Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Setting 6-Minute Minimal Examination Time Improves the Detection of Focal Upper Gastrointestinal Tract Lesions During Endoscopy: A Multicenter Prospective Study.

INTRODUCTION: Positive correlation between examination time and neoplasm detection using esophagogastroduodenoscopy (EGD) has been described by observational studies, but the effect of setting minimal examination time still requires investigation. METHODS: This prospective, 2-stage, interventional study was conducted in 7 tertiary hospitals in China, enrolling consecutive patients undergoing intravenously sedated diagnostic EGDs. In stage I, the baseline examination time was collected without informing the endoscopists. In stage II, the minimal examination time was set for the same endoscopist according to the median examination time of normal EGDs in stage I. The primary outcome was the focal lesion detection rate (FDR), defined as the proportion of subjects with at least one focal lesion among all subjects. RESULTS: A total of 847 and 1,079 EGDs performed by 21 endoscopists were included in stages I and II, respectively. In stage II, the minimal examination time was set as 6 minutes, and the median time for normal EGD increased from 5.8 to 6.3 minutes ( P < 0.001). Between the 2 stages, the FDR was significantly improved (33.6% vs 39.3%, P = 0.011), and the effect of the intervention was significant (odds ratio, 1.25; 95% confidence interval, 1.03-1.52; P = 0.022) even after adjusting for subjects' age, smoking status, endoscopists' baseline examination time, and working experience. The detection rate of high-risk lesions (neoplastic lesions and advanced atrophic gastritis) was also significantly higher in stage II (3.3% vs 5.4%, P = 0.029). In the endoscopist-level analysis, all practitioners reached a median examination time of 6 minutes, and the coefficients of variation of FDR (36.9%-26.2%) and examination time (19.6%-6.9%) decreased in stage II. DISCUSSION: Setting a 6-minute minimal examination time significantly improved the detection of focal lesions during EGDs and has the potential to be implemented for quality improvement.

Four-Hour Fasting for Semifluids and 2-Hour Fasting for Water Improves the Patient Experience of Esophagogastroduodenoscopy: A Randomized Controlled Trial.

Background/Aims: We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water ("4+2") fasting protocol. Methods: In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a "4+2" protocol group or a conventional fasting group. The participants' comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants' comfort during fasting. Results: One hundred and six and 108 participants were randomized to the "4+2" protocol and control groups, respectively. Participants' comfort before EGD was significantly higher in the "4+2" protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0-2.0] vs 3.0 [1.0-4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the "4+2" protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0-5.0] vs 4.0 [4.0-5.0], p=0.266). No adverse events were observed during the study. Conclusions: The "4+2" protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD.

Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways.

BACKGROUND: Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms. METHODS: Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis. RESULTS: Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo. At the molecular level, Western blot analysis indicated that shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38. Interaction of TRAF6 and RANK was prevented, and downstream MAPK and NF-κB signaling pathways were downregulated. CONCLUSION: Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo. Shikonin is a promising candidate for treatment of postmenopausal osteoporosis.

Muscone Ameliorates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κb Ligand-Induced Osteoclastogenesis by Suppressing TNF Receptor-Associated Factor 6-Mediated Signaling Pathways.

Postmenopausal osteoporosis is caused by the deficiency of estrogen, which breaks bone homeostasis and induces levels of pro-inflammatory cytokines. Muscone is a potent anti-inflammatory agent and is used to treat bone fracture in traditional Chinese medicine. However, its anti-osteoclastogenic effects remain unclear. For in vitro study, morphology tests of osteoclastogenesis were firstly performed. And then, factors in RANK-induced NF-κB and MAPK pathways were examined by RT-PCR and Western blot, and the binding of TNF receptor-associated factor (TRAF)6 to RANK was inspected by coimmunoprecipitation and immunofluorescence staining. For in vivo experiments, C57BL/6 ovariectomized (OVX) mice were used for detection, including H&E staining, TRAP staining, and micro CT. As a result, muscone reduced OVX-induced bone loss in mice and osteoclast differentiation in vitro, by inhibiting TRAF6 binding to RANK, and then suppressed NF-κB and MAPK signaling pathways. The expression of the downstream biomarkers was finally inhibited, including NFATc1, CTR, TRAP, cathepsin K, and MMP-9. The inflammatory factors, TNF-a and IL-6, were also reduced by muscone. Taken together, muscone inhibited the binding of TRAF6 to RANK induced by RANKL, thus blocking NF-kB and MAPK pathways, and down-regulating related gene expression. Finally, muscone inhibited osteoclastogenesis and osteoclast function by blocking RANK-TRAF6 binding, as well as downstream signaling pathways in vitro. Muscone also reduced ovariectomy-induced bone loss in vivo.

