Correlation between capsule endoscopy classification and CT lymphangiography of primary intestinal lymphangiectasia.

AIM: To investigate the correlation between capsule endoscopy (CE) classification of primary intestinal lymphangiectasia (PIL) and computed tomography (CT) lymphangiography (CTL). MATERIALS AND METHODS: A total of 52 patients with diagnosed PIL were enrolled. All patients were examined using CTL and small intestinal CE before surgery. CE assessments included the morphology, scope, colour, and size of lesions. CTL assessments included intestinal wall, lymphatic vessel dilatation, lymph fluid reflux, and lymphatic fistula. Patients were divided into three groups according to type diagnosed by CE, and the CTL characteristics were analysed among the groups. RESULTS: CE showed 15 patients with type I, 27 with II, and 10 with type III. Intestinal wall thickening was observed in 15 type I, 21 type II, and seven type III. Pericardial effusion was observed in only three type I patients; the difference among types was statistically significant (p=0.02). Abnormal contrast agent distribution in the intestinal wall and mesentery was observed in 15 type II patients, and the difference was significantly greater than that of types I and III (p=0.02). Abnormal contrast agent distribution in the abdominal cavity was observed in 12 type II, and the difference was statistically significant (p=0.03). CONCLUSION: The CE PIL classification reflects the extent and scope of intestinal mucosa lesions; CTL more systematically demonstrates abnormal lymphatic vessels or reflux, and its manifestations of PIL are related to the CE classification. The combination of CTL with CE is useful for accurately evaluating PIL, and provides guidance for preoperative assessment and treatment management of PIL patients.

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator.

The AMP-activated protein kinase (AMPK) αßγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2ß2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2ß2-specific activators, here we perform structure/function analysis of the 2-hydroxybiphenyl group of SC4, an activator with tendency for α2-selectivity that is also capable of potently activating ß2 complexes. Substitution of the LHS 2-hydroxyphenyl group with polar-substituted cyclohexene-based probes resulted in two AMPK agonists, MSG010 and MSG011, which did not display α2-selectivity when screened against a panel of AMPK complexes. By radiolabel kinase assay, MSG010 and MSG011 activated α2ß2γ1 AMPK with one order of magnitude greater potency than the pan AMPK activator MK-8722. A crystal structure of MSG011 complexed to AMPK α2ß1γ1 revealed a similar binding mode to SC4 and the potential importance of an interaction between the SC4 2-hydroxyl group and α2-Lys31 for directing α2-selectivity. MSG011 induced robust AMPK signalling in mouse primary hepatocytes and commonly used cell lines, and in most cases this occurred in the absence of changes in phosphorylation of the kinase activation loop residue α-Thr172, a classical marker of AMP-induced AMPK activity. These findings will guide future design of α2ß2-selective AMPK activators, that we hypothesise may avoid off-target complications associated with indiscriminate activation of AMPK throughout the body.

[Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study].

Objective: To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test. Methods: This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ (2) test. A kappa test was used to compare the consistency between groups. Results: After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea (Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences (P < 0.001). Conclusion: The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

[Comparison of initial periodontal therapy and its correlation with white blood cell level in periodontitis patients with or without diabetes mellitus].

