Effect of food additives on key bacterial taxa and the mucosa-associated microbiota in Crohn's disease. The ENIGMA study.

Food additives have been linked to the pro-inflammatory microbial dysbiosis associated with Crohn's disease (CD) but the underlying ecological dynamics are unknown. Here, we examine how selection of food additives affects the growth of multiple strains of a key beneficial bacterium (Faecalibacterium prausnitzii), axenic clinical isolates of proinflammatory bacteria from CD patients (Proteus, Morganella, and Klebsiella spp.), and the consortia of mucosa-associated microbiota recovered from multiple Crohn's disease patients. Bacterial growth of the axenic isolates was evaluated using a habitat-simulating medium supplemented with either sodium sulfite, aluminum silicate, carrageenan, carboxymethylcellulose, polysorbate 80, saccharin, sucralose, or aspartame, intended to approximate concentrations found in food. The microbial consortia recovered from post-operative CD patient mucosal biopsy samples were challenged with either carboxymethylcellulose and/or polysorbate 80, and the bacterial communities compared to unchallenged consortia by 16S rRNA gene amplicon profiling. Growth of all F. prausnitzii strains was arrested when either sodium sulfite or polysorbate 80 was added to cultures at baseline or mid-exponential phase of growth, and the inhibitory effects on the Gram-negative bacteria by sodium sulfite were conditional on oxygen availability. The effects from polysorbate 80, saccharin, carrageenan, and/or carboxymethylcellulose on these bacteria were strain-specific. In addition to their direct effects on bacterial growth, polysorbate 80 and/or carboxymethylcellulose can drive profound changes in the CD mucosa-associated microbiota via niche expansion of Proteus and/or Veillonellaceae - both implicated in early Crohn's disease recurrence. These studies on the interaction of food additives with the enteric microbiota provide a basis for dietary management in Crohn's disease.

[Research advances of music therapy and its application in the field of burn treatment].

Different from other trauma, the scar and pigmentation formed after healing of burn wound not only hinder beauty but also easily lead to a series of sequential psychological problems, such as depression and anxiety. Music therapy, as a supplementary treatment, is widely used in many fields including medical and health care and psychological regulation. However, affected by factors such as medical resources, the awareness and acceptance of music therapy among burn treatment workers in China are still low. Based on the clinical characteristics of burns, this paper matches the applicability of music therapy with it, summarizes the supplementary application of music therapy in the field of burn treatment, expounds this natural science with both science and aesthetics, and puts forward feasible suggestions for its future development.

Can buccal infiltration of articaine replace traditional inferior alveolar nerve block for the treatment of mandibular molars in pediatric patients?: A systematic review and meta-analysis.

BACKGROUND: It is unclear if buccal articaine infiltration can be used as an alternative to standard inferior alveolar nerve block (IANB) for treating mandibular molars in pediatric patients. Therefore, this study aimed to pool evidence to compare the efficacy of buccal infiltration of articaine vs IANB with lignocaine for pediatric dental procedures. MATERIAL AND METHODS: We searched the PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases for randomized controlled trials (RCTs) comparing the two techniques in pediatric patients and reporting the success of anesthesia and/or pain during treatment. PRISMA guidelines were followed. RESULTS: Seven RCTs were included. Pooled analysis of five studies indicated no statistically significant difference in the success rates of the two anesthetic techniques (OR: 1.02; 95% CI: 0.13, 7.96; I2=69%, p=0.98). Meta-analysis of data from the four studies demonstrated no statistically significant difference in pain during the procedure with buccal infiltration of articaine or IANB with lignocaine (SMD: 0.62; 95% CI: -1.37, 0.12; I2=88%, p=0.10). CONCLUSIONS: Evidence suggests that buccal infiltration of articaine is a viable alternative to IANB with lignocaine in pediatric patients for treating mandibular molars. Based on the confidence intervals, there may be a tendency of higher success rates with buccal infiltration of articaine.

[Effect analysis of sequential laser application in treating the hypertrophic scars of burn children at early stage].

