[Effect of Da Vinci robotic transanal minimally invasive surgery for rectal neoplasms].

Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.

[Study on the application value of fecal SDC2 gene methylation detection in colorectal cancer screening of urban residents in Zengcheng District in Guangzhou City].

Objective: To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (mSDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods: A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. mSDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of mSDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of mSDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results: A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of mSDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of mSDC2 was negatively correlated with the proportion of advanced colorectal neoplasms (χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion: The CRC screening strategy of fecal mSDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of mSDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

[Association analysis between genetic variants of matrix metalloproteinase enzyme 2 gene and the blood pressure of children and adolescents].

Objective: To explore the association between genetic variants of matrix metalloproteinase enzyme 2 (MMP2) gene and the blood pressure of children and adolescents. Methods: This cross-sectional study was performed in 2016 and included 4 155 children and adolescents in the urban area of Guangzhou. Physical examinations (including body height, weight, and blood pressure), questionnaires (including general characteristics, physical exercise, parental educational level, household income, etc.), and blood sampling were performed. Multivariable linear regression models were used to investigate the associations of MMP2 genetic variations (rs243865, rs7201) and the genetic risk score (GRS) level with standardized blood pressure. Mediating effect of standardized body mass index (BMI) was further assessed by process analysis in the association between GRS level and blood pressure, and potential additive interaction between physical activity and GRS level was analyzed using the product term in the regression model. Results: A total of 4 155 primary and secondary schoolchildren were finally included in the analysis, consisting of 1 401 (33.7%) second grade pupils of primary school, 1 422 (34.2%) first grade pupils of middle school, and 1 332 (32.1%) first-grade students of senior high school. After adjusting for age, sex, parental educational level, and family income, as compared to the rs243865 TT genotype, the CC/CT genotype increased diastolic blood pressure (DBP) by 0.461 standard deviations (SD) (ß for dominant model=0.461, 95%CI 0.199-0.723). When compared to the rs7201 CC genotype, the AA/AC genotype showed 0.147 SD higher systolic blood pressure (SBP) (ß for recessive model=0.147, 95%CI 0.014-0.279) and 0.171 SD increased DBP (ß for recessive model=0.171, 95%CI 0.039-0.304). For each increment of GRS level, SBP and DBP increased by 0.151 SD (ß for dominant model=0.151, 95%CI 0.029-0.272) and 0.242 SD (ß=0.242, 95%CI 0.120-0.363), respectively. The mediating effect of BMI accounted for 28.3% and 12.6% of the total effect of GRS on SBP and DBP, respectively. After controlling BMI, the direct effect of GRS on DBP remained statistically significant (P<0.001). The insufficient moderate-to-vigorous physical activity (<0.5 h/d) showed a significant interaction with GRS on SBP under additive scale (ß for interaction=0.518, 95%CI 0.088-0.949, P=0.018). Conclusions: rs243865 and rs7201 variants in MMP2 gene are associated with the elevated blood pressure of children and adolescents. Obesity may yield a mediation role in the associations, while insufficient physical activity may have a positively additive interaction with MMP2 genetic variants.

Protein-protein interaction network and potential drug target candidates of Streptococcus suis.

AIMS: This study aimed to explore potential drug targets of Streptococcus suis at the system level. METHODS AND RESULTS: A homologous protein mapping method was used in the construction of a protein-protein interaction (PPI) network of S. suis, which presented 1147 non-redundant interaction pairs among 286 proteins. The parameters of PPI networks were calculated and showed scale-free network properties. In all, 41 possibly essential proteins identified from 47 highly connected proteins were selected as potential drug target candidates. Of these proteins, 30 were already regarded as drug targets in other bacterial species. Six transporters with high connections to other functional proteins were identified as probably not essential but important functional proteins. Afterward, the subnetwork centred with cell division protein FtsZ was used in confirming the PPI network through bacterial two-hybrid analysis. CONCLUSIONS: The predicted PPI network covers 13·04% of the proteome in S. suis. The selected 41 potential drug target candidates are conserved between S. suis and several model bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The predictions included proteins known to be drug targets, and a verifying experiment confirmed the reliability of predicted interactions. This work is the first to present systematic computational PPI data for S. suis and provides potential drug targets, which are valuable in exploring novel anti-streptococcus drugs.

