Objective: To analyze the relationship between Toll like receptor ( TLR ) 9 and TLR 7 gene polymorphisms among children with hand-foot-mouth disease in a medical institution of Jinan City from 2020 to 2023, so as to provide reference for prevention of hand-foot-mouth disease. Methods: Data of 284 preschool children aged 3-6 with hand-foot-mouth disease, including the season pattern, clinical manifestations, pathogen distribution, were collected in department of pediatric infectious diseases of the Second Children & Women s Healthcare of Jinan from 2020 to 2023. The distribution conditions of TLR 9 and TLR 7 genotypes of enterovirus 71 (EV71) subtype and coxsackievirus A16 (CA16) subtype were compared by Chi square test. Hardy Weinberg equilibrium test was used to characteristic sample population distribution, and Logistic regression analysis in the additive genetic model was adopted to evaluate the relationship between TLR 9 and TLR 7 gene polymorphisms with hand-foot-mouth disease subtype. Results: The time to admission after symptom onset with hand-foot-mouth disease among 284 children was mostly >2-4 d ( 45.42% ), followed by ≤2 d ( 44.72% ). The season pattern was mostly in summer (58.10%). The severity was mostly mild ( 69.72% ), and the main clinical manifestations were skin rash (100.00%) and fever (65.49%). The majority pathogen was EV71 (60.56%). Hardy Weinberg equilibrium test showed good population representation ( P >0.05). Logistic regression analysis was applied to analyze the relationship between TLR9 rs 187084 locus and hand-foot-mouth disease subtypes under the additive genetic model after adjusting for age and gender of the study population, and it was found that compared with those without C allele, each additional C allele increased the risk of CA16 subtype hand-foot-mouth disease by 109% ( OR=2.09, 95%CI =1.13-3.27). Analysis of relationship between TLR 7 rs 3853839 locus and hand-foot-mouth disease subtype showed that compared with those without C allele, the risk of EV71 subtype hand-foot-mouth disease increased by 57% for each additional C allele ( OR=1.57, 95%CI = 1.10 -2.11) ( P <0.05). Conclusions From 2020 to 2023, children with hand-foot-mouth disease in a medical institution of Jinan City is mostly mild and caused by EV71 infection. The polymorphism of rs 3853839 locus of TLR 7 may be related to EV71 infection in children with hand-foot-mouth disease, and the polymorphism of rs 187084 locus of TLR 9 may be related to CA16 infection.

Objective:To analyze the evaluation of the application effect and deficiency of nurses acting as standardized parents in the graduation examination of standardized residency training of pediatrics and further improve and promote the level of standardized parents.Methods:A questionnaire survey was used to collect the scores of nurse standardized parents by students and examiners who took part in the graduation examination of standardized residency training of pediatrics in 2021. And the self-evaluation scores of standardized parents were collected. Counting data were represented by the number of cases and composition ratio. A Chi-square test was used to compare the rates.Results:A total of 125 questionnaires from students and 37 questionnaires from nurse standardized parents were collected, and the overall satisfaction (very satisfied + satisfied) of standardized parents reached 121 (96.80%). In the three dimensions of simulation ability, compliance with question-and-answer rules, and simulated attitude, students believed that the consistency between standardized parents and actual parents in simulated altitude was lower than that in the simulation ability and compliance with question-and-answer rules ( P=0.007, P=0.001). The overall satisfaction of standardized parents (very satisfied + satisfied) reached 87.38% (388/444). There were 26 (70.27%) nurse standardized parents who had the lowest satisfaction with their own performance ability, followed by 28 (75.68%) cases of imitation ability and 30 (81.08%) cases of adaptability. Conclusions:It is feasible to adopt nurse standardized parents in the assessment of standardized residency training of pediatrics, and both students and examiners have higher satisfaction. The next step is to improve the training of nurses standardized parents in the attitude of simulation and, at the same time, enhance the training of imitation ability and adaptability, so as to further expand the construction of standardized parents.

Hyperuricemia is caused by a of purine metabolism disorder and/or reduced uric acid excretion, and the prevalence of hyperuricemia in China has increased significantly in recent years. According to the etiology, hyperuricemia can be primary or secondary. The endocrine system related diseases are one of the important causes leading to secondary hyperuricemia, which is easily missed in general practitice. This article reviews the clinical characteristics and research progress of hyperuricemia secondary to endocrine diseases.

