Objective:Biological markers of the ventrolateral orbitofrontal cortex(vlOFC)involved in pain regula-tion were screened.Methods:Chronic inflammatory pain was induced in male C57BL/6J mice by injection of complete Freund's adjuvant(CFA)into the left posterior plantar.Paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were detected to evalue hyperalgesia.Transcriptome sequencing was performed on fresh tissue from vlOFC of mice after behavioral tests.The differentially expressed genes(DEGs)were screened by bioinformatics method,and their biological functions and pathways were enriched.Results:Compared with the PBS group,the left hindpaw me-chanical pain threshold and the paw withdrawal latency caused by heat pain were significantly reduced in the CFA group(P＜0.001).The DEGs of vlOFC in the two groups were 497,of which 143 were up-regulated and 354 were down-reg-ulated.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGGs)analysis showed that:In chro-nic inflammatory pain model mice,DEGs of vlOFC were mainly manifested in biological processes such as organic cation transport,neurotransmitter transport,and regulation of cytoplasmic calcium ion concentration.It is related to G protein-coupled receptors(GPCRs),neuropeptides and ammonium transport.DEGs mainly focuses on neuroactive ligand-receptor interactions,cytokine-cytokine receptor interactions,and cAMP signaling pathways.Reactome functional en-richment analysis showed that the pathway with the highest number of DEGs enriched and the lowest P value-adjusted was GPCRs ligand binding.Conclusion:Ion transport,neurotransmitter transport and binding,and GPCRs-related ac-tivities in vlOFC are involved in the regulation of chronic inflammatory pain.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

Objective: To investigate the safety and feasibility of caudal-medial approach combined with "page-turning" middle lymphadenectomy in the laparoscopic right hemicolectomy. Methods: A descriptive cohort study was conducted. Clinical data of 35 patients who underwent laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy at Department of Gastrointestinal Surgery, Guangdong Hospital of Chinese Medicine from April 2018 to May 2020 were retrospectively analyzed. All operations were performed consecutively by the same surgeon. The caudal-medial approach was used to dissect the right Toldt's fascia and the anterior pancreaticoduodenal space in a caudal-to-cranial and medial-to-lateral manner guided by the duodenum. The "page-turning" middle lymphadenectomy was used to dissect the mesocolon along the superior mesenteric vein with ileocolic vein, Henle's trunk and pancreas exposed preferentially. Results: All the 35 patients completed the operation successfully, and there was no damage and bleeding of superior mesenteric vessels and their branches. The operative time was (186.9±46.2) minutes, and the blood loss was 50 (10-200) ml. The first time to flatus was (2.1±0.6) days, and the time to fluid intake was (2.5±0.8) days. The postoperative hospital stay was 6 (3-18) d. The overall morbidity of postoperative complication was 8.6% (3/35), including grade II in 1 cases (2.8%) and grade IIIa in 2 case (5.7%) according to the Clavien-Dindo grading standard. The total number of lymph node dissected was 30.2±5.6, and the positive lymph node was 0 (0-7). Tumor staging revealed 5 cases of stage I, 18 cases of stage II, 11 cases of stage III, and 1 case of stage IVA. In this study, the median follow-up time was 15 (4-29) months. One patient died due to cerebrovascular accident 12 months after surgery, and no tumor recurrence or metastasis was observed in all other patients. Conclusions: Laparoscopic radical right hemicolectomy using caudal-medial approach combined with "page-turning" middle lymphadenectomy is safe and feasible. The anterior pancreaticoduodenal space is preferentially mobilized, which reduces the difficulty of central vascular dissection.
Cohort Studies ; Colectomy ; Colonic Neoplasms/surgery* ; Humans ; Laparoscopy ; Lymph Node Excision ; Retrospective Studies