[Effects of FRNK on activation and migration of hepatic stellate cells].

Objective: To investigate the effect of focal adhesion kinase related non kinase (FRNK) on the activation and migration of hepatic stellate cells (HSCs). Methods: Human liver tissue was divided into healthy control group and fibrosis group from March 2019 to September 2019 in Affiliated Hospital of Guizhou Medical University. C57BL/6 mice were divided into wild type (WT) and FRNK gene knockout type (FRNK-/-) groups. The liver fibrosis model was established with carbon tetrachloride (CCl4). After that, FRNK gene overexpression (Ad-FRNK) was constructed with adenovirus vector. HE and Masson staining were used to evaluate the pathological changes and fiber deposition of liver tissue. Western blot was used to detect the expression of PY397-FAK and α-SMA protein. Mouse primary HSCs were extracted, and the effect of FRNK on HSCs migration was detected by wound healing, activation of Rac and Rho was detected by Western blot. Results: The expression of PY397-FAK protein in human liver tissue with hepatic fibrosis was significantly higher than that in healthy control group (0.88±0.09 vs. 0.73±0.09). FRNK was significantly lower than that in control group(0.68±0.09 vs. 0.79±0.11). After animal model was set up, the degree of liver fibrosis in FRNK-/-mice (153±13)% was more serious than that in WT (100%) group. The expression of PY397-FAK and α-SMA protein was significantly elevated (2.50±0.23 vs. 0.75±0.09, 1.46±0.20 vs. 0.92±0.10). After FRNK gene was re-expressed (100%), the degree of liver fibrosis was mainly reversed [(74±6)%], and the expression of PY397-FAK and α-SMA was accordingly decreased(0.68±0.11 vs. 1.12±0.19,0.68±0.10 vs. 0.85±0.06). In vitro, FRNK inhibited the migration of HSCs [WT∶FRNK-/-∶Ad-FRNK,(339±49)%∶(580±53)%∶(259±33)%] and the activation of Rac and Rho proteins (Rac: 0.54±0.07 vs. 0.91±0.10 vs. 0.77±0.12,Rho:0.45±0.05 vs. 0.64±0.06 vs. 0.53±0.07), all P<0.01. Conclusions: FRNK can inhibit the activation and migration of HSCs which contributed to liver fibrosis. The potential mechanism is related to down regulation of PY397-FAK and inhibition of Rac and Rho activation.

[Effects of the relationship between adenomyotic lesions and embryo implantation site on pregnancy outcomes in pregnant patients with adenomyosis].

