Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Objective:To investigate the effect of Asarinin on the survival time of transplanted heart after allogeneic heterotopic heart transplantation and to further verify the anti-immune rejection effect of Asarinin in spleen and peripheral blood.Methods:Using 64 Wistar rats as donors, 64 SD rats as recipients to establish the allogeneic heterotopic heart transplantation model in rats.After successful transplantation, 64 rats were use simple randomization divided into control group, cyclosporine A(CsA) group, Asarinin group and half CsA + half Asarinin group with 16 rats in each group.CsA group was given 5 mg/kg by gavage; Asarinin group was given 25 mg/kg; half dose group was given CsA 2.5 mg/kg+ Asarinin 12.5 mg/kg and the control group was given the same volume of normal saline by gavage.After administration for 1 week, half of them were used to observe the survival time.The other half of the rats were fully anesthetized with chloral hydrate, spleen and peripheral blood were taken.Half of the spleen was taken to observe the slices under the microscope.The other half of spleen was used RT-PCR to detect the relative expression of IFN-γ and IL-4.The expression of co-stimulatory molecules CD80, CD86 and CD40 in peripheral blood were detected by flow cytometry.Results:Survival time of transplanted heart was control group (8.4±0.9), CsA group (30.5±8.3), Asarinin group (16.5±4.3) and half-dose group (26.1±5.2) days.Compared with control group, survival time of heart transplantation became prolonged in all groups and the difference was statistically significant ( P<0.05). HE staining of splenic tissue showed that, as compared with control group, the injury of each group was alleviated.The relative expression of IFN-γ in spleen was control group (1.055±0.083), CsA group (0.396±0.038), Asarinin group (0.833±0.094) and half-dose group (0.862±0.104). The last three groups were lower than control group and the difference was statistically significant ( P<0.05). The relative expression of IL-4 in spleen was control group (1.429±0.234), CsA group (3.808±0.729), Asarinin group (2.209±0.306) and half-dose group (2.323±0.321). The last three groups all spiked as compared with control group and the difference was statistically significant ( P<0.05). The expressions of CD80, CD86 and CD40 in peripheral blood were control group (98.21±0.54), (85.78±0.89) and (96.36±0.66), CsA group (89.26±0.36), (56.86±2.32) and (88.11±1.61), Asarinin group (94.19±0.47), (79.01±1.12) and (87.86±1.67) and half-dose group (94.87±0.74), (80.81±0.98) and (89.71±0.97) respectively.The last three groups were lower than control group and the difference was statistically significant ( P<0.05). Conclusions:Asarinin can prolong the survival time of transplanted heart after allogeneic heterotopic heart transplantation in rats, inhibit the immune injury of spleen after allogeneic heterotopic heart transplantation in rats, decrease IFN-γ in spleen, increase IL-4 in spleen and inhibit the expression of peripheral blood costimulatory molecules CD80, CD86 and CD40.

Objective To investigate the prevalence of allergic and infectious diseases in children， and to assess the influence of indoor and outdoor environmental factors on these two common diseases in children. Methods A questionnaire was used to investigate the prevalence of allergic and infectious diseases in 140 children of 7 years old in Laizhou Bay， Shandong Province. Logistic regression was used to analyze the associations between indoor and outdoor environmental factors and children’s allergic and infectious diseases， respectively. Results The prevalence of previous eczema and other allergic diseases for the past year in children was 37.9% and 15.0%， respectively， and the prevalence of infectious diseases for the past year was 35.7%. As for allergic diseases， eye irritation due to outdoor air （ OR =2.977； 95% CI ： 1.407‒6.296） and nose irritation due to outdoor air （ OR =5.147； 95% CI ： 1.272‒20.827） were the risk factors for previous eczema in children. Indoor musty taste increased the risks of urticaria （ OR =4.306； 95% CI ： 1.062‒17.454） and previous eczema （ OR =3.853； 95% CI ： 1.080‒13.743）. The use of cockroach killers indoors increased the risk of rhinitis （ OR =6.102； 95% CI ：1.297‒28.697）. As for infectious diseases， having outdoor pollution sources increased the risk of gastrointestinal infection （ OR =4.937； 95% CI ： 1.050‒23.216）， and the use of mosquito coils and clothing mothproofing agents increased the risks of respiratory （ OR =6.333； 95% CI ： 1.397‒28.714） and gastrointestinal infections （ OR =3.218； 95% CI ： 1.074‒9.644）， respectively. However， we did not find associations between indoor passive smoking and allergic or infectious diseases. Conclusion Except outdoor passive smoking， all the other indoor and outdoor environmental factors increase the risks of children’s allergies and infectious diseases.

