1.Feasibility and prognostic value of estimated plasma volume status in assessing volume status during early fluid resuscitation in patients with sepsis.
Xiaodong LIU ; Fei WANG ; Wangbin XU ; Man YANG ; Xiao YANG ; Dongmei DAI ; Leyun XIAO-LI ; Xinghui GUAN ; Xiaoyang SU ; Yuemeng CUI ; Lei CAI
Chinese Critical Care Medicine 2025;37(7):620-627
OBJECTIVE:
To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS).
METHODS:
A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO2), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method.
RESULTS:
Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r1 = -0.367, r2 = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r1 = 0.286, r2 = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO2 (ΔPcv-aCO2; r1 = -0.321, r2 = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007].
CONCLUSIONS
ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans
;
Prognosis
;
Fluid Therapy
;
Sepsis/physiopathology*
;
Prospective Studies
;
Plasma Volume
;
Intensive Care Units
;
Resuscitation
;
Male
;
Female
;
Middle Aged
;
Shock, Septic/therapy*
2.Efficacy of CO2 Fractional Laser Combined with Interferon in Treating Persistent High-Risk HPV Infection of the Cervix
Xinghui CHEN ; Lisha MA ; Yuan WANG ; Lichi ZHANG ; Aiju CHEN ; Hongxian LI ; Junjing HE
Journal of Kunming Medical University 2025;46(7):139-145
Objective To investigate the clinical efficacy of intravaginal CO2 fractional laser combined with interferon in treating persistent high-risk HPV infection of the cervix and its impact on vaginal microecology.Methods A total of 211 patients with persistent high-risk HPV infection of the cervix who visited Kunming Maternal and Child Health Care Hospital from June 2022 to July 2024 were selected and randomly divided into a follow-up(blank control)group(n=70),an interferon treatment group(n=70),and a combined treatment group(n=71).The follow-up group received regular follow-ups.The interferon treatment group was treated with recombinant human interferon α-2b,and the combined treatment group received a combination of CO2 matrix laser and interferon treatment.The total effective rate,levels of inflammatory factors,and vaginal microecological recovery were compared among the three groups at 3 and 6 months after treatment.Results Overall efficacy:The overall efficacy rates of the combined treatment group at 3 months and 6 months were 73.24%and 81.69%,respectively,significantly higher than those of the interferon group(47.14%and 60.00%)and the blank control group(11.43%and 18.57%)(all P<0.001).Inflammatory factors:Post-treatment levels of IL-1 and TNF-α in the combined treatment group were significantly lower than those in the other two groups(P<0.001).Vaginal microbiota:The combined treatment group had a significantly higher rate of normal PH(84.51%)and normal lactobacillus levels(92.96%)compared to the other two groups(P<0.001).Conclusion CO2 lattice laser combined with interferon can effectively eliminate HPV,improve inflammation and vaginal microenvironment,and demonstrates superior efficacy to monotherapy,with good safety.
