New US capsule endoscopy for superficial and submucosal imaging of the esophagus: the first-in-human study.

BACKGROUND AND AIMS: EUS is essential in diagnosing and staging of esophageal subepithelial lesions and tumors. However, EUS is invasive, relies on highly trained endoscopists, and typically requires sedation. The newly developed US capsule endoscopy (USCE), which incorporates both white-light and US imaging modalities into a tethered capsule, is a minimally invasive method for obtaining superficial and submucosal information of the esophagus. This study aimed to assess the feasibility and safety of this USCE system. METHODS: Twenty participants were enrolled: 10 healthy volunteers and 10 patients with esophageal lesions indicated for EUS. Participants first underwent USCE and subsequently EUS within 48 hours. The primary outcome was the technical success rate of USCE. Secondary outcomes were safety, visualization of the esophagus, and comfort assessment. RESULTS: The technical success rate of USCE was 95% because 1 patient failed to swallow the capsule. No adverse events were observed. The esophagus was well visualized, and all lesions were detected under USCE optical mode in 19 participants. For healthy volunteers, the US images of normal esophageal walls were all characterized by differentiated 7-layer architecture under both USCE and EUS. For 9 patients, the features of esophageal lesions were recognized clearly under USCE, and presumptive diagnoses derived from USCE were all consistent with those from EUS. Most participants preferred USCE to EUS. CONCLUSIONS: The novel USCE is feasible and safe to observe the esophageal mucosa and acquire submucosal information, which has the potential to be widely used in the clinic. (Clinical trial registration number: NCT05054933.).

Detachable string magnetically controlled capsule endoscopy for complete viewing of the esophagus and stomach.

BACKGROUND: Esophageal capsule endoscopy is reported to be insufficiently accurate to replace esophagogastroduodenoscopy (EGD) because the passage of the capsule through the esophagus is passive and precludes a thorough investigation. We developed a modified capsule endoscopy technique, called detachable string magnetically controlled capsule endoscopy (DS-MCE), and performed a pilot study to assess the feasibility and safety of this novel technique. METHODS: 4 healthy volunteers and 21 patients with suspected esophageal disease first underwent DS-MCE followed by EGD within 1 week. Outcomes included technical success of DS-MCE, adverse events, discomfort, and diagnostic accuracy. RESULTS: DS-MCE was successfully carried out in all 25 participants. No adverse events were observed. Mean overall discomfort score during DS-MCE was 0.96 (range 0 - 3). DS-MCE diagnoses were in accordance with EGD in all 25 participants. The per-patient sensitivity of DS-MCE for esophageal disease detection was 100 %. The accuracy of DS-MCE for grading esophageal varices and reflux esophagitis were 66.7 % and 100 %, respectively. CONCLUSIONS: DS-MCE was a feasible, safe, and well-tolerated method for viewing the esophagus and proceeding with gastric examination after string detachment.

Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy.

BACKGROUND/AIMS: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. METHODS: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). RESULTS: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21-0.74; Oxford classification 0.48, 95% CI 0.28-0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23-0.92; Oxford classification 0.59, 95% CI 0.10-0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. CONCLUSIONS: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

Magnetic Steering of Capsule Endoscopy Improves Small Bowel Capsule Endoscopy Completion Rate.

