Human beings are inevitably exposed to toxic substances as a result of influences of potential contamination factors in the environment,food and medicines,which poses a threat to human health.In order to effectively screen and prevent the exposure or intake of such substances,it is neces-sary to develop in vitro assays for the detection and toxicity evaluation of toxic substances.High content screening(HCS)has been recognized as an important tool for toxicity testing and risk assessment of compounds due to its high throughput and automation advantages,and has been widely used in in vitro toxicology research.In this review,we described the system components of HCS and its workflow in toxicity screening and toxicity evaluation by focusing on cases of their application in toxicity detection and evaluation studies,including the cytotoxicity,hepatotoxicity,nephrotoxicity,genotoxicity,neurotox-icity,cardiotoxicity,and developmental toxicity.In addition,the applications and developments of machine learning in HCS were explored,especially to the advantages of supervised and unsupervised machine learning strategies for high throughput image screening and data analysis.Finally,the future applications of HCS in toxicity screening and evaluation are outlined,especially in terms of binding new models and gene editing technology.

Objective:To analyze the ideal entry parameters and entry points for C 7 pedicle screws based on three-dimensional CT reconstruction model. Methods:A retrospective case series study was used to analyze the cervical spine CT image data of 50 adult volunteers collected from April 2021 to March 2022 at Taizhou People′s Hospital Affiliated to Nanjing Medical University, including 25 males and 25 females; aged 20-67 years [(43.8±13.5)years]. No significant structural abnormalities were seen in the cervicothorax of all volunteers. First, the 50 CT images were imported into the medical engineering software Mimics 17.0 to reconstruct the three-dimensional C 7 model, and the C 7 pedicle screw diameter (PSD), pedicle screw length (PSL), sagittal angle (SA) and lateral angle (LA) were measured. Then, the anatomical markers, namely the lateral notch and the midpoint of the inferior edge of the C 6 articular process, were used to measure the horizontal distance between the midpoint of the inferior edge of the C 6 articular process and the ideal entry point (line segment A), and the horizontal and vertical distances between the lateral notch and the ideal entry point (line segments B and C). Finally, the lateral notch and the midpoint of the inferior edge of the C 6 articular process were used as markers to observe the distribution of entry points. The values of the above measured parameters were recorded and compared with each other to analyze the differences between different sides and genders. Intra-group correlation coefficients (ICC) were also used to assess intra- and inter-observer agreement. Results:All 100 pedicles from 50 C 7 models were accessed, with the PSD being (6.5±0.7)mm, PSL being (31.8±4.5)mm, SA being (89.8±8.8)°, LA being (31.0±6.7)°, line segment A being 0.9(-0.4, 2.1) mm, line segment B being (5.8±1.7)mm, and line segment C being (3.6±1.5)mm. All ideal entry points were located medial above the lateral notch; moreover, with the midpoint of the inferior edge of the C 6 articular process as a reference, 71 (71%) of the entry points were located laterally and 29 (29%) were located medially. The 12 mm area around the midpoint of the inferior edge of the C 6 articular process was divided into 6 sections, with 47% of the entry points being located within 2 mm lateral to the midpoint, 25% within 2 mm medial to the midpoint, 19% within 2-4 mm lateral to the midpoint, and only 9% within 50% lateral to the midpoint. The measured parameters were not significantly different between the left and right sides (all P>0.05). The PSD, SA, and line segment B in males were (6.8±0.7)mm, (92.0±8.2)°, and (6.3±1.6)mm, which were significantly greater than those in females [(6.2±0.6)mm, (87.5±8.0)°, and (5.3±1.6)mm] (all P<0.01). The remaining parameters were similar between two genders (all P>0.05). All measured parameters had high intra- and inter-observer agreement (ICC: 0.84-0.91), except for line segment A that had moderate intra- and inter-observer agreement (ICC: 0.46-0.63). Conclusions:For C 7 pedicle screw implantation, when the surface of the lateral mass is used as the reference plane, SA is approximately 90°; with reference to the lateral notch, all the ideal entry points are located medially above it; with reference to the midpoint of the inferior edge of the C 6 articular process, approximately 70% of the entry points are located laterally. There are no significant differences in the parameters between the different sides of screw implantation on pedicles. The measured parameters show high intra- and inter-observer agreement, except for line segment A.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

