ObjectiveTo investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning.Methods Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2×107 TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Results Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value):0.237±0.075 vs. 0.674±0.011, PON1 protein (gray value): 0.602±0.086 vs. 0.998±0.124, Nrf2 mRNA (gray value): 0.089±0.012 vs. 0.126±0.010, GSH (mg/g): 3.84±0.33 vs. 5.52±0.40, SOD (μg/g): 0.383±0.040 vs. 0.564±0.052, CAT (ng/g): 7.32±1.28 vs. 12.46±1.54, allP< 0.05], and remarkable increase in MDA content (nmol/g: 7.78±0.41 vs. 2.34±0.25,P< 0.05). With the extension of time, PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels gradually increased, MDA content gradually decreased, Nrf2 mRNA expression level had risen to the level of control group at 24 hours (0.133±0.019 vs. 0.126±0.009,P> 0.05), and it was higher than that of the control group at 48 hours (0.206±0.028 vs. 0.124±0.010,P< 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726±0.021 vs. 0.237±0.075, PON1 protein (gray value): 0.739±0.050 vs. 0.602±0.086, Nrf2 mRNA (gray value): 0.158±0.007 vs. 0.089±0.012, GSH (mg/g): 4.30±0.22 vs. 3.84±0.33, SOD (μg/g): 0.454±0.062 vs. 0.383±0.040, CAT (ng/g): 8.98±1.02 vs. 7.32±1.28, allP< 0.05], and a decrease in MDA content (nmol/g: 6.56±0.44 vs. 7.78±0.41,P< 0.05).Conclusion Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.

Objective:To explore the clinical characteristics of patients with colchicine poisoning, and analyze the risk factors affecting the prognosis of colchicine poisoning and its value in the prognostic assessment.Methods:Patients with colchicine poisoning admitted to the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to October 2022 were retrospectively included and divided into the survival group and death group according to the 14-d outcome. The general conditions of the two groups of patients were compared, and the clinical characteristics of patients with colchicine poisoning were analyzed. The differences of laboratory indexes, electrocardiogram, cardiac ultrasound and other clinical indexes during the first admission of patients between the two groups were compared, and their value in the prognosis evaluation of patients with colchicine poisoning was explored.Results:There were 41 patients with colchicine poisoning, aged 15-85 years, including 35 males and 6 females. There were 27 patients (65.9%) in the survival group and 14 patients (34.1%) in the death group, including accumulative poisoning (58.7%) and suicide poisoning (41.3%). The main clinical manifestations of patients with colchicine poisoning were gastrointestinal symptoms (82.93%), multiple organ dysfunction (78.05%), infectious fever (73.17%), myocardial damage (48.78%), coagulation dysfunction (46.34%), and bone marrow suppression (41.46%). Intestinal obstruction (19.51%) and rhabdomyolysis (2.44%) occurred in some patients. Multivariate Logistic regression analysis showed that the increase in absolute value of QTc interval ( OR=1.028, 95% CI: 1.000~1.056, P<0.05), lactic acid ( OR=1.599, 95% CI: 1.088~2.350, P<0.05), prothrombin time ( OR=1.205, 95% CI: 1.002~1.450, P<0.05), D-dimer ( OR=1.242, 95% CI: 1.089~1.417, P<0.05), and alkaline phosphatase ( OR=1.013, 95% CI: 1.002~1.024, P<0.05) were the risk factors for the prognosis of patients with colchicine poisoning. The decrease in the absolute value of ADL score ( OR=0.947, 95% CI: 0.909~0.988, P<0.05) and indirect bilirubin ( OR=0.756, 95% CI: 0.572~0.999, P<0.05) were the protective factors for the prognosis of patients with colchicine poisoning. D-dimer (AUC=0.913), lactic acid (AUC= 0.875) and alkaline phosphatase (AUC=0.770) had predictive value for the prognosis of patients with colchicine poisoning, and their cut-off values were 8.965 mg/L, 4.05 mmol/L and 230.5 U/L, respectively. Conclusions:The patients with colchicine poisoning have multiple organ dysfunction on admission, and are in a critical condition. The early levels of D-dimer, lactic acid and alkaline phosphatase could effectively predict the prognosis of patients with colchicine poisoning.