Objective: To investigate the relationship between embryo implantation site and adenomyotic lesions in pregnant patients with adenomyosis and its effects on pregnancy outcomes. Methods: Between January 2018 and December 2020, the clinical data of 95 pregnant patients with adenomyosis who were hospitalized in the Women's Hospital, School of Medicine, Zhejiang University, which could identify the implantation site of embryo or placenta (≥11 weeks of pregnancy) through the nuchal translucency test under ultrasonography were analyzed retrospectively. According to the relationship between embryo implantation site and adenomyotic lesions, 95 patients were divided into two groups:short-distance group (n=59, the embryo or placenta implantation was very close to or over the adenomyotic lesion), and long-distance group (n=36, the implantation site of embryo or placenta was far away from the lesion, or the implantation site and the adenomyotic lesion were on different sides of the uterus). Next, taking 28 weeks of pregnancy as cut-off value, 95 patients were divided into <28 weeks of pregnancy group (pregnancy was terminated because of adverse pregnancy outcome before 28 weeks) and ≥28 weeks of pregnancy group (pregnancy lasted to 28 weeks and later), the differences of pregnancy outcomes between the two groups in different gestation times were analyzed. Results: (1) The age of 95 pregnant patients with adenomyosis was (34.8±3.5) years. There were no significant differences with regard to age, uterine size before pregnancy, the proportions of primipara, assisted reproductive technology conception, endometriosis, history of estrogen and progesterone treatment, diffuse adenomyotic lesions between the short-distance group and the long-distance group (all P>0.05). (2) Among the 95 patients, 12 patients (13%, 12/95) had adverse pregnancy outcomes before 28 weeks of pregnancy (i.e. pregnancy <28 weeks), including 11 cases (19%, 11/59) in the short-distance group and 1 case (3%, 1/36) in the long-distance group, there was significant difference between the two groups (χ²=5.100, P=0.027). Among the 11 patients with adverse pregnancy outcomes at <28 weeks of gestation in the short-distance group, 1 case had threatened rupture of uterus before delivery of twin pregnancy at 26 weeks of gestation, 5 cases had intra uterine fetal death in the second trimester of pregnancy, 4 cases had late inevitable abortion, and 1 case had live birth of singleton at 26 weeks of gestation. In the long-distance group, one patient with adverse pregnancy outcome less than 28 weeks of pregnancy was late inevitable abortion. (3) Of the 95 patients, 83 cases were pregnant for ≥28 weeks (48 cases in the short-distance group and 35 cases in the long-distance group), and their final pregnancy outcome was all live birth. Compared with the long-distance group, the incidence of placental abnormalities (60% vs 14%), fetal distress (27% vs 6%), preterm delivery (67% vs 23%) and intrapartum bleeding [median 350 ml (range: 100-1 500 ml) vs 300 ml (range: 100-800 ml)] in the short-distance group were significantly higher (all P<0.05). While the gestational weeks in the short-distance group [median 37 weeks (range: 30-41 weeks) vs 38 weeks (range: 28-41 weeks)] and neonatal birth weight [median 2 790 g (range: 1 170-4 040 g) vs 3 010 g (range: 980-4 320 g)] decreased significantly (all P<0.05), compared with those in the long-distance group. Conclusion: Patients with pregnancy complicated with adenomyosis are prone to adverse pregnancy outcomes if the embryo implantation is located on or very close to adenomyotic lesions, so close monitoring and early intervention should be carried out to improve pregnancy outcomes.

[Feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia].

Objective: To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia. Methods: This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared. Results: A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group (P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups (P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions: Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.

[Perioperative maternal complications of twin-twin transfusion syndrome after fetoscopic laser photocoagulation].

Objective: To analyze the perioperative maternal complications of twin-twin transfusion syndrome (TTTS) after fetolascopic laser photocoagulation (FLP). Methods: A retrospective study was conducted among 182 cases with TTTS received FLP in Shanghai First Maternity and Infant Hospital from January 2010 to December 2018. The types, incidence and related factors of perioperative maternal complications as well as the changes of maternal laboratory parameters before and after FLP were analyzed. Results: The age of 182 TTTS pregnant women was (29.8±3.9) years old, body mass index (BMI) before pregnancy was (21.3±2.9) kg/m2. The median gestational week of FLP treatment was 22.0 weeks, the preoperative cervical length was (34.1±9.0) mm, and the median preoperative maximum vertical pocket was 12.0 cm. During the perioperative period of FLP treatment, 22 cases (12.1%, 22/182) presented maternal complications, among which 4 cases (2.2%, 4/182) presented severe postoperative maternal complications, including 3 cases of pulmonary edema and 1 case of pulmonary embolism accompanied with right cardiac insufficiency. There were 18 cases (9.9%, 18/182) of common maternal complications during the perioperative period, including 6 cases (3.3%, 6/182) of intraoperative hemorrhage, 5 cases (2.7%, 5/182) of intraoperative amniotic fluid leakage into the pelvic cavity, 5 cases (2.7%, 5/182) of premature rupture of membrane 72 hours after the operation, 1 case (0.5%, 1/182) of inevitable abortion, and 1 case (0.5%, 1/182) of infection. The analysis of related risk factors found that maternal complications were only related to BMI before pregnancy, and the BMI of TTTS pregnant women with complications was lower than that of those without complications, the difference was statistically significant (P<0.01). The hemoglobin level, hematocrit and albumin level of TTTS pregnant women were significantly decreased at 4-6 hours and 24 hours after FLP respectively, compared with those before surgery (P<0.01), and there were no significant correlations with the amount of amniodrainage during surgery (P>0.05 for all). Conclusions: The overall incidence of perioperative maternal complications in the treatment of TTTS by FLP is not high, among which the serious complications mainly include pulmonary edema and pulmonary embolism. Timely correction of maternal hemodilution that may occur in TTTS pregnant women could achieve a good prognosis after FLP.

Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn's Disease.

BACKGROUND & AIMS: As more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohn's disease (CD) who respond to vedolizumab. METHODS: We collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (n = 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD. RESULTS: In the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity. CONCLUSIONS: We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

Conservative management in hypertriglyceridemia-associated pancreatitis.

BACKGROUND: Severe hypertriglyceridemia (serum triglyceride >10 mmol L-1 ) is implicated in ~9% of acute pancreatitis cases. Certain guidelines list severe hypertriglyceridemia as an indication for plasmapheresis. OBJECTIVE: We assembled the natural trajectory of triglyceride levels in patients with acute pancreatitis due to severe hypertriglyceridemia who were managed conservatively without plasmapheresis to evaluate the effectiveness of this approach. METHODS: A retrospective chart review was performed on 22 hospital admissions for acute pancreatitis episodes considered to be caused by severe hypertriglyceridemia. Patients were managed supportively, with cessation of oral intake (NPO) and intravenous hydration. Insulin infusion was used in 12 patients to manage concurrent hyperglycaemia. RESULTS: Triglyceride levels for the group were evaluated using a mixed-effects model. The average triglyceride level fell from 45.4 mmol L-1 on presentation to 13.3 mmol L-1 within 48 h, corresponding to a mean 69.8% decrease. Regression analysis showed a triglyceride half-life of 30.6 h. Findings were similar for NPO-only and insulin infusion subgroups. CONCLUSION: Patients with severe hypertriglyceridemia and acute pancreatitis can be conservatively managed safely and effectively without plasmapheresis.

Donepezil for gait and falls in mild cognitive impairment: a randomized controlled trial.

BACKGROUND AND PURPOSE: Cognitive enhancers are commonly prescribed to people with Alzheimer's disease and related dementias to improve cognition and function. However, their effectiveness for individuals in the pre-stages of dementia, particularly in functional motor outcomes, remains unknown. We aimed to determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic neurotransmission, on gait performance in mild cognitive impairment (MCI). METHODS: This was a double-blind, placebo-controlled trial including 60 older adults with MCI, randomized to receive donepezil (10 mg/daily, maximal dose) or placebo. Primary outcome was gait speed (cm/s) under single and three dual-task conditions (counting backwards by 1 or 7 and naming animals) measured using an electronic walkway. Dual-task gait cost (DTC), a valid measure of motor-cognitive interaction, was calculated as the percentage change between single (S) and dual-task (D) gait speeds: [(S - D)/S] × 100. Secondary outcomes included attention, executive function, balance and falls. RESULTS: After 6 months, the donepezil group experienced an improvement in dual-task gait speed (range 4-11 cm/s), although this was not statistically significant. The donepezil group showed a significant reduction in DTC (improvement) by counting backwards by 1 and 7 compared with placebo (10.25% vs. 1.75%, P = 0.048; 21.38% vs. 14.64%, P = 0.037, intention-to-treat analysis). Per-protocol analyses showed that all three DTCs improved in the donepezil group, along with a non-significant reduction of rate of falls. CONCLUSIONS: Donepezil treatment improved dual-task gait speed and DTC in elderly patients with MCI. Our results support the concept of reducing falls in MCI by targeting the motor-cognitive interface.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

The HealtheSteps™ lifestyle prescription program to improve physical activity and modifiable risk factors for chronic disease: a pragmatic randomized controlled trial.

