Clinical outcomes of children with COVID-19 infection in a low-risk centre in Malaysia.

INTRODUCTION: According to WHO, long-COVID or post- COVID-19 condition is defined as the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. A systematic review and meta-analyses published in 2022, which mainly focus on the Western population, revealed that the prevalence of long COVID was 25.24%. Literature regarding long-COVID in children in Asia was scarce. The objectives of our study were to assess the long-term effect of COVID-19 infection in children and its correlation to their acute COVID- 19 infection. MATERIALS AND METHODS: This study was conducted in Hospital Kepala Batas (HKB), a district hospital in Penang State, Malaysia, which was the designated regional COVID hospital during the pandemic. It was a retrospective observational study, where children who were admitted from November 2020 to March 2021, and attended follow-up clinics from Jan 2021 to May 2021, were recruited. RESULTS: This study comprised 90 subjects, from 3 months old to 12 years old, mean of 6.5 years old. When comparing asymptomatic and symptomatic children, children with comorbidities were more likely to be symptomatic with a pvalue of 0.045 using the Pearson Chi-square test. All our patients' symptoms resolved upon discharge. During followup at 2-4 months after COVID-19 infection, all children were reported as back to their usual selves. Fifteen patients had recurrent symptoms. Most of their symptoms pointed towards an acute infection. One patient had two episodes of illness, while the rest had one. The most common symptoms were cough, fever and runny nose. The average duration of illness of these 16 episodes was 4.5 days with a standard deviation of 2.48. None of these symptoms lasted more than seven days. None of them required hospital admission. None of them had recurrent COVID-19 infections. Tweleve out of 72 children who had been going to school stopped physical school after COVID-19 infection. Our findings differed from other studies. These could be due to the limitations that we faced. CONCLUSION: Most children who contracted COVID-19 infection recovered fully after acute infection, and most of them recovered fully without long-term sequelae.

[Research progress on autologous vascularized graft bone implant repair for maxillofacial bone defect].

Maxillofacial bone defect can seriously affect the patient's appearance, mastication, deglutition and speech function. At present, autologous bone grafting combined with implant repair is an effective method for reconstruction of maxillofacial bone defects. Due to the differences in density, nutrition, immunity and other aspects of bone graft at different donor sites, there may be a potential impact on implant repair. In this paper, the biological characteristics of vascularized autologous bone used in maxillofacial bone defect repair were reviewed, and the risk factors of implantation on the bone graft were discussed. It provides support for clinicians in the selection of bone graft donor site and the design of prosthesis.

Shoulder instability in military personnel: diagnosis and outcomes of arthroscopic stabilisation.

INTRODUCTION: Shoulder instability is a common problem for military personnel due to the highly physical demands of work and training. This study assessed the pattern of glenoid labrum tears suffered by serving UK military personnel, the reliability of preoperative diagnostic methods (magnetic resonance arthrogram (MRA) vs clinical examination) and, finally, the outcomes of arthroscopic stabilisation in terms of satisfaction, pain, and return to sport and full deployment. METHODS: Retrospective demographic and clinical data were collected for all patients within our unit who underwent arthroscopic shoulder stabilisation between September 2016 and January 2019. Patients underwent clinical examination for instability and subsequent imaging with MRA. For service evaluation, patient-reported outcome measure data and occupational outcome data were gathered preoperatively and postoperatively. RESULTS: 41 military patients with shoulder instability were treated with arthroscopic stabilisation. 24.4% had an isolated anterior tear, and 41.5% had complex two-zone or pan-labral tears identified on arthroscopy. Clinical examination showed higher sensitivity, accuracy and negative predictive value for all labral tear patterns compared with MRA. Mean preoperative Oxford Shoulder Instability Score score was 18.58 (SE ±1.67) and mean postoperative score was 41.5 (SE ±1.13). 82.14% of the patients returned to full deployment during the study period and 85% had returned to sports. CONCLUSION: Complex labral tear patterns are common in military personnel with shoulder instability, and clinical examination appears to be more effective than imaging at predicting injury pattern. Patients respond well to arthroscopic stabilisation with good rates of return to work and sport, regardless of chronicity of injury.