Objective:To observe any regulatory effect of a pulsed electromagnetic field (PEMF) on A2A adenosine receptors (A2ARs) in the nucleus pulposus of rats with intervertebral disc degeneration (IDD), and to explore any combination with the A2ARs′ agonist-mediating ROS/PI3K/Akt signaling pathway.Methods:Fifty Sprague-Dawley rats were randomly divided into a control group, an intervertebral disc degeneration group (the model group), an A2AR agonist CGS-21680 treatment group (the agonist group), a PEMF group and a PEMF combined with CGS-21680 treatment group (the observation group). IDD was modeled in all except the rats in the control group. 100μL of CGS-21680 (100μg/kg) was injected into the L 5-6 intervertebral discs of the agonist group, while the PEMF group was given 30 minutes of PEMF intervention daily for 14 days at 1.5mT and 75Hz with a pulse width of 150μs. The observation group was injected with CGS-21680 and then given the same PEMF intervention. Primary nucleus pulposus cells from each group (50ng/mL) were cultured and the expressions of 8-OHDG, SOD, MDA and ROS were detected by immunohistochemistry, immunofluorescence or with an ELISA kit. The A2AR, PI3K, AKT and p-AKT protein levels were detected using western blotting. Results:The nucleus pulposus cells and the annulus fibrosus were obviously wrinkled, necrotic and broken in the model group but the annulus fibrosus was intact and the nucleus pulposus was almost normal in the observation group. Compared with the model group, the levels of SOD and A2AR, PI3K, p-AKT and AKT protein were higher in the agonist, PEMF and observation groups, while the expressions of MDA, ROS and 8-OHDG were weaker. The ROS level in the observation group was significantly lower than that in the agonist and PEMF groups, and the phosphorylation level of p-AKT in the observation group was significantly higher than in the agonist and PEMF groups. The average levels of SOD, A2AR, PI3K, p-AKT and AKT protein in the nucleus pulposus cells of the agonist, PEMF and observation groups were significantly higher than the IL-1β group′s average, while the average levels of MDA, ROS and 8-OHDG were significantly lower. The ROS levels in the observation group were significantly lower than in the agonist and PEMF groups, while the A2AR protein content and p-AKT phosphorylation in the observation group were significantly greater. The average Bax levels in the nucleus pulposus cells of the agonist, PEMF and observation groups were significantly lower than that in the IL-1β group, and the expression of Bcl-2 was significantly increased. There was significantly less apoptosis observed in the observation group than in the agonist and PEMF groups, while the expression of Bcl-2 was significantly higher.Conclusions:PEMF plays an anti-oxidative stress role by up-regulating A2AR activity and reducing ROS generation. Treatment with PEMF and A2AR agonist could further activate the phosphorylation of PI3K/Akt, down-regulate Bax and up-regulate Bcl-2, thus inhibiting the apoptosis of nucleus pulposus cells and alleviating the malignant progression of IDD.

Objective:To analyze and summarize the clinical efficacy and safety of lymphocyte apheresis combined with plasma exchange in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage.Methods:A observational study was conducted. A total of 69 hepatitis B virus-related liver failure at the ascending stage patients who were hospitalized at Affiliated Guangzhou Eighth People's Hospital of Guangzhou Medical University from January 2016 to December 2020 were enrolled in this study. The patients were grouped according to their condition and wishes, including 38 patients treated with conservative medical treatment (control group) and 31 patients treated with lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment (study group). Clinical data were compared between the two groups 1-4 weeks after treatment, including dynamic changes of total bilirubin (TBil), international normalized ratio (INR), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, and the rate of clinical improvement at 4 weeks after treatment. In addition, the adverse effects and dynamic changes of white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), and hemoglobin (Hb) within 4 weeks after treatment were compared between the two groups.Results:Both groups showed significant improvement in clinical parameters after 1-4 weeks of initiation of therapy. The improvement of TBil, INR and MELD score at 1-4 weeks after treatment were significantly better in the treatment group than those in the control group [TBil (μmol/L): 248 (117, 335) vs. 398 (328, 464) at 1 week, 173 (116, 278) vs. 326 (184, 476) at 2 weeks, 107 (84, 235) vs. 355 (129, 467) at 3 weeks, 70 (61, 172) vs. 290 (82, 534) at 4 weeks; INR: 1.72±0.70 vs. 2.13±0.69 at 1 week, 1.67±0.61 vs. 2.28±1.35 at 2 weeks, 1.65±0.75 vs. 2.15±0.92 at 3 weeks, 1.61±0.93 vs. 2.19±1.17 at 4 weeks; MELD score: 18.35±5.32 vs. 23.38±4.56 at 1 week, 16.47±5.16 vs. 23.71±7.94 at 2 weeks, 16.30±5.75 vs. 22.64±6.99 at 3 weeks, 14.63±6.76 vs. 20.97±8.19 at 4 weeks], with significant differences (all P < 0.05). In addition, ALT levels at 1 week and 2 weeks after treatment in the study group were significantly lower than those in the control group [U/L: 128 (93, 206) vs. 240 (167, 436) at 1 week, 64 (42, 110) vs. 85 (69, 143) at 2 weeks, both P < 0.05]. The rate of clinical improvement at 4 weeks after treatment in the study group was 54.84% (17/31), which was significantly higher than that in the control group [28.95% (11/38)], with statistically significant difference ( P < 0.05). There was no significant difference in the rate of new infection between the study group and the control group [22.58% (7/31) vs. 34.21% (13/38), P > 0.05]. Additionally, expect that the PLT level at 1 week after treatment in the study group was significantly lower than that in the control group (×10 9/L: 101±42 vs. 128±59, P < 0.01), there was no significant difference in WBC, LYM or Hb at different time points after treatment between the two groups. Conclusion:Clinical efficacy of lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage is superior to conservative medical treatment alone, which can improve clinical improvement rate and recovery rate of liver function with high safety.