Objective: To explore the effects of sequential application of intensive pulsed light and carbon dioxide laser in treating the hypertrophic scars of burn children at early stage. Methods: A retrospective cohort before-after control study in the same patients was conducted. From January 2016 to December 2018, 145 burn children with hypertrophic scar at the early stage who met the inclusion criteria were admitted to the First Hospital of Jilin University, including 82 males and 63 females, aged 1 to 12 (3 (2, 6)) years. All the children were firstly treated with intense pulsed light therapy (no anesthesia or intravenous-inhalation combined anesthesia) at an interval of once per month, and then changed to carbon dioxide laser therapy (topical anesthesia or intravenous-inhalation combined anesthesia) when the degree of scar hyperemia was reduced, at an interval of once every 3 months, for a total of 3 times. Before the first intense pulsed light treatment (hereinafter referred to as before the first treatment) and 3 months after the last carbon dioxide laser treatment (hereinafter referred to as after the last treatment), scar scoring was evaluated by Vancouver Scar Scale (VSS), and scar hyperemia (denoted as hemoglobin level) was measured with Antera 3D® camera. The times of intense pulsed light, the time of single treatment, the anesthesia method, and the time of intravenous-inhalation combined anesthesia of intense pulsed light and carbon dioxide laser treatment were analyzed. After the last treatment, Likert Scale was used to evaluate the efficacy satisfaction of both doctors and patients. Adverse reactions were recorded during the treatment. Data were statistically analyzed with Wilcoxon signed rank sum test, and paired sample t test. Results: The color, vascular distribution, thickness, and softness scores, and total score in VSS scoring of scars of children after the last treatment were significantly lower than those before the first treatment (Z=-6.05, -10.34, -9.84, -9.28, -10.43, P<0.01). The hemoglobin level of scar of children after the last treatment was 1.86±0.24, significantly lower than 2.27±0.32 before the first treatment (t=17.65, P<0.01). A total of 411 times of intense pulsed light therapy were performed, (2.8±0.6) times per person, and the single treatment time was 35 (20, 45) s. There were 392 times (95.38%) without anesthesia, and 19 times (4.62%) with intravenous-inhalation combined anesthesia with time of 6 (5, 8) min. The single treatment time of carbon dioxide laser therapy was 5 (3, 10) min. There were 364 times (83.68%) of topical anesthesia and 71 times (16.32%) of intravenous-inhalation combined anesthesia with time of 10 (8, 15) min. After the last treatment, the efficacy satisfaction scores of doctors and patients were (4.3±0.7) and (3.8±1.0) points, respectively. Blisters occurred in 5 cases after intense pulsed light treatment, which were healed naturally after drainage. One child developed local skin infection, skin redness and swelling accompanied by purulent exudate after carbon dioxide laser treatment, which was improved after skin disinfection and external use of mupirocin ointment. No inflammatory pigmentation, worsening of hyperplasia of scar, erythema, or other skin adverse reactions or anesthetics-related adverse reactions occurred in any child. Conclusions: Sequential application of intense pulsed light and carbon dioxide laser to treat the hypertrophic scars of burn children at early stage can obviously improve the appearance and texture of scar, with higher satisfaction of doctors and patients and fewer adverse reactions.

Switchable CAR-T Cells Outperformed Traditional Antibody-Redirected Therapeutics Targeting Breast Cancers.

Various antibody-redirected immunotherapeutic approaches, including antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor-T (CAR-T) cells, have been devised to produce specific activity against various cancer types. Using genetically encoded unnatural amino acids, we generated a homogeneous Her2-targeted ADC, a T cell-redirected bsAb, and a FITC-modified antibody capable of redirecting anti-FITC CAR-T (switchable CAR-T; sCAR-T) cells to target different Her2-expressing breast cancers. sCAR-T cells showed activity against Her2-expressing tumor cells comparable to that of conventional anti-Her2 CAR-T cells and superior to that of ADC- and bsAb-based approaches. To prevent antigen escape, we designed bispecific sCAR-T cells targeting both the Her2 receptor and IGF1R, which showed an overall improved activity against cancer cells with low Her2 expression. This study increases our understanding of various explored cancer therapeutics and underscores the efficient application of sCAR-T cells as a promising therapeutic option for breast cancer patients with low or heterogeneous antigen expression.