[Recognise of iodine effect on thyroid diseases and metabolism].

Iodine is an essential trace element for human and an antioxidant. It not only participates in the synthesis of thyroid hormone, but also plays a role in metabolic diseases. Previous studies mainly focused on the effect of iodine on thyroid diseases, but ignored the effect on metabolism. After the implementation of the universal salt iodization (USI) of China, the possible consequences of excessive iodine were emphasized while the harm of iodine deficiency was forgetten. The paper re-examines the effects of iodine nutrition on thyroid diseases and metabolism. Iodine deficiency can lead to an increased risk of iodine deficiency disorders and thyroid diseases, and increase prevalence of metabolic syndrome and its components. Moderate iodine excess is beneficial to metabolism, but it can increase the risk of hyperthyroidism and subclinical hypothyroidism. The average urinary iodine concentration in 100-299 µg/L is the appropriate iodine nutrition state. According to the present iodized content of salt in China, iodized salt is an economical and effective way to ensure adequate iodine nutrition.

[Survey on the prevalence and related factors of thyroid disorders in different iodine intake regions in China in 2015-2017].

Objective: To observe the prevalence and related factors of thyroid diseases in different iodine intake areas from 2015 to 2017 after the implementation of national salt iodization policy in China for 20 years. Methods: A cross-sectional survey. Multi-stage stratified cluster random sampling was used to randomly select subjects meeting the inclusion criteria from 31 provinces, municipalities and autonomous regions in China from January 2015 to December 2017, and stratified by age and sex. The survey included questionnaire, physical examination and thyroid ultrasonography. At the same time, the concentrations of serum thyrotropin, thyroxine, thyroid peroxidase antibody (TPOAb), thyroid globulin antibody (TgAb) and urinary iodine were measured.To determine whether the patient has a certain thyroid disease according to the above results. Different iodine nutrition areas were defined according to urinary iodine concentration, and the influence of iodine nutrition status in different iodine intake areas on thyroid diseases was analyzed. Results: A total of 78 470 adults were included, including 39 893 in the area of moderate iodine, 28 779 in the area of adequate iodine, and 9 798 in the area of excessive iodine.In the above three regions, the prevalence of subclinical hyperthyroidism (hyperthyroidism) was 0.45% (95%CI: 0.39%-0.52%), 0.50%(95%CI: 0.35%-0.70%)and 0.27%(95%CI: 0.20%-0.35%), respectively, with statistical significance(χ²=6.92, P=0.003). The prevalence of subclinical hypothyroidism (hypothyroidism) was 11.36% (95%CI: 10.73%-12.02%), 13.57%(95%CI: 11.70%-15.69%) and 16.18%(95%CI: 12.41%-20.82%), respectively, with statistical significance(χ²=5.08, P=0.009). The prevalence rates of Graves' disease, TPOAb, goiter and thyroid nodule among the three regions were statistically significant (all P<0.05). There were no significant differences in the prevalence of clinical hyperthyroidism and clinical hypothyroidism and the positive rate of TgAb among the three regions (all P>0.05). Multivariate logistic regression model analysis showed that excess iodine was a risk factor for subclinical hypothyroidism (OR=1.24, 95%CI: 1.06-1.44), and a protective factor for thyroid nodules (OR=0.73, 95%CI: 0.57-0.94). Iodine overdose was a risk factor for subclinical hypothyroidism (OR=1.47, 95%CI: 1.08-2.01), while it was a protective factor for subclinical hyperthyroidism (OR=0.56, 95%CI: 0.41-0.77), and TPOAb positive (OR=0.93, 95%CI: 0.87-0.99), goiter (OR=0.33, 95%CI: 0.17-0.66) and thyroid nodule (OR=0.77, 95%CI: 0.61-0.97). Conclusions: There are significant differences in the prevalence of subclinical hyperthyroidism, subclinical hypothyroidism, positive TPOAb, thyroid nodule and goiter in different iodine intake regions. Different iodine intake levels have an effect on the incidence of thyroid diseases.

[Application of single incision plus one port laparoscopic surgery in radical right hemicolon cancer surgery].