The etiology and pathogenesis of keloid are still not clear. It is believed that the formation of keloid is due to the joint action of many factors, during which process the external factor of fibroblast play an important role. Reprogramming of glucose metabolism in keloid fibroblasts is a new research direction. TGF-β 1 and its related TGF-β 1/Smad signalling pathway are considered to be the most closely related to the formation of keloid. This article reviews the research progress on extracellular factors, glucose metabolism and signaling pathways of keloids.

The etiology and pathogenesis of keloid are still not clear. It is believed that the formation of keloid is due to the joint action of many factors, during which process the external factor of fibroblast play an important role. Reprogramming of glucose metabolism in keloid fibroblasts is a new research direction. TGF-β 1 and its related TGF-β 1/Smad signalling pathway are considered to be the most closely related to the formation of keloid. This article reviews the research progress on extracellular factors, glucose metabolism and signaling pathways of keloids.

ObjectiveTo investigate the differentially expressed proteins in the plasma exosome of acute-on-chronic liver failure (ACLF) patients with different prognoses, to analyze their functions and biological processes, and to provide a basis for clinical diagnosis. MethodsA prospective study was performed for 10 ACLF patients who were hospitalized and diagnosed in Beijing YouAn Hospital, Capital Medical University, from July 2019 to October 2019, and the patients were followed up for 90 days. The patients who died or received liver transplantation were enrolled as liver transplantation/death group (5 patients), and the patients who survived were enrolled as survival group (5 patients). The Mann-Whitney U test was used for comparison of general data between the two groups. The label-free quantitative proteomic method was used for identification and quantitative analysis of plasma exosome proteins to screen out differentially expressed proteins, and a functional enrichment analysis was performed. R-3.5.1 software was used to perform a hierarchical cluster analysis of differentially expressed proteins to analyze the biological processes involving these proteins. ResultsA total of 860 proteins were identified by the exosome proteomic analysis, and according to the criteria of upregulation ＞1.2 folds or downregulation ＞1.2 folds (P＜0.05), there were 116 differentially expressed proteins. Compared with the liver transplantation/death group, the survival group had 62 upregulated proteins and 54 downregulated proteins. The bioinformatics analysis showed that these differentially expressed proteins mainly participated in immune reaction, signal transduction, vesicle-mediated transport, cell death, and cell proliferation and were closely associated with the signaling pathways including inflammatory response, carbohydrate and amino acid metabolism, hepatocyte injury, and hepatocyte regeneration. ConclusionDifferentially expressed proteins screened out by the label-free quantitative proteomic method can be used as serological markers for the early diagnosis and prognostic evaluation of ACLF.

