Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

Objective To investigate the food allergy situation of children in Changping District of Beijing,and to explore the influence of allergic family history,gender and mode of delivery on food allergy in children,the distribution of food allergy in different age groups,the types of food allergy that are easy to cause in this area,and the comorbidities of food allergy.Methods A total of 515 children aged 0 to 14 years who were admitted to the general pediatric outpatient and emergency department and inpatient of Beijing Changping Hospital from April to November 2023.Using immunoblotting to detect specific immunoglobulin E in the serum of pediatric patients,and using SPSS 26.0 statistical software to perform binomial tests on gender and delivery mode non parameters;Using custom Excel functions to statistically analyze the family history of allergies,the number of people in different age groups,and the frequency of allergic foods in each group;Use a self-made mini program to statistically analyze the combination of comorbid allergic diseases.Results ① The number of male children with food allergies(306 cases)was higher than that of female children(209 cases),and the difference was statistically significant(P＜0.05).(2)There were 109 cases of pediatric patients with parents who had no history of allergic diseases,accounting for 21.17％of the total cases;There were a total of 406 cases where at least one parent had a family history of allergies,accounting for 78.83％of the total cases.Among them,228 cases(44.27％)had one parent with a history of allergies,and 178 cases(34.56％)had both parents with a history of allergies.③ Among 515 children with positive food allergens,there were 10 cases(1.94％)in infancy,37 cases(7.19％)in early childhood,235 cases(45.63％)in preschool,192 cases(37.28％)in school age,and 41 cases(7.96％)in adolescence.The highest positivity rate for food allergens is in milk(444 times),followed by egg white(70 times),cashew nuts(57 times),crab(37 times),beef(26 times),mango(24 times),shrimp(21 times),pineapple(6 times),and shellfish(1 time).Milk protein is the most common allergen in all age groups.(4)Among 515 children with food allergies,399 cases were single food allergies,accounting for 77.47％;116 cases of multiple food allergies(2 or more types of food allergies),accounting for 22.53％.⑤ The most common comorbidity of food allergies is food allergy related gastrointestinal diseases combined with allergic rhinitis,with a total of 267 cases;Secondly,there were 192 cases of allergic rhinitis combined with chronic cough,and 124 cases of food allergy related gastrointestinal diseases combined with chronic cough.Conclusion Milk is the main allergen of food allergy in people of age 14 and under,and gastrointestinal symptoms are the most common in children with food allergy.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

Objective:To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene. Methods:Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing.Results:All of the six patients had presented with severe short stature (< 3 s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c. 5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c. 5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c. 5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c. 5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c. 5156G>T was rated as a pathogenic variant (PS2+ PM1+ PM2_Supporting + PM5+ PP3). Conclusion:All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

Objective:To analyze the research progress and hotspots on drug resistance of helicobacter pylori in China and abroad since 2000, in order to provide theoretical reference and basis for the study of digestive system diseases.Methods:The Chinese and English literature related to helicobacter pylori resistance, which were included in the Chinese National Knowledge Infrastructure (CNKI) database and the Web of Science database, were searched from 2000 to 2021. We imported the retrieved literature into Citespace6.1.R2 software, performed visual analysis on authors, countries and institutions, keywords, cited literature, and drew visual graphs.Results:A total of 2 824 Chinese literature and 1 885 English literature were included. The authors with the highest volume of publications in Chinese and English literature are Hu Fulian and Gisbert JP, respectively. The institutions with the highest volume of publications are the First School of Medicine, Beijing University and the Baylor School of Medicine in the United States. The keywords with high centrality in Chinese literature include clarithromycin, eradication rate, drug resistance, amoxicillin, metronidazole, etc. In the analysis of cited literature, it was observed that the Maastricht Consensus report holds an important position in this field.Conclusions:The use of Citespace visualization analysis has intuitively elucidated the research hotspots on the drug resistance of Helicobacter pylori.