Objective: To investigate the feasibility and advantages of the SILS+1 technique in the radical right hemicolectomy, by comparing the short-term efficacy, postoperative recovery of intestinal function, and stress and inflammatory response of patients with right-sided colon cancer undergoing the conventional 5-hole laparoscopic technique or the single incision plus one port laparoscopic surgery (SILS+1). Methods: A retrospective cohort study was performed. Thirty-five patients with right-sided colon cancer undergoing SILS+1 surgery at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from January 2018 to September 2020 were enrolled in the SILS+1 group. Then a total of 44 patients who underwent completely 5-hole laparoscopic right hemicolectomy at the same time were selected as the conventional laparoscopic surgery (CLS) group. The intraoperative observation indexes (operative time, intraoperative blood loss, and incision length) and postoperative observation indexes (time to ambulation after surgery, time to flatus, pain score in the first 3 days after surgery, hospitalization days, number of lymph node dissections, postoperative complication morbidity, and postoperative total protein, albumin and C-reaction protein) were compared between the two groups. Results: There was no conversion to laparotomy or laparoscopic-assisted surgery in both groups. All the patients successfully completed radical right hemicolectomy under total laparoscopy. There were no statistically significant differences in gender, age, body mass index or tumor stage between the two groups (all P>0.05). Compared with the CLS group, the SILS+1 group had shorter incision length [(5.1±0.6) cm vs. (8.5±4.1) cm, t=4.124, P=0.012], shorter time to the first ambulation (median: 27.6 h vs. 49.3 h, Z=4.386, P=0.026), and shorter time to the first flatus (median:42.8 h vs. 63.2 h, Z=13.086, P=0.012), lower postoperative pain score [postoperative 1-d: 2.0 ± 1.1 vs. 3.6 ± 0.9; postoperative 2-d: 1.4 ± 0.2 vs. 2.9±1.4; postoperative 3-d: 1.1 ± 0.1 vs. 2.3±0.3, F=49.128, P=0.003), shorter postoperative hospital stay [(9.1 ± 2.7) d vs. (11.2 ± 2.2) d, t=3.267,P=0.001], which were all statistically significant (all P<0.05). On the second day after surgery, as compared to CLS group, SILS+1 group had higher total protein level [(59.7±18.2) g/L vs. (43.0±12.3) g/L, t=2.214, P=0.003], higher albumin level [(33.6±7.3) g/L vs. (23.7±5.4) g/L, t=5.845, P<0.001], but lower C-reactive protein level [(16.3 ± 3.1) g/L vs. (63.3 ± 4.5) g/L, t=4.961, P<0.001], which were all statistically significant. There were no significant differences in the operative time, intraoperative blood loss, number of harvested lymph node, number of metastatic lymph node, and postoperative complication morbidity (all P>0.05). Conclusions: The SILS+1 technique has good operability and potential for popularization. Under the premise of radical resection, this technology not only reduces incision number and postoperative physical pain, but also speeds up postoperative recovery and shortens hospital stay.

[MicroRNA-23a knockdown attenuates angiotensin â ¡ induced hypertrophy in rat H9c2 cells via activating PTEN and AMPK pathway].

