Objective To analyze the typical biomarker of cancer-related fibroblasts-fibroblast activation protein-α(FAP)expression in tumor tissue and perinephric adipose tissue and its clinical value in risk stratification of clear cell renal cell carcinoma(ccRCC).Methods A retrospective cross-sectional study was conducted on ccRCC patients who underwent nephrectomy in Dongfeng General Hospital of Sinopharm Affiliated to Hubei Medical College from June 2018 to September 2022.The expression of FAP in ccRCC renal tumor tissue(n=114),non-neoplastic renal cortex tissue(n=68)and perirenal adipose tissue(n=60)was detected by immunohistochemical staining,and immunohistochemical images were quantitatively analyzed.The benign adipose tissue around the kidneys from 19 patients with benign kidney disease were collected as a control group,and also detect FAP expression.Receiver operating characteristic(ROC)curves was used to analyze the ability of FAP expression in perirenal adipose tissue to diagnose ccRCC and predict distant metastasis.Results Compared with matched non-neoplastic renal tissues,the expression of FAP in ccRCC was not up-regulated.The receiver operating characteristic(ROC)curve analysis showed that the percentage of FAP positive staining in ccRCC tissue had good tumor clinical stage,tumor size and distant metastasis potential(P＜0.001),and the area under the curve(AUC)were 0.90(95％CI:0.81-0.98),0.79(95％CI:0.66-0.92)and 0.86(95％CI:0.74-0.99),respectively.The percentage of FAP positive staining in perinephric adipose tissue of ccRCC can predict distant metastasis,and the AUC is 0.91(95％CI:0.84～0.97).The staining intensity of FAP expression in perinephric adipose tissue of ccrcc(191.77±3.14 vs.188.90±2.89,P＜0.001)was slightly higher than that of benign renal disease,and the staining intensity of FAP in perinephric adipose tissue had a certain distinguishing value for benign and malignant renal tumors,with AUC of 0.68(95％CI:0.60～0.77).Conclusion FAP in tumor and perinephric adipose tissue is expected to be one of the effective indicators of ccrcc risk stratification.

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.

ObjectiveFocused on the laboratory animal domestication and breeding of domestic cats, to explore the feeding management methods and breeding techniques of experimental cats. MethodsSeven Chinese garden cats from three litters were introduced from the rural suburbs of Guangzhou, and a breeding seed colony was established. The cats were domesticated in captivity, bred, closed breeding and transmission according to the feeding and management methods of laboratory animal. The population reproduction, the number of pregnancies per year, the litter season, the birth and weaning quality of the cats, and the survival rate of weaning were statistically collected. ResultsThe young breeding cats were able to adapt to the cage feeding management. In the transmission breeding and the expanded breeding colony, the number of female cats pregnant with one, two or three litters a year accounted for 63.2%, 26.3% and 10.5%, respectively. The proportions of litters born from the 1st to the 4th quarters were 20.7%, 20.7%, 27.6%, and 31.0%. A total of 29 pregnancies and 101 kittens were got from 19 female cats, with an average of (3.5±1.33) kittens per litter. The birth weights of female and male cats were (89.31±13.69) g and (93.47±15.12) g, respectively. Sixty-seven kittens survived from weaning. The average survival rate was 60.86%, and the weaning weights of female and male cats were (361.62±82.77) g and (376.0±91.71) g, respectively. ConclusionDomestic Chinese garden cats can adapt to laboratory animal feeding and breeding rules, and have strong fertility. They can normally pregnant and breeding throughout the year. The kittens grow to 5-6 months of age can meet the weight requirements for the examination of pharmaceutical hypotensive substances, and can be used as experimental cats for pharmaceutical examination with clear origin.

