Objective To investigate the effects and mechanisms of oridonin(ORI)on human keloid-derived fi-broblasts(HKF).Methods The effects of ORI on the proliferation activity of HKF were assessed using the CCK-8 assay.The experiment was divided into control and experimental groups.Cell scratch and Transwell assays were conducted to evaluate the migration and invasion capabilities of HKF.Real-time quantitative PCR(RT-qPCR)and Western blot were used to examine the impact of ORI on the expression of extracellular matrix-related mRNA and fi-bronectin 1(FN1),α-smooth muscle actin(α-SMA),type Ⅰ collagen(COL Ⅰ),and COL Ⅲ in HKF.The ex-periment was also divided into control,model,and transforming growth factor(TGF)-β1+ORI groups.RT-qPCR and Western blot were utilized to determine the effects of ORI on the expression of TGF-β1-induced mRNA and nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),Smad2,Smad3,phosphorylated Smad2(p-Smad2),and p-Smad3 in HKF.Results CCK-8 assay demonstrated that the cell inhibition rate of HKF progressively increased with increasing concentra-tions of ORI.Compared with the control group,the experimental group exhibited a significant reduction in the mi-gration area at 24 hours and a decrease in the number of invasive cells.Furthermore,there was a significant down-regulation in the expression levels of FN1,α-SMA,COL Ⅰ,and COL Ⅲ(P＜0.05).In comparison with the con-trol group,the model group showed a significant upregulation in the expression of NLRP3,ASC,Smad2,Smad3,p-Smad2,and p-Smad3(P＜0.05).Relative to the model group,the TGF-β1+ORI group demonstrated a signifi-cant downregulation in the expression of NLRP3,ASC,Smad2,Smad3,p-Smad2,and p-Smad3(P＜0.05).Conclusion ORI the proliferation,migration,and invasiveness of HKF,as well as the formation and deposition of the extracellular matrix,through the blockade of the TGF-β1/Smad signaling pathway and the NLRP3-mediated in-flammatory response.

BACKGROUND: Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer. METHODS: MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I2 statistic, and publication bias was evaluated using a Deeks' funnel plot and linear regression test. RESULTS: A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies. CONCLUSIONS Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.
Humans ; Adult ; Middle Aged ; Aged ; Lung Neoplasms/diagnostic imaging* ; Early Detection of Cancer ; Sensitivity and Specificity ; Mass Screening ; Tomography, X-Ray Computed

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are leading causes of long-term disability. It is estimated that more than half of the survivors of severe unilateral injury are unable to use the denervated limb. Previous studies have focused on neuroprotective interventions in the affected hemisphere to limit brain lesions and neurorepair measures to promote recovery. However, the ability to increase plasticity in the injured brain is restricted and difficult to improve. Therefore, over several decades, researchers have been prompted to enhance the compensation by the unaffected hemisphere. Animal experiments have revealed that regrowth of ipsilateral descending fibers from the unaffected hemisphere to denervated motor neurons plays a significant role in the restoration of motor function. In addition, several clinical treatments have been designed to restore ipsilateral motor control, including brain stimulation, nerve