Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse. AIM: To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up. METHODS: This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS). RESULTS: EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003). CONCLUSION: In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.

Temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) may present as comorbid conditions, but treatment options are ineffective. The purpose of this study was to investigate whether valproate (VPA) attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress, which represents a model of pain associated with TMD and FMS comorbidity, and to explore the potential mechanisms. The results showed that VPA inhibited somatic hyperalgesia induced by orofacial inflammation combined with stress, and down-regulated the interleukin-6 (IL-6) expression in the L4-L5 spinal dorsal horn of female rats. The anti-nociceptive effect of VPA was blocked by single or 5 consecutive day intrathecal administration of recombinant rat IL-6. Orofacial inflammation combined with stress up-regulated the ratio of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) to STAT1 (p-STAT1/STAT1) in the spinal cord. VPA did not affect the STAT1 expression, while it down-regulated the ratio of p-STAT1/STAT1. The expression of STAT3 and the ratio of p-STAT3/STAT3 were not affected by orofacial inflammation combined with stress and VPA treatment. Intrathecal administration of exogenous IL-6 up-regulated the ratio of p-STAT1/STAT1. These data indicate that VPA attenuated somatic hyperalgesia induced by orofacial inflammation combined with stress via inhibiting spinal IL-6 in female rats, and the mechanism may involve the alteration of activation status of spinal STAT1. Thus, VPA may be a new candidate analgesic that targets IL-6 and STAT1 for the treatment of pain associated with the comorbidity of TMD and FMS.

Design, Synthesis, Insecticidal Activity, and SAR of Aryl Isoxazoline Derivatives Containing Pyrazole-5-carboxamide Motif.

It is important to develop new insecticides with a new mode of action because of increasing pesticide resistance. In this study, a series of novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate and no activity against Aphis craccivora and Tetranychus cinnabarinus. Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had the best insecticidal activity against M. separate, which is comparable with the positive control fluralaner. The molecular docking results of compound IA-8 and fluralaner with the GABA model demonstrated the same docking mode between compound IA-8 and positive control fluralaner in the active site of GABA. Molecular structure comparisons and ADMET analysis can potentially be used to design more active compounds. The structure-activity relationships are also discussed. This work provided an excellent insecticide for further optimization.

Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS: A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS: The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS: Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.

[Clinical Practice of Multiple Disciplinary Team Care Model Following the Concept of Palliative Care for Advanced Head and Neck Cancer:Report of One Case].

We provided the palliative care of a multiple disciplinary team care mode to a patient diagnosed with advanced head and neck cancer and her caregivers.People-centered integrated health services were provided according to the specific needs and preferences of individuals.The team-based palliative care relieved the suffering and improved the quality of life of the patient and that of her family who were facing challenges associated with life-threatening illness.

Design, Synthesis, and Pesticidal Activities of Pyrimidin-4-amine Derivatives Bearing a 5-(Trifluoromethyl)-1,2,4-oxadiazole Moiety.

It is important to discover new pesticides with new modes of action because of the increasing evolution of pesticide resistance. In this study, a series of novel pyrimidin-4-amine derivatives containing a 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 29 compounds synthesized possessed excellent insecticidal activity against Mythimna separata, Aphis medicagini, and Tetranychus cinnabarinus and fungicidal activity against Pseudoperonospora cubensis. Among these pyrimidin-4-amine compounds, 5-chloro-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U7) and 5-bromo-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl) pyrimidin-4-amine(U8) had broad-spectrum insecticidal and fungicidal activity. The LC50 values were 3.57 ± 0.42, 4.22 ± 0.47, and 3.14 ± 0.73 mg/L for U7, U8, and flufenerim against M. separata, respectively. The EC50 values were 24.94 ± 2.13, 30.79 ± 2.21, and 3.18 ± 0.21 mg/L for U7, U8, and azoxystrobin against P. cubensis, respectively. The AChE enzymatic activity testing revealed that the enzyme activities of compounds U7, U8, and flufenerim are 0.215, 0.184, and 0.184 U/mg prot, respectively. The molecular docking results of compounds U7, U8, and flufenerim with the AChE model demonstrated the opposite docking mode between compound U7 or U8 and positive control flufenerim in the active site of AChE. The structure-activity relationships are also discussed. This work provided excellent pesticide for further optimization. Density functional theory analysis can potentially be used to design more active compounds.