3.Characteristics of Oral Breath Odor Map of Chronic Atrophic Gastritis Patients with Dampness-Heat Syndrome: A Cross-Sectional Study
Xuejuan LIN ; Yanyu HUANG ; Long ZHU ; Donglin CAO ; Shanshan DING ; Xinghui LI ; Yingying HU ; Meng LAN ; Weirong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1687-1694
ObjectiveTo explore the recognition of oral breath odor map of chronic atrophic gastritis (CAG) patients with dampness-heat syndrome by electronic nose technique. MethodsPatients with chronic gastritis were recruited, including 60 cases in CAG group of dampness-heat syndrome, 50 cases in CAG group of non-dampness-heat syndrome, 60 cases in chronic non-atrophic gastritis (CNAG) group of dampness-heat syndrome, 50 cases in CNAG group of non-dampness-heat syndrome, and 30 cases of healthy volunteers were selected to set up the health control group. Ten cases in the CAG dampness-heat group and 50 cases in the CAG non-dampness-heat group were selected to form the CAG group, and 10 cases in CNAG dampness-heat group and 50 cases in CNAG non-dampness-heat group were selected to form the CNAG group. In addition to the health control group, the remaining patients were tested for Helicobacter pylori (Hp); the electronic nose (GISXM-MQWA01) was used to collect the oral breath odor of all the participants to draw the mapping, and amplitudes and slopes of each curve (including curves A, B, C, D, E, F, G, H, I, J) of the oral odor mapping of health control group, CAG group, CNAG group, CAG dampness-heat group, CAG non-dampness-heat group, and CNAG dampness-heat group was compared. The modified transformer model was used to classify the odor mapping characteristics, and the confusion matrix method was used to evaluate the classification model, with metrics including accuracy and area under ROC curve (AUC). ResultsThe Hp positivity rate in CAG dampness-heat group was 80.00% (48/60), CAG non-dampness-heat group was 62.00% (31/50), CNAG dampness-heat group was 46.67% (28/60), and CNAG non-dampness-heat group was 42.00% (21/50); the difference in Hp positivity rate between CAG dampness-heat group and CAG non-dampness-heat group was statistically significant (P<0.05). The amplitudes of response curves A, B, C, D, F, G, and I, and slopes of A and F in the odor mapping of the CAG group were lower than those in health control group, while the amplitude and slope of curve E were higher than those in the health control group and CNAG group (P<0.05 or P<0.01); The amplitude of the response curves A, B, C, D, F, G, and I, and slopes of A, D, and F in the CNAG group were lower than those in the health control group (P<0.05 or P<0.01). The amplitude of response curve D and slope of response curve J in the odor mapping of the CAG dampness-heat group were higher than those in CNAG dampness-heat group, the amplitude of curve F was lower than that in CAG non-dampness-heat group, and the amplitude of curve H and slopes of curve A, H, and J were higher than those in CAG non-dampness-heat group (P<0.05). The recognition accuracy of CAG group and health control group reached 77.78%, AUC = 0.88; the recognition accuracy of CAG group and CNAG group was 69.44%, AUC = 0.61; the recognition accuracy of CAG dampness-heat group and CAG non-dampness-heat group reached 75.8%, AUC=0.70. ConclusionElectronic nose technology can make a more accurate identification of the oral breath odor in CAG patients with dampness-heat syndrome, with a decrease in the amplitude of the curve F and an increase in the amplitude of the curve H and in the slopes of the curves A, H, and J may as the characteristics of their odor mapping.
4.Long-term efficacy and literature review of liver transplant recipients with hepatic myelopathy
Zhaoxian LI ; Yan XIE ; Li ZHANG ; Jisan SUN ; Yanyan SUN ; Xinghui YU ; Zhongyang SHEN ; Wentao JIANG
Chinese Journal of Organ Transplantation 2024;45(1):34-40
Objective:To explore the long-term therapeutic efficacy and outcomes of liver transplantation for patients with hepatic myelopathy (HM).Methods:Retrospective analysis of 24 adult liver transplantation recipients due to HM at First Central Municipal Hospital from January 2006 to October 2022. HM was extensively classified by the severity of lower extremity symptoms, degree of muscle stiffness, capability for independent ambulation and muscle strength. Furthermore, their long-term outcomes were examined. From January 2000 to October 2022, the databases of China National Knowledge Infrastructure (CNKI) , Google Scholar, PubMed and Web of Science were searched with such keywords as "肝性脊髓病and肝移植" "Hepatic Myelopathy and Liver Transplantation" .Results:After liver transplantation, liver functions and blood ammonia normalized and most clinical symptoms improved. During a follow-up period of (12-190) months, 19 patients showed a lowered grade of HC as compared to pre-transplantation. Four cases achieved a complete recovery of extremity function. No change occurred in severity grade for the remaining 5 patients. However, 4 of them experienced varying degrees of improvement in muscle strength and independent walking capability. This review summarized the clinical characteristics and clinical outcomes of 17 patients from both domestic and international sources. Most of them experiences varying degrees of symptomatic improvements after liver transplantation (16 cases).Conclusions:This study has confirmed the effectiveness of liver transplantation for HM and its contribution to the long-term patient recovery.