BACKGROUND: Capsule endoscopy is currently available as a noninvasive and effective diagnostic modality to identify small bowel abnormalities, with a completion rate to the cecum between 75.1 and 95.6%. A novel magnetically controlled capsule endoscopy (MCE) system could facilitate passage of the capsule through the pylorus, thereby reducing the gastric transit time (GTT). OBJECTIVE: We performed this study to determine whether magnetic steering could improve the capsule endoscopy completion rate (CECR) compared to standard protocol. METHODS: Patients referred for MCE in our center from June 2017 to November 2017 were prospectively enrolled. Magnetic steering of the capsule through the pylorus was performed after standard gastric examination. CECR, GTT, pyloric transit time (PTT), and rapid gastric transit (GTT ≤ 30 min) rate were compared with a historical control group enrolled from January 2017 to May 2017. RESULTS: CECR was significantly higher in the intervention group (n = 107) than control group (n = 120) (100% vs. 94.2%, P = 0.02), with a significantly shorter GTT (22.2 vs. 84.5 min, P < 0.001) and PTT (4.4 vs. 56.7 min, P < 0.001). Rapid gastric transit rate in the intervention group was significantly higher than the control group (58.9% vs. 15.0%, P < 0.001). There were no statistical differences in the diagnostic yields between the two groups. CONCLUSIONS: Magnetic steering of capsule endoscopy improves small bowel CECR by reducing GTT, adding further support to MCE as a practical tool for noninvasive examination of both the stomach and small bowel. Trial registration ClinicalTrials.gov, ID: NCT03482661.

Repetitive Position Change Improves Gastric Cleanliness for Magnetically Controlled Capsule Gastroscopy.

BACKGROUND AND AIMS: Good gastric preparation is essential for magnetically controlled capsule gastroscopy (MCCG) examination. This study aims to determine if repetitive position change after dimethicone premedication could further improve gastric cleanliness for MCCG. METHODS: Consecutive patients referred for MCCG in our center from May 7 to May 31, 2018 were prospectively enrolled and randomized to undergo repetitive position change for 15 min (position change group) or not (conventional group) after ingesting dimethicone. Primary outcome was gastric cleanliness score and secondary outcomes were detection rate of positive findings, number of lesions per patient, gastric examination time, and safety of MCCG. RESULTS: Totals of 43 and 40 were included in the position change and conventional groups, respectively. Gastric cleanliness score in the position change group was significantly higher than in the conventional group (21.2 ± 1.0 vs. 18.6 ± 2.0, P  < 0.001), as was the proportion of acceptable gastric cleanliness (gastric cleanliness score ≥ 18) (100% vs. 72.5%, P  < 0.001). There was no statistical difference in detection rate of positive findings between the two groups (27.9% vs. 27.5%, P  = 0.97). In the position change group, the gastric examination time was significantly reduced (13.2 ± 4.0 vs. 15.3 ± 5.1, P = 0.043). No adverse events were observed. CONCLUSIONS: Repetitive position change after dimethicone premedication significantly improves gastric cleanliness for MCCG examination. Clinical Trial Registration ClinicalTrials.gov, ID: NCT03514966.

Impact of magnetic steering on gastric transit time of a capsule endoscopy (with video).

BACKGROUNDS AND AIMS: Delayed gastric transit of the capsule may lead to incomplete small bowel examination, reducing the diagnostic yield. Thus, this study was designed to determine if magnetic steering could enhance capsule gastric emptying and mucosal visualization within the duodenum. METHODS: The intervention group comprised 100 patients undergoing magnetic-controlled capsule endoscopy between May to September 2017 in whom magnetic control was used to assist transpyloric passage of the capsule and duodenal inspection. A cohort of 100 patients who had undergone the procedure before May 2017 was randomly selected from the database as an historic control group in whom transpyloric movement of the capsule occurred spontaneously (without magnetic assistance). The difference in the pyloric transit time (PTT) and duodenal papilla detection rate (DPDR) between the 2 groups were compared, and related factors were also investigated. RESULTS: Transpyloric passage of the capsule under magnetic control was successfully performed in 59 patients (59%). Median PTT was greatly reduced in the intervention group from 58.38 minutes (range, 13.45-87.47) to 4.69 minutes (range, 1.56-55.00; P < .001), and DPDR was also greatly improved with magnetic steering (30.5% vs 9%, P < .001). Magnetic steering, male gender, and higher body mass index were independently associated with reduced gastric transit time and magnetic steering with an enhanced DPDR. CONCLUSIONS: Magnetic steering of the capsule can enhance gastric emptying of the capsule and may prove useful in nonobese and female patients who appeared to have longer gastric transit time and achieved a better DPDR than that under the action of peristalsis alone. (Clinical trial registration number: NCT03441945.).