BACKGROUND: Our objective was to determine the influence of the HealtheSteps™ lifestyle prescription program on physical activity and modifiable risk factors for chronic disease in individuals at risk. METHODS: One hundred eighteen participants were recruited from 5 sites in Southwestern Ontario, Canada and randomized to either the intervention (HealtheSteps™ program, n = 59) or a wait-list control group (n = 59). The study comprised three phases: an Active Phase (0 to 6 months) consisted of bi-monthly in-person lifestyle coaching with access to a suite of eHealth technology supports (Heathesteps app, telephone coaching and a private HealtheSteps™ social network) followed by a Minimally-Supported Phase I (6 to 12 months), in which in-person coaching was removed, but participants still had access to the full suite of eHealth technology supports. In the final stage, Minimally-Supported Phase II (12 to 18 months), access to the eHealth technology supports was restricted to the HealtheSteps™ app. Assessments were conducted at baseline, 6, 12 and 18 months. The study primary outcome was the 6-month change in average number of steps per day. Secondary outcomes included: self-reported physical activity and sedentary time; self-reported eating habits; weight and body composition measures; blood pressure and health-related quality of life. Data from all participants were analyzed using an intent-to-treat approach. We applied mixed effects models for repeated measurements and adjusted for age, sex, and site in the statistical analyses. RESULTS: Participants in HealtheSteps™ increased step counts (between-group [95% confidence interval]: 3132 [1969 to 4294], p < 0.001), decreased their sitting time (- 0.08 [- 0.16 to - 0.006], p = 0.03), and improved their overall healthful eating (- 1.5 [- 2.42 to - 0.58], p = 0.002) to a greater extent compared to control at 6 months. Furthermore, exploratory results showed that these individuals maintained these outcomes 12 months later, after a minimally-supported phase; and retained improvements in sedentary time and improved healthful eating after 18 months. No differences in self-reported physical activity, health-related quality of life, weight, waist circumference or blood pressure were observed between groups at 6 months. CONCLUSIONS: Our findings suggest that HealtheSteps™ is effective at increasing physical activity (i.e., step counts per day), decreasing weekday sitting time, and improving healthful eating in adults at increased risk for chronic disease after 6 months; however, we did not see change in other risk factors. Nonetheless, the maintenance of these behaviours with minimal support after 12 and even 18 months indicates the promise of HealtheSteps™ for long-term sustainability. TRIAL REGISTRATION: The trial was registered on April 6, 2015 with ClinicalTrials.gov (identifier: NCT02413385 ).

[Clinical analysis of 43 cases of retroperitoneal laparoscopic renal biopsy].

Objective: Percutaneous renal biopsycurrently is the most important and widely used method of renal biopsy. However, there still are some patients in whom a percutaneous approach may be considered a major risk. In these patients, renal biopsy under direct vision is a reliable alternative. We described our personal technique and experience in a series of Chinese patients who underwent retroperitoneal laparoscopic renal biopsy. Methods: We retrospectively reviewed the patients who had performed retroperitoneal laparoscopic renal biopsy over a 4-year period (Jan 2013 to Jan 2017).Forty-three patients with renal dysfunction were involved inour center.Especially some patients showed atrophic kidney and poor visualization on ultrasonography. The patients' abnormal conditions includeddialysis (10 cases), morbid obesity (5 cases), deaf-mutes (2 cases) and uncontrolled severe hypertension. The kidney was approached via alaparoscopic retroperitoneal route using athree-ports technique. Then biopsies were performed bya 16-gaugebiopsy needle, and hemostasis was achieved by compression.In less cases, a topical spray hemostatic gel was required. Results: Biopsy was performed successfully in all cases and adequate renal tissue was acquired.Mean operative time was 59.4 minutes, mean blood loss was 36.5 ml.Under general anesthesia, no anesthetic accidents and related complications were recorded. Forty-onepatients were discharged within 24 h after operation. Onepatient occurred disseminated intravascular coagulationduring operation. Red blood cell transfusion and fresh-frozen plasma infusion were performed. Injury at hilum of kidney was detected in another patient. And extrapyelogenic repair surgery was performed. Conclusions: The retroperitoneallaparoscopic renal biopsy is a safe, reliable, minimallyinvasive alternative renal biopsy method with better haemostasis, fewer complications and a rapid recovery. As the helpful supplement of percutaneous renal biopsy, this technique may have to be used more often in the future.

[Analysis of new occupational diseases in Hengyang from 2006 to 2017].