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been a good target for herbicide discovery. In order to discover novel HPPD herbicides, a series of pyrazole aromatic ketone analogs were designed and synthesized. RESULTS: The 25 pyrazole aromatic ketone analogs synthesized were tested for herbicidal activity and compounds A1, A3, A4, A17, A20 and A25 displayed excellent herbicidal activity against Chenopodium serotinum, Stellaria media and Brassica juncea at 37.5 g ha-1 . In addition, compounds A1, A5, A9, A10, A16, A17, A20 and A25 exhibited good crop selectivity for wheat, maize and rice at 150 g ha-1 . Inhibition activities against AtHPPD proved the compounds were HPPD inhibitors. The structure-activity relationship of these pyrazole aromatic ketone analogs was studied using molecular docking. CONCLUSION: These pyrazole aromatic ketone derivatives could be used as lead structures for development of HPPD herbicides against dicotyledonous weeds with further structure modification. © 2019 Society of Chemical Industry.

Low-Intensity Pulsed Ultrasound Treatment Accelerates Angiogenesis by Activating YAP/TAZ in Human Umbilical Vein Endothelial Cells.

As a non-invasive method, low-intensity pulsed ultrasound (LIPUS) can accelerate fracture healing. The mechanisms responsible for the enhanced fracture healing need to be studied further. Activation of YAP/TAZ, key mediators of the Hippo signaling pathway, could promote angiogenesis and vascular remodeling. The purpose of this study was to determine whether LIPUS treatment can activate YAP/TAZ. Human umbilical vein endothelial cells (HUVEC) were used. After LIPUS treatment, Western blot and immunofluorescence staining were used for YAP/TAZ activation. Small interfering RNA (siRNA) of YAP and short hairpin LATS1/2 (shLATS1/2) were used to check whether there is cross-talk with the Hippo pathway. The phosphorylated YAP (p-127 and p-397) protein increased more than 3-fold 0.5 h after LIPUS treatment (p < 0.05). TAZ protein increased 3.0-, 2.0- and 1.5-fold 0.5, 6 and 12 h after LIPUS treatment. We found that LIPUS treatment activates YAP/TAZ, which is translocated into the cell nucleus to activate target genes. This process can be inactivated by siYAP and activated by shLATS1/2. The cross-talk with the Hippo pathway can initiate angiogenesis so as to accelerate fracture healing by LIPUS.

Synthesis and in vivo fungicidal activity of some new quinoline derivatives against rice blast.

BACKGROUND: Quinoline derivatives possess excellent fungicidal activity against rice blast, but quinoline derivatives have not been thoroughly explored as fungicides. In the process of designing new fungicides, the 1,1,1,2,3,3,3-heptafluoropropan-2-yl group was introduced in order to find new structure quinoline derivatives. RESULTS: Seventeen new quinoline derivatives containing 1,1,1,2,3,3,3-heptafluoropropan-2-yl moiety were designed and synthesised. In vivo fungicidal activities of these compounds were tested against rice blast. Some of the compounds provided effective control at 100 mg L-1 , and a few compounds were effective at 10 mg L-1 . Furthermore, a density functional theory study established the structure-activity relationships of the synthesised compounds. CONCLUSION: Quinoline derivatives, especially benzyl (2,3,8-trimethyl-6-(perfluoropropan-2-yl)quinolin-4-yl) carbonate, which possess good control effective against rice blast and cucumber powdery mildew, may become new lead compounds for the development of fungicides with further structure modification. © 2017 Society of Chemical Industry.

Synthesis, nematocidal activity and SAR study of novel difluoromethylpyrazole carboxamide derivatives containing flexible alkyl chain moieties.

A series of novel difluoromethylpyrazole carboxamides derivatives were synthesized by introduction of flexible alkyl chain. Nematicidal bioassay results showed that some of them exhibited good control efficacy against M. incognita, which indicated that these difluoromethylpyrazole carboxamides derivatives might be potential novel lead compounds for discovery new nematicides. The nematicidal activity was affected by the substituted position in the molecule, especially the substitution group on the alkyl chain. It was found that the compound 6-9 and 6-23 possess about 50% inhibition effect against M. incognita even at 5.0 and 1.0 mg L-1. Meanwhile, greenhouse field trial showed the nematicidal activity of compound 6-9 is a litter weaker than that of Abamectin. The mammalian toxicology results indicated that compound 6-9 was a low-toxicity and low-sensitive compound. In conclusion compound 6-9 is a potential candidate for further development. In addition, the molecular docking simulations revealed that compounds 6 with a flexible NHCOO show its binding affinities for the acetylcholine receptor (AChR), which may provide useful information for further design novel nematicides.

Synthesis, nematocidal activity and docking study of novel chiral 1-(3-chloropyridin-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives.

A series of novel chiral fluorinated pyrazole carboxamides derivatives were designed and synthesized. All these title compounds were confirmed by NMR and MS. The primarily nematocidal activity results indicated that some of them exhibited good control efficacy against the tomato root-knot nematode disease caused by Meloidogyne incognita. The docking results indicated that compound 5n interact with amino acid residue Tyr 121, Trp 279 of AchE via hydrogen bond.

