Successful outcome of neoadjuvant PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy for potentially unresectable esophagogastric junctional squamous cell carcinoma: a case report.

Background: Esophagogastric junctional squamous cell carcinoma (EJSCC) is quite rare among all gastric carcinoma, its potential resectable rate is low due to the late diagnosis. Recently, programmed death-1 (PD-1) blockade combined with anti-angiogenesis have gained accumulated clinical experiences in treating solid tumors. This is the first reported case with EJSCC who achieved a partial remission (PR) after neoadjuvant PD-1 blockade, vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor plus chemotherapy. Case Description: We present an EJSCC case treated with novel neoadjuvant treatment. A 64-year-old Chinese male had the symptom of chocking for 3 months. An enhanced abdominal computed tomography (CT) scan found a locally advanced, potentially unresectable esophagogastric junctional (EGJ) mass, and the preoperative immunohistochemistry result exhibited a highly positive programmed death-ligand 1 (PD-L1) expression, so the patient received three courses of neoadjuvant camrelizumab (200 mg/day), apatinib (750 mg/day), albumin paclitaxel (200 mg/day) and nedaplatin (70 mg/day), he was well tolerant without any adverse event, and he underwent radical surgery after a significant tumor shrinkage. The patient recovered well after surgery, and he has received four cycles of camrelizumab and apatinib as maintenance treatment. There is no recurrence 7 months after surgery. Conclusions: PD-1 blockade, VEGFR-2 inhibitor plus chemotherapy is effective and safe for the patient with EJSCC.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway.

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway. Methods: Sprague-Dawley rats (male, 250-280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions. Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05). Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.

Structural variation of the complete chloroplast genome and plastid phylogenomics of the genus Asteropyrum (Ranunculaceae).

Two complete chloroplast genome sequences of Asteropyrum, as well as those of 25 other species from Ranunculaceae, were assembled using both Illumina and Sanger sequencing methods to address the structural variation of the cp genome and the controversial systematic position of the genus. Synteny and plastome structure were compared across the family. The cp genomes of the only two subspecies of Asteropyrum were found to be differentiated with marked sequence variation and different inverted repeat-single copy (IR-SC) borders. The plastomes of both subspecies contains 112 genes. However, the IR region of subspecies peltatum carries 27 genes, whereas that of subspecies cavaleriei has only 25 genes. Gene inversions, transpositions, and IR expansion-contraction were very commonly detected in Ranunculaceae. The plastome of Asteropyrum has the longest IR regions in the family, but has no gene inversions or transpositions. Non-coding regions of the cp genome were not ideal markers for inferring the generic relationships of the family, but they may be applied to interpret species relationship within the genus. Plastid phylogenomic analysis using complete cp genome with Bayesian method and partitioned modeling obtained a fully resolved phylogenetic framework for Ranunculaceae. Asteropyrum was detected to be sister to Caltha, and diverged early from subfamily Ranunculoideae.

Modulation of transcription of genes related to the hypothalamic-pituitary-gonadal and the hypothalamic-pituitary-adrenal axes in zebrafish (Danio rerio) embryos/larvae by androstenedione.

This study aimed to determine the effects of Androstenodione (AED) on the transcriptional expression of genes involved in the hypothalamic-pituitary-gonadal (HPG) and the hypothalamic-pituitary-adrenal (HPA) axes in the zebrafish embryos/larvae. Zebrafish embryos were exposed to 0, 4.0, 45.0, 487.0, and 980.0 ng/L of AED from the day of fertilization to 144 h post fertilization (hpf), during which the transcriptional profiles of key genes related to the HPG and HPA axes were examined daily using quantitative real-time PCR. The AED exposure significantly up-regulated several receptor signaling pathways and the key genes involved in various steps of the steroidogenic pathways were also affected. In addition, the AED exposure could significantly modulate the transcriptional profiles of the other target genes related to hypothalamic and pituitary hormones. The findings of this study suggest that AED, at environmentally relevant concentrations, affects the adrenal endocrine systems and the reproduction of zebrafish by interrupting the HPG and HPA axes.

Meta-analysis of hand-sewn versus mechanical gastrojejunal anastomosis during laparoscopic Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most performed bariatric procedures in treating morbid obesity. There is no consensus on which technique used for gastrojejunal anastomosis is optimal. The meta-analysis aimed to solve the issue by comparing hand-sewn with mechanical gastrojejunostomy during LRYGB for morbid obesity. METHODS: PubMed, Embase, Cochrane Library, Scopus, Google Scholar and Research Gate were searched (from inception to April 2016). Primary outcome was operation time. Secondary outcomes were postoperative complications (anastomotic leak, stricture, bleeding, marginal ulcer and wound infection), percent excess weight loss during one-year follow-up, reoperation, and postoperative hospital stay. Odds ratios (OR) were calculated for dichotomous outcomes and mean differences (MD) for continuous outcomes. RESULTS: Twelve trials were included comprising 13,626 patients (3309 hand-sewn vs. 6791 circular vs. 3526 linear). There was no difference in operation time when hand-sewn anastomosis was compared with mechanical gastrojejunostomy (MD, -6.00; 95% confidence interval (CI), -34.85 to 22.85; P = 0.68), circular stapled anastomosis (MD, -5.24; 95% CI, -32.71 to 22.24; P = 0.71) or linear stapled anastomosis (MD, - 3.75; 95% CI, -64.81 to 57.31; P = 0.90). Hand-sewn anastomosis had significantly lower incidence rate of postoperative bleeding (OR, 0.48; 95% CI, 0.31-0.74; P = 0.001) and wound infection (OR, 0.19; 95% CI, 0.08-0.45; P = 0.0002) than circular stapled anastomosis; there were no significant differences in the other secondary outcome. And there were no significant differences in all the comparable outcomes between hand-sewn anastomosis and linear stapled anastomosis. CONCLUSIONS: This meta-analysis revealed no significant differences between mechanical and hand-sewn anastomosis except for greater incidence rates of postoperative bleeding and wound infection with the use of circular staplers. Besides, more trials with adequate power are required and a cost analysis also worth trying. REGISTRATION NO. IN PROSPERO: CRD42015020025.