Screening for gastric cancer with magnetically controlled capsule gastroscopy in asymptomatic individuals.

BACKGROUND AND AIMS: Gastric cancer (GC) is the fourth most common cancer and the fourth leading cause of cancer death worldwide. In some Asian countries, screening EGD has greatly improved the survival rate. However, patients' discomfort and the need for sedation may limit adherence to screening programs. Previous studies have shown good tolerance and good agreement of magnetically controlled capsule gastroscopy (MCCG) with EGD. This study was designed to assess the application of MCCG in GC detection in an asymptomatic population. METHODS: In this observational cohort study, 3182 asymptomatic individuals undergoing MCCG in 99 participating medical examination centers from April to December 2016 were enrolled. Patients with ulcers and suspected malignancies were referred for gastroscopy and biopsy. The detection rate of GC and focal lesions were used to explore the application of MCCG in asymptomatic individuals. RESULTS: Seven patients (0.22%) were diagnosed with GC among the enrolled 3182 individuals, accounting for 0.74% (7/948) in patients over 50 years. No gender disparity was observed. EGD and biopsy confirmed adenocarcinoma in all cases of suspected malignancy. Benign polyps, gastric ulcers, and submucosal tumors were found in 10.4%, 4.9%, and 3.6% of patients, respectively. There was a trend for the prevalence of focal lesions to increase with age. MCCG examination proved to be safe. CONCLUSIONS: MCCG can detect cancer and benign lesions and is safe and clinically feasible in a large population. Studies of its role in a screening program should be considered.

Aging promotes progression of IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND: There has been considerable interest in whether old age is associated with IgA nephropathy (IgAN) progression, which is still controversial. METHODS: We searched multiple databases for studies published from 1980 to 2012. The inclusion criteria were case-control, cohort studies published in any language. The included studies needed to have an older group. IgAN was proven by biopsy. RESULTS: We included 9 studies with a total of 6,543 patients. The meta-analyses of other risk factors between the older group (>50 years old) and the non-older group (15-50 years old) found significant differences in the presence of hypertension, proteinuria, serum cholesterol levels and baseline renal function. In the overall analysis, compared to the non-older group, older age significantly increased the incidence of developing end-stage renal disease [ESRD; relative risk (RR) random model 1.95; 95% CI: 1.27-3.01]. In the subgroup analyses, we found the age limit and traditional risk factors of IgAN may be the sources of heterogeneity between studies. Moreover, the RR (2.56) of the Asian countries was much higher than the RR (1.11) of the European countries. CONCLUSIONS: This comprehensive review revealed that old age is a real risk factor for IgAN progression to ESRD. The incidence of ESRD in the older IgAN patients was 1.95 times higher than that in the non-older IgAN patients. Moreover, the risk of IgAN progression to ESRD of the older patients in Asia was higher than that of the older patients in Europe.

Orange-peel derived carbon-loaded low content ruthenium nanoparticles as ultra-high performance alkaline water HER electrocatalysts.