Objective:To investigate the risk factors for death in children with acute necrotizing encephalopathy (ANE) in pediatric intensive care unit (PICU).Methods:This was a multicenter retrospective study. Thirty-nine children with ANE were from PICUs in 4 centers from December 1, 2014 to December 1, 2020. The 4 participating centers were Beijing Children′s Hospital, Shengjing Hospital of China Medical University, Hebei Children′s Hospital, and Bao′an Maternity & Child Health Hospital. Patients were divided into survival and non-survival groups by the outcome at discharge, and the differences in clinical data between the two groups were compared. Risk factors for death in children with ANE and the odds ratios ( OR) were analyzed by univariable Logistic regression. Results:Thirty-nine children with ANE were included. There were 18 males and 21 females. The median onset age was 30 months. The mortality at discharge was 41% (16/39). The onset age of most patients (74%, 29/39) was younger than 4 years old. Influenza virus was the most common precursor infection (80%, 20/25). Patients with shock at PICU admission were more common in the non-survival group (12/16 vs. 17% (4/23), P=0.001). Glasgow coma score (GCS) at PICU admission was significantly lower in the non-survival group than survival group (3 (3, 6) vs. 6 (5, 7), Z=-2.598, P=0.009). The optimal cut-off value was 4. The proportion of patients with GCS ≤ 4 at PICU admission was higher in the non-survival group (10/16 vs. 22% (5/23), P=0.018). ANE severity score (ANE-SS) at PICU admission was significantly higher in the non-survival group (5 (2, 6) vs. 2 (1, 4), Z=-2.436, P=0.015). The proportion of patients with high risk ANE-SS was higher in non-survival group than the survival group (9/16 vs. 22% (5/23), P=0.043). The proportion of application of high-dose methylprednisolone (20 mg/(kg·d)) was significantly higher in survival group than non-survival group (43% (10/23) vs. 1/13, P=0.031). Univariable Logistic regression indicated that risk factors for death in children with ANE were shock ( OR=14.250, 95% CI 2.985-68.018, P=0.001), GCS≤4 ( OR=6.000, 95% CI 1.456-24.733, P=0.013) and high risk ANE-SS ( OR=4.629, 95% CI 1.142-18.752, P=0.032) at PICU admission. Conclusions:ANE usually occurs in children under 4 years old after influenza infection. Shock, GCS≤4 and high risk ANE-SS at PICU admission were risk factors for death in children with ANE. High-dose methylprednisolone may improve the prognosis of children with ANE.

Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for treatment of duodenal lesions.Methods:A retrospective analysis was performed on the data of 45 patients with 46 duodenal lesions who underwent ESD at the Second Xiangya Hospital of Central South University from January 2011 to May 2019. The lesion features, en bloc resection rate, complete resection rate, complications, postoperative pathology and recurrence were assessed.Results:Among the 45 patients, 20 were males and 25 were females, with age of 52.0±11.8 years. Of the 46 lesions, 31 (67.4%) were located in the duodenal bulb, 12 (26.1%) in the descending part, and 3 (6.5%) at the junction of bulb and descending part. The diameter of the lesions was 2.4±1.9 cm. There were 14 (30.4%) lesions originated from mucosal layer, 29 (63.1%) from submucosal layer, and 3 (6.5%) from muscularis propria.Postoperative pathology showed 11 (23.9%) cases of Brunner gland tumors, 9 (19.6%) neuroendocrine tumors, 5 (10.9%) ectopic pancreas, 5 (10.9%) lipomas, and 16 (34.8%) other pathological patterns. All 45 patients with 46 lesions underwent ESD successfully, and the en bloc resection rate was 100.0% (46/46), complete resection rate was 91.3% (42/46). Intraoperative bleeding occurred in 1 case (2.2%), which was successfully treated by endoscopy. One (2.2%) delayed perforation occurred and was treated by surgical intervention. Electrocoagulation syndrome occurred in 1 case (2.2%), which was relieved after conservative medical therapy. Two cases received further surgery after ESD. The mean hospital stay was 6.2 days (ranged 2-21 days) and no death occurred. Forty-one cases were followed up for 1-78 months, with mean time of 30 months. During the follow-up period, local recurrence occurred in 1 patient (2.4%).Conclusion:ESD is an effective and safe treatment for duodenal lesions and has a good clinical practical value.