Clinicopathological features of primary gastric neuroendocrine neoplasms: A single-center analysis.

OBJECTIVE: To assess the clinical characteristics, diagnosis and therapeutic modalities for gastric neuroendocrine neoplasms (GNENs) among the Chinese population in a single institution. METHODS: A total of 57 patients with histologically confirmed GNENs, who were diagnosed between 1995 and 2015 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinical, imaging and histopathologic characteristics as well as the treatments of GNENs were collected and analyzed. RESULTS: Patients with GNENs mostly presented with non-specific symptoms. Gastric body was the most common site of involvement. The choice of imaging modality, such as endoscopy and computed tomography depended on the tumor subtype. Chromogranin A (CgA) and synaptophysin were indispensable immunohistochemical markers for diagnosis. Significant inter-group differences in the positivity rate of CD56 were observed among the three grades (G1, G2 and G3). Therapeutic modalities included endoscopic intervention, surgical resection and pharmacotherapy, which were largely guided by the tumor subtype and the presence or absence of distant metastasis or tumor recurrence. CONCLUSIONS: Routine endoscopic examination is recommended for the early diagnosis of GNENs. Histopathological examination can make the definite diagnosis of GNENs and clarify the nature of gastric polyps. A multidisciplinary approach is important in the management of patients with GNENs.

Internal hemipelvectomy with reconstruction for primary pelvic neoplasm: a systematic review.

BACKGROUND: Hemipelvectomy is a major operation with significant risks including infection, prosthesis failure and fracture. This systematic review was designed to review the functional outcomes, oncologic outcomes and complications in patients who received internal hemipelvectomy and pelvic reconstruction for primary pelvic tumour. METHODS: Searches on MEDLINE, the Cochrane Library, Embase and Google Scholar were performed to locate studies involving patients receiving internal hemipelvectomy and pelvic reconstruction using a prosthesis, implant or bone graft. All studies were either prospective or retrospective observational studies published in English. RESULTS: This systematic review included 12 studies from 1990 to 2011 involving 217 patients from 5 to 77 years of age who had received follow-up for a period from 3 weeks to 15 years. Among the 12 studies, the mortality rate, disease-free rate and incidence of local recurrence were 10-69.2, 23.1-90.0 and 9.1-41.7%, respectively. The post-operative Musculoskeletal Tumor Society (MSTS) functional score ranged from 50 to 70 in the more recent studies. Compared with prostheses and other implants, patients who received allografts had the highest post-operative function, as shown by their MSTS scores, but also had a greater incidence of post-operative infection. On the other hand, the prosthesis group was associated with the highest percentage of fracture and dislocations, as well as other significant complications. CONCLUSION: This comprehensive review provided informative details regarding the goals, outcomes and complications associated with this procedure and underscored the need for further investigation into the various surgical approaches currently available.

Acute clenbuterol induces hypotension, atrioventricular block and cardiac asystole in the rabbit.

Clenbuterol is a long-lasting ß-adrenoceptor (ß-AR) agonist and was once medicated as a bronchial dilatator, and is also used by body-building enthusiasts and athletes and in livestock breeding because of its anabolic effect on skeletal muscles and ability to promote lipolysis. Though prohibited from pharmacological uses, clenbuterol intoxication cases are frequently reported, and most of the cardiac symptoms are tachyarrhythmia. Here, we reported a different cardiovascular toxic response to clenbuterol. Using a rabbit model, we tested the dose-response pattern of the cardiovascular system to intravenous administration of clenbuterol. Routine arterial blood pressure (BP) and surface electrocardiogram (ECG) were monitored. We observed that clenbuterol at a lower dose (0.4 mg/kg, n = 3) did not significantly affect the ECG, but decreased the mean BP roughly by 15-18 mmHg. At a medial dose (3.6 mg/kg, n = 3), clenbuterol induced significant hypotension (mean BP dropped by about 30 mmHg), first-degree atrioventricular (AV) block and intermittent ectopic activities with a relatively slow rate. The hypotension and arrhythmia recovered slowly, and animals did not die. Higher-dose clenbuterol (10 mg/kg, n = 6) induced severe hypotension, second-degree AV block (Mobitz type II), 2:1 ventricular capture and progressive prolongations of P-R intervals and QRS duration, and the animals soon died of cardiac asystole. Different from other reports, we had not observed lethal tachyarrhythmia in all experiments except for the slight heart rate acceleration during the recovery stage of medial clenbuterol dosage. These results indicate that acute intravenous administration of clenbuterol has serious, dose-dependent cardiovascular toxicities and is even life threatening.