Carbon materials have a very wide range of applications in the field of electrocatalysis, both as catalyst bodies and as excellent supports for catalysts. In this work, we obtained a graphitic-like orange-peel derived carbon (OPC) material through pre-carbonization and KOH activation strategies using discarded orange-peel as a raw material. OPC has good graphitization characteristics and a few-layer structure, making it very suitable as a support for nanoparticle catalysts. In order to compare the performance of OPC, we used commercial graphene as the benchmark, made two carbon materials uniformly loaded with ruthenium nanoparticles under the same conditions, and obtained two HER catalysts (Ru/OPC and Ru/rGO). The results indicate that Ru/OPC has excellent HER catalytic performance under alkaline conditions, not only superior to Ru/rGO, but also surpassing commercial Pt/C. In 1 M KOH; the overpotential of Ru/OPC is only 3 mV at -10 mA cm-2, greatly exceeding those of Ru/rGO (100 mV) and Pt/C (31 mV). Under high current density (j), the performance of Ru/OPC is even better; the overpotential is 79 mV and 136 mV at -100 mA cm-2 and -200 mA cm-2, respectively. More importantly, Ru/OPC also has a very high TOF and long-term stability, with a TOF of up to 10.62 H2 s-1 at an overpotential of 100 mV and almost no attenuation after 72 h of operation at -50 mA cm-2. Ru/OPC also exhibits good catalytic performance under acidic conditions, significantly superior to that of Ru/rGO. For Ru/OPC, the overpotential is 86 mV, 167 mV and 214 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively. Under the same conditions, the overpotential of Ru/rGO is 143 mV, 253 mV and 306 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively.

5G-based remote magnetically controlled capsule endoscopy for examination of the stomach and small bowel.

BACKGROUND AND AIMS: Remote endoscopy can improve diagnostic efficiency of gastrointestinal (GI) diseases for patients in remote areas. A novel remote magnetically controlled capsule endoscopy (MCE) system based on a 5G network was developed for real-time remote GI examinations. We aimed to evaluate the feasibility and safety of the 5G-based remote MCE for examination of the stomach and small bowel. METHODS: This was a prospective, nonrandomized, comparative study. Consecutive participants enrolled in the First People's Hospital of Yinchuan underwent remote MCE examinations performed by an endoscopist located in Changhai Hospital. Consecutive participants enrolled in Changhai Hospital underwent conventional MCE examinations performed by the same endoscopist. The main outcomes included the complete visualization rate of the stomach and small bowel, safety assessment and network latency time of remote MCE examinations. RESULTS: From March 2021 to June 2021, 20 participants in each group were enrolled. The complete visualization rate of the stomach and small bowel was 100% in both groups (p > 0.999) without any adverse event. The median network latency time of remote MCE group was 19.948 ms. Gastric examination time (8.96 vs. 8.92 min, p = 0.234), maneuverability (15.00 vs. 15.00, p = 0.317), image quality (1.00 vs. 1.00, p > 0.999) and diagnostic yields in the stomach and small bowel (55% vs. 30%, 5% vs. 0%, both p > 0.05) were comparable between remote and conventional MCE groups. All participants in remote MCE group considered remote MCE acceptable and necessary. CONCLUSIONS: 5G-based remote MCE was a feasible and safe method for viewing the stomach and small bowel.

Immune response pattern varies with the natural history of chronic hepatitis B.

BACKGROUND: Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant (IT), immune active (IA), inactive carrier (IC) and hepatitis B envelope antigen (HBeAg)-negative hepatitis (ENEG). AIM: To investigate the immune status of natural killer (NK) and T cells in different phases of chronic hepatitis B. METHODS: The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus (HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected subjects. RESULTS: The ability of NK cells to produce IFN-γ was markedly attenuated in HBV-infected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEG phases, as evidenced by the upregulation of NKp44 in CD56bright NK cells and CD69 in CD56dim NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-α expression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other phases. CONCLUSION: Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.

Automatic Delineation of the Clinical Target Volume in Rectal Cancer for Radiation Therapy using Three-dimensional Fully Convolutional Neural Networks.

Accurate, robust, and fast delineation of the clinical target volume (CTV) for the use in radiotherapy of rectal cancer (RC) is highly sought-after. Convolutional neural networks (CNNs) have proven themselves very effective in various segmentation tasks on medical images. Despite this, their application in CTV delineation is not yet fully explored. This study uses the three-dimensional fully convolutional neural network architecture called V-net for CTV delineation. The West China Hospital (Chengdu, China) provided this study with 120 annotated CT scans. For improved performance and to battle data scarcity, the available scans were augmented. Trained on 100 CT-scans for 20 hours and tested on 20 previously unseen CT-scans the network achieved a mean dice similarity coefficient (DSC) of 0.90 and a mean delineation time per CTV of 0.60 seconds. The proposed method is compared with two other state-of-the-art CNNs and is shown to be superior.