Preventive intraperitoneal hyperthermic perfusion chemotherapy for patients with T4 stage colon adenocarcinoma.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be an effective treatment for peritoneal tumors; whether preventive HIPEC after radical resection for T4 stage colon adenocarcinoma could decrease peritoneal recurrence remains unknown. The aim of the present study was to compare peritoneal recurrence and short-term survival in patients with T4 stage colon adenocarcinoma undergoing HIPEC plus adjuvant chemotherapy or adjuvant chemotherapy alone following surgery. METHODS: We retrospectively reviewed T4 stage colon adenocarcinoma patients who had radical tumor resection at our institution between January 2014 and January 2019. Clinical data were extracted from the database at our institution, and patient survival and long-term complications were assessed through repeated outpatient examinations and telephone interviews. RESULTS: A total of 352 patients were included in this study; 157 patients received postoperative HIPEC plus adjuvant chemotherapy (HIPEC group), 195 patients received adjuvant chemotherapy alone (conventional chemotherapy group). Forty-one (26.1%) patients in the HIPEC group had a peritoneal recurrence and the peritoneum was the first site of tumor recurrence in 6 (14.6%) of them. However, 73 (37.4%) patients experienced peritoneal recurrence in the conventional group, and the peritoneum was the first site of tumor recurrence in 25 (34.2%) (p = 0.019). Disease-free survival in the HIPEC group at 1 and 3 years was 93.3% and 61.1%, respectively, versus 89.3% and 51.7% in the conventional chemotherapy group (p = 0.038). Overall survival in the HIPEC group at 1 and 3 years was 100.0% and 82.7%, respectively, versus 100.0% and 76.9% in the conventional chemotherapy group (p = 0.420). The two groups did not differ with respect to severe complications. CONCLUSIONS: Preventive HIPEC after radical surgery may decrease peritoneal recurrence and promote disease-free survival for T4 stage colon adenocarcinoma. Large-scale randomized controlled studies are needed to confirm the results of our study.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

[Technical essentials and safety analysis of "rolling carpet" cytoreduction surgery in stage â ¢c epithelial ovarian cancer].

Objective: To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy （"rolling carpet" surgery） in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality. Methods: From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent "rolled carpet" CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of "rolled carpet" CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of "rolling carpet" CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups. Results: (1) Clinicopathological features: the age of patients in "rolling carpet" CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the "rolled carpet" CRS group, all patients （100%, 30/30） were performed optimal CRS, reaching completeness of cytoreduction score （CC score）, named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients （77%, 23/30） reached CC-0 score, 5 cases （17%, 6/30） reached CC-1 score, 2 cases （7%, 2/30） reached CC-2 score, and there were statistical significance between the two groups (P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the "rolled carpet" CRS group and the traditional CRS groups (P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion: It is safe and feasible to perform "rolled carpet" CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.

[Maternal periconceptional folic acid supplementation and its effects on the prevalence of fetal neural tube defects].

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.

Effects of cottonseed meal on slaughter performance, meat quality, and meat chemical composition in Jiangnan White goslings.

Cottonseed meal (CSM), which is an unconventional protein material with abundant sources, high protein content, and a relatively cheap price, can be used in poultry diets. The aim of this study was to investigate the effects of CSM on slaughter performance, meat quality and meat chemical composition in Jiangnan White goslings. A total of 300 healthy 28-day-old male goslings were randomly divided into 5 treatments, with 6 pens containing 10 geese each. Five isonitrogenous and isocaloric experimental diets were formulated such that 0% (a corn-soybean meal basal diet, control), 25% (CSM25), 50% (CSM50), 75% (CSM75), and 100% (CSM100) protein from soybean meal was replaced with CSM (corresponding to 0, 6.73, 13.46, 20.18, and 26.91% CSM in the feed, respectively). On day 70, 1 goose from each pen (6 geese per treatment) was randomly selected and killed to measure the slaughter performance, meat quality, and the meat amino acid (AA) and fatty acid (FA) compositions. The results showed that dietary CSM did not affect the slaughter performance or meat quality of geese (P > 0.05). The fat content of breast muscle in the CSM100 group was higher than that in the control group (P < 0.05). A concentration of 13.46% or more dietary CSM increased the threonine content but decreased the cysteine content, and 20.18% dietary CSM also decreased the valine content (P < 0.05). Dietary CSM concentration had no effect on the content of total saturated FAs (SFAs, P > 0.05), but 20.18 and 26.91% dietary CSM increased the content of total monounsaturated FAs and decreased the content of total polyunsaturated FAs (PUFAs) and PUFA/SFA in the breast muscle of geese (P < 0.05). In conclusion, dietary CSM did not affect the slaughter performance or meat quality of geese, but the replacement of soybean meal with CSM in whole or high proportion altered the composition of AAs and FAs in breast muscle.