Objective:To investigate the effects of letrozole combined with human menopausal gonadotropin (HMG) on pregnancy rate and prognosis in patients with refractory polycystic ovary syndrome (PCOS).Methods:A total of 102 patients with refractory PCOS who received treatment in Jinhua Hongyue Women's and Children's Hospital between May 2019 and May 2020 were included in this study. They were randomly assigned to observation and control groups ( n = 51/group). All patients received the same treatment in the early period. During later ovulation induction period, patients in the control group were administered HMG and those in the observation group were given letrozole combined with HMG. Before treatment and 3 months after treatment, sex hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2), testosterone (T)], arterial hemodynamic indicators around the follicle [end diastolic velocity (EDV), peak systolic velocity (PSV), pulsation index (PI)], endometrial thickness and classification were compared between the two groups. The ovulation rate and pregnancy rate as well as pregnancy outcomes at 6 months of follow-up were recorded in each group. Results:After 3 months of treatment, FSH, LH, E 2 and T levels in each group were significantly decreased compared with those before treatment (all P < 0.05). FSH, LH, E 2 and T levels in the observation group were (1.85 ± 0.45) U/L, (9.86 ± 1.47) U/L, (81.25 ± 10.47) pmol/L, (1.75 ± 0.26) nmol/L, respectively, which were significantly lower than those in the control group [(3.12 ± 1.47) U/L, (12.58 ± 2.14) U/L, (109.25 ± 27.14) pmol/L, (3.58 ± 0.76) nmol/L, t = 5.90, 7.48, 6.87, 16.27, all P < 0.05). EDV in each group was significantly decreased after 3 months of treatment compared with that before treatment (both P < 0.05). After treatment, EDV in the observation group was significantly lower than that in the control group [(3.12 ± 1.42) cm/s vs. (5.14 ± 1.89) cm/s, t = 21.14, P < 0.001]. PSV in each group was significantly increased after treatment compared with that before treatment (both P < 0.05). After treatment, PSV in the observation group was significantly higher than that in the control group [(13.36 ± 2.01) cm/s vs. (10.24 ± 2.47) cm/s, t = 4.21, P < 0.001]. In each group, PI measured after treatment was not significantly different from that measured before treatment (both P > 0.05). After treatment, endometrial thickness in the observation group was significantly higher than that in the control group [(9.09 ± 1.58) mm vs. (8.41 ± 1.42) mm, t = 2.28, P < 0.05]. Ovulation rate in the observation group was significantly higher than that in the control group [88.24% (45/51) vs. 70.59% (36/51), χ2 = 4.85, P < 0.05]. There were no significant differences in endometrial type, biochemical pregnancy, clinical pregnancy rate, abortion rate, and premature delivery rate between the two groups (all P > 0.05). Conclusion:Letrozole combined with HMG has an ideal effect on refractory PCOS. It can improve the levels of sex hormones, restore the hemodynamic status in ovarian stroma and increase ovulation rate.