[Protective effects of beta-asarone on cultured rat cortical neurons damage induced by glutamate].

OBJECTIVE: To study the protective effects of beta-asarone on cultured rat cortical neurons damage induced by glutamate. METHODS: The protective effects of beta-asarone on cultured rat cortical neurons after glutamate intoxication were observed with morphology, extent of damage, livability, Intracellular calcium concentration and apoptosis ratio. RESULTS: Morphological changes, LDH leakage and intracellular calcium concentration increasing, cell survival decreasing were observed in cultured rat cortical neurons exposured to glutamate; 7.5, 15, 30 microg/ml beta-asarone could increase cell survival, decrease LDH leakage and apoptosis ratio; 15, 30 microg/ml beta-asarone could reduce intracellular calcium concentration. CONCLUSION: The results suggest that beta-asarone prevents the toxicity of glutamate, and it maybe attribute to its effect of anticalcium.

[Effects of beta-asarone on morphology and cell viability in PC12 cells and cultured rat cortical neurons].

OBJECTIVE: To observe the effects of beta-asarone on the morphology and cell viability in PC12 cells and cultured neonate rat cortical neurons. METHODS: The cultured neonate rat cortical neurocytes were stained immunocytochemically with NSE, GFAP antibodies, respectively; Morphological changes were observed under phase contrast microscope after PC12 cells and cultured rat cortical neurons with beta-asarone of different concentrationfor 24h in vitro, and the cell viability of PC12 and cortical neurons were examined by MTT assay. RESULTS: Most of the cultured neonate rat cortical neurocytes were positively stained with NSE antibody, and positively with GFAP in a less degree; Treatment of PC12 cells with concentrations of 7.5, 15, 30, 60 microg/ml beta-asarone for 24 h could facilitate the proliferation in PC12 cells, 120, 240, 480 microg/ml beta-asarone could inhibit the proliferation inversely, and with the concentration of beta-asarone increasing, the inhibition was enhanced; Treatment of cultured neonate rat cortical neurons with concentrations of 7.5, 15, 30, 60,120 nicrog/ml beta-asarone for 24 h, there were no visible effects on morphology and cell viability, 240 microg/ml beta-asarone could facilitate the proliferation obviously, but 480 microg/ml beta-asarone induced injury on neurons. CONCLUSION: beta-asarone maybe has anti-tumor and protective effects on cultured neurons.

Abelmoschus manihot - a traditional Chinese medicine versus losartan potassium for treating IgA nephropathy: study protocol for a randomized controlled trial.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, but effective therapy remains limited and many patients progress to end-stage renal disease (ESRD). Only angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blockers (ARB) show a high level of evidence (1B level) of being of value in the treatment for IgAN according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. However, traditional Chinese medicine has raised attention in kidney disease research. Abelmoschus manihot, a single medicament of traditional Chinese medicine has shown therapeutic effects in primary glomerular disease according to the randomized controlled clinical trial that we have completed. Here, we conduct a new study to assess the efficacy and safety of Abelmoschus manihot in IgAN. Also, this study is currently the largest double-blind, randomized controlled registered clinical research for the treatment of IgAN. METHODS: We will conduct a multicenter, prospective, double-blind, double-dummy randomized controlled study. The study is designed as a noninferiority clinical trial. Approximately 1600 biopsy-proven IgAN patients will be enrolled at 100 centers in China and followed up for as long as 48 weeks. IgAN patients will be randomized assigned to the Abelmoschus manihot group (in the form of a huangkui capsule, 2.5 g, three times per day) and the losartan potassium group (losartan potassium, 100 mg/d). The primary outcome is the change in 24-h proteinuria from baseline after 48 weeks of treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after 48 weeks of treatment, the incidence of endpoint events (proteinuria ≥3.5 g/24 h, the doubling of serum creatinine, or receiving blood purification treatment) are the secondary outcomes. Twenty-four-hour proteinuria and eGFR are measured at 0, 4, 12, 24, 36 and 48 weeks. DISCUSSION: This study will be of sufficient size and scope to evaluate the efficacy and safety of Abelmoschus manihot compared to losartan potassium in treating patients with IgAN. The results of this study may provide a new, effective and safe treatment strategy for IgAN. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02231125 . Registered on 30 August 2014.

