basin was mainly rated between mild pollution and moderate pollution, and the pollution was concentrated in the municipal administrative area and the mining activity area. The pollution of the soil in Jinchengjiang and Nandan counties was closely related to the frequent local mining activities.

Childhood-Onset Adult Growth Hormone Deficiency: Clinical, Hormonal, and Radiological Assessment in a Single Center in China.

BACKGROUND: Although growth hormone deficiency (GHD) is an important issue in pediatric patients, adult GHD (AGHD) is a neglected field of endocrinology in China. The aim of this study is to characterize the clinical, hormonal, and radiological features in childhood-onset AGHD (CO AGHD) in a single center in China and to compare them with counterparts from Japan. METHODS: The medical records of 78 Chinese patients with CO AGHD were reviewed and compared with data from the HypoCCS database study from Japan (N = 69). RESULTS: The majority of our patients had pituitary stalk interruption, while hypothalamo-pituitary tumors were the most common cause of CO AGHD in Japan. Chinese patients had a lag of 6 years for diagnosis. The majority of both groups had multiple pituitary hormone deficiencies. Body mass index and lipid profiles were similar between the 2 patient groups. Dyslipidemia and hyperuricemia were the most common metabolic disturbances in Chinese patients. CONCLUSIONS: Our findings confirm that there are possible regional differences in the etiology, metabolic characteristics, and hormonal status in CO AGHD patients in different countries in Asia.

PCBs and OCPs in fish along coastal fisheries in China: Distribution and health risk assessment.

PCBs and OCPs were analyzed in fish (bass) taken along Chinese coastal fisheries. In the bass muscle, PCB, DDT and HCH concentrations were in the range of 1.02-2.2ng/g, 0.44-1.74 and 2.84-106.11ng/gww, respectively. Spatial distribution showed that the concentrations of target contaminants in bass from south fisheries were in general much lower than those from north fisheries in China. The ratios of OCP congeners suggested that technical DDT was not the main input and a recent usage of lindane or old technical HCH residuals could be the source of HCHs. The OCC concentrations in liver (127-442.43ng/gww) from selected samples were 8-12 and 10-14 times higher than those in gills and muscles, respectively. Based on the maximum allowable fish assumption rate (CRlim and CRmm), it could cause human health risk, by consuming bass samples taken from highly contaminated fisheries including QD and ST.