[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.

[The application value of Gd-EOB-DTPA enhanced MRI based radiomics in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia in hepatobiliary phase].

Objective: To investigate the application value of Gd-EOB-DTPA enhanced MRI based radiomics model in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia (FNH) in hepatobiliary phase. Methods: A total of 88 patients with HCC or FNH confirmed by surgical or puncture pathology who underwent preoperative Gd-EOB-DTPA enhanced MRI (all lesions showed iso-or hyperintensity in hepatobiliary phase) between January 2015 and February 2023 in The First Affiliated Hospital of Soochow University and Nantong No.3 People's Hospital were retrospectively evaluated, which including 58 males and 30 females, aged [M(Q1, Q3)]56 (40, 67) years, including 61 patients with HCC and 27 patients with FNH. The included cases were divided into training (43 cases of HCC, 19 cases of FNH) and validation cohort (18 cases of HCC, 8 cases of FNH) in the ratio of 7∶3 using the random seeding method. A total of 1 781 radiomics features were extracted from Gd-EOB-DTPA enhanced MRI in the arterial, portal and hepatobiliary phases, respectively. The independent three phase models, combined three phases model and combined clinical-radiomics model was established using Auto-Encoder (AE) and Native Bayes (NB) classifier, respectively. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of these models. DeLong test was used to compare the areas under curve (AUC). Results: In the validation cohort, the combined clinical-radiomics model had the highest AUC (AUC=0.938, 95%CI: 0.828-1.000). The AUC, accuracy, sensitivity, specificity of the clinical-radiomics combined model using AE classifier in the validation cohort were 0.896 (95%CI: 0.760-1.000), 88.5%, 88.9%, 87.5%. The AUC of the clinical-radiomics combined model using NB classifier in the validation cohort were 0.938 (95%CI: 0.828-1.000), 92.3%, 88.9%, 100.0%. Conclusion: Gd-EOB-DTPA enhanced MRI combined clinical-radiomics model has certain value in preoperative differentiation of iso-or hyperintensity in the hepatobiliary phase HCC and FNH, with a high accuracy, sensitivity and specificity.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

[A comparison of current guidelines for the management of intrahepatic cholangiocarcinoma worldwide].

Intrahepatic cholangiocarcinoma (ICC) is the second most common human liver malignancy and its incidence rate has been gradually increasing worldwide over the past decades. Surgical resection (R0 resection) is the preferred potentially curative treatment for ICC patients. However, due to its conceal clinical features and high invasiveness, most patients have lost the opportunity for surgical resection at the time of diagnosis. In recent years, with the rapid development of targeted therapy and immunotherapy, which is represented by immune checkpoint inhibitors, clinicians are expected to provide more effective treatment options for patients with mid-stage or advanced ICC. At present, there are still controversial opinions on different guidelines regarding preoperative biliary drainage, the extent of hepatectomy, the definition of R0 resection, the width of the resection margin, lymph node dissection, postoperative recurrence, adjuvant therapy, etc. In this review, 12 guidelines or expert consensus published worldwide from 2012 to 2022 (including 4 Chinese guidelines, 4 European guidelines, 2 American guidelines and 2 Japanese guidelines) were retrieved. Focusing on sorting and comparing the current views on clinical management of ICC in different guidelines, this review aims to provide reference information for ICC clinical management and decision-making.

Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice.

Emerging evidence indicates that the alterations in the gut microbiota-brain axis (GBA), which is the bilateral connection between the gut microbial communities and brain function, are involved in several mental illnesses, including depression. Certain probiotic strains have been revealed to improve depressive behaviours and the dysregulation of 5-hydroxytryptamine (5-HT) metabolism in depression. Here we evaluated the potential antidepressant effects of Lactobacillus helveticus strains using an in vitro enterochromaffin cell model (RIN14B). The L. helveticus strain WHH1889 was shown to significantly promote the level of 5-hydroxytryptamine (5-HTP, 5-HT precursor) and the gene expression of tryptophan hydroxylase 1 (Tph1), which is the key synthetase in the 5-HT biosynthesis in RIN14B cells. Ingestion of 0.2 ml WHH1889 (1´109 cfu/ml) in a chronic unpredictable mild stress (CUMS) mouse model of depression for five weeks normalised depressive and anxiety-like behaviours in the forced swim test, tail suspension test, sucrose preference test, and open field test. Meanwhile, the CUMS-induced elevated level of serum corticosterone and declined levels of hippocampal 5-HT and 5-HTP were reversed by WHH1889. Furthermore, the disturbances of the gut microbiome composition with reduced microbial diversity were also improved by WHH1889, accompanied by the increased colonic 5-HTP level and Tph1 gene expression. In summary, these findings indicate that WHH1889 exerts antidepressant-like effects on CUMS mice, which is associated with the modulations of the 5-HT/5-HTP metabolism and gut microbiome composition. Therefore, ingestion of the L. helveticus strain WHH1889 with antidepressant potentials may become an encouraging therapeutic option in the treatment of depression.

Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations.

Mutations V32I, I50V and I84V in the HIV-1 protease (PR) induce drug resistance towards drug amprenavir (APV). Multiple short molecular dynamics (MSMD) simulations and molecular mechanics generalized Born surface area (MM-GBSA) method were utilized to investigate drug-resistant mechanism of V32I, I50V and I84V towards APV. Dynamic information arising from MSMD simulations suggest that V32I, I50V and I84V highly affect structural flexibility, motion modes and conformational behaviours of two flaps in the PR. Binding free energies calculated by MM-GBSA method suggest that the decrease in binding enthalpy and the increase in binding entropy induced by mutations V32I, I50V and I84V are responsible for drug resistance of the mutated PRs on APV. The energetic contributions of separate residues on binding of APV to the PR show that V32I, I50V and I84V highly disturb the interactions of two flaps with APV and mostly drive the decrease in binding ability of APV to the PR. Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV. This study can provide useful dynamics information for the design of potent inhibitors relieving drug resistance.

[Morvan syndrome with positive anti LGI1/CASPR2 antibodies in serum/cerebrospinal fluid:a case report and literature review].

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

[The prediction value of enhanced magnetic resonance imaging nomogram model for dual phenotype hepatocellular carcinoma].

Objective: To explore the value of enhanced magnetic resonance imaging nomogram model in the prediction of dual-phenotype hepatocellular carcinoma(DPHCC). Methods: Data of 116 patients of hepatocellular carcinoma (HCC) confirmed by postoperative pathology, who underwent preoperative enhanced MRI between January 2016 and March 2021 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, of these, there are 87 males and 28 females, aged 30-79 (59±10) years, including 31 patients with DPHCC and 85 patients with non-DPHCC. The patients were randomly divided into training set(51 cases of non-DPHCC,19 cases of DPHCC)and validation set(34 cases of non-DPHCC, 12 cases of DPHCC) in a ratio of 6∶4, according to random number table,clinical and imaging characteristics of the two groups were compared. The statistically significant parameters were included in multivariate logistic regression to identify the independent predictors and for the establishment of the nomogram model. The receiver operating characteristic curves were used to evaluate the prediction ability of the models, the corrected curve was used to validate the model. Results: In the training group, the proportions of rim arterial phase hyperenhancement in the DPHCC was significantly higher than that of the non-DPHCC [47.4%(9/19)vs 7.8%(4/51),P<0.001]. Rim arterial phase hyper-enhancement and enhanced capsule were significant predictors for DPHCC[OR=10.17(1.70-60.80),0.17(0.03-0.93),all P<0.05]. In the training group, the area under curve (AUC), sensitivity and specificity of the nomogram were 0.888 (95%CI: 0.806-0.969), 78.9% and 86.3%. In the validation group, the above three indicators were 0.811(95%CI: 0.655-0.968), 75.0% and 82.4%. Conclusion: Enhanced MRI nomogram model has certain value in prediction of DPHCC, with high sensitivity and specificity.

[Relationship between body mass index and sexual development in Chinese children].

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

[Value of the application of enhanced CT radiomics and machine learning in preoperative prediction of microvascular invasion in hepatocellular carcinoma].

