Type 1 diabetes, a complex genetic disease, is determined by both genetic and environmental factors. After excluding the five susceptibility loci discovered by genetic linkage studies and candidate-gene association studies, more than 30 new susceptibility loci have been found to be related with type 1 diabetes as a result of genome-wide association study.

Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.

Liver transplantation is an effective treatment of end-stage liver diseases. However, liver ischemia-reperfusion injury (IRI) and rejection significantly cause the decrease of survival rate of liver graft. Therefore, it is urgent to explore a novel method, which can not only alleviate liver IRI, but also promote immune tolerance of allograft, thereby improving the survival rate of liver graft. Extracellular vesicle (EV) is nanoparticle released from cells into the extracellular microenvironment, which may alleviate graft injury by repairing autophagy, immunosuppression and accelerating tissue regeneration. Hence, EV becomes a research hot spot in the field of liver transplantation. Nevertheless, the clinical application of EV encounters multiple challenges, such as separation, purification, identification, storage of EV and how to deliver EV to the target cells. In this article, the mechanism of EV in liver IRI, the challenges in clinical application of EV and the potential application of EV were reviewed, aiming to provide reference for the clinical application of EV in liver transplantation.

Objective: To investigate expressions of Toll-like receptor(TLR)-2, TLR-4 and TLR-6 in peripheral blood mononuclear cells (PBMC) and serum immunoglobulin G (IgG) and IgM levels in pediatric idiopathic nephrotic syndrome (INS). The correlation between Toll-like receptors (TLR-2, TLR-4 and TLR-6) and serum immunoglobulin levels (IgG and IgM) will be proven in the pathogenesis of childhood INS in active stage (AS) and remission stage (RS). Methods: Forty-two INS patients (experimental group, 32 boys, 10 girls) and 29 healthy individuals (healthy control group, 19 boys, 10 girls) were enrolled in the present study from June, 2017 to October, 2018 in the First Affiliated Hospital of Xinxiang Medical University. There were no significant differences in gender (χ²=0.966, P=0.326) and age (t=-0.139, P=0.89) between 2 groups.TLR-2 mRNA, TLR-4 mRNA and TLR-6 mRNA expressions of PBMC were evaluated by using real-time PCR in both INS children with AS and RS and healthy children.The blood samples were drawn to detect by way of immunoturbidimetry serum immunoglobulin (IgG and IgM) levels in both INS children with AS and healthy children.The correlation between Toll-like receptors (TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin (IgG, IgM) levels were analyzed by using spearman correlation analysis. Results: The expression levels of TLR-2 mRNA in INS children with AS, RS and healthy children were 1.85±0.30, 1.00±0.23 and 0.85±0.12, respectively, and the expression levels of TLR-4 mRNA were 1.24±0.27, 0.80±0.23 and 0.68±0.09, respectively, while the expression levels of TLR-6 mRNA were 1.35±0.23, 0.92±0.19 and 0.79±0.15, respectively, so the differences were statistically significant(F=198.453, 67.013, 82.405, all P<0.01). The serum IgG level(2.90±0.89) g/L was lower in INS children with AS compared with the controls(9.21±1.88) g/L.However, the serum IgM level (2.87±0.96) g/L was higher in INS children with AS when compared with the controls(1.48±0.30), and the differences were statistically significant(t=-16.810, 8.701, all P<0.05). No significant correlation was noted between Toll-like receptors(TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin levels (IgG, IgM) (all P>0.05). Conclusions The results indicate that Toll-like receptors (TLR-2, TLR-4 and TLR-6) and immunoglobulin (IgG, IgM) might play a role in the pathogenesis of pediatric INS via distinct pathway.