Objective:To investigate the effects of acupoint massage combined with high-frequency repetitive transcranial magnetic stimulation on post-stroke depression and quality of life.Methods:A total of 169 patients with post-stroke depression who were admitted to the Department of Neurological Intensive Care Unit of Zhengzhou University First Affiliated Hospital from June 2017 to June 2019 were selected as the research subjects. The patients were divided into observation group (85 cases) and control group (84 cases) by random number table method. The control group was treated with high frequency repetitive transcranial magnetic stimulation, and the observation group was treated with high frequency repetitive transcranial magnetic stimulation combined with acupoint massage, high frequency repetitive transcranial magnetic stimulation 5 times a week, 28 minutes each time, 8 weeks of intervention, acupoint massage once a day, 1-2 minutes each acupoint, 8 weeks of intervention. The state of depression and the improvement of quality of life were observed, and the adverse reactions were recorded.Results:The total effective rate of depressive symptoms improvement in the observation group was 83.53% (71/85), which was higher than that of the control group 70.24% (59/84), the difference was statistically significant ( χ 2 value was 4.204, P<0.05). After the intervention, the Hamilton Depression (HAMD) scores of both groups decreased, and the trend decreased with time, and the decline of the observation group was higher than that of the control group, the difference was statistically significant ( Ftime value was 888.220, Fgroup value was 191.331, Finteraction value was 14.955, P<0.01 or 0.05). The observation group ′s physiological function, physiological function, energy, social function, general health status, emotional function, and mental health score were (57.25 ± 10.33), (64.41 ± 13.35), (67.26 ± 12.93), (70.43 ± 14.15), (64.64 ± 12.52), (72.71 ± 13.24), (75.24 ± 12.90) points, higher than the control group ′s (51.83 ± 10.22), (55.40 ± 12.90), (62.84 ± 12.81), (66.03 ± 13.94), (59.37 ± 11.26), (67.54 ± 13.07), (70.85 ± 12.66) points, the difference was statistically significant ( t value was 2.036-4.461, P<0.01 or 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusions:Acupoint massage combined with high-frequency repetitive transcranial magnetic stimulation has a effective in the treatment of post-stroke depression, which can significantly improve the depression status and quality of life.

Objective:To explore the effect of hydrogen sulfide (H 2S) on expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signal pathway in rats with intestinal ischemia/reperfusion (IRI) injury. Methods:Thirty male Wistar rats were divided into sham operation group (Sham group), IRI group, and H 2S precursor sodium hydrosuphide (NaHS) intervention group (IRI+NaHS group) by random number table method, with 10 rats in each group. The animal model of IRI was established by 60 minutes superior mesenteric artery (SMA) blockage with non-invasive vascular clamp and 120 minutes reflow. SMA was dissociated and peritoneum cavity was closed in Sham group. The rats in IRI+NaHS group was received NaHS (100 μmol/kg bolus+1.07 mmol·kg -1·h -1 infusion) 10 minutes prior to the onset of reperfusion, while the rats in IRI group and Sham group were received equal volume of normal sodium. Blood in vena cava was collected. H 2S was detected by sensitive sulfide electrode. Rats were sacrificed after blood collection. Histopathology change was observed by hematoxylin-eosin (HE) staining, ileal pathological score was studied by Chiu score. The protein expressions of phosphated Akt (p-Akt), Akt, PI3K, cleaved caspase-9, mammalian target of rapamycin (mTOR) were determined by Western Blot. Results:Compared with the Sham group, there was intestinal mucosa structure disorder edema and shedding villous fracture in the IRI group. Ileal pathological score in IRI group was significantly increased (4.21±0.15 vs. 0.15±0.03, P < 0.01), while plasma H 2S in IRI group was significantly decreased (μmol/L: 26.72±3.17 vs. 38.34±5.24, P < 0.01). Ileal p-Akt, PI3K, caspase-9 and mTOR protein in IRI group were significantly increased (p-Akt/GAPDH: 2.67±0.12 vs. 0.24±0.05, PI3K/GAPDH: 1.42±0.07 vs. 0.57±0.08, caspase-9/GAPDH: 4.23±0.61 vs. 0.13±0.02, mTOR/GAPDH: 2.17±0.23 vs. 0.23±0.02, all P < 0.01). Compared with the IRI group, pathological changes of intestinal mucosa in the IRI+NaHS group was improved, ileal pathological score was significantly decreased (1.56±0.02 vs. 4.21±0.15, P < 0.01), plasma H 2S was significantly increased (μmol/L: 32.36±2.45 vs. 26.72±3.17, P < 0.01) and ileal p-Akt, PI3K were significantly increased (p-Akt/GAPDH: 5.12±0.08 vs. 2.67±0.12, PI3K/GAPDH: 3.14±0.05 vs. 1.42±0.07, both P < 0.01), while caspase-9, mTOR in IRI+NaHS group were significantly decreased (caspase-9/GAPDH: 2.12±0.24 vs. 4.23±0.61, mTOR/GAPDH: 1.37±0.28 vs. 2.17±0.23, both P < 0.01). Conclusion:H 2S attenuates intestinal injury in IRI rats by up-regulating PI3K/Akt signal pathway and down-regulating caspase-9 and mTOR.