Objective:To explore the predictive value of the serum C-reactive protein (CRP)/albumin (ALB) ratio (CAR) for organ damage in tsutsugamushi disease.Methods:The clinical data of 166 patients with tsutsugamushi disease admitted to the First Affiliated Hospital of Wenzhou Medical University from January 1, 2010 to December 31, 2020 were retrospectively analyzed. The patients were divided into the organ damage group (72 cases) and non-organ damage group (94 cases) according to the organ damage criteria. The general data and laboratory test results of the two groups of patients were compared. The significant indicators of univariate analysis were analyzed by multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of CAR for organ damage in patients with tsutsugamushi disease.Results:There were no significant differences in age, sex, days of fever, and admission body temperature between the organ damage group and non-organ damage group ( P>0.05). However, the body mass index, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA), length of hospital stay, hospitalization expense, percentage of neutrophils (NEUT), lymphocyte count, procalcitonin, CRP, and CAR in the organ damage group were significantly higher than those in the non-organ damage group ( P<0.05), and ALB was significantly lower than that in the non-organ damage group ( P<0.05). Multivariate logistic regression analysis showed that APACHEⅡ( P=0.039), NEUT ( P=0.003), and CAR ( P=0.011) were independent risk factors for tsutsugamushi disease complicated by organ damage. The ROC curve showed that the AUCs of APACHEⅡ, NEUT, and CAR were 0.655, 0.716, and 0.727, respectively. When the cut-off value of CAR was 2.86, the sensitivity was 55.6%, and the specificity was 79.8%. Conclusions:Elevated CAR is an independent risk factor for tsutsugamushi disease complicated with organ damage and can be used as an important indicator to evaluate the presence or absence of organ damage in patients with tsutsugamushi disease.

Objective:To explore the relationship between hematocrit, early fluid therapy, and clinical outcomes in patients with septic shock, and to provide evidence for fluid resuscitation therapy and prognosis assessment in these patients.Methods:The clinical information of patients with septic shock who were diagnosed and treated in the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2018 to December 31, 2020 were collected. Taking the survival or death of patients 28 days after admission as the end point of clinical research, the patients were divided into the survival and death groups. After analyzing the basic data of the two groups, the univariate and multivariate COX regression analyses were used to analyze the evaluation value of Δ Hematocrit (HCT) d2-d1 and ΔHCT d3-d1 on the prognosis of patients with septic shock. At the same time, the Kaplan-Meier survival curve was used to analyze the overall survival rate of patients with septic shock, and the smooth curve fitting graph was used to verify its relationship with net fluid intake and death. Results:There were 241 cases in the survival group and 67 cases in the death group. Univariate COX analysis showed statistically significant differences between the survival and death groups in acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) ( P=0.0006), red cell volume distribution width (RDW) ( P=0.0043), age ( P=0.0184), ΔHCT d2-d1 ( P=0.0136), ΔHCT d3-d1 ( P=0.0204), and white blood cell (WBC) ( P=0.0444). Multivariate COX analysis showed that ΔHCT d2-d1 ( P=0.0115) and ΔHCT d3-d1 ( P=0.0029) were independent risk factors for death in EICU patients with septic shock. ΔHCT d2-d1 and ΔHCT d3-d1 were divided into three groups according to the three-digit method. The Kaplan-Meier survival curve showed no significant difference among the three groups in the overall survival rate related to ΔHCT d2-d1 ( P=0.16), but there was a statistically significant difference in the overall survival rate among the three groups related to ΔHCT d3-d1 ( P=0.025). The smooth fitting curve of ΔHCT d3-d1, net fluid intake, and prognosis showed that ΔHCT d3-d1 was negatively correlated with net fluid intake, and the middle ΔHCT d3-d1 group had the best prognosis. Conclusions:The value of ΔHCT d3-d1 is related to the net fluid intake of patients with septic shock. An appropriate decrease in HCT on the third day can improve the prognosis of patients with septic shock. The dynamic changes of hematocrit can provide a certain basis for fluid resuscitation and prognosis evaluation in patients with septic shock.