5.Association of the -c.108C>T and c. 192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women
Xinyuan ZHANG ; Ping FAN ; Qingqing LIU ; Xinghui LIU ; Huai BAI ; Yujie WU ; Suiyan LI
Chinese Journal of Medical Genetics 2024;41(7):866-871
Objective:To assess the association of -c.108C>T and c. 192Q>R polymorphisms of paraoxonase 1 ( PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women. Methods:This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c. 192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed.Results:No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c. 192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls ( P>0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE ( P = 0.007). Total antioxidant capacity(TAC)and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype ( P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype ( P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype ( P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype ( P = 0.015). Conclusion:The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.
6.Analysis of the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021
Jingbin PAN ; Tao ZHOU ; Luodan SUO ; Liyong YUAN ; Yaru QUAN ; Haihong WANG ; Xinghui PENG ; Tao WANG ; Zonglong ZHU ; Yanfei WANG ; Dan ZHAO ; Li LU
Chinese Journal of Preventive Medicine 2024;58(3):285-291
Objective:To analyze the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021.Methods:Herpes zoster cases were collected from a surveillance system in Beijing City from December 2017 to April 2021. The cases included individuals under 20 years old from seven sentinel hospitals located in two districts (Miyun District and Changping District). The basic information, the rash date of rash onset and the location and number of lesions were investigated at the first visit to the hospital, and the lesion swab samples were collected for laboratory testing. A telephone follow-up was conducted 21 days after the onset of the rash to investigate the degree of pain, duration of the rash and duration of pain. The individuals who still experienced neuralgia were further investigated for their pain condition at 90 days after the onset of the rash, to discover cases with postherpetic neuralgia. DNA was extracted from the rash fluid, and the ORF62 gene region was amplified and sequenced to obtain the viral sequence. The wild-type strain or chickenpox vaccine strain was identified by using sequence alignment, and the clinical characteristics of cases with different varicella vaccinations were compared.Results:A total of 78 herpes zoster cases under 20 years old were investigated during 2017-2021 in Beijing City, and 61 cases completed the follow-up survey. The age range of 61 cases was 1.83 to 20.54 years with a median age of 17.50 years. There were 36 males (59.02%) and 25 females (40.98%). Among them, there were 29 cases with the chickenpox vaccine immunization history (18 cases with one dose, 5 cases with two doses and 6 cases with unknown doses), 13 cases with no vaccination history and 19 cases with unknown vaccination history. Among the 78 cases, the herpetic fluid samples of 64 cases were positive for VZV, including 62 cases identified as wild-type strains and two cases as vaccine strains. The two vaccine strain cases were both 2-year-old girls who had received one dose of varicella vaccine and developed herpes zoster 3 months and 13 months after vaccination. Among the 29 cases with chickenpox vaccine immunization history, the majority had 10 to 49 lesions, accounting for 58.62% (17 cases). The trunk was the most common site of lesions, accounting for 44.83% (13 cases). About 51.72% (15 cases) reported "no or mild" pain intensity. The median ( Q1, Q3) scores for the worst pain, duration of pain and the time to crusting of lesions in the herpes zoster cases were 3 (1.5, 5) points, 10 (1.5, 12.5) days and 10 (6.5, 13) days, respectively. There was no statistically significant difference in the constituent ratio of the location of lesions, number of lesions and pain degree among the cases with vaccination history, without vaccination history and with unknown vaccination history ( P>0.05). There was also no statistically significant difference in the distribution of pain score, duration of lesions and duration of pain across the three groups ( P>0.05). Conclusion:Wild strains are the predominant pathogens in herpes zoster cases under 20 years old in Beijing City during 2017-2021. The varicella vaccination has no significant impact on the clinical manifestations of herpes zoster cases.