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Objective: To explore the function of cluster needling at scalp points therapy on regulating differential protein's expression at different time points in middle cerebral artery occlusion (MCAO) model rats. Methods: Fifty-four rats were divided into three groups randomly and 18 rats in each group. The groups respectively were the model group (group M, n = 18), cluster needling at scalp points group (group C, n = 18), false operation group (group F, n = 18). Each group was then assigned in three subgroups, including 24-h, 7-day, and 14-day subgroups. Six rats in each subgroup. Acupuncture at Baihui (GV20) and 2 points beside Baihui, which was 3-4 mm away from the midline. Longa score was used to eval-uated neurological effects. Proteomics methods were used to identify differentially expression proteins with a standard of fold change greater than 1.5 and P<.05 at different times. Results: 1. Nerve function scoring: The nerve function scores at 7 and 14 days decreased in group C, which showed better neural function than group M (P<.05). 2. Fold change in proteins:Group M showed 932 differentially expressed proteins compared with group F, and among them, 414 proteins showed significant changes in expression after acupuncture. The expression levels of Cdc42 and GFAP were increased, and Mag, Shank2, and MBP levels were decreased. In the Gene Ontology analysis, the cellular component consisted of the terms cytoplasm, cytoskeleton, lysosome, and plasma membrane. The main related biological processes were cell-cell signaling, protein transport, aging, and cell adhesion. Many synaptic and metabolic pathways were found by KEGG analysis. Conclusion: Cluster needling at scalp acupoints can improve the nerve function score and improve dyskinesia in MCAO model rats. Cluster needling at scalp acupoints can regulate the expression of 414 proteins, including Cdc42, GFAP, Mag, Shank2, and MBP, which are related to cerebral ischemia. The differential proteins are major concentration in cytoplasm, cytoskeleton, lysosomes, and plasma mem-brane, participate in cell-cell signaling, protein transport, aging, and cell adhesion, and act through multiple synaptic and metabolic pathways to exert their biological functions.

Objective To study the transport risk and factors that influence deaths of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.Method All infants transferred to our neonatal intensive care unit (NICU) by our hospital transport team or local hospital transport team from January 2014 to December 2015 were included in our study.Their clinical data were retrospectively studied.The risks of transport between hospitals were analyzed.The risk factors of deaths within and after 7 days of admission were further analyzed by multivariate Logistic regression analysis.The receiver operation characteristic (ROC) curve was used to assess the sensitivity and specificity of mortality index for neonatal transportation (MINT),transport related mortality score (TREMS),transport risk index of physiologic stability (TRIPS) for predicting mortality of preterm infants.Result (1) A total of 527 cases of ELBW/VLBW infants were included in our study.There were no deaths during transport.There were 10.2％ (54/527) died within and 8.9％ (42/473) died after 7 days of hospitalization.(2) Multivariate Logistic regression analysis showed that scleredema of newborn,secondary transport,gastrointestinal malformations,metabolic acidosis,high TREMS score,and high MINT score were risk factors of mortality within 7 days of admission for ELBW/VLBW infants;necrotizing enterocolitis,intraventricular hemorrhage ≥ three degree,high MINT score and low admission weight were risk factors of mortality after 7 days of admission.(3) The area under the ROC curve for MINT,TREMS,and TRIPS score were 0.672,0.655 and 0.665,respectively.The cut-off values for MINT score (cut-off 8,sensitivity 0.444,specificity 0.829),for TREMS score (cut-off 2,sensitivity 0.500,specificity 0.757,for TRIPS score (cut-off 20,sensitivity 0.444,specificity O.829) were selected to predict mortality within 7 days of admission.Conclusion (1) Secondary transport is the transport-related risk factor of mortality within 7 days of admission for ELBW/VLBW infants.(2) High MINT score is the risk factor of mortality within and after 7 days of admission.(3) If MINT ≥ 8,TREMS ≥2,or TRIPS ≥20,it might significantly increase the risk of mortality of ELBW/ VLBW infants within 7 days of admission after transport.

Objective To study the occurrence of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants and to determine the risk factors of severe BPD.Method From January 2007 to January 2017,ELBW infants admitted to neonatal intensive care unit (NICU) in Hunan Children's Hospital were retrospectively analyzed.They were assigned into severe and mild/moderate groups based on the severity of BPD.The general condition,maternal status,prenatal and delivery room treatment,transportation,clinical courses,therapy and outcome in NICU of the two groups were compared,and the risk factors of severe BPD were analyzed.Result A total of 367 cases were hospitalized during the 10 years.281 ELBW infants with complete medical records survived longer than 28 days were enrolled in this study.Among them,233 had BPD.Among BPD infants,116 cases were in the severe BPD group,47 cases (40.5％) died.117 cases were in the mild/moderate BPD group and 1 case (0.9％) died.The difference between the two groups was statistically significant (P ＜ 0.05).Multivariate Logistic regression analysis showed that the risk factors of severe BPD were duration of mechanical ventilation ≥ 7 days (OR =7.518,95 ％ CI 3.197 ～ 17.676),ventilator-associated pneumonia (OR =3.047,95 ％ CI 1.436 ～ 6.464),1 min Apgar score ≤7 (OR =2.341,95 ％ CI 1.142 ～ 4.796) and patent ductus arteriosus (OR =2.223,95 ％ CI 1.079 ～4.582).Conclusion The incidence and mortality of BPD,especially severe BPD,are high in ELBW infants.Avoiding asphyxia,shortening the time of mechanical ventilation,preventing infection and closing ductus arteriosus are important measures to reduce the severity of BPD.