Objective: To investigate the potential risk factors for influencing renal recovery at discharge in critically ill patients with acute kidney injury (AKI) requiringcontinuous renal replacement therapy (CRRT). Methods: This was a single-center, retrospective study. Critically ill patients with AKI requiring CRRT adimitted to the Department of Intensive Care Unit (ICU) in Taizhou Municipal Hospital, Zhejiang province, from June 2014 to December 2017 were included and divided into two groups according to the status of renal recovery at discharge as renal recovery group and renal non-recovery group. The data of acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score at adimission to ICU, initial serum creatinine (initial SCr) and lactate level and initial estimated glomerular filtration rate (initial eGFR) at time of AKI diagnosis, and total time of RRT and duration of anuria before CRRT were analyzed. Length of ICU stay and length of hospital stay in both groups were also analyzed. Multivariate logistic regression was taken to analyze the potential risk factors for influencing renal recovery at discharge in critically ill patients with AKI. Results: A total of 115 critically ill patients with AKI requiring CRRT were included, of which whom 45 cases were in renal recovery group and 70 cases were in renal non-recovery group, and the renal recovery rate at discharge was 39.1%(45/115); 59 patients were dead during hospitalization and the hospital mortality was 51.3%(59/115). Compared with renal non-recovery group, renal recovery group have a lower value of APACHEⅡ score [(21.73 ± 2.66) scores vs. (23.19 ± 4.41) scores, P=0.03), SOFA score [(11.02 ± 2.22) scores vs. (12.79 ± 2.82) scores, P=0.001], lactate level [(3.82 ± 1.34) mmol/L vs. (4.47 ± 1.52) mmol/L, P=0.021], initial SCr [(2.151 ± 0.677) mg/dl vs. (2.505 ± 0.792) mg/dl, P=0.015], duration of anuria before CRRT[(11.80 ± 4.71) h vs. (19.11 ± 5.98) h, P=0.005] and total time of RRT [(8.64 ± 3.42) d vs. (15.81 ± 5.07) d, P=0.001], and have a higher value of initial eGFR [(36.26 ± 14.74) ml/(min·1.73 m²) vs. (30.07 ± 10.38) ml/(min·1.73 m²), P=0.009]. In addition, length of ICU stay [(12.58 ± 4.78) d vs. (15.30 ± 5.45) d, P=0.007] and length of hospital stay [(19.58 ± 6.44) d vs. (22.11 ± 5.90) d, P=0.032] in renal recovery group were also significantly lower than those in renal non-recovery group. Multivariate logistic regression analysis indicated that SOFA score (OR=0.700, 95% CI 0.521-0.941, P=0.018), duration of anuria before CRRT (OR=0.782, 95%CI 0.689-0.888,P < 0.01) and total time of RRT (OR=0.673, 95% CI 0.565-0.801; P < 0.01) were independent risk factors influencing renal recovery at discharge in critically ill patients with AKI, and initial eGFR was a independent protective factor. Conclusions As to critically ill patients with AKI requiring CRRT, there are many factors that affect renal recovery at discharge,. SOFA score, duration of anuria before CRRT and total time of RRT are independent risk factors, and initial eGFR is an independent protective factor.