[Effects of recombinant human granulocyte macrophage colony stimulating factor gel on treatment of full-thickness frostbite wounds on foot and hand].

Objective: To explore the effects of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) gel on treatment of thefull-thickness frostbite wounds on foot and hand. Methods: From November 2013 to April 2017, a total of 45 patients of 71 full-thickness frostbite wounds on foot and hand meeting the inclusion criteria were admitted to the First Hospital of Jilin University and the prospective randomized controlled study was done. The patients were divided into rhGM-CSF group of 24 patients with 35 wounds and control group of 21 patients with 36 wounds according to the random number table. There were 20 males and 4 females, aged (38±13) years among patients in rhGM-CSF group, and there were 19 males and 2 females, aged (36±14) years among patients in control group. Patients in 2 groups were performed with the same systemic treatment of rewarming, anti-inflammation, pain relief, anti-infection, anti-coagulation, and thrombolysis. Wounds of patients in rhGM-CSF group and control group were respectively treated with rhGM-CSF gel and aloe vera gel for external usage with 10 mg for every square centimeter and dressing change once every 24 hours, until wounds healed completely. The wound inflammatory response was scored on treatment day (TD) 1, 3, 7, 14, wound secretion was collected for bacteria culture and positive bacteria detection rate was calculated before treatment and on TD 6 and 12, adverse drug reaction after drug use was observed, and the complete wound healing time was recorded. Data were processed with Fisher's exact probability test, analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: The scores of wound inflammatory response of patients in 2 groups on TD 1 and 3 were close (t=0.37, 2.93, P>0.05). The scores of wound inflammatory response of patients on TD 7 and 14 in rhGM-CSF group were significantly higher than those in control group (t=5.77, 5.83, P<0.01). The results of bacteria culture of wound secretion of patients in 2 groups before treatment were negative. The positive bacteria detection rates of wound secretion of patients in rhGM-CSF group on TD 6 and 12 were 5.71% (2/35) and 22.86% (8/35), which were slightly lower than 13.89% (5/36) and 30.56%(11/36) in control group respectively, but there was no significantly statistical difference (P>0.05). No adverse drug response occurred in patients in rhGM-CSF group, while 1 patient in control group had adverse drug response, with symptoms of redness and swelling of wounds and patchy erythema on skin around wounds, which were alleviated by irrigating with normal saline. The complete wound healing time of patients in rhGM-CSF was (12.3±0.5) d, which was significantly shorter than (16.5±0.8) d in control group (t=24.89, P<0.05). Conclusions: The topical rhGM-CSF gel has effects of shortening time of wound healing and reducing inflammatory response of wound on treatment of full-thickness frostbite wounds on foot and hand, which is safe in clinical application.

[Study on maternal-fetal status of Pb, Cd, As, Hg, Mn and Se elements and transplacental transfer efficiency].