Objective:To explore the effect of health education based on theory of planned behavior combined with stepped care model on negative emotion, psychological flexibility and quality of life in patients with lung cancer undergoing chemotherapy.Methods:From October 2020 to December 2021, 108 chemotherapy patients who underwent lung cancer surgery in Affiliated Hospital of Weifang Medical College and had anxiety or depression that scores was greater than 7 in any dimension of the Hospital Anxiety and Depression Scale (HADS) were selected as the study subjects. The study subjects were divided into observation group ( n=46) and control group ( n=48) by random digits table method. Routine care was implemented in the control group. The observation group implemented health education based on the theory of planned behavior combined with stepped care model intervention. The HADS scale was used every 4 weeks to assess negative emotion in both groups. In observation, patients with negative emotion relief stop the next stage of nursing intervention, and patients without relief continue the next stage of higher intensity nursing intervention. Results:Before the intervention, there were no significant difference in the scores of negative emotion, psychological flexibility and quality of life between the two groups ( P>0.05). After intervention, the scores of all dimensions of negative emotion and the total score in the observation group were significantly lower than those in the control group, and the differences had statistical significance ( t=4.86, 3.19 and 4.53, all P<0.05). After the intervention the scores of psychological flexibility and quality of life dimensions and the total score in the observation group were higher than those in the control group, the differences had statistical significance (t values were -6.01--2.89, all P<0.05). After the intervention, there was no significant difference in the remission rate of negative emotions between the clinical observation stage of the observation group and the concurrent control group ( P>0.05). The remission rates of guided self-help, problem-solving therapy, psychological or drug therapy and total negative emotions in the observation group were 38.46%(15/39), 33.33%(8/24), 6/16 and 78.26%(36/46), respectively, which were higher than those in the control group, and the differences had statistical significance ( χ2 values were 7.04 - 13.80, all P<0.05). Conclusions:Health education based on the theory of planned behavior combined with stepped care model can effectively alleviate the negative emotions of lung cancer patients undergoing chemotherapy and improve psychological flexibility and quality of life.

Objective:To develop a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction.Methods:The preliminary contents of the assessment system were determined through a literature review and expert interviews, and two rounds of questionnaire-based consultation was conducted with 20 experts using the Delphi method. With the use of Excel 2016 and SPSS 26.0, we calculated the coefficient of judgement basis (Ca), the coefficient of familiarity (Cs), the coefficient of authority (Cr), and Kendall's coefficient of concordance ( W ) as well as the mean, standard deviation, and coefficient of variation of all parameters, to identify the specific items and weights for the homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction. Results:In the two rounds of consultation, experts were both 100.00% active in responding to the questionnaires; the coefficients of authority of experts were 0.889 and 0.935, respectively; the coefficients of familiarity were 0.856 and 0.936, respectively; the coefficients of judgment were 0.922 and 0.934, respectively; and Kendall's coefficients of concordance were 0.476 and 0.563, respectively. Finally, 7 first-level items and 21 second-level items were included in the content framework of the homogeneous management evaluation system.Conclusions:The construction process of the homogeneous management evaluation system of clinical observership teaching is complete and reliable, which can provide a reference for the homogeneous management of clinical observership teaching, but further verification and improvement are needed.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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Cachexia/therapy* ; Combined Modality Therapy ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasms/complications* ; Nutritional Support/adverse effects* ; Quality of Life

Objective: To investigate the value of tumor perfusion parameter measured by using double contrast-enhanced ultrasound (DCEUS) QontraXt three-dimensional pseudocolor quantitative analysis to the therapeutic effect evaluation of preoperative neoadjuvant chemotherapy (NAC) in advanced gastric cancer (AGC) patients. Methods: Eighty-nine AGC patients underwent 3 cycles of preoperative NAC (XELOX) followed by complete resection of lesion. The DCEUS QontraXt three-dimensional pseudocolor was performed one or two weeks before the NAC and operation were applied, respectively. The peak enhancement (PE), time to peak (TP), sharpness of the bolus (β) and area under the enhancement curve (AUC) of primary gastric tumor were measured by QontraXt three-dimensional pseudocolor quantitative analysis. These DCEUS parameters between respond and non-respond groups before and after NAC therapy were compared. The prediction accuracy of DCEUS to the therapeutic effect evaluation of preoperative NAC was determined by the receive operating characteristic (ROC) curves. Results: Among 89 AGC patients, 52 patients responded to NAC therapy, while 37 patients resisted to NAC therapy. Twelve cases in respond group and 26 cases in non-respond group were mucinous carcinoma. Forty cases in respond group and 11 cases in non-respond group were non-mucinous carcinoma (P<0.05). In responder group, the PE and TP before NAC were (53.7±9.3)% and (14 521±2 667) ms, and (32.2±5.5)% and (17 235±1 898) ms after NAC. The ratio of changes of PE (ΔPE) and TP (ΔTP) were 0.43±0.17 and 0.36±0.14, respectively. In non-respond group, the PE and TP before NAC were (54.4±7.2)% and (13 869±3 247) ms, and (45.3±6.1)% and (15 127±1 423) ms after NAC therapy. The ratio of ΔPE and ΔTP were 0.24±0.20 and 0.22±0.12. The PE and TP after NAC, the ratio of ΔPE and ΔTP were significant different among these two groups (all of P<0.05). The ROC curves showed that the ratio of ΔPE in assessing the respond of gastric cancer patients to NAC was superior compared to other parameters (AUC=0.784, P=0.004). The optimal cut-off value of the ratio of ΔPE was 24% and its sensitivity and specificity to the therapeutic effect evaluation of NAC in gastric cancer were 82.7% and 64.9%. Conclusion DCEUS QontraXt three-dimensional pseudocolor quantitative analysis might be a novel, noninvasive and reliable method to evaluate the therapeutic effect of preoperative NAC in AGC patients.