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 observe the efficacy and safety of olaparib combined with bevacizumab in patients with recurrent platinum-sensitive ovarian cancer, and the effect on serum levels of human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) and circulating tumor cells (CTCs).Methods:A total of 96 patients with recurrent platinum-sensitive ovarian cancer admitted to Dongfeng Hospital Affiliated to Hubei Medical College from June 2018 to June 2019 were selected and divided into control group ( n=48) and study group ( n=48) according to the random number table method. The control group was given doxorubicin liposomes combined with carboplatin chemotherapy for 6 cycles, and the study group was given olaparib combined with bevacizumab, continuous olaparib, and bevacizumab for 6 cycles. The median progression-free survival (PFS), the objective effective rate (ORR), disease control rate (DCR) of the two groups were evaluated, the changes of serum HE4, CA125 and CTCs levels of the two groups after treatment were compared, and the adverse drug reactions of patients during treatment were observed. Results:The median PFS of the study group was 8.3 months, which was longer than 5.5 months of the control group, with a statistically significant difference ( χ2=5.134, P=0.025). The ORR and DCR of the study group were 52.08% (25/48) and 81.25% (39/48), which were significantly higher than 31.25% (15/48) and 62.50% (30/48) of the control group, with statistically significant differences ( χ2=4.286, P=0.038; χ2=4.174, P=0.041). After 6 cycles treatment, serum HE4 [(123.60±31.52) pmol/L vs. (178.01±46.22) pmol/L], CA125 [(33.52±10.61)U/L vs. (50.32±11.09) U/L] and CTCs [(2.19±0.24) pcs/5 ml vs. (3.25±0.31) pcs/5 ml] of the study group were significantly lower than those of the control group, with statistically significant differences ( t=8.489, P=0.025; t=7.562, P=0.032; t=9.341, P=0.017). The incidences of gastrointestinal reactions [35.42% (17/48) vs. 64.58% (31/48)], bone marrow suppression [18.75% (9/48) vs. 41.67% (20/48)], liver and kidney function damage [2.08% (1/48) vs. 14.58% (7/48)], cardiotoxicity [4.17% (2/48) vs. 18.75% (9/48)], allergy reaction [0 (0) vs. 8.33% (4/48)], neurotoxicity [2.08% (1/48) vs. 16.67% (8/48)] and other adverse reactions of the study group were significantly lower than those of the control group, with statistically significant differences ( χ2=8.167, P=0.004; χ2=7.584, P=0.006; χ2=4.909, P=0.027; χ2=5.031, P=0.025; χ2=4.174, P=0.041; χ2=6.008, P=0.014). Conclusion:For patients with recurrent platinum-sensitive ovarian cancer, olalapril combined with bevacizumab has better curative effect than doxorubicin liposome combined with carboplatin chemotherapy, and can prolong the survival period of patients, down-regulate serum HE4, CA125 and CTCs levels, with low incidence of adverse reactions.

ABSTRACT OBJECTIVE：To compare the effectiveness and economics of peramivir and oseltamivir in the treatment of influenza complicated with febrile seizures in children. METHODS：In retrospective study，152 children with influenza complicated with febrile seizures were collected from our hospital during Dec. 2018 to Mar. 2019.They were divided into peramivir group（81 cases） and oseltamivir group （71 cases）. Fever remission time， medication duration， hospital duration， clinical efficacy （determined by convulsion，cough，nasal obstruction，runny nose，sore throat，etc.），the incidence of rash，the number of children with combined antibiotic and TCM were compared between 2 groups. Cost-effectiveness analysis was used to evaluate cost-effectiveness ratio（CER）and incremental cost-effectiveness ratio（ICER）of medication regimen in 2 groups. The sensitivity analysis of the effect and total cost were carried out with Logistic regression and multiple linear regression respectively through CER and ICER calculated by reducing 15％ drug price. RESULTS：There was no statistical significance in fever remission time， medication duration，hospitalization duration，the incidence of rash and proportion of children with combined antibiotics between 2 groups（P＞0.05）. There was statistical significance in proportion of children with combined TCM and clinical effect，and the proportion of children with combined TCM in peramivir group was significantly lower than oseltamivir group（P＜0.001）. Clinical effect of peramivir group was significantly better than that of oseltamivir group（P＝0.021）. Total cost of peramivir group and oseltamivir group were 5 442.84 yuan/person and 5 571.71 yuan/person（P＝0.795）；CER of them were 54.47 and 56.51；ICER of peramivir group was － 89.38. The results of sensitivity analysis were consistent with those of basic analysis.CONCLUSIONS： Compared with oseltamivir，peramivir is more effective and less costly for children with influenza and febrile seizures.

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.