OBJECTIVE: To compare the clinical efficacy of initial periodontal therapy in periodontitis patients with or without type 2 diabetes mellitus and its correlation with white blood cell counts. METHODS: In this study, 32 chronic periodontitis patients without systemic disease (CP group) and 27 chronic periodontitis patients with type 2 diabetes mellitus (CP+DM group) were enrolled. At admission, all the patients went through periodontal examination and fasting blood examination(baseline). Probing depth (PD), attachment loss (AL), bleeding index (BI), plaque index (PLI), white blood cells (WBC) counts and fasting blood glucose (FBG) were recorded respectively, while hemoglobin A1c (HbA1c) was recorded only in CP+DM group. After that, initial periodontal therapy was performed. All the tests were repeated 3 and 6 months after treatment. The changes of periodontal clinical indexes and WBC levels were compared between the two groups before and after treatment, and the correlation between WBC and periodontal clinical indexes and glucose metabolism indexes were analyzed by generalized linear mixed model. RESULTS: At baseline, the periodontal inflammation and destruction were similar in CP and CP+DM group, but the WBC level was significantly higher in CP+DM groups [(6.01±1.26)×109/L vs. (7.14±1.99)×109/L, P=0.01]. After 3 and 6 months of initial periodontal therapy, the mean PD, AL, BI, and PLI in CP+DM and CP groups were significantly lower than the baseline, and the PD in CP+DM group was further decreased by 6 months compared with 3 months [(3.33±0.62) mm vs. (3.61±0.60) mm, P < 0.05]. However, none of these periodontal indexes showed significant difference between the two groups by 3 or 6 months. In CP+DM group, HbA1c at 3 months and 6 months were significantly lower than the baseline [(7.09±0.79)% vs. (7.64±1.16)%, P < 0.05; (7.06±0.78)% vs. (7.64±1.16)%, P < 0.05], and FBG was significantly lower than the baseline by 6 months [(7.35±1.14) mmol/L vs. (8.40±1.43) mmol/L, P < 0.05]. The WBC level in CP group was significantly lower than the baseline level by 3 months [(5.35±1.37)×109/L vs. (6.01±1.26)×109/L, P < 0.05], while that in CP+DM group was significantly lower than the baseline level by 6 months [(6.00±1.37)×109/L vs. (7.14±1.99)×109/L, P < 0.05]. The analysis of genera-lized linear mixed model showed that WBC level was significantly positively correlated with PD and FBG (P < 0.05). CONCLUSION: Initial periodontal therapy can effectively improve the periodontal clinical status of patients with or without type 2 diabetes mellitus, and have benefits on glycemic control in diabetic patients. However, the response of periodontal indexes and WBC level to initial therapy were relatively delayed in diabetic patients. WBC plays an important role in the correlation between diabetes mellitus and periodontitis.

[Influencing factors analysis on live birth outcome of D3 cleavage stage frozen-thawed embryo after overnight culture and development of nomogram prediction model].

Objective: To analyze the factors affecting the live birth outcome of D3 cleavage stage frozen-thawed embryos after overnight culture, and establish a nomogram model to predict the live birth probability. Methods: The clinical data of assisted reproductive patients treated with D3 cleavage stage frozen-thawed embryo transfer in the First Affiliated Hospital of Zhengzhou University from January 2017 to July 2020 were analyzed retrospectively. A total of 5 456 patients were divided into modeling group and validation group according to the ratio of 7∶3. The modeling group [3 831 patients with average age of (33±6) years] was used to evaluate the independent risk factors of the patient's live birth outcome through multivariate logistic regression analysis and construct the nomogram prediction model. The validation group [1 625 patients with average age of (33±6) years] was used to verify and calibrate the performance of the model. Results: The results of multivariate logistic regression analysis showed that the risk factors related to live birth outcome of D3 frozen-thawed embryos after overnight culture included: female age (OR=0.901,95%CI:0.889-0.914,P<0.001), body mass index (BMI) (OR=0.979,95%CI:0.957-1.002,P=0.072), endometrial thickness on the transfer day (OR=1.121,95%CI:1.080-1.164,P<0.001), the number of transferred embryos (OR=2.192,95%CI:1.867-2.579,P<0.001) and embryo division resumed after overnight culture (OR=1.405,95%CI:1.213-1.627,P<0.001). The area under the curve (AUC) of the nomogram model in the modeling group was 0.716 and that in the validation group was 0.739.Both sets of calibration curves fited well with the ideal curve, which illustrated that the model had good predictive ability. Conclusions: The female age, BMI endometrial thickness on the transfer day, the number of transferred embryos and the embryo division resumed after overnight culture are risk factors for the live birth outcome of frozen-thawed embryos after overnight culture. The nomogram established based on the above factors can help predict the probability of live birth after frozen-thawed embryo transfer.