Efficacy and safety of Flos Abelmoschus manihot (Malvaceae) on type 2 diabetic nephropathy: A systematic review.

OBJECTIVE: To evaluate the efficacy and safety of Flos Abelmoschus manihot (Malvaceae) on type 2 diabetic nephropathy (DN). METHODS: The Cochrane Library, PubMed/MEDLINE, Excerpta Medical Database, Chinese electronic literature databases, and the references of relevant articles were searched in March 2012 for randomized controlled trials (RCTs) that reported the effects of Flos A. manihot on type 2 DN patients with overt but subnephrotic-range proteinuria (500-3,500 mg/24 h). The quality of trials was evaluated using the Cochrane-recommended method. The results were summarized as risk ratios (RRs) for dichotomous outcomes or mean differences (MDs) for continuous outcomes. RESULTS: Seven trials (531 patients) were included. Flos A. manihot significantly decreased proteinuria [MD -317.32 mg/24 h, 95% confidence interval (CI) [-470.48, -164.17],P<0.01]. After excluding a trial that only included patients with well-preserved renal function, Flos A. manihot was associated with a significant decrease in serum creatinine (MD -11.99 µmol/L, 95% CI [-16.95, -7.04],P<0.01). Serious adverse events were not observed. The most common adverse event was mild to moderate gastrointestinal discomfort; however, patients receiving this herb did not have an increased risk for tolerated gastrointestinal discomfort (RR 1.48, 95% CI [0.39, 5.68],P=0.57). CONCLUSIONS: Flos A. manihot may be considered as an important adjunctive therapy with the first-line and indispensable therapeutic strategies for type 2 DN. High-quality RCTs are urgently needed to confirm the effect of Flos A. manihot on definite endpoints such as end-stage renal disease.

Lack of associations of the COMT Val158Met polymorphism with risk of endometrial and ovarian cancer: a pooled analysis of case-control studies.

This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk.

Validation of a differential diagnostic model of diabetic nephropathy and non-diabetic renal diseases and the establishment of a new diagnostic model.

BACKGROUND: The aims of the present study were to validate the differential diagnostic model of diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) established in 2003 and to establish a new diagnostic model suitable for the current clinical characteristics of DN. METHODS: We examined 200 patients with Type 2 diabetes who underwent kidney biopsy from 2004 to 2012. The 2003 differential diagnostic model based on the data collected from 1993 to 2003 was evaluated by the diagnostic test and changes in the clinical differentiation parameters of DN and NDRD were analyzed. Logistic regression, receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analysis were applied. RESULTS: The 2003 diagnostic model showed an accuracy of 77.5%. A significantly elevated incidence of hematuria, longer history of diabetes, and reduced level of glycated hemoglobin (HbA1c) were observed in the DN group from 2004 to 2012 compared with DN group from 1993 to 2003. Histories of diabetes mellitus (Dm), systolic blood pressure (Bp), HbA1c (Gh), hematuria (Hu), diabetic retinopathy (Dr), and hemoglobin (Hb) are independently related to DN. Thus, a new diagnostic model was constructed as follows: PDN = exp (0.846 + 0.022 Dm + 0.033Bp + 2.050 Gh-2.664 Hu-0.078 Hb + 2.942Dr)/[1 + exp (0.846 + 0.022 Dm + 0.033 Bp + 2.050 Gh-2.664 Hu-0.078 Hb + 2.942 Dr)].Validation tests determined that the accuracy of the new model were 90.9%. CONCLUSIONS: Changes in people with DN, clinical characteristics have reduced the diagnostic efficacy of the 2003 diagnostic model. The newly established model can provide a better, more current differentiation between DN and NDRD.