Objective To analyze the accuracy of the new generation intraocular lens(IOL)formula and the Wang-Koch(WK)adjustment in individuals with severe myopia undergoing combined anterior-posterior surgery.Methods A total of 100 patients(100 eyes)with axial length(AL)＞26 mm undergoing combined anterior and posterior segment surgery in our department from June 2015 to June 2021 were enrolled in this study.Totally 13 IOL calculation formulas,such as Barrett Universal Ⅱ(BU Ⅱ),Emmetropia Verifying Optical(EVO),Kane,Haigis,Hoffer Q,Holladay,and SRK/T as well as the first generation linear WK eye axis optimization formula(Haigis-WK1,SRK/T-WK1,Hoffer Q-WK1,Holladay 1-WK1)and the second generation linear WK eye axis optimization formula(SRK/T-WK2,Holladay 1-WK2),were utilized to determine IOL diopter.The mean prediction error(ME),mean absolute error(MAE),median absolute error(MedAE),and percentage of prediction error within different refractive thresholds were calculated to assess the accuracy of each formula.In order to investigate the impact of AL on accuracy of IOL calculation,the patients were categorized into group A(38 eyes,26.00 mm＜AL≤28.00 mm),group B(28 eyes,28.00 mm＜AL≤30.00 mm),and group C(34 eyes,AL＞30.00 mm).Additionally,the patients were also divided into silicone oil(63 eyes)and non-silicone oil(37 eyes)groups based on preoperative intraocular filling to determine the effect of intraocular filling on IOL calculation.Results The MedAE values of the new-generation IOL formulas(BU Ⅱ,EVO,and Kane)were significantly lower(0.34D,0.31D,0.35D)than those of traditional formulas(P＜0.05).Additionally,the percentage of prediction errors within±0.25 D,±0.50 D,±0.75 D,and±1.00 D were significantly higher with the new formulas when compared to traditional ones(P＜0.05).Traditional formulas exhibited a hyperopic deviation(0.35D～0.65 D),which could be corrected using the WK eye axis adjustment.WK2 was effective in improving the accuracy of calculation in SRK/T and Holladay 1 formulas,and there was no statistical difference in the MedAE values of SRK/T-WK2 and Holladay 1-WK2 formulas with the new-generation IOL formulas.When comparing the formulas across different axial eye length groups in terms of MedAE,the new IOL formulas(BU Ⅱ,kane and EVO)and WK-corrected formulas(Haigis-WK1,SRK/T-WK 1,SRK/T-WK2,Hoffer Q-WK1,Holladay 1-WK1,Holladay 1-WK2)showed no significant differences among the different AL groups.However,there were significant differences in the MedAE values of traditional formulas among the different AL groups(P＜0.01),with group C displaying the largest MedAE values(Haigis:0.84D,SRK/T:1.10D,Hoffer Q:1.23D,Holladay 1:1.20D).Comparing the MedAE values of different formulas in various preoperative intraocular filling groups,it was observed that the MedAE values of the new-generation IOL formulas(BU Ⅱ,kane and EVO),Haigis,and SRK/T formulas were significantly higher in the silicone oil-filled eye group than the non-silicone oil-filled eye group(P＜0.05).Conclusion In patients with high myopia undergoing combined anterior and posterior segment surgery,the precision and consistency of the new-generation IOL formulas and the second-generation linear WK axis correction formula exhibit significant improvements when compared to traditional formulas.

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.