Objective: To investigate the effect of intracoronary administration of nicorandil prior to primary percutaneous coronary intervention (PPCI) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospective controlled randomized trial. Patients were assigned into three groups with random number table: the nicorandil group (patients received intracoronary administration of 6 mg nicorandil after guide wire or balloon successfully crossed the target lesion, n=53), the nitroglycerin group (patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion, n=52) and the control group(patients received routine treatment, n=53). The primary outcomes were myocardial perfusion, including the levels of corrected TIMI frame count (cTFC), and the incidence of no reflow or slow flow after PPCI. The secondary outcomes included the incidence of major adverse cardiovascular events (MACE) during hospitalization (all-cause death, reperfusion arrhythmia within 2 hours after PPCI, angina within 24 hours after PPCI, new heart failure or worsening cardiac function, and repeat revascularization) and within 3 months of follow-up (all-cause death, nonfatal myocardial infarction, repeat revascularization, post-infarction angina, and re-hospitalization for congestive heart failure). Results: The age of enrolled patients was (62.9±11.3) years old, and 130 cases (82.3%) of them were male. The median time of symptom-onset to balloon was 4.50 (3.20, 6.43) hours. There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames, (24.74±8.66)frames, and(27.06±10.40)frames), incidence of no reflow or slow flow after PPCI(5.7%(3/53), 13.5%(7/52), and 22.6%(12/53)), ST-segment resolution at 2 hours after procedure(90.6%(48/53), 84.6%(44/52), and 74.5%(38/53)), and reperfusion arrhythmia at 2 hours after procedure(15.1%(8/53), 36.6%(19/52), and 34.0%(18/53)) among the 3 groups(P<0.01 or 0.05). In the multivariate logistic regression models, intracoronary administration of nicorandil could lower the cTFC level (OR=0.17, 95%CI 0.10-0.41, P=0.001), acted as a protecting factor on lowering the incidence of no reflow or slow flow (OR=0.13, 95%CI 0.02-0.96, P=0.045) and reperfusion arrhythmia (OR=0.26, 95%CI 0.09-0.74, P=0.012), as well as facilitating the ST-segment resolution at 2 hours after procedure (OR=4.62, 95%CI 1.14-18.82, P=0.033). However, observed parameters were similar between intracoronary administration of nitroglycerin group compared with control group (all P>0.05). MACE within 3 months of follow-up were similar among the 3 groups(all P>0.05). Conclusion Intracoronary administration of nicorandil prior to balloon dilation can significantly improve the myocardial perfusion and reduce the occurrence of reperfusion arrhythmia during PPCI for STEMI, but does not affect the short-term prognosis in STEMI patients.

Objective To compared analgesic effect of sufentanil and fentanyl in surgery patients during mechanical ventilation, and to explore the rational dosage of analgesic and sedative drugs. Methods A prospective randomized controlled trial was conducted. 600 postoperative critically ill patients underwent mechanical ventilation for 12-72 hours admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from April 2013 to March 2015 were enrolled. They were randomly divided into two groups, sufentanil and fentanyl was used for analgesia respectively, and 300 patients in each group. The initiate dosage of sufentanil and fentanil was 5 μg/h and 50 μg/h, and the dosage was adjusted. A postoperative pain score (Prince-Henry score) of 0-1, and Richmond agitation-sedation scale (RASS) score -1-0 were targeted. 1 mg/kg of propofol was used if patient could not fall in sleep or felt anxious after loading dose of sufentanil (5 μg) or fentanil (50 μg) for 5 minutes. The use of analgesic drugs, the proportion and dosage of propofol was observed in the two groups, and adverse reactions were recorded. Results The mean dose of sufentanil for analgesia was (0.07±0.02) μg·kg-1·h-1, and the mean dose of fentanyl was (0.67±0.12) μg·kg-1·h-1. The patients in the two groups received propofol 40 to 60 mg/h in night, and the use proportion of propofol in sufentanil group was slightly less than that in fentanyl group (25.7% vs. 28.3%), but the difference was not statistically significant (P > 0.05). It was found by subgroup age analysis that, the mean analgesic dose of sufentanil or fentanyl in patients over 80 years old was lower than that in 70-79 years, 60-69 years and < 60 years groups but without statistical significance. There were 11 cases (3.7%) and 21 cases (7.0%) patients suffered from respiratory depression in sufentanil group and fentanyl group, respectively, without statistical significance (P = 0.069). The hemodynamics of patients in two groups was stable during analgesia, and no accidental extubation due to restlessness was found. Conclusions A smaller dose of sufentanil for postoperative patients underwent mechanical ventilation with satisfactory analgesia was (0.07±0.02) μg·kg-1·h-1, but need to be added with 40-60 mg/h and a small dose of propofol to improve anxiety and sleep. The proportion of patients needing propofol addition was slightly lower than that of fentanyl.