[Pancreas multidisciplinary team optimizes the diagnosis and treatment of pancreas-related diseases and improves the prognosis of pancreatic cancer patients].

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

[Establishment of a nomogram model for predicting hematoma expansion in intracerebral hemorrhage and its multidimensional evaluation].

Objective: To establish a nomogram model for hematoma expansion (HE) prediction after intracerebral hemorrhage (ICH) and evaluate its performance in a multidimensionally way. Methods: A total of 348 ICH patients who were firstly diagnosed and hospitalized in the Second Affiliated Hospital of Soochow University from January 2017 to December 2019 were collected retrospectively. There were 236 males and 112 females, and their age ranged from 18 to 94 (62.0±14.6) years. All patients were divided into HE group (n=121) or non-HE group (n=227) according to the presence or absence of HE. The clinical and imaging features were compared between the two groups. Multivariate logistic regression analysis was performed for determining the independent predicting factors for HE prediction and a Nomogram model was established by using these factors. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effectiveness, accuracy and clinical practicability of the model, respectively. Bootstrap method was used for internal validation. Results: There were significant differences in onset time, swirl sign, history of anticoagulants administrations, systolic blood pressure when admission, Glasgow coma scale (GCS) scores and RBC distribution width between the two groups[(1.77(1.0, 2.5) h vs 2(1, 3) h, 72 cases (59.5%) vs 94 cases (41.4%), 17 cases (14.0%) vs 15 cases (6.6%), (170.69±29.19) mmHg(1 mmHg=0.133 kPa) vs (163.84±26.07) mmHg, 11(8, 14) scores vs 14(10, 15) scores, 44.3% (41.2%, 46.8%) vs 42.4% (40.1%, 45.3%);respectively, all P<0.05]. Multivariate logistic regression analysis demonstrated that onset time (OR=0.809, 95%CI: 0.682-1.961, P=0.015), swirl sign (OR=0.562, 95%CI:0.349-0.905, P=0.018), history of anticoagulants administrations (OR=0.394, 95%CI: 0.180-1.861, P=0.020), and GCS (OR=0.881, 95%CI: 0.815-1.952, P=0.001) were the predicting factors for HE. The area under the curve (AUC) of the Nomogram model was 0.735(95%CI: 0.687-0.805), which demonstrated that the model has an ideal prediction effectiveness. The calibration curve showed that the prediction probability of HE of the model fits well with the actual probability, and with high calibration. DCA showed relatively wide range of optional threshold probability of the model (ranging from 14% to 72%), the clinical practicability of this model was high. The internal validation results showed a C-index of 0.703, indicated a good discrimination power. Conclusion: The established Nomogram model can predict the HE of ICH with good prediction effectiveness, discrimination power and with good clinical practicability, which can be capable of providing an intuitive and visual guidance tool for timely identifying ICH patients who may have HE.

Serial low-dose quantitative CT perfusion for the evaluation of delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage.

AIM: To investigate the appropriate time and computed tomography perfusion (CTP) parameters for predicting delayed cerebral ischaemia (DCI) following aneurysmal subarachnoid haemorrhage (aSAH). MATERIALS AND METHODS: All patients underwent baseline CTP within 24 hours and follow-up CTP on day 4 and day 7 after aSAH. The quantitative and semi-quantitative parameters, cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), relative CBV and CBF (rCBV, rCBF), and MTT and TTP difference (ΔMTT, ΔTTP) were compared between the DCI and non-DCI (NDCI) groups at the three time points. RESULTS: Thirty-nine patients were included. Twelve patients developed DCI. CBF, rCBF, and ΔMTT were significantly different in the DCI group among all time points (p<0.05), but these parameters did not significantly change from day 4 to day 7. CBF and rCBF in the DCI group were lower than in the NDCI group. ΔMTT in the DCI group was longer than in the NDCI group, but significant differences were only found in the two follow-up CTPs (both p<0.05). The optimal threshold values distinguishing DCI and NDCI were 40.1 ml/100 g/min for CBF, 0.90 for rCBF and 0.33 seconds for ΔMTT. The follow-up CTP on day 4 was an appropriate time to predict DCI after aSAH. CONCLUSIONS: The follow-up CTP on day 4 after aSAH can be helpful for the early identification of DCI. CBF, rCBF, and ΔMTT were found to be the best prognosticators for the development of DCI.