Objective: To explore the value of machine learning models in preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on dual-phase contrast-enhanced CT radiomics features. Methods: The data of 148 patients [106 males and 42 females, with an average age of (58±11) years] with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 88 cases of positive MVI and 60 cases of negative MVI. According to the ratio of 7∶3, the patients were randomly divided into the training and validation sets, respectively. The three-dimensional (3D) radiomics features of HCC in arterial phase (AP) and portal venous phase (PP) were extracted by MaZda software, and the optimal feature subset was obtained by combining three feature selection methods (FPM method) and Lasso regression. Then, six machine learning methods were used to build the prediction models. Receiver operating characteristic (ROC) curves were drawn to evaluate the prediction ability of the aforementioned models, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. Results: Radiomics features of HCC in AP and PP were extracted by MaZda software, with 239 in each phase. There were 7 optimal features in AP and 14 optimal features in PP selected by FPM method and Lasso regression, respectively. The AUCs of decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model, and neural network based on the 7 optimal features in AP in the validation set were 0.736, 0.910, 0.913, 0.915, 0.897, 0.648, respectively. The SVM had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 95.35%, 95.83% and 94.74%, respectively. Likewise, the AUCs of machine learning models in prediction of MVI in HCC based on the 14 optimal features in PP in the validation set were 0.873, 0.876, 0.913, 0.859, 0.877, 0.834, respectively, and there were no significant differences (all P>0.05). The random forest had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 90.70%, 87.50% and 94.74%, respectively. Conclusion: Machine learning models based on dual-phase enhanced CT radiomics features can be used in preoperative prediction of MVI in HCC, particularly the SVM and random forest models have high prediction efficiency.

[Survey of height and weight of children and adolescents at different Tanner stages in urban China].

Objective: To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight. Methods: A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results: The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion: The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

[Measurement and evaluation of the quadriceps muscle mass in young men based on magnetic resonance imaging].

OBJECTIVE: To investigate the correlation between the quadriceps cross-sectional area (CSA) and quadriceps muscle volume (QMV) at different horizontal levels from the upper edge of the patella, and to determine the best observation position. METHODS: Thigh magnetic resonance imaging (MRI) images of 22 Chinese young men [age: (29±6) years] with anterior cruciate ligament (ACL) rupture were examined. The CSA was measured at 18, 15, and 12 cm above the upper edge of the pate-lla (denoted by CSA-18, CSA-15 and CSA-12 respectively), and the QMV and CSA were determined by semiautomatic segmentation. A curve model was established to estimate QMV. Bland-Altman analysis was performed to determine the confidence limits of the volumes. RESULTS: On the unaffected side, the mean QMV was (1 944.45±323.77) cm3. The quadriceps CSA at the upper edge of the patella at 18, 15, and 12 cm was (80.80±12.16) cm2, (77.53±12.03) cm2, and (72.68±10.51) cm2, respectively. The coefficients of determination (R2), ascertained using curve estimation models, for the 3 positions were 0.819, 0.755, and 0.684 (P < 0.001), and the standard deviations of the volume estimated value (SEE) were 7.4%, 8.7%, and 9.8%. The fitting equations of the three horizontal positions were all good, but the fitting degree of CSA-18 was the highest. The Bland-Altman scatter plot showed that the arithmetic means of the QMV at 18, 15 and 12 cm from the upper edge of the patella 0.8 cm3, -1.1 cm3, and 0.9 cm3 and 95% limits of agreement (LoA) were (-268.8, 270.5), (-315.2, 313.1), and (-355.7, 357.5), respectively. The estimated QMV was in good agreement with the measured value. The difference between the estimated CSA-18 and measured values was the smallest. The results on the affected side were consistent. CONCLUSION: The correlation between QMV and CSA in the young men with the upper edge of patella as baseline was reliable and consistent. Among them, CSA-18 had the highest correlation with the QMV. However, different observation sites could be selected for different injuries of the quadriceps.

[Changing prevalence of overweight and obesity among Chinese children aged 6-15 from 2009-2019].

Objective: To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019. Methods: Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants' data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results: Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% (n=1 773) anel 12.5% (n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% (n=2 496) to 19.1% (n=2 781) (χ²=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 (t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% (n=202) and 3.1% (n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% (n=1 233) to 22.8% (n=1 365) significantly (χ²=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 (t=1.426, P<0.01), and the rate of obesity decreased from 9.8% (n=315) to7.9% (n=256) (χ²=6.46, P<0.05), the overweight rate was not stafistically significant (P=0.10), respectively. The obesity rate of boys had risen from 16.4% (n=1 265) to 18.2% (1 407) (χ²=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% (n=1 393) to 20.5% (n=1 579) (χ²=14.26, P<0.01). The overweight+obesity rate rose from 34.4% (n=2 658) to 38.7% (n=2 986) (χ²=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% (n=468) to 5.9% (n=406) (χ²=4.546, P<0.05), the overweight rate rose from 16.0% (n=1 103) to 17.5% (n=1 202) (χ²=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% (n=1 571) to 23.4% (n=1 608) (χ²=0.53, P>0.05). Conclusions: The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.