Objective: To understand the levels of Pb, Cd, As, Hg, Mn, and Se in maternal and umbilical cord blood, and to explore the transplacental transfer efficiency (TTE). Methods: From September 2010 to December 2013, a total of 773 pregnant women and their newborns (Laizhou Bay Birth Cohort) were recruited from a second grade hospital in the south bank of Laizhou Bay, Bohai, Shandong Province. According to different detection methods, the six measured elements are classified into three groups including the Hg measurement group (595 mother-newborn pairs), the Pb measurement group (534 mother-newborn pairs), and the Cd, As, Mn and Se measurement group (244 mother-newborn pairs). The demographic characteristics of pregnant women and their newborns were obtained by the questionnaire. The concentrations of elements in maternal and umbilical cord blood were detected and the TTE of each element (elemental concentration in cord blood/elemental concentration in maternal blood) was calculated. The correlation of elements between maternal and cord blood was analyzed using Spearman's rank correlation coefficient. Results: The mean±SD of maternal age, gestational week and newborn birth weight of 773 mother-infant pairs were (28.34±4.50) years, (39.47±1.39) weeks and (3 419.47±497.39) g respectively. The median concentrations of Pb, Cd, As, Hg, Mn and As in maternal and cord blood were 31.12 and 30.02, 1.19 and 0.47, 8.05 and 6.03, 0.69 and 1.26, 100.70 and 105.55, 127.25 and 115.00 µg/L, respectively. The TTE of Pb, Cd, As, Hg, Mn, and Se was 0.98, 0.41, 0.73, 1.73, 0.96 and 0.91, respectively. Pb, Cd, Hg, Mn, and Se showed a significant positive correlation between maternal blood and cord blood, with Spearman correlation coefficients of 0.397, 0.298, 0.698, 0.555, and 0.285 (all P values<0.001). Conclusion: Each element was commonly detected in maternal blood and cord blood. The TTE of Hg was the highest.

[Preliminary efficacy analysis of Cheng's Giraffe reconstruction after proximal gastrectomy in adenocarcinoma of esophagogastric junction].

Objective: To investigate the safety and feasibility of proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction for the treatment of early Siewert II adenocarcinoma of esophagogastric junction (AEG). Methods: Indication of Cheng's Giraffe esophagogastric reconstruction: (1) Siewert II AEG or Siewert III AEG with diameter < 4 cm; (2) preoperative staging as cT1-2N0M0. A descriptive case series study was carried out. Clinical data of 34 patients with Siewert II AEG undergoing proximal partial gastrectomy and Cheng's Giraffe esophagogastric reconstruction at Department of Abdominal Surgery of Zhejiang Cancer Hospital and Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from February to July 2018 were retrospectively collected and analyzed, including 14 cases in IA stage, 11 cases in IIA stage and 8 cases in IIB stage. Brief procedure of Cheng's Giraffe esophagogastric reconstruction was as follows: Firstly, 12 cm long tubular stomach was formed by longitudinal incision 4 cm away from the great curvature of the stomach. Secondly, the gastric fundus and His angle were formed. Finally, the distance from His angle to esophagal-tubular gastric anastomosis should be more than 5 cm. The reflux disease questionare (RDQ) scores, radionuclide gastric emptying scintigraphy, and 24-hour multichannel intraluminal (MII)-pH monitoring technology were used to evaluate postoperative gastric emptying and gastroesophageal reflux. Result: All 34 patients successfully completed proximal partial gastrectomy with Cheng's Giraffe esophagogastric reconstruction, including 13 cases by open surgery and 21 cases by laparoscopic surgery. The operation time was (144.6±39.8) minutes, the blood loss during operation was (35.4±17.2) ml. No laparoscopic case was converted to open surgery and no postoperative complication was observed. The postoperative hospital stay was (8.4±2.5) days. The postoperative RDQ score was 4.4±3.1 one month after operation, and 3.3±2.5 six months after operation. Gastric-half emptying time was (67.0±21.5) minutes, and the residual ratio was (52.2±7.7)% in 1 hour, (36.4±3.1)% in 2 hours and (28.8±3.6)% in 3 hours at postoperative 1-month. The 24-hour MII-pH monitoring at postoperative 2-month revealed the frequency of acid reflux was (12.6±7.9) times, frequency of non-acid reflux was (19.6±9.7) times, DeMeester score was 5.8±2.9. Conclusion: Cheng's Giraffe esophagogastric reconstruction is safe and feasible in the treatment of Siewert type II AEG, and has good dynamic and anti-reflux effects.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

Identification of a novel biomarker for pyridoxine-dependent epilepsy: Implications for newborn screening.