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.

Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes. Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%). Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.

[Phosphatase and tensin homolog deleted on chromosome ten deficiency sensitizes tumor cells to lithium chloride treatment].

Objective: To identify the therapeutic efficacy of lithium chloride (LiCl) on phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient tumors. Methods: First, the Catalogue of Somatic Mutations in Cancer for mutation spectrum of human endometrial carcinoma samples was analyzed. Second, the relationship between PTEN abundance and LiCl inhibition of endometrial cancer cell lines using Pten(+/+) and Pten(-/-) mouse embryonic fibroblast (MEF) lines was investigated. Moreover, potential alterations of mammalian target of rapamycin (mTOR) signaling pathway after treatment with LiCl were checked.Last,LiCl's efficacy on PTEN null tumors was studied. Results: PTEN was mutated in 39% of endometrial carcinomas. LiCl preferentially inhibited the proliferation of PTEN-deficient endometrial carcinoma cells and MEFs. Furthermore, LiCl blocked PTEN-deficient tumor development. Mechanistically, LiCl down-regulated mTOR signaling. Conclusions: PTEN is the most frequently mutated gene in endometrial carcinoma.By targeting mTOR signaling pathway,LiCl is a promising regimen for the treatment of tumors with PTEN deficiency.

[The association of Vitamin D levels with lipid metabolism during pregnancy].

Vitamin D deficiency is common in pregnant women, and it is associated with multiple gestational complications, fetal intrauterine dysplasia, and maternal and infant health in postpartum period. Vitamin D involved in lipid metabolism may affect maternal-fetal health during pregnancy through this biological pathway. This review provides an overview of three main aspects, including, the effect of vitamin D on the mechanism of lipid metabolism, the relationship between vitamin D and lipid metabolites in pregnant women and women with pregnancy complications. An association between vitamin D status and lipid metabolism at different stages of pregnancy has been justified in most current studies, and the underlying mechanism has also been partly elucidated. Given some gestational complications, such as gestational diabetes and pre-eclampsia, pregnant women with these conditions are often associated with abnormal lipid metabolism and vitamin D deficiency. There is no doubt that the studies on the vitamin D supplementation and lipid metabolism improvement could have crucial clinical significance for this population. More randomized controlled trials with multi-center, large sample and multi-dose interventions are needed in the future to provide scientific evidence for clinical practice.

[Trends analysis of vitamin D status among pregnant women in Hefei during 2015-2017]. / 2015­2017å¹´åˆè‚¥å¸‚å­•å¦‡ç»´ç”Ÿç´ DçŠ¶æ€å˜åŒ–è¶‹åŠ¿ç ”ç©¶

From March 2015 to February 2018, 4 728 women aged 18 to 45 years old with single-pregnancy at the gestational age of 13 to 27 weeks in Hefei were recruited to analyze the trend of vitamin D status. The average levels of serum 25(OH)D in 2015, 2016 and 2017 were (43.22±18.41) nmol/L, (39.3±15.1) nmol/L and (36.6±17.0) nmol/L, and the prevalence of vitamin D deficiency were 69.5%, 77.6% and 81.4%, respectively. Compared with 2015, the levels of serum 25(OH)D in pregnant women in 2016 and 2017 decreased by 5.23 (95%CI: 4.10-6.35) nmol/L and 7.98 (95%CI: 6.77-9.19) nmol/L. The OR (95%CI) values for the risk of vitamin D deficiency were 1.88 (95%CI: 1.57-2.24) and 2.41 (95%CI: 1.98-2.93).

[Prospective cohort study on association between peri-conceptional air pollution exposure and gestational diabetes mellitus].