Objective: To investigate if microRNA (miR) -23a knockdown could attenuate angiotensin Ⅱ(AngⅡ) induced cardiac hypertrophy by activating phosphatase and tensin homolog deleted on chromosome ten(PTEN) and AMP-activated protein kinase(AMPK) pathway. Methods: Rat H9c2 cells were cultured in DMEM high glucose medium and put in 5% CO(2) incubator at 37 ℃(normal group). After 48 hours of culture, H9c2 cells were stimulated with 10 nmol/L AngⅡ to establish cell hypertrophy model (AngⅡgroup). The H9c2 cells were inoculated in a 6-well cell culture plate and cultured in an incubator at 37 ℃. When the confluence degree of cell growth was about 70%, the cells were transfected with different reagents, and 24 hours after transfection, 10 nmol/L AngⅡ was used to interfere with the cells. The H9c2 cells were divided into different groups according to the reagents, namely AngⅡ+anti-miR group(transfected with miR-23a inhibitor), Ang Ⅱ+NC group(transfected with miR-23a inhibitor negative control), Ang Ⅱ+anti-miR+si-PTEN group(cotransfected with miR-23a inhibitor and PTEN small interference RNA(siRNA)), and AngⅡ+anti-miR+si-NC group(cotransfected with miR-23a inhibitor and PTEN siRNA negative control). The surface area of single cell was measured by Image J software.The mRNA expression levels of α-actin 1 (ACTA1) and ß-myosin heavy chain (ß-MHC) and miR-23a were detected by quantitative real-time PCR(qRT-PCR). The expression levels of PTEN and AMPK signal pathway related proteins were detected by Western blot. In order to verify whether miR-23a targets PTEN gene, double luciferase reporter gene experiment was performed. The luciferase reporter gene vector recombinant plasmids of wild type pGL-WT-PTEN and mutant pGL-MUT-PTEN were constructed and prepared after normal sequencing. H9c2 cells was inoculated into 24-well cell culture plate and cultured overnight in 37 ℃ incubator. The cells were co-transfected with miR-23a mimic or miR-23a mimic negative control and wild type or mutant reporter gene recombinant plasmid. Forty-eight hours after transfection, firefly luciferase activity and sea kidney luciferase activity were measured, and the ratio of them was recorded as relative luciferase activity. Results: Compared with the normal group, the cell surface area, the mRNA expression levels of ACTA1, ß-MHC and miR-23a were significantly higher, while the protein expression levels of PTEN and p-AMPK were significantly lower in the Ang Ⅱ group(all P<0.05). The results of double luciferase reporter gene assay showed that the relative luciferase activity of cells co-transfected with miR-23a mimic and wild-type reporter gene recombinant plasmid was lower than that of miR-23a mimic negative control (P<0.05), and PTEN served as the target gene of miR-23a. In AngⅡ+anti-miR group the mRNA expression levels of miR-23a, ACTA1 and ß-MHC were lower, and the cell surface area was smaller, while the protein expression levels of PTEN and p-AMPK were higher than that in AngⅡ group and AngⅡ+NC group(all P<0.05). Compared with AngⅡ+anti-miR group, the cell surface area was bigger, the expression of ACTA1 and ß-MHC mRNA was up-regulated, and the protein expression levels of PTEN and p-AMPK were down-regulated in Ang Ⅱ+anti-miR+si-PTEN group(all P<0.05). Conclusion: Inhibition of miR-23a can attenuate Ang Ⅱ-induced hypertrophy in H9c2 cells through targeting PTEN and activating AMPK signaling pathway.

Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.

PURPOSE: The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. METHODS: 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. RESULTS: Iodine deficiency (UIC < 100 µg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. CONCLUSIONS: Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

[25-hydroxyvitamin D, sex hormone levels and cardiovascular risk among men in northeast area of Henan province].

Objective: To examine associations of 25-hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors. Methods: A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey-2014 (TIDE) research--Henan sub-center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses. Results: The age of the subjects was (46.6±15.9) years (19-85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), hypertension, diabetes, triglyceride, high-density lipoproteincholesterol, total cholesterol, low-density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (ß=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (ß=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 µg/L (ß=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (ß=-0.051, P=0.027). Conclusions: Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.

[Effect of preservation of left colic artery on postoperative anastomotic leakage of patients with rectal cancer after neoadjuvant therapy].