Objective: To analyze the situation of new occupational diseases in Hengyang City from 2006 to 2017, and put forward prevention and control strategies. Methods: The data of the new occupational disease report of Hengyang city in the Occupational Disease and Occupational Health Information Monitoring System from January 1, 2006 to December 31, 2017 was collected, and the age, working years, and the region and industry of the new occupational disease patients were analyzed. Results: From 2006 to 2017, there were 7 categories, 30 kinds and 2 110 cases of new occupational diseases in Hengyang City, including 1 117 cases of pneumoconiosis, 951 cases of chronic occupational poisoning, 15 cases of acute occupational poisoning, 12 cases of occupational otolaryngological and stomatological diseases, 7 cases of occupational skin diseases, 6 cases of occupational diseases caused by physical factors, and 1 case of occupational eye diseases(cataracts), 1 case of occupational tumor (lung cancer and skin cancer caused by arsenic and its compounds). New occupational diseases were mainly concentrated in Changning and Leiyang County-level city (87.82%, 1 853/2110), among which occupational poisoning had the most incidence in Changning County-level city (97.83%, 945/966), and pneumoconiosis had the most incidence in Leiyang County-level city (67.05%, 749/1 117). New occupational diseases were mainly concentrated in the manufacturing and mining industries (95.59%, 2 017/2 110). Pneumoconiosis (63.74%, 712/1 117) and acute occupational poisoning (60.00%, 9/15) were mainly caused by small businesses. Chronic occupational poisoning (61.62%, 586/951) and occupational otolaryngological and stomatological diseases (75.00%, 9/12) were mainly caused by large enterprises. Conclusion: The new occupational diseases in Hengyang city are mostly pneumoconiosis and chronic occupational poisoning, and we should focus on strengthening the prevention and control of occupational diseases in the mining industry and manufacturing industry.

Endoscopic scoring indices for evaluation of disease activity in ulcerative colitis.

BACKGROUND: Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The operating properties of the existing endoscopic scoring indices are unclear. OBJECTIVES: A systematic review was undertaken to evaluate the development and operating characteristics of endoscopic scoring indices for the evaluation of ulcerative colitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2016. We also searched references and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization). SELECTION CRITERIA: Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated endoscopic indices for evaluation of ulcerative colitis disease activity were considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with ulcerative colitis using conventional clinical, radiologic and endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the studies identified from the literature search. These authors also independently extracted and recorded data on the number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as reliability (intra-rater and inter-rater), validity (content, construct, criterion), responsiveness and feasibility. Any disagreements regarding study inclusion or data extraction were resolved by discussion and consensus with a third author. Risk of bias was assessed by determining whether assessors were blinded to clinical information and whether assessors scored the endoscopic index independently. We also assessed the methodological quality of the validation studies using the COSMIN checklist MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion criteria and were included in the review. Of the 20 included validation studies, 19 endoscopic scoring indices were assessed, including the Azzolini Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score, Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore, Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score, Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who performed the endoscopic scoring were blinded to clinical and/or histologic information in ten of the included studies, not blinded to clinical and/or histologic information in one of the included studies, and it was unclear whether blinding occurred in the remaining nine included studies. Independent observation was confirmed in four of the included studies, unclear in five of the included studies, and non-applicable (since inter-rater reliability was not assessed) in the remaining eleven included studies. The methodological quality (COSMIN checklist) of most of the included studies was rated as 'good' or 'excellent'. One study that assessed responsiveness was rated as 'fair'. The inter-rater reliability of nine endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was assessed in seven studies, with estimates of correlation, ƙ, ranging from 0.44 to 0.97. The iIntra-rater reliability of seven endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies, with estimates of correlation, ƙ, ranging from 0.41 to 0.86. No studies assessed content validity. Three studies evaluated the criterion validity of three endoscopic scoring indices including the Rachmilewitz Endoscopic Score, Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with objective markers of disease activity including albumin, blood leukocytes, C-reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8 concentration and platelet count. Correlation estimates ranged from r = -0.19 to 0.83. Thirteen endoscopic scoring indices were tested for construct validity in 13 studies. Estimates of correlation between the endoscopic scoring indices and other measures of disease activity ranged from r = 0.27 to 0.93. Two studies explored the responsiveness of four endoscopic scoring indices including the Mayo Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS. One study concluded that the Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease change in ulcerative colitis. The other included study concluded that the UCEIS may be the most accurate endoscopic scoring tool. None of the included studies formally assessed feasibility. AUTHORS' CONCLUSIONS: While the UCEIS, UCCIS and Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of these instruments have been fully validated and only two studies assessed responsiveness. Further research on the operating properties of these indices is needed given the lack of a fully-validated endoscopic scoring instrument for the evaluation of disease activity in ulcerative colitis.