Objective To assess and compare the roles of plasma concentrations of neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C for early diagnosis and treatment of septic acute kidney injury (AKI) in adult Surgical critically ill patient . Methods One hundred patients were divided into two groups ,the group of 63 cases of AKI and AKI group of 37 cases ,plasma NGAL and Cystatin C level of the 2 groups were determined by the method of enzyme‐linked immunosorbent (ELISA) ,latex en‐hanced immune turbidimetry (PETIA) respectively on arrival in the surgical intensive care unit(SICU) (T0 ) and 24 h after arrival in SICU(T1 ) .Results Compared with patients in non AKI group ,both plasma NGAL and Cystatin C level of patients in AKI group on T0 and T1 increased significantly ,the difference between the two groups had significant statistical difference (P<0 .01);Although ,plasma NGAL on T1 performed less well (AUC=0 .69) ,with a threshold value of 92 ng/mL(70 .3% sensitivity ,57%specificity) .Plasma NGAL showed significant discrimination for AKI diagnosis (AUC=0 .85) with a threshold value of 65 .95 ng/mL(81 .8% sensitivity ,76 .2% specificity) on T0 .Both plasma Cystatin C on T0 and T1 worked well for the diagnosis of AKI (AUC=0 .90 ,0 .88 ,thresholds 1 .49 and 1 .47 mg/L ,respectively) ,with diagnostic sensitivity of 89 .2% ,82 .5% respectively ,speci‐ficity of 83 .8% ,76 .2% respectively .Conclusion Plasma NGAL and Cystatin C are useful markers in predicting AKI in surgical critically ill patients ,the early diagnosis value of plasma Cystatin C for AKI is better than plasma NGAL on arrival in the surgical intensive care unit .

Objective To screen for biomarkers in urine from patients with steroid-resistant nephrotic syndrome (SRNS) using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) Proteinchip technology. Methods Urine samples from 9 SRNS patients, 32 steroid-sensitive nephrotie syndrome (SSNS) patients and 45 normal controls were analyzed using UA gold chip. Proteomic spectra were generated by mass spectrometry. Results Four differentially expressed biomarkers were identified with relative molecular weight of 6 703, 7 212, 11 820, 14 356. It was found that these protein peaks with relative molecular weigh of 7 212, 11 820, 14 356 were highly expressed in SRNS and 6 703 were lowly expressed in SRNS. The diagnostic cast that is constructed with these four protein to differentiate SRNS from SSNS with sensitivity of 88.89% and specificity of 93.75%. Conclusions SELDI-TOF-MS Proteinchip technology is a non-invasive, quick, easy, and convenient, and high-throughput analyzing method capable of screening several biomarkers from the urines of SRNS patients and has better clinical value.

AIM: To explore the histocompatibility of pinealocyte microencapsules in vivo. METHODS: The pineal glands of neonatal rats were removed under operating microscope and pinealocytes were isolated through collagenase and trypsin digestion. Pinealocytes were cultured for one week in vitro and collected immediately after digesting was encapsulated in APA microencapsules. The cells and empty capsules were transplanted into abdominal cavity or intermuscular space respectively and retrieved at the 15th or 30th day after operation. Morphological observation, HE staining, cell counting, and HPLC technique were used to analyze the shape, proliferation and function, the degree of inflammation fibrosis of retrieved microencapsules. RESULTS: The retrieve rate of cell capsule from abdominal cavity was about 85 % . The retrieved capsules had integrated profile mostly although some were damaged. The amount of macrophages attached to capsule wall and the thickness of wall increased gradually following the period of transplantation. However, the retrieve rate, wall thickness had no difference between retrieved cell and empty capsules at the same time. Secretion ability of pinealocytes in capsule retrieved at 15th day after operation decreased rapidly and those retrieved at 30th day after operation lossed secretion function. CONCLUSION: APA microencapsules had histocompatibility relatively in vivo and protected pinealocytes in capsule from immunologic rejection of the host. The survival time was about 20 days. During this period cells in capsule maintained activity and MT secretion ability.