Objective: To explore the association between the exposure to major air pollutants in pre-pregnancy and early pregnancy (peri-conceptional period) and gestational diabetes mellitus (GDM). Methods: From March 2015 to April 2018, 4 817 pregnancies were recruited at three prenatal check-ups hospital in Hefei (Hefei First People's Hospital, Hefei. Maternal and Child Care Hospital and the First Affiliated Hospital of Anhui Medical University), China. Questionnaire was used to collect the demographic data, the health status and lifestyle of pregnant women. GDM was diagnosed according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2017 Edition). Logistic regression was used to investigate the association of exposure to major air pollutants (PM(2.5), PM(10), SO(2), CO and NO(2)) during different periods of pre-pregnancy (12 weeks before pregnancy) and first trimester (12 weeks after last menstruation) and duration of exposure to high levels of pollutants with GDM. Results: The mean±SD of the age of subjects was (29.14±4.19) years old and the prevalence of GDM was 21.4% (n=1 030). The results of multivariate logistic regression analysis showed that after adjusting for confounding factors, the risk of GDM increased gradually with the prolonged exposure time of high-concentration pollutants compared with pregnant women who were not exposed to high pollution during the pre-pregnancy (χ(2)=61.28, P(trend)<0.001) with the OR (95%CI) values for exposure time of 1, 2, and 3 months about 1.42 (1.10-1.84), 1.73 (1.29-2.33), and 2.51 (1.75-3.59), respectively. In the pre-pregnancy period, in every 10 µg/m(3) increase of PM(2.5) and PM(10), the OR (95%CI) values of GDM were 1.14 (1.08-1.20) and 1.13 (1.08-1.19), respectively; for each increase of 1 µg/m(3) and 0.10 mg/m(3) of SO(2) and CO, the OR (95% CI) values of GDM were 1.03 (1.01-1.05) and 1.07 (1.01-1.13), respectively. For every 1 µg/m(3) increase in the average concentration of SO(2) in the first trimester, the OR (95%CI) value of GDM was 1.02 (1.01-1.05). Conclusion: PM(2.5), PM(10), SO(2) and CO exposure during the pre-pregnancy and SO(2) exposure in first trimester were positively correlated with the risk of GDM.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Lipopolysaccharide derived from the digestive tract provokes oxidative stress in the liver of dairy cows fed a high-grain diet.

The aims of this study were to measure oxidative stress parameters and to investigate the molecular mechanism triggered by grain-induced subacute ruminal acidosis in mid-lactation cows. Twelve Holstein-Friesian cows with an average weight of 455±28kg were divided into 2 groups and subjected to 2 diets over 18wk: either a low-grain (forage-to-concentrate ratio=6:4) or a high-grain (forage-to-concentrate ratio=4:6) diet based on dry matter. Being fed a long-term high-grain diet resulted in a significant decrease in rumen pH and a significant increase in ruminal lipopolysaccharide (LPS) at 4 h postfeeding in the morning. The increase was also observed in LPS concentrations in the portal vein, hepatic vein, and jugular vein blood plasma as well as reduced milk yield in a high-grain diet. Cows fed a high-grain diet had lower levels of catalase and glutathione peroxidase (GPx) activity and total antioxidant capacity than cows fed a low-grain diet; however, super oxide dismutase (SOD) activity and malondialdehyde (MDA) levels were higher in both the liver and the plasma of high-grain than in low-grain cows. Positive correlations were observed between plasma LPS versus hepatic MDA, plasma MDA, and hepatic SOD activity, whereas hepatic GPx and plasma GPx were negatively correlated with plasma LPS. The relative mRNA abundances of GPX1 and CAT were significantly lower in the liver of cows fed a high-grain diet than those fed a low-grain diet, whereas SOD1 was significantly higher in cows fed a high-grain diet than cows fed a low-grain diet. The expression levels of Nrf2, NQO1, MT1E, UGT1A1, MGST3, and MT1A were downregulated, whereas NF-kB was upregulated, in cows fed a high-grain diet. Furthermore, nuclear factor E2-related factor 2 (Nrf2) total protein and mRNA levels were significantly lower than in low-grains. Our results demonstrate the relationship between the translocated LPS and the suppression of cellular antioxidant defense capacity, which lead to increased oxidative stress and suggests that the Nrf2-dependent antioxidant response may be affected by higher levels of LPS translocated to the bloodstream.