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment.

BACKGROUND: Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. METHODS: The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. DISCUSSION: The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. TRIAL REGISTRATION: Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .

[Clinicopathologic features of lipoprotein glomerulopathy: observation of 6 cases].

Objective: To investigate the clinicopathologic features of lipoprotein glomerulopathy (LPG). Methods: A total of 6 cases (5 males and 1 female, with a mean age of 27.5 years and age range of 11-53 years) of lipoprotein glomerulopathy with complete clinicopathologic data were enrolled. Except for light microscope, immunofluorescence and electron microscopic examination, renal biopsy tissues were checked by oil red O staining. The gene map of apolipoprotein E (ApoE) of 2 cases were analyzed. Results: All 6 cases presented with heavy proteinuria or nephrotic syndrome, and high level of low-density lipoprotein (LDL), very low-density lipoprotein (vLDL), ApoE. Family history of LPG was found in 3 cases, and 2 patients progressed to uremia, or even to death. Pathologic features showed that lipoprotein deposited in glomerulus capillary lumen and renal tubular epithelial cells. Gene analysis demonstrated that 2 cases expressed abnormal ApoE gene (162G>C and 455G>C). Conclusions: Lipoprotein glomerulopathy is autosomal-recessive disease with mutation of ApoE. Common clinical manifestations of LPG are heavy proteinuria or nephrotic syndrome, with a poor prognosis. Renal biopsy pathologic diagnosis can confirm this kidney disease. Emboli of lipoprotein being observed in glomerulus capillary lumen is the pathological feature of LPG.

[Perinatal outcomes of thoraco-amniotic shunting for severe primary fetal hydrothorax].

Objective: To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods: 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital, Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results: Totally, 28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1% (2/22) cases. Catheter displacement occurred in 18% (4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21 (95%, 21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62% (13/21) newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81% (17/21) . The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion: Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.

Reliability of EUS indices to detect inflammation in ulcerative colitis.

BACKGROUND AND AIMS: EUS is a potentially useful modality to assess severity of inflammation in ulcerative colitis (UC). We assessed the reliability of existing EUS indices and correlated them with endoscopic and histologic scores. METHODS: Four blinded endosonographers assessed 58 endoscopic and EUS videos in triplicate, from patients with UC. Intrarater and interrater reliability of the hyperemia and Tsuga scores were estimated by using intra-class correlation coefficients (ICCs). Correlation with the Mayo endoscopy score, modified Baron score (MBS), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Geboes histopathology score (GHS) were calculated by using bootstrapping methods. A RAND consensus process led to development of standardized definitions and a revised EUS-UC score. RESULTS: ICCs for intrarater reliability were 0.76 (95% confidence interval [CI], 0.71-0.80) for the hyperemia score and 0.85 (95% CI, 0.79-0.89) for the Tsuga score. Corresponding values for interrater reliability were 0.34 (95% CI, 0.25-0.42) and 0.36 (95% CI, 0.24-0.46). Correlation between hyperemia and Tsuga scores to Mayo scoring system, MBS, UCEIS, and the GHS were 0.39 (95% CI, 0.15-0.61) and 0.28 (95% CI, 0.04-0.51), 0.38 (95% CI, 0.16-0.57) and 0.25 (95% CI, -0.01-0.48), 0.41 (95% CI, 0.16-0.62) and 0.27 (95% CI, 0.01-0.50), 0.37 (95% CI, -0.01-0.48) and 0.24 (95% CI, 0.13-0.57), respectively. The revised EUS-UC score included bowel wall thickening, depth of inflammation, and hyperemia. CONCLUSIONS: Although substantial to almost perfect intrarater agreement existed for EUS indices in UC, interrater agreement was fair. Standardization of item definitions with development of a revised evaluative instrument has potential application as an evaluative and prognostic tool for UC. (Clinical trial registration number: NCT01852760.).