Decoding molecular mechanism underlying binding of drugs to HIV-1 protease with molecular dynamics simulations and MM-GBSA calculations.

HIV-1 protease (PR) is thought to be efficient targets of anti-AIDS drug design. Molecular dynamics (MD) simulations and multiple post-processing analysis technologies were applied to decipher molecular mechanism underlying binding of three drugs Lopinavir (LPV), Nelfinavir (NFV) and Atazanavir (ATV) to the PR. Binding free energies calculated by molecular mechanics generalized Born surface area (MM-GBSA) suggest that compensation between binding enthalpy and entropy plays a vital role in binding of drugs to PR. Dynamics analyses show that binding of LPV, NFV and ATV highly affects structural flexibility, motion modes and dynamics behaviour of the PR, especially for two flaps. Computational alanine scanning and interaction network analysis verify that although three drugs have structural difference, they share similar binding modes to the PR and common interaction clusters with the PR. The current findings also confirm that residues located interaction clusters, such as Asp25/Asp25', Gly27/Gly27', Ala28/Ala28', Asp29, Ile47/Ile47', Gly49/Gly49', Ile50/Ile50', Val82/Val82' and Ile84/Ile84, can be used as efficient targets of clinically available inhibitors towards the PR.

Insights into effect of the Asp25/Asp25' protonation states on binding of inhibitors Amprenavir and MKP97 to HIV-1 protease using molecular dynamics simulations and MM-GBSA calculations.

The protonation states of two aspartic acids in the catalytic strands of HIV-1 protease (PR) remarkably affect bindings of inhibitors to PR. It is requisite for the design of potent inhibitors towards PR to investigate the influences of Asp25/Asp25' protonated states on dynamics behaviour of PR and binding mechanism of inhibitors to PR. In this work, molecular dynamics (MD) simulations, MM-GBSA method and principal component (PC) analysis were coupled to explore the effect of Asp25/Asp25' protonation states on conformational changes of PR and bindings of Amprenavir and MKP97 to PR. The results show that the Asp25/Asp25' protonation states exert different impacts on structural fluctuations, flexibility and motion modes of PR. Dynamics analysis verifies that Asp25/Asp25' protonated states highly affect conformational dynamics of two flaps in PR. The binding free energy calculations results suggest that the Asp25/Asp25' protonated states obviously strengthen bindings of inhibitors to PR compared to the non-protonation state. Calculations of residue-based free energy decomposition indicate that the Asp25/Asp25' protonation not only disturbs the interaction network of inhibitors with PR but also stabilizes bindings of inhibitors to PR by cancelling the electrostatic repulsive interaction. Therefore, special attentions should be paid to the Asp25/Asp25' protonation in the design of potent inhibitors towards PR.

[Systemic anti-inflammation is the key for the treat-to-target in severe immune-related skin disorders].

Immune-related skin disorders (inflammatory skin diseases and autoimmune diseases) are important diseases in dermatology. Systemic inflammation is the fundamental cause that makes these diseases difficult to control and easy to relapse. The treatment pattern of rheumatic immune diseases could be used as a reference to reach the treat-to-target (T2T) of severe immune/inflammatory skin disorders, thus to reduce systemic inflammatory damage, to effectively control symptoms in the long term, to improve the quality of life, and to help patients back to normal study/work/life status.

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.

Circular RNA circGFRA1 promotes angiogenesis, cell proliferation and migration of hepatocellular carcinoma by combining with miR-149.