Objective: To evaluate the effect of preservation of left colic artery (LCA) on postoperative anastomotic leakage in patients with rectal cancer after neoadjuvant therapy. Methods: A retrospective cohort study was conducted to collect data of rectal cancer patients at Department of Gastrointestinal Surgery of Fujian Cancer Hospital from September 2014 to August 2017. Inclusion criteria: (1) age of 18 to 79 years; (2) rectal adenocarcinoma confirmed by postoperative pathology; (3) patients without preoperative serious cardiovascular and cerebrovascular disease receiving preoperative neoadjuvant radiotherapy or chemoradiotherapy; (4) laparoscopic-assisted anterior rectal resection and distal ileostomy were performed simultaneously; (5) complete clinical data. Exclusion criteria: patients with extensive abdominal metastasis, or distant organ metastasis during operation, and combined organ resection. According to whether LCA was retained during operation, the patients were divided into two groups, then the intraoperative and postoperative clinical outcomes were compared. Moreover, univariate analysis and multivariate logistic regression were used to analyze risk factors of postoperative anastomotic leakage. Results: A total of 125 patients were included in this study, including 56 patients in the retained LCA group and 69 patients in the non-retained LCA group. Differences in baseline data, such as gender, age, diabetes mellitus, body mass index, hemoglobin, distance between tumor and anal margin, maximum diameter of tumor, preoperative neoadjuvant therapy, and ypTNM stage, between retained LCA group and non-retained LCA group were not statistically significant (all P>0.05), indicating that two groups were comparable. Meanwhile there were no significant differences in operation time, intraoperative blood loss, total number of lymph node harvested, number of harvested lymph node at the root of inferior mesenteric artery, circumferential margin, anastomotic bleeding, or postoperative hospital stay between two groups (all P>0.05). Thirteen patients in the non-retained LCA group (18.8%) developed postoperative anastomotic leakage, including 7 cases of grade A, 5 cases of grade B and 1 case of grade C, while in the retained LCA group, only 5.4% (3/56) of patients developed postoperative anastomotic leakage, including 1 case of grade A and 2 cases of grade B without case of grade C, whose difference was statistically significant (U=1674.500, P=0.028). Univariate analysis showed that preoperative hemoglobin <120 g/L and non-retained LCA were associated with postoperative anastomotic leakage (both P<0.05). Multivariate analysis cofirmed that preoperative hemoglobin < 120 g/L (OR=3.508, 95% CI: 1.158 to 10.628, P=0.017) and non-retained LCA (OR=4.065, 95%CI: 1.074 to 15.388, P=0.031) were independent risk factors for postoperative anastomotic leakage. Median follow-up time was 31 months (16 to 51 months), and no long-term complication was found. Local recurrence and distant metastasis were found in 1 case (1.8%) and 7 case (12.5%) in the retained LCA group, while those were found in 2 cases (2.9%) and 5 cases (7.2%) respectively, in the non-retained LCA group, whose differences were not statistically significant (P=1.000, P=0.321 respectively). Conclusion: Preservation of left colic artery not only can ensure radical lymph node dissection efficacy under the condition of similar operation time and blood loss, but also can effectively reduce the incidence of postoperative anastomotic leakage for rectal cancer patients after neoadjuvant therapy.

The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China.

OBJECTIVES: To explore the effect of isolated maternal hypothyroxinemia (IMH) during the first and second trimester of gestation on pregnancy outcomes. To explore whether levothyroxine (L-T4) treatment of women who had IMH identified in the first trimester improves pregnancy outcomes. METHODS: Women in the early pregnancy in the iodine-sufficient area (n = 3398) were recruited to this prospective cohort study (ChiCTR-TRC-12002326). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were detected. Women with IMH before 12 weeks chose to receive L-T4 or remain untreated. The L-T4 dose was adjusted to attain a normal FT4 and TSH level. Pregnancy outcomes were evaluated during follow-up. RESULTS: IMH in the first trimester was not associated with increased risk of adverse pregnancy outcome compared with controls. The incidence of macrosomia (p = 0.022) and gestational hypertension (p = 0.018) was significantly higher in IMH identified in the second trimester of gestation compared with controls. IMH identified in the second trimester of gestation was a risk factor for macrosomia [adjusted odds ratio (aOR) 1.942, 95% CI 1.076-3.503, p = 0.027] and gestational hypertension (aOR 4.203, 95% CI 1.611-10.968, p < 0.01), when body mass index in the early pregnancy was < 25 kg/m2. CONCLUSIONS: IMH in the first trimester did not increase the risk of adverse outcomes irrespective of whether women received L-T4 treatment. However, IMH identified in the second trimester was associated with increased risk of adverse pregnancy outcome. The results suggest that thyroid function follow-up during the second trimester is necessary, even if thyroid function is normal during the first trimester.

Spontaneous Omental Infarction: An Unusual Etiology of Abdominal Pain.