Objective:To investigate the role of IL-6 trans-signaling pathway in perioperative neurocognitive disorder in mice.Methods:Eighty-four SPF healthy male C57BL/6 wild-type mice and 84 SPF healthy male IL-6R -/- mice, aged 12-14 weeks, weighing 25-35 g, were used.The 84 wild-type mice were divided into 4 groups ( n=21 each) using a random number table method: sham group (SH group), surgery group (S group), sgp130Fc (specific IL-6 trans-signaling pathway blocker) group (F group), and sgp130Fc+ surgery group (FS group). In S group and FS group, internal fixation was performed under general anesthesia with sevoflurane after tibial fracture.Mice only received anaesthesia with sevoflurane in SH group and F group.In FS group and F group, sgp130Fc 10 mg/kg was intraperitoneally injected before anesthesia.Blood samples were collected from the celiac vein at 24 h after surgery for determination of the concentrations of interleukin 6 (IL-6), IL-1β and tumor necrosis factor (TNF)-α in plasma by enzyme-linked immunosorbent assay (ELISA). Then the mice were sacrificed, brains were removed, and hippocampal tissues were obtained for measurement of the contents of IL-6, IL-1β and TNF-α (by ELISA) and for observation of activation of microglias in the hippocampal DG region (by immunofluorescence staining, n=6). Cognitive function was evaluated by contextual fear conditioning test ( n=15) on 3 days after surgery.Eighty-four IL-6R -/- mice were randomly divided into 4 groups ( n=21 each): sham group (KO-SH group), surgery group (KO-S group), saline group (KO-C group), and hyper IL-6 (specific IL-6 trans-signaling pathway activator) group (KO-H group). The treatment in KO-SH group and KO-S group was the same as those previously described in SH group and S group, respectively.0.9% NaCl solution 100 μl was intraperitoneally injected in KO-C group, 100 μl hyper IL-6 40 μg/kg was intraperitoneally injected in KO-H group, and 24 h later blood was collected from the celiac vein for measurement of the concentrations of IL-6, IL-1β and TNF-α in plasma by ELISA.Then the mice were sacrificed, brains were removed, and hippocampal tissues were obtained for determination of the contents of IL-6, IL-1β and TNF-α (by ELISA) and for observation of activation of microglias in the hippocampal DG region (by immunofluorescence staining, n=6). Cognitive function was evaluated by contextual fear conditioning test ( n=15) on 3 days after surgery. Results:Compared with SH group, the percentage of freezing time in the contextual fear conditioning test was significantly decreased, and the activation of microglias in the hippocampal DG region and levels of IL-6, IL-1β and TNF-α in plasma and hippocampi were increased in S group ( P<0.05). Compared with S group, the percentage of freezing time in the contextual fear conditioning test was significantly increased, and the activation of microglias in the hippocampal DG region and levels of IL-6, IL-1β and TNF-α in plasma and hippocampus were decreased in FS group ( P<0.05). There were no significant differences in the percentage of freezing time, activation of microglias in the hippocampal DG region, and levels of IL-6, IL-1β and TNF-α in plasma and hippocampi between KO-S group and KO-SH group ( P>0.05). Compared with KO-C group, the percentage of freezing time in the contextual fear conditioning test was significantly decreased, and the activiation of microglias in the hippocampal DG region and levels of IL-6, IL-1β and TNF-α in plasma and hippocampus were increased in KO-H group ( P<0.05). Conclusions:IL-6 trans-signaling pathway is involved in the process of perioperative neurocognitive disorder in mice.

Objective:To evaluate the test-retest reliability of MRI criteria in the 2019 Bosniak classification of cystic renal masses (CRMs) and to analyze the impact of lesions′ property, size and readers′ experience on the test-retest reliability.Methods:From January 2009 to June 2019, 207 patients with 207 CRMs were included in this retrospective study. All of them underwent renal MRI and surgical-pathologic examination. According to Bosniak classification, version 2019, all CRMs were independently classified twice by eight radiologists with different levels of experience. All radiologists were blinded to the pathology of the lesions. By using intraclass correlation coefficient (ICC), test-retest reliability was evaluated for all CRMs and for subgroups with different pathological properties (benign and malignant) and different sizes (≤40 mm and>40 mm). The test-retest reliability of 4 senior readers (≥10 years of experience) and 4 junior readers (<10 years of experience) were evaluated respectively. The comparison of ICC was performed using Z test. Results:The 207 CRMs included 111 benign lesions (83 benign cysts, 28 benign tumors) and 96 malignant tumors. There were 87 lesions with maximum diameter ≤40 mm and 120 with maximum diameter>40 mm. The test-retest reliability (ICC) of each reader for all lesions was 0.776-0.888, the overall ICC was 0.848 (95%CI 0.821-0.872). The ICCs of senior and junior readers were 0.853 (95%CI 0.824-0.880) and 0.843 (95%CI 0.811-0.871) respectively, without significant difference between the two groups ( Z=0.85, P=0.374). The ICC of all readers was 0.827 for benign lesions and 0.654 for malignant lesions, showing significant difference ( Z=2.80, P=0.005). The ICC was 0.770 for lesions ≤40 mm and 0.876 for lesions>40 mm, which was significantly different ( Z=-2.36, P=0.018). For CRM subgroups with different pathological properties and different sizes, there was no significant difference in test-retest reliability between senior and junior readers (all P>0.05). Conclusion:The test-retest reliability of MRI criteria in the 2019 Bosniak classification of CRMs is excellent and unaffected by readers′ experience. The reliabilities are not consistent among CRMs of different pathological properties and different sizes, but all reached the level of good and above.