Objective To understand the present condition of preclinical dental undergraduate in-terns' AIDS-related knowledge. Methods The questionnaire was designed referring to domestic and foreign relevant questionnaires. The cluster sampling method was used to conduct the questionnaire survey among the undergraduates who started their clinical internship in July 2016 in three domestic colleges, using SPSS 14.0 statistical software to analyze it. Results In this survey, 144 questionnaires were distributed, and 144 ones were filled out and sent back. The survey results suggested that 97.22％ (140) of interns held a posi-tive attitude towards aiding HIV-infected patients despite that 96.53％ (139) of interns knew that dental medical staff was considered to be highly susceptible with HIV. In spite of the fact that most interns knew AIDS-related knowledge and protection measures, 40.28％ (58) of interns were not clear about incubation period of AIDS, and the average awareness of children's AIDS and methods to disinfect HIV-infected dental instruments was less than half in the interns. Meanwhile it was found that 86.81％ (125) of interns didn't perform well in terms of complying with the principles of confidentiality in AIDS prevention and treatment. Conclusion Dental clinical interns' attitudes towards AIDS-infected patients should be praised. Further-more, they should accept education about infection control to have a deeper understanding about AIDS-related clinical manifestations and legal knowledge in order to reduce the probability of nosocomial infec-tion of AIDS.

Objective To realize the clinical characteristics of fungemia in premature infants.Methods Clinical characteristics of fungemia in premature infants in the intensive care unit of a children''s hospital between January 2011 and December 2015 were analyzed retrospectively, general condition of premature infants, laboratory-related indicators, and antimicrobial susceptibility testing results were compared.Results From January 2011 to December 2015, 42 premature infants with confirmed fungemia were treated in this hospital, 22 (52.38％) of whom were with fungemia caused by Candida albicans(C.albicans), 13 (30.95％) by Candida parapsilosis (C.parapsilosis), 3 by Candida krusei (C.krusei), and 4 by other fungi.Patients were grouped according to the main pathogens causing infection: C.parapsilosis group and C.albicans group.Maternal genitourinary tract infection rate and incidence of fungal meningitis in C.albicans group were both higher than C.parapsilosis group(27.27％ vs 7.69％, 27.27％ vs 0.00％ respectively), peripherally inserted central catheter (PICC) rate in C.albicans group was lower than that in C.parapsilosis group(22.73％ vs 69.23％), platelet count in C.parapsilosis group was lower than C.albicans group, differences were all statistically significant (all P<0.05).Conclusion The major fungi causing fungemia in premature infants were C.parapsilosis and C.albicans, maternal reproductive system infection during pregnancy can easily lead to candidemia, premature infants with candidemia are more vulnerable to developing fungal meningitis;PICC is more likely to lead to C.parapsilosis fungemia, and platelet decline is more obvious.

Objective To analyze the clinical and laboratory manifestations of primary Sj(o)gren's syndrom (pSS) with neurological involvement.Methods One hundred and forty eight patients fulfilling the 2002 American-European pSS classification criteria were retrospectively analyzed.Neurological manifestations were diagnosed based on the clinical,biological,electrophysiological,and imaging findings.Biographical,clinical,and laboratory data were compared between patients with and without neurological manifestations.Statistical methods used were Mann-Whitney U test,Chi-square test and Fisher exact probability.Results The prevalence of neurological involvement in pSS was 20.3％ (30/148),and the incidence of peripheral neuropathy,the central neuropathy and combination of the central neuropathy with peripheral neuropathy were 10.1％(15/148),9.5％(14/148) and 0.7％(1/148),respectively.The clinical spectrum of peripheral neuropathies encountered in Sj(o)gren's syndrome (SS) patients varied,with the pure sensory neuropathies being the most common,followed by sensorimotor neurophathies.Motor neuron disease was the most common type of central neurophathies.Compared with those without neurological manifestations,the duration of peripheral nerve system/central nerve system (PNS/CNS)-pSS patients was relatively short [(55±76) months vs (100±108) months,Z=-2.682,P＜0.05],and the antinuclear antibody (ANA) titer and RF titer were lower [(234±248) vs (377±339),Z=-2.008,P＜0.05;(126±279) U/ml vs (359±1 445) U/ml,Z=-2.243,P＜0.05].In PNS/CNS-pSS patients,the most common clinical manifestations included numbness (50％),pain (23％),and muscle weakness (63％).Conclusion The prevalence of neurological involvement in pSS is high.The duration is relatively short and the disease activity is high,but the disease features are atypical and may be neglected by rheumatologists.