A 49-year-old lady with previous scars complained of acute abdominal pain for two days. Her right hypochondrium was tender and guarding upon assessment. The laboratory investigations were unremarkable. Due to a diagnostic incongruity, computed tomography of the abdomen was performed showing a suspicious lesion at anterolateral aspect of the ascending colon. Surgical intervention was decided and intraoperative finding was consistent with spontaneous omental infarction. Omentectomy was undertaken and final histology was compatible with the intraoperative diagnosis. Although it is exceptional, omental infarction should be considered as part of the differential diagnoses of right-sided acute abdominal pain with normal laboratory investigations. This case highlights its unexpected discovery and we describe its literature reviews.

Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation.

BACKGROUND: The non-linear mixed amount with zero amounts response surface model can be used to describe drug interactions and predict loss of response to noxious stimuli and respiratory depression. We aimed to determine whether this response surface model could be used to model sedation with the triple drug combination of midazolam, alfentanil and propofol. METHODS: Sedation was monitored in 56 patients undergoing gastrointestinal endoscopy (modelling group) using modified alertness/sedation scores. A total of 227 combinations of effect-site concentrations were derived from pharmacokinetic models. Accuracy and the area under the receiver operating characteristic curve were calculated. Accuracy was defined as an absolute difference <0.5 between the binary patient responses and the predicted probability of loss of responsiveness. Validation was performed with a separate group (validation group) of 47 patients. RESULTS: Effect-site concentration ranged from 0 to 108 ng ml-1 for midazolam, 0-156 ng ml-1 for alfentanil, and 0-2.6 µg ml-1 for propofol in both groups. Synergy was strongest with midazolam and alfentanil (24.3% decrease in U50, concentration for half maximal drug effect). Adding propofol, a third drug, offered little additional synergy (25.8% decrease in U50). Two patients (3%) experienced respiratory depression. Model accuracy was 83% and 76%, area under the curve was 0.87 and 0.80 for the modelling and validation group, respectively. CONCLUSION: The non-linear mixed amount with zero amounts triple interaction response surface model predicts patient sedation responses during endoscopy with combinations of midazolam, alfentanil, or propofol that fall within clinical use. Our model also suggests a safety margin of alfentanil fraction <0.12 that avoids respiratory depression after loss of responsiveness.

Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: Molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory disease. This study aimed to investigate the frequencies and distributions of inherited variants in PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP genes in Chinese patients with HLH. A total of 265 patients diagnosed with HLH from January, 2010 to December, 2016 were recruited and analyzed for the 6 genes. Genetic variants were observed in 87 (32.83%) patients. 36 (13.58%) exhibited variants in UNC13D, 18 (6.79%) exhibited PRF1 variants, 10 (3.77%) had variants in XIAP, 9 (3.40%) exhibited variants in STXBP2, 6 (2.26%) carried variants in SH2D1A, 1 (0.38%) had STX11 variant, and 7 (2.64%) exhibited digenic variants. Monoallelic variants were the most common, which accounted for 49.43% of all cases with variants. All variants were confirmed to be germline-derived. The present study describes a distinct variant spectrum in Chinese patients with HLH, whereby UNC13D is the most frequently mutated gene with missense variants that are the most common molecular defects. The variant profile of Chinese HLH patients is quite different from that of Western cohorts but similar to that of Korean patients, yet showing its own uniqueness. This racial difference shows the role of genetic background in the occurrence of HLH.

Eradication of hepatitis C virus profoundly prolongs survival in hepatocellular carcinoma patients receiving transarterial chemoembolization.

Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C (CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC-HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence-free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient-based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child-Turcotte-Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2-year cumulative overall survival rate and recurrence-free survival rate among patients with SVR, non-SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non-SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC-HCC patients receiving TACE treatment after complete response.

[Advance and review: implant-abutment microgap].

Implant-abutment microgap (IAM) exists in two-piece implant systems. Researchers have proved that IAM influences success rate of dental implants in the long term. The relationship between IAM and the biological, mechanical complication of dental implants has been proven in some studies. Implant-abutment connection type, abutment material and insertion torque may all have impact on IAM size. On the other hand, ways to reduce or seal this gap are discussed in some literature. The relationship between IAM and bacteria colonization, long-term implantation complication and its influencing factors are discussed in this review.

Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver Cirrhosis.

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)-related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV-related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir-based anti-HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%-0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow-up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV-related liver cirrhosis is feasible under entecavir-based anti-HBV treatment. Successful application of small left livers in end-stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients.

Change in serum TSH levels within the reference range was associated with variation of future blood pressure: a 5-year follow-up study.

Controversy exists on the relationship between serum thyrotropin (TSH) and blood pressure, and only a few prospective studies are available up to now. The study aimed to investigate the association between serum TSH within the reference range and blood pressure through a 5-year follow-up study. A total of 623 subjects with normal TSH were followed up for 5 years, including the measurement of demographic data, blood pressure, height, weight and serum TSH. Finally, 531 subjects were included in this prospective study. Body mass index (BMI), prevalence of hypertension, and systolic and diastolic blood pressure were all higher at follow-up than at baseline. Adjusted for age, gender, smoking status, BMI and homoeostasis model assessment of insulin resistance (HOMA-IR) at baseline, multiple linear regression analyses found no relationship between serum TSH at baseline and levels of blood pressure at follow-up, but the changes in serum TSH levels during follow-up was positively associated with the changes in systolic blood pressure (B=2.134, P<0.05), which became more significant in women but not significant in men. The change of systolic blood pressure in group of TSH increase >0.5 mIU l-1 was significantly higher than in group of TSH decrease >0.5 mIU l-1 within reference, after adjusting for age, gender, smoking status, BMI and HOMA-IR at baseline. This result became more significant in women, but no statistical significance was observed in men. Co-variation with serum TSH levels and blood pressure was observed during 5-year follow-up among people with normal TSH.

Expression and distribution of SP and its NK1 receptor in the brain-gut axis in neonatal maternally separated rat model with visceral hypersensitivity.

Neurokinin-1 receptor (NK1R) is a high affinity Substance P (SP) receptor and plays a key role in visceral hypersensitivity in irritable bowel syndrome (IBS). Early life stress is a significant risk factor in IBS. The aim of the present study was to investigate the influence of neonatal maternal separation on the expression and distribution of SP and its receptor along the brain-gut axis in a neonatal maternally separated rat model with visceral hypersensitivity. Male neonatal Sprague-Dawley rats, 2-21-day old, were randomly distributed into maternal separation groups of 3 h daily maternal separation (MS) or non-handling (NH). These rats underwent colorectal balloon distention (CRD) upon reaching adulthood. Immunofluorescence was used to examine the distal colon, lumbosacral spinal cord, and the brainstem to semi-quantitatively determine SP and NK1R expression before and after CRD. The following features were assessed: percentage SP-positive area in colonic muscle layer, the number of NK1R-positive myenteric plexus, SP-positive area and NK1-positivity score in the dorsal horn and the brainstem. Neither of these was altered in the MS and NH groups before or after CRD. These results suggest that the SP system might play little role in the development of visceral hyperalgesia in the neonatal maternal separation rat model.

Construction of a protein-protein interaction network of Wilms' tumor and pathway prediction of molecular complexes.

Wilms' tumor (WT), or nephroblastoma, is the most common malignant renal cancer that affects the pediatric population. Great progress has been achieved in the treatment of WT, but it cannot be cured at present. Nonetheless, a protein-protein interaction network of WT should provide some new ideas and methods. The purpose of this study was to analyze the protein-protein interaction network of WT. We screened the confirmed disease-related genes using the Online Mendelian Inheritance in Man database, created a protein-protein interaction network based on biological function in the Cytoscape software, and detected molecular complexes and relevant pathways that may be included in the network. The results showed that the protein-protein interaction network of WT contains 654 nodes, 1544 edges, and 5 molecular complexes. Among them, complex 1 is predicted to be related to the Jak-STAT signaling pathway, regulation of hematopoiesis by cytokines, cytokine-cytokine receptor interaction, cytokine and inflammatory responses, and hematopoietic cell lineage pathways. Molecular complex 4 shows a correlation of WT with colorectal cancer and the ErbB signaling pathway. The proposed method can provide the bioinformatic foundation for further elucidation of the mechanisms of WT development.