Objective:To explore the effect of combining pulsed electromagnetic field (PEMF) stimulation with A 2A adenosine receptor agonist CGS-21680 on apoptosis and inflammation of nucleus pulposus cells in cases of intervertebral disc degeneration. Methods:Forty-eight Sprague-Dawley rats were randomly divided into a sham operation group (Sham group), an intervertebral disc degenerative disease group (Model group), an A 2A adenosine receptor agonist CGS-21680 group (Agonist group), and a group in which PEMF was combined with CGS-21680 (Observation group). The rat model of intervertebral disc degeneration (IDD) was established in all other groups than the sham operation group. The rats in the Agonist group were injected with 100μL of CGS-21680 (100μg/kg) at the L 5-6 intervertebral disc. The Observation group was injected with CGS-21680 similarly but then received 14 conse-cutive days of PEMF stimulation (30min/time). The Sham and Model groups were injected with the same amount of normal saline solution. Eight weeks later, HE staining was used to evaluate the pathological changes in the intervertebral disc tissues. The expression of type II collagen was determined by immunohistochemistry. The content and mRNA expression of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined using enzyme-linked immunosorbent assays and reverse transcription-polymerase chain reactions (RT-PCRs). The protein and mRNA levels of A 2A, NLRP3 and caspase-3 were determined by western blotting and RT-PCR. Results:The degeneration in the nucleus pulposus and annulus fibrosus in the Model group was significant, while significantly less shrinkage, necrosis and fibrous annulus rupture was observed in the Observation group. Compared with Model and Agonist groups, the positive expression of Col Ⅱ in the nucleus pulposus, A 2AR protein levels and relative expression of its mRNA had all increased significantly in the Observation group, while the average levels and mRNA expression of pro-inflammatory cytokines IL-6 and TNF-α had decreased significantly. The average protein level and mRNA expression of NLRP3 and caspase-3 in the intervertebral disc tissues of the Observation group were significantly lower than in the Model and Agonist groups. Conclusions:Combining pulsed electromagnetic field stimulation with A 2A adenosine receptor agonist CGS-21680 can inhibit the apoptosis of nucleus pulposus cells, alleviate disease response and delay IDD by up-regulating the activity of A 2A receptors and down-regulating the expressions of pro-inflammatory factors IL-6, TNF-α, NLRP3 and caspase-3 in nucleus pulposus cells.

Objective:To explore the current status of alcoholic hepatitis diagnosis by clinicians’ in China.Methods:Clinical data of inpatients confirmed with alcohol-associated liver disease diagnosed at Tongliao Infectious Disease Hospital of Inner Mongolia from June 1, 2018 to May 31, 2019 were retrospectively analyzed. The consistency of clinical diagnosis of alcoholic hepatitis was judged according to the diagnostic criteria recommended by the National Institute of Alcohol Abuse and Alcoholism (USA), and then the alcoholic hepatitis severity assessment model recommended by international guidelines, including Maddrey discriminant function, Model for end-stage liver disease, and Glasgow alcoholic hepatitis score and ABIC scores (age, total bilirubin, international normalized ratio and creatinine) were applied to evaluate this group of cases.Results:Among 79 cases with alcohol-associated liver disease, 75 were males and 4 were females, age ranged between 27~75 (51.1±8.8) years. Alcohol consumption varied from 60 g/d to 600g/d, with an average consumption of 148.8 ± 76.6 g/d. The alcohol consumption duration ranged from 4 to 50 [average (23.9 ± 9.6)] years. According to the initial discharge diagnosis, there were 47 and 32 cases in alcoholic hepatitis and alcoholic liver cirrhosis group, respectively. The mean erythrocyte volume, serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were increased in alcoholic liver cirrhosis than alcoholic hepatitis group, while albumin and total cholesterol were lowered in alcoholic liver cirrhosis than alcoholic hepatitis group, and coagulation indexes were significantly extended. Alpha-fetoprotein of both groups were in the normal range; however, it was significantly higher in the alcoholic hepatitis group than the alcoholic cirrhosis group. The 10 cases in the alcoholic cirrhosis group met the definition and diagnosis of alcoholic hepatitis defined by the National Institute of Alcohol Abuse and Alcoholism (USA), but there was no case in the alcoholic hepatitis group. Among the 10 diagnosed cases of alcoholic hepatitis, 5, 6, 1 and 3 cases met the diagnostic criteria of Maddrey discriminant function, Model for end-stage liver disease, Glasgow alcoholic hepatitis score, and ABIC score for severe alcoholic hepatitis, respectively. The Maddrey discriminant function, ABIC score, and Glasgow alcoholic hepatitis score within the Model for end-stage liver disease scores> 20 points had 5, 1, and 3 cases, respectively.Conclusion:Alcoholic hepatitis is over-diagnosed by clinicians. Alcoholic hepatitis patients have the base of liver cirrhosis who meet the diagnostic criteria of National Institute of Alcohol Abuse and Alcoholism (USA). Patients with Model for end-stage liver disease score > 20 points have good consistency with Maddrey discriminant function score ≥ 32 points, and both can be used to evaluate the alcoholic hepatitis patient clinical severity.