7.Analysis of the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021
Jingbin PAN ; Tao ZHOU ; Luodan SUO ; Liyong YUAN ; Yaru QUAN ; Haihong WANG ; Xinghui PENG ; Tao WANG ; Zonglong ZHU ; Yanfei WANG ; Dan ZHAO ; Li LU
Chinese Journal of Preventive Medicine 2024;58(3):285-291
Objective:To analyze the etiological features and clinical characteristics of herpes zoster cases under 20 years old in Beijing City from 2017 to 2021.Methods:Herpes zoster cases were collected from a surveillance system in Beijing City from December 2017 to April 2021. The cases included individuals under 20 years old from seven sentinel hospitals located in two districts (Miyun District and Changping District). The basic information, the rash date of rash onset and the location and number of lesions were investigated at the first visit to the hospital, and the lesion swab samples were collected for laboratory testing. A telephone follow-up was conducted 21 days after the onset of the rash to investigate the degree of pain, duration of the rash and duration of pain. The individuals who still experienced neuralgia were further investigated for their pain condition at 90 days after the onset of the rash, to discover cases with postherpetic neuralgia. DNA was extracted from the rash fluid, and the ORF62 gene region was amplified and sequenced to obtain the viral sequence. The wild-type strain or chickenpox vaccine strain was identified by using sequence alignment, and the clinical characteristics of cases with different varicella vaccinations were compared.Results:A total of 78 herpes zoster cases under 20 years old were investigated during 2017-2021 in Beijing City, and 61 cases completed the follow-up survey. The age range of 61 cases was 1.83 to 20.54 years with a median age of 17.50 years. There were 36 males (59.02%) and 25 females (40.98%). Among them, there were 29 cases with the chickenpox vaccine immunization history (18 cases with one dose, 5 cases with two doses and 6 cases with unknown doses), 13 cases with no vaccination history and 19 cases with unknown vaccination history. Among the 78 cases, the herpetic fluid samples of 64 cases were positive for VZV, including 62 cases identified as wild-type strains and two cases as vaccine strains. The two vaccine strain cases were both 2-year-old girls who had received one dose of varicella vaccine and developed herpes zoster 3 months and 13 months after vaccination. Among the 29 cases with chickenpox vaccine immunization history, the majority had 10 to 49 lesions, accounting for 58.62% (17 cases). The trunk was the most common site of lesions, accounting for 44.83% (13 cases). About 51.72% (15 cases) reported "no or mild" pain intensity. The median ( Q1, Q3) scores for the worst pain, duration of pain and the time to crusting of lesions in the herpes zoster cases were 3 (1.5, 5) points, 10 (1.5, 12.5) days and 10 (6.5, 13) days, respectively. There was no statistically significant difference in the constituent ratio of the location of lesions, number of lesions and pain degree among the cases with vaccination history, without vaccination history and with unknown vaccination history ( P>0.05). There was also no statistically significant difference in the distribution of pain score, duration of lesions and duration of pain across the three groups ( P>0.05). Conclusion:Wild strains are the predominant pathogens in herpes zoster cases under 20 years old in Beijing City during 2017-2021. The varicella vaccination has no significant impact on the clinical manifestations of herpes zoster cases.
8.-75 G/A Polymorphism of Apolipoprotein A1 Gene Promoter Region in Normal Pregnant Women and Patients With Gestational Diabetes Mellitus
Ruoyu LI ; Huai BAI ; Linbo GUAN ; Xinghui LIU ; Ping FAN ; Mi ZHOU ; Yujie WU ; Yufeng WANG ; Zhengting ZHU ; Guoyu WANG ; Yonghong WANG ; Dehua LI
Journal of Sichuan University (Medical Sciences) 2024;55(1):125-131