OBJECTIVE: We aimed to explore the effect of circGFRA1 on the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. PATIENTS AND METHODS: First, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the level of circGFRA1 in HCC tissues and cells. Survival analysis was applied to detect the effect of highly expressed circGFRA1 on the prognosis of HCC patients. Subsequently, circGFRA1 level was silenced in HCC cells, and proliferative, migration and angiogenesis activity of HCC cells was examined using Cell Counting Kit-8 (CCK-8), transwell test, and angiogenesis experiment. Then, we predicted the binding target of circGFRA1 through the bioinformatics website, and verified it through qRT-PCR and Dual-Luciferase reporter assay. Lastly, the interaction between them was verified through a series of in vitro experiments. RESULTS: qRT-PCR analysis showed that circGFRA1 was abnormally highly expressed in HCC tissues and HCC cells, and the high expression of circGFRA1 may lead to poor prognosis in patients with HCC. After transfecting si-circGFRA1 in HCC cells, CCK-8 and transwell experiments showed that the proliferative ability and migration of HCC cells were inhibited. Moreover, angiogenesis experiments showed that the knockdown of circGFRA1 can inhibit the blood vessels replenishment of HCC cells. The bioinformatics website suggested that miR-149 may be able to bind circGFRA1. MiR-149 was upregulated by the knockdown of circGFRA1 in HCC cells. Pearson analysis suggested that the expression levels of the two genes were negatively correlated. Dual-Luciferase reporter assay further indicated that circGFRA1 can bind to miR-149. Reverse experiment showed that the knockdown of miR-149 can partially restore the inhibited proliferative, migration, and angiogenesis activity of HCC cells caused by circGFRA1 knockdown. CONCLUSIONS: CircGFRA1 is highly expressed in HCC and its level is negatively correlated with miR-149 expression. CircGFRA1 can promote the proliferative, migration and angiogenic activity of HCC by binding miR-149.

[Analysis of the diagnotic results and complications of pneumoconiosis patients with different insurance types].

Objective: By comparing the diagnotic results and complications of pneumoconiosis patients with work-related injury insurance and non-work-related injury insurance, to provide reference for improving the medical insurance of pneumoconiosis patients. Methods: In May 2019, the diagnotic results and complications of 3204 patients with pneumoconiosis who were hospitalized in the second department of Hunan Prevention and Treatment Institute for Occupational Diseases from January 2017 to March 2019 were retrospectively analyzed. Results: Among the 3204 patients, 896 cases (28.0%) were in stage I, 790 cases (24.6%) were in stage II, and 1518 cases (47.4%) were in stage III. 1490 cases (46.5%) of pneumoconiosis patients have complications, mainly chronic obstructive pulmonary disease (COPD) (42.3%, 1354/3204) and lung infection (23.6%, 755/3204) . 584 cases (18.2%) were covered by work-related injury insurance, and the diagnosis of pneumoconiosis patients was mainly in the stage I (61.0%, 356/584) . 2620 cases (81.8%) were covered by non-work-related injury insurance, and the diagnosis of pneumoconiosis patients was mainly in the stage III (56.0%, 1466/2620) . The complication rate of non-work-related injury insurance patients (50.1%, 1312/2620) was higher than that of work-related injury insurance patients (30.5%, 178/584) (χ(2)=73.72, P<0.01) . Conclusion: The inpatients with pneumoconiosis in Hunan Province are still mainly covered by non-work-related injury insurance, and the diagnotic period and complication rate are significantly higher than those of work-related injury insurance patients. Therefore, pneumoconiosis patients should be provided with medical security, early diagnosis and early intervention, to prevent and delay the occurrence of complications.

Probing molecular mechanism of inhibitor bindings to bromodomain-containing protein 4 based on molecular dynamics simulations and principal component analysis.

It is well known that bromodomain-containing protein 4 (BRD4) has been thought as a promising target utilized for treating various human diseases, such as inflammatory disorders, malignant tumours, acute myelogenous leukaemia (AML), bone diseases, etc. For this study, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA) were integrated together to uncover binding modes of inhibitors 8P9, 8PU, and 8PX to BRD4(1). The results obtained from binding free energy calculations show that van der Waals interactions act as the main regulator in bindings of inhibitors to BRD4(1). The information stemming from PCA reveals that inhibitor associations extremely affect conformational changes, internal dynamics, and movement patterns of BRD4(1). Residue-based free energy decomposition method was wielded to unveil contributions of independent residues to inhibitor bindings and the data signify that hydrogen bonding interactions and hydrophobic interactions are decisive factors affecting bindings of inhibitors to BRD4(1). Meanwhile, eight residues Trp81, Pro82, Val87, Leu92, Leu94, Cys136, Asn140, and Ile146 are recognized as the common hot interaction spots of three inhibitors with BRD4(1). The results from this work are expected to provide a meaningfully theoretical guidance for design and development of effective inhibitors inhibiting of the activity of BRD4.