Objective: To investigate the effect of three-dimensional conformal radiotherapy (3D-CRT) combined with PC chemotherapy (paclitaxel + carboplatin) on non-small cell lung cancer (NSCLC) patients and the serum levels of CA125, tissue inhibitor of metalloproteinase-1 (TIMP-1), serum amyloid A (SAA) and T-lymphocyte subsets. Methods: A total of 100 patients with NSCLC treated in Affiliated Hospital of Guangdong Medical University from May 2015 to December 2017 were selected as the study subjects. They were divided into control group and observation group according to random number table method, with 50 cases in each group. The observation group was treated with 3D-CRT combined with PC chemotherapy, while the control group was treated with PC chemotherapy. The two groups were treated for 4 cycles. The therapeutic effect, serum CA125, TIMP-1, SAA, T-lymphocyte subsets and adverse reactions were compared between the two groups. Results: Four cases were lost to follow-up both in the two groups. The overall response rate in the observation group (43.48%, 20/46) was higher than that in the control group (23.91%, 11/46; χ²=3.941, P=0.047). The serum levels of CA125, TIMP-1 and SAA of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The serum levels of CA125, TIMP-1 and SAA in the observation group after treatment were (12.31±1.13) U/ml, (275.31±13.69) pg/ml and (47.21±7.21) mg/L, which were lower than those in the control group [(30.36±1.98) U/ml, (320.36±17.23) pg/ml, (65.92±8.36) mg/L], with significant differences (t=53.699, P<0.001; t=13.884, P<0.001; t=11.495, P<0.001). The levels of CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺ /CD8⁺ of the two groups had no significant difference before treatment, and the levels of these indexes decreased after treatment. The levels of CD3⁺ , CD4⁺ , CD8⁺ and CD4⁺ /CD8⁺ in the observation group were (35.27±10.31)%, (20.27±6.72)%, (15.89±3.37)% and 0.91±0.37, which were higher than those in the control group [(30.77±9.27)%, (15.27±5.73)%, (12.02±2.69)% and 0.75±0.39], with significant differences (t=2.201, P=0.030; t=3.840, P<0.001; t=6.087, P<0.001; t=2.019, P=0.047). There were no significant differences in the adverse reactions such as nausea and vomiting [63.04% (29/46) vs. 43.48% (20/46); χ²=3.537, P=0.060], phlebitis [6.52% (3/46) vs. 4.35% (2/46); χ²=0.000, P>0.999], abnormal liver function [6.52% (3/46) vs. 2.17% (1/46); χ²=0.261, P=0.609] and myelosuppression [8.70% (4/46) vs. 6.52% (3/46); χ²=0.000, P>0.999] between the observation group and the control group. Conclusion For patients with NSCLC, 3D-CRT combined with PC chemotherapy can improve the overall response rate, decrease the levels of serum CA125, TIMP-1 and SAA, and improve the immune function of patients. The therapeutic effect is remarkable and the safety is good. The therapeutic scheme is suitable for the treatment of NSCLC.

Trichuris suis infection in pigs is ubiquitous in intensive and extensive farms, which causes potential threat to human health. The objective of this research was to investigate the prevalence of T. suis in pigs in Hunan province. Total 2,267 fresh fecal samples distributed in 28 pig farms from 7 different administrative regions (Hunan province) were evaluated for the existence of T. suis eggs using saturated NaCl floating method. The average infection rate of T. suis in pigs was 8.91% in Hunan province. To determine genetic variation of the gained T. suis isolates in the present study, the internal transcribed spacer (ITS) regions from nuclear ribosomal DNA (rDNA) of 7 T. suis isolates were cloned and analyzed. Nucleotide diversities were 1.0–3.5% and 0–3.8% for ITS-1 and ITS-2, respectively. Phylogenetic analyses indicated that all isolates collected in the present study and T. suis available in Genbank generated a monophyletic clade. The present investigation revealed high infection rates of T. suis in pigs in Hunan province, which shed light on making effective measures to prevent and control T. suis infection in pigs in Hunan province.