Non-obese type 2 diabetes patients present intestinal B cell dysregulations associated with hyperactive intestinal Tfh cells.

Most current studies of type 2 diabetes (T2D) focus on obesity in the pathogenesis of the disease. However, many individuals develop T2D at non-obese body mass index (BMI) level. It is yet unclear whether certain etiological mechanisms discovered in these obese models can apply to non-obese T2D patients. In the present study, we focused on one aspect that was potentially involved in T2D development, the intestinal inflammation, and examined the difference between non-obese T2D patients and BMI-matched healthy controls. We found that non-obese T2D patients presented significantly higher levels of fecal IgG than BMI-matched controls. Compared to active Crohn's disease patients, both T2D and healthy controls presented lower levels of fecal IgG. In the mucosal biopsies, the B cells and plasmablasts from T2D patients presented a slight but significant increase in the frequencies of cells with surface IgG expression compared to those from healthy individuals. The potential mechanism resulting in increased IgG expression was then examined. The CD4+CXCR5+ T cells (Tfh) from non-obese T2D patients were highly enriched in IFN-γ-producing cells and depleted in IL-4- and IL-17-producing cells. Presence of mucosal CD4+CXCR5+ T cells significantly increased IgG production from mucosal samples. Interestingly, when stimulated with E. coli, a common intestinal microbe, the CD4+CXCR5+ T cells from T2D patients presented significantly higher IFN-γ expression than CD4+CXCR5+ T cells from BMI-matched controls Together, these results demonstrated that non-obese T2D patients presented a low-grade inflammation in the intestinal tract, possibly supported by bacteria-responding CD4+CXCR5+ T cells.

Bibliometric analysis of global scientific activity on umbilical cord mesenchymal stem cells: a swiftly expanding and shifting focus.

Several studies have focused on umbilical cord-derived mesenchymal stem cells (UC-MSCs) due to their potential therapeutic effects in a cluster of diseases. However, there has been no bibliometric analysis evaluating the evolution in UC-MSC research. Therefore, this study aimed to assess scientific activity regarding UC-MSC research. Publications on UC-MSCs were retrieved from the Science Citation Index-Expanded (SCI-E) of the Web of Science (WoS) from 1975 to 2017. Statistical analyses were performed using Excel, GraphPad Prism 5, and VOSviewer software. Comparative analyses were employed to assess contributions between different countries, institutes, and researchers. With 21.26 citations per paper, 1206 papers cited 25,517 times were included. Mainland China contributed the most with 558 papers, with the most citations (6858 times) and the highest H-index (43). South Korea ranked first for number of papers per million people and per trillion gross domestic product (GDP). Keywords were stratified into two clusters by VOSviewer software: cluster 1, "treatments and effects"; and cluster 2, "characteristics". The average appearing years (AAY) of keywords in cluster 1 was more recent than that in cluster 2. For promising hotspots, "TNF-α" showed the latest AAY at 2014.09, followed by "migration", "angiogenesis", and "apoptosis". We conclude that the number of publications has been continuously growing dramatically since 2002 and that mainland China and South Korea are the most productive regions. The focus gradually shifts from "characteristics" to "treatments and effects". Attention should be drawn to the latest hotspots, such as "TNF-α", "migration", "angiogenesis", and "apoptosis". Furthermore, funding agencies might increase investments in exploring the therapeutic potential of UC-MSCs.