Objective To investigate the-75 G/A single-nucleotide polymorphism in the promoter region of apolipoprotein A1 gene(apoA1)and its association with gestational diabetes mellitus(GDM)in pregnant women and to provide references for the exploration in the molecular genetic basis of GDM.Methods A total of 626 GDM patients and 1022 normal pregnant women,ie,the controls,were included in the study.The genotyping of apoA1-75 G/A polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)analysis.Total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),and glucose(Glu)were measured by enzymatic methods.Plasma insulin(INS)was measured by chemiluminescence immunoassay.The protein levels of apoA1 and apoB were measured by the turbidimetric immunoassay.Results Allele frequencies of G and A were 0.718 and 0.282 in the GDM group and 0.713 and 0.287 in the control group,respectively.Distribution of the genotype frequencies was found to be in Hardy-Weinberg equilibrium in both the GDM and control groups.There was no significant difference in the frequencies of alleles G and A and the genotypes of apoA1-75 G/A polymorphism between the GDM and the control group(P>0.05).In the GDM group,the carriers with the genotype AA were associated with significantly higher levels of TC,HDL-C,and apoA1 than those with genotypes GG and GA did(all P<0.05).After the GDM patients were divided into obese and non-obese subgroups,the genotype-related apoA1 variation was observed only in obese patients,while the genotype-related TC and HDL-C variations were evident in non-obese patients(P<0.05).In the control group,carriers of genotypes AA and GA had higher systolic blood pressure(SBP)and HDL-C than the carriers of genotype GG did(all P<0.05).Carriers of genotypes AA had significantly lower Glu levels than carriers of genotypes GG and GA did(P<0.05).The control subjects were further divided into subgroups according to their body mass index(BMI).Analysis of the subgroups showed that AA carriers were associated with higher SBP levels in the obese control women only,while lower Glu levels were evident in both obese and non-obese control women.Conclusion These results suggest that-75 G/A polymorphism in the apoA1 gene is not associated with GDM.However,the genetic variation is closed associated with the plasma apoA1,HDL-C,and TC levels in GDM patients and plasma HDL-C,Glu,and SBP levels in the control subjects.The apoA1 variant-associated lipids and SBP variation is BMI dependent in both groups.
9.Assessment of Dietary Arsenic Exposure Levels and the Associated Health Risks in Chongqing City,China
Xinghui DAI ; Mintao LI ; Jiahui CHEN ; Ping FENG ; Jingrong CHEN ; Jian ZHAO ; Qianru ZHOU ; Shuquan LUO ; Huadong ZHANG ; Xiaofeng YAN ; Jiao HUO ; Xuemei LIAN
Journal of Sichuan University (Medical Sciences) 2024;55(6):1573-1580
Objective To determine the levels of arsenic in food in Chongqing city,and to assess the levels of dietary arsenic exposure and the associated potential health risks in residents of Chongqing city.Methods By using the monitoring data on arsenic levels in food in Chongqing between 2018 and 2023 in combination with the local dietary survey data for Chongqing from the 2018 China Nutrition and Health Survey Program,and adopting the 2-dimensional Monte Carlo simulation,we made an estimate of the dietary arsenic exposure levels of Chongqing residents.The margin of exposure(MOE)method was applied to assess both non-carcinogenic risks(skin damage)and carcinogenic risks(lung cancer and urinary system cancers)associated with dietary intake of arsenic.Results Out of 4900 food samples,the detection rate of arsenic was 36.40%,with the average levels ranging from the median bound(MB)of 0.020 7 to the upper bound(UB)of 0.023 4 mg/kg.The highest average levels were found in rice and its products,with an MB of 0.0981 and a UB of 0.098 5 mg/kg.The daily average exposure to inorganic arsenic for residents of different ages,sexes,and places of residence was highest in individuals aged 3 to 6,with an MB of 1.046 μg/(kg·d)and a UB of 1.116 μg/(kg·d),and lowest among individuals aged 60 and older.Arsenic exposure was higher in males than that in females and higher in people living in rural areas compared to those in urban areas.In terms of non-carcinogenic risks,the MOE values for inorganic arsenic were always higher than 1 in various populations.As for carcinogenic risks,the MOE values were all less than 100 in various populations.Rice and its products were the main source of dietary arsenic exposure in Chongqing,accounting for 69.97%to 74.37%of the total exposure.Conclusion The non-carcinogenic risk caused by dietary arsenic exposure in Chongqing is relatively low,but there may be a certain level of carcinogenic risk.Continued attentions should be given to dietary arsenic exposure levels in young children.
10.The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.
Yiwei ZHU ; Lin LEI ; Xinghui WANG ; Linfang CHEN ; Wei LI ; Jinxia LI ; Chenchen ZHAO ; Xiliang DU ; Yuxiang SONG ; Wenwen GAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2023;13(4):1616-1630
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.

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