[Study on the disease burden of Chinese adolescent in 2015].

Objective: To discuss the main causes and risk factors of disability and death among current Chinese adolescents. Methods: Subnational data of China from Global Burden of Disease Study 2015 (GBD 2015) was used to rank the causes and risk factors leading to death and disability adjusted life years (DALY) in Chinese adolescents aged between 10 and 19 years old, and thereby to analyze the main cauese and risk factors of death and DALY among Chinese adolescents in different genders. Results: In 2015, among Chinese adolescents aged 10-19 years old, the total DALY was 13 million 490 thousand years, and the total number of deaths was 63 258 cases. The top 3 causes of DALY were skin and subcutaneous diseases, iron-deficiency anemia and road injuries, resulting in DALY (constituent ratio) of 1 411 (10.5%), 1 094 (8.1%) and 1 029 (7.6%) thousand years respectively. The top 3 causes of death were road injuries, drowning and leukemia, causing 13 881 (21.9%), 9 895 (15.6%) and 4 620 (7.3%) deaths (constituent ratio) respectively. The top 3 risk factors of DALY were iron deficiency, alcohol use and drug use, causing 1 094 (8.1%), 487 (3.6%) and 220 thousand years (1.6%) DALY (constituent ratio) respectively. The top 3 risk factors of death were alcohol use, occupational injuries and drug use, causing 5 957 (9.4%), 1 523 (2.4%) and 810 (1.3%) deaths respectively. Conclusion: Unintentional injury was the top cause of DALY and death in Chinese adolescents, followed by skin and subcutaneous diseases and iron-deficiency anemia. Iron deficiency and alcohol use were the top two risk factors of DALY and death.

[Application of three-dimensional printing personalized acetabular wing-plate in treatment of complex acetabular fractures via lateral-rectus approach].

Objective: To investigate reduction and fixation of complex acetabular fractures using three-dimensional (3D) printing technique and personalized acetabular wing-plate via lateral-rectus approach. Methods: From March to July 2016, 8 patients with complex acetabular fractures were surgically managed through 3D printing personalized acetabular wing-plate via lateral-rectus approach at Department of Orthopedics, the Third Affiliated Hospital of Southern Medical University. There were 4 male patients and 4 female patients, with an average age of 57 years (ranging from 31 to 76 years). According to Letournel-Judet classification, there were 2 anterior+ posterior hemitransverse fractures and 6 both-column fractures, without posterior wall fracture or contralateral pelvic fracture. The CT data files of acetabular fracture were imported into the computer and 3D printing technique was used to print the fractures models after reduction by digital orthopedic technique. The acetabular wing-plate was designed and printed with titanium. All fractures were treated via the lateral-rectus approach in a horizontal position after general anesthesia. The anterior column and the quadrilateral surface fractures were fixed by 3D printing personalized acetabular wing-plate, and the posterior column fractures were reduction and fixed by antegrade lag screws under direct vision. Results: All the 8 cases underwent the operation successfully. Postoperative X-ray and CT examination showed excellent or good reduction of anterior and posterior column, without any operation complications. Only 1 case with 75 years old was found screw loosening in the pubic bone with osteoporosis after 1 month's follow-up, who didn't accept any treatment because the patient didn't feel discomfort. According to the Matta radiological evaluation, the reduction of the acetabular fracture was rated as excellent in 3 cases, good in 4 cases and fair in 1 case. All patients were followed up for 3 to 6 months and all patients had achieved bone union. According to the modified Merle D'Aubigné and Postel scoring system, 5 cases were excellent, 2 cases were good, 1 case was fair. Conclusions: Surgical management of complex acetabular fracture via lateral-rectus approach combine with 3D printing personalized acetabular wing-plate can effectively improve reduction quality and fixation effect. It will be truly accurate, personalized and minimally invasive.