Pyridoxine-dependent epilepsy (PDE) is often characterized as an early onset epileptic encephalopathy with dramatic clinical improvement following pyridoxine supplementation. Unfortunately, not all patients present with classic neonatal seizures or respond to an initial pyridoxine trial, which can result in the under diagnosis of this treatable disorder. Restriction of lysine intake and transport is associated with improved neurologic outcomes, although treatment should be started in the first year of life to be effective. Because of the documented diagnostic delay and benefit of early treatment, we aimed to develop a newborn screening method for PDE. Previous studies have demonstrated the accumulation of Δ1 -piperideine-6-carboxylate and α-aminoadipic semialdehyde in individuals with PDE, although these metabolites are unstable at room temperature (RT) limiting their utility for newborn screening. As a result, we sought to identify a biomarker that could be applied to current newborn screening paradigms. We identified a novel metabolite, 6-oxo-pipecolate (6-oxo-PIP), which accumulates in substantial amounts in blood, plasma, urine, and cerebral spinal fluid of individuals with PDE. Using a stable isotope-labeled internal standard, we developed a nonderivatized liquid chromatography tandem mass spectrometry-based method to quantify 6-oxo-PIP. This method replicates the analytical techniques used in many laboratories and could be used with few modifications in newborn screening programs. Furthermore, 6-oxo-PIP was measurable in urine for 4 months even when stored at RT. Herein, we report a novel biomarker for PDE that is stable at RT and can be quantified using current newborn screening techniques.

Effects of cottonseed meal on growth performance, small intestinal morphology, digestive enzyme activities, and serum biochemical parameters of geese.

Cottonseed meal (CSM), an oil industry by-product, is an attractive alternative protein source in poultry diets. To investigate the effects of CSM on growth performance, small intestinal morphology, digestive enzyme activities, and serum biochemical parameters of geese, a total of 300 healthy, 28-day-old, male Jiangnan geese were randomly divided into 5 treatments, with 6 pens of 10 geese each. Five isonitrogenous and isocaloric experimental diets were formulated to produce diets in which 0% (control), 25% (CSM25), 50% (CSM50), 75% (CSM75), and 100% (CSM100) of protein from soybean meal was replaced by CSM (corresponding to 0, 6.73, 13.46, 20.18, and 26.91% CSM in the feed, respectively). At 28, 42, and 70 d, BW and feed intake for each pen were measured. Blood, small intestine, and chyme samples were collected at 70 d. The results showed that dietary 13.46% CSM or more decreased BW at 42 d and ADG from 28 to 42 d but increased the feed/gain ratio (F/G) from 28 to 42 d (P < 0.05). From 42 to 70 d, geese in the CSM groups had higher ADFI and ADG than those of the control group (P < 0.05). Geese in the CSM75 and CSM100 groups had a higher ADG from 28 to 70 d and BW at 70 d and a lower F/G from 42 to 70 d than those of the control group (P < 0.05). Dietary 6.73% CSM also improved ADFI from 28 to 70 d (P < 0.05). Compared to the control, geese in the CSM groups had decreased pepsin and lipase activities, and those in the CSM25, CSM50, and CSM75 groups had increased villus height in the jejunum at 70 d (P < 0.05). All groups had similar concentrations of total protein, blood urea nitrogen, uric acid, cholesterol, triglyceride, calcium, and phosphorus in serum (P > 0.05). In conclusion, excessive use of CSM (>6.73%) decreased growth performance at an early age (28 to 42 d) in geese, whereas 6.73 to 26.91% CSM in feed improved growth performance from 28 to 70 d.

Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial.

NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable cancer of the esophagus or gastroesophageal junction. Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma, T1N1 or T2-3N0-1 and M0-M1a (AJCC 6th ed.), were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1-5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by esophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate in the primary tumor. Survival and recurrence patterns were evaluated as secondary endpoints. Between 2006 and 2013, 181 patients were enrolled in Sweden and Norway. All three chemotherapy cycles were delivered to 73% of the patients allocated to chemoradiotherapy and to 86% of the patients allocated to chemotherapy. 87% of those allocated to chemoradiotherapy received full dose radiotherapy. 87% in the chemoradiotherapy group and 86% in the chemotherapy group underwent tumor resection. Initial results showed that patients allocated to chemoradiotherapy more often responded with complete histopathological response in the primary tumor (28% vs. 9%). Treatment-related complications were similar between the groups although postoperative complications were more severe in the chemoradiotherapy group. This article reports the long-term results. Five-year progression-free survival was 38.9% (95% CI 28.9%-48.8%) in the chemoradiotherapy group versus 33.0% (95% CI 23.6%-42.7%) in the chemotherapy group, P = 0.82. Five-year overall survival was 42.2% (95% CI 31.9%-52.1%) versus 39.6% (95% CI 29.5%-49.4%), P = 0.60. There were no differences in recurrence patterns between the treatment groups. This is to our knowledge that the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed by esophageal resection in patients with cancer in the esophagus or gastroesophageal junction. Despite a higher tumor tissue response in those who received neoadjuvant chemoradiotherapy, no survival advantages were seen. Consequently, the results do not support unselected addition of radiotherapy to neoadjuvant chemotherapy as a standard of care in patients with resectable esophageal cancer.

Drug-loaded nanobubbles for ultrasound-mediated antitumor treatment.

Polylactic acid (PLA) bubbles that can act both as ultrasound contrast agents and drug carriers have the disadvantage of low encapsulation efficiency and do not allow effective extravasation into the tumor tissue. In this regard, PLA and lecithin are considered drug carriers. The present study used a modified ultrasonic double emulsion-solvent evaporation technology in order to prepare paclitaxel-loaded PLA-lecithin nanobubbles. X-ray diffraction analysis (XRD) was used to investigate the state of the drug in the bubbles, whereas the tumor weight and the inhibition rate of tumor bearing mice in the ultrasound-mediated function were further examined. The results indicated that the nanobubbles prepared with a mass ratio of PLA and lecithin at 50:250 were characterized as inner hollow. The size of these particles was approximately 615 nm, and the drug loading and encapsulation reached 8.34±0.67% and 91.42±5.48%, respectively. Paclitaxel was distributed in the shell of the bubbles in an amorphous state, and the in vitro drug release was characterized by sustained release, zero release and ultrasound mediated drug release. The injection of H22 hematoma-bearing mice with ultrasound-mediated drug-loaded PLA-lecithin nano-scaled bubbles could reduce the toxicity and increase the antitumor efficacy compared with paclitaxel.

Oral administration of short chain fatty acids could attenuate fat deposition of pigs.

Short chain fatty acids (SCFAs) are the main products of indigestible carbohydrates that are fermented by microbiota in the hindgut. This study was designed to investigate the effects of oral SCFAs administration on the lipid metabolism of weaned pigs. A total of 21 barrows were randomly allocated into three groups, including control group (orally infused with 200 mL physiological saline per day), low dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 20.04 mM, propionic acid 7.71 mM and butyric acid 4.89 mM per day), and high dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 40.08 mM, propionic acid 15.42 mM and butyric acid 9.78 mM per day). The results showed that the average daily feed intake of SCFAs groups were lower than that of control group (P<0.05). Oral administration of SCFAs decreased the concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol and insulin (P<0.05), and increased the leptin concentration in serum (P<0.05). The total fat, as well as TC and TG levels in liver, was decreased by oral SCFAs administration (P<0.05). In addition, SCFAs down-regulated the mRNA expressions of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (P<0.05), and enhanced the mRNA expression of carnitine palmitoyltransferase-1α (CPT-1α) in liver (P<0.05). SCFAs also decreased FAS, acetyl-CoA carboxylase (ACC) and peroxisome proliferator activated receptor σ mRNA expressions in longissimus dorsi (P<0.05). And in abdominal fat, SCFAs reduced FAS and ACC mRNA expressions (P<0.05), and increased CPT-1α mRNA expression (P<0.05). These results suggested that oral administration of SCFAs could attenuate fat deposition in weaned pigs via reducing lipogenesis and enhancing lipolysis of different tissues.