Agriculture ; China ; Clone Cells ; Databases, Nucleic Acid ; DNA, Ribosomal ; Eggs ; Genetic Variation ; Humans ; Methods ; Ovum ; Prevalence ; Swine ; Trichuris

AIM:To investigate the effect of hydrogen sulfide (H2S) on the expression of MAPKs and ileal epithelial cell apoptosis in the rats with intestinal ischemia-reperfusion ( I/R) injury.METHODS:Healthy female Wistar rats were randomly divided into sham operation group, I/R group, I/R+sodium hydrosulfide ( NaHS) group .The animal model of intestinal ischemia reperfusion was established.Apoptosis index ( AI) of ileal epithelial cell was measured by TUNEL assay.H2 S was detected by sensitive sulfide electrode.The mRNA expression of ERK, JNK and p38MAPK was detected by RT-PCR.The protein levels of phosphorylation( p)-ERK, p-JNK, p-NF-κB P65 and p38MAPK were deter-mined by Western blot.RESULTS:H2 S, ERK mRNA and p-ERK in I/R group were significantly higher than those in I/R+NaHS group and sham group while JNK mRNA, p38MAPK mRNA, p-JNK, p-p38MAPK, p-NF-κB P65 and AI were predominantly higher than those in I/R+NaHS group and sham group (P<0.01).CONCLUSION:H2S attenuates ileal epithelial cell apoptosis in the rats with intestinal I/R injury by down-regulating ERK mRNA p-ERk and up-regulating JNK mRNA, p38MAPK mRNA and phosphorylation of JNK, p38MAPK and NF-κB P65.

Objective To study the change in endogenous hydrogen sulfide (H2S) in patients with acute pancreatitis and its relationship to coagulation function. Methods A prospective case control study was conducted. Forty patients with mild acute pancreatitis (MAP group) and 40 with severe acute pancreatitis (SAP group) admitted to Yiwu Central Hospital in Zhejiang Province from December 2002 to March 2015 were enrolled. Forty healthy persons served as control (healthy control group). Blood was collected to determine the levels of H2S, blood coagulation factor Ⅷ (FⅧ), von Willebrand factor (vWF), plasminogen (PLG), antithrombin (AT), platelet count (PLT), tissue factor (TF), tumor necrosis factor-α (TNF-α), and protease activated receptor-1 (PAR-1). The correlations among the above parameters were analyzed. Results There was no statistical significance in sex, age, body weight and time of disease among three groups, indicating it was comparable among the groups. Compared with healthy control group, the levels of H2S, FⅧ, vWF, TF, TNF-α, and PAR-1 in MAP and SAP groups were significantly elevated [H2S (μmol/L): 67.42±6.34, 112.47±12.69 vs. 42.57±4.18, FⅧ: (67.5±5.8)%, (82.3±4.7)% vs. (57.2±6.4)%, vWF: (112.6±9.7)%, (142.5±12.5)% vs. (76.4±8.2)%, TF (ng/L): 45.27±4.34, 64.76±6.25 vs. 18.15±1.89, TNF-α (ng/L): 197.67±13.62, 324.72±25.54 vs. 20.08±2.57, PAR-1 (fluorescence intensity): 32.16±4.43, 56.12±7.07 vs. 12.27±2.12, all P < 0.01], and PLG and AT activity were significantly decreased [PLG: (52.4±4.7)%, (36.7±3.2)% vs. (62.1±5.6)%, AT: (43.2±6.9)%, (35.5±5.4)% vs. (53.6±6.1)%, all P < 0.01]. The changes in the parameters in SAP group were more remarkable than those in MAP group (all P < 0.01). PLT in SAP group was significantly lower than that in healthy control and MAP groups (×109/L: 8.5±1.1 vs. 15.7±2.8, 12.4±1.9, both P < 0.01). H2S was positively correlated with FⅧ, vWF, TF, TNF-α, and PAR-1 (r value was 0.56, 0.61, 0.72, 0.66, 0.64, respectively, all P < 0.01), and it was negatively correlated with PLG and AT (r value was -0.64, -0.57, both P < 0.01). Conclusion As an inflammatory factor, endogenous H2S deteriorates coagulation function in patients with acute pancreatitis by up-regulating TF, TNF-α, and PAR-1.