Objective: To study the effects of patient-controlled intravenous analgesia(PCIA) with Dexmedetomidine, Ropivacaine by local incision infiltration and combined analgesia on inflammatory factors and rapid rehabilitation in infants aged 3-6 months after radical resection of megacolon. Methods: From June 2016 to March 2018, 90 infants aged 3-6 months underwent radical resection of megacolon in Henan Provincial Children′s Hospital as the subjects.According to the postoperative analgesia mode applied to the children, they were divided into Dexmedetomidine group, Ropivacaine group and combined group (Dexmedetomidine PCIA combined with local infiltration of Ropivacaine), 30 cases in each group.The serum levels of interleukin(IL)-6 and IL-10 were measured and recorded 2 hours before operation and 24 hours after operation, and the analgesic scores of 4, 8, 12 and 24 hours after operation were recorded.The rapid recovery index of each group, standard and the number of complications were compared. Results: Compared with 2 hours before operation, the serum levels of IL-6 in the Dexmedetomidine group, Ropivacaine group and combined group [(24.61±1.44) ng/L vs.(13.84±0.65) ng/L, (26.39±1.29) ng/L vs.(13.85±0.67) ng/L, (20.58±2.06) ng/L vs.(13.87±0.63) ng/L], IL-10[(27.63±1.52) ng/L vs.(15.79±1.48) ng/L, (28.29±2.34) ng/L vs.(15.41±1.37) ng/L, (23.21±2.71) ng/L vs.(15.47±1.52) ng/L] were significantly higher (all P<0.05), while the levels of IL-6, IL-10 in combined group were lower than those in Dexmedetomidine group and Ropivacaine group (t_a=9.172, 9.835; t_b=10.221, 11.034, all P<0.05). At 4 h, 8 h, 12 h, 24 h after operation.The analgesic scores in combined group were(1.89±0.23) scores, (1.87±0.15) scores, (1.95±0.17) scores, (2.08±0.18) scores, those of dexmedetomidine group were(2.06±0.24) scores, (2.08±0.18) scores, (2.76±0.29) scores, (2.55±0.31) scores, those of Ropivacaine group were(2.10±0.26) scores, (2.15±0.26) scores, (2.32±0.19) scores, (3.00±0.28) scores, and the analgesic scores in combined group were significantly lower than those in Dexmedetomidine group and Ropivacaine group(t_a=8.526, 9.364, 10.287, 9.521; t_b=8.729, 9.514, 11.037, 9.184, all P<0.05). In comparison with the first exhaust time, anal extubation time, hospitalization days, hospitalization expenses and antibiotic use time in the three groups, it was found that combined group was significantly better than Dexmedetomidine group and Ropivacaine group(t_a=8.315, 8.294, 7.883, 9.261, 10.487; t_b=8.582, 8.329, 7.916, 9.348, 10.862, all P<0.05). The incidence of complications in the combined group, Dexmedetomidine group, and Ropivacaine group were not significantly different in 3 groups(χ²=0.577, P=0.749). Conclusions The continuous anesthesia of Dexmedetomidine combined with local infiltration of Ropivacaine incision can alleviate the postoperative inflammatory reaction and promote the rapid recovery of children.