Incidence and risk of severe neutropenia in advanced cancer patients treated with cetuximab: a meta-analysis.

BACKGROUND AND AIM: Neutropenia is a serious adverse event for patients who are treated with cetuximab, an inhibitor of endothelial growth factor receptor. However, there is no consistent result of the relationship between cetuximab and neutropenia in randomized controlled trials (RCTs). We did a systematic review and meta-analysis of published RCTs to assess the overall risk of neutropenia associated with cetuximab. METHODS: PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and American Society of Clinical Oncology conferences were searched for relevant RCTs. Quantitative and qualitative analyses were carried out to evaluate the association between neutropenia and cetuximab. Both the fixed-effect model and random-effects model were used. RESULTS: A total of 7186 patients with a variety of advanced cancers from 14 trials were included in our analysis. The overall incidence of neutropenia in patients receiving cetuximab was 33% (95% CI 26, 43). Patients treated with cetuximab had a significantly increased risk of neutropenia compared with patients treated with control medication, with a relative risk (RR) of 1.12 (95% CI 1.05, 1.19; fixed-effect model). Risk varied with tumor type. Higher risks were observed in patients with colorectal carcinoma (RR 1.17; 95% CI 1.04, 1.32; fixed-effect model) and non-small cell lung cancer (RR 1.07; 95% CI 0.99, 1.16; fixed-effect model). CONCLUSION: Cetuximab is associated with a significant risk of neutropenia in patients with advanced cancer receiving concurrent chemotherapy.

Systematic review of TCF2 anomalies in renal cysts and diabetes syndrome/maturity onset diabetes of the young type 5.

OBJECTIVE: There is a paucity of published works that systematically evaluate gene anomalies or clinical features of patients with renal cysts and diabetes syndrome (RCAD)/maturity onset diabetes of the young type 5 (MODY5). The purpose of this review was to systematically assess the detection rate, genetic and phenotypic implications of heterozygous autosomal dominant TCF2 anomalies. DATA SOURCES: MEDLINE database was searched to select articles recorded in English from 1997 to 2008. The focus was monoallelic germline TCF2 gene mutations/deletions. Biallelic inactivation, polymorphisms, DNA modification (hypomethylation and hypermethylation), loci associated with cancer risk, and somatic TCF2 anomalies were all excluded. STUDY SELECTION: After searching the literature, 50 articles were selected. RESULTS: The detection rate of TCF2 anomalies was 9.7% and varied considerably among MODY (1.4%), renal structure anomalies (RSA) (21.4%) and RSA with MODY (41.2%) subgroups. Mutations were strikingly located within the DNA binding domain and varied among exons of the DNA binding domain: exons 2 and 4 were the hottest spots, while mutations were sporadically distributed in exon 3. The consistent phenotypes were RSA (89.6%) and diabetes mellitus (DM) (45.0%). However, the concurrence of RSA and DM was relatively low (27.5%), which hinders the optimal performance of genetic testing and obtainment of timely diagnosis. Other organ involvements were complementary and necessary for the early identification of patients with TCF2 anomalies. Analysis of phenotypes of TCF2 point mutations showed significant differences in the detection rates of RSA, impaired renal function (IRF) and DM according to mutation type but not mutation location. CONCLUSION: These valuable features of TCF2 anomalies that previously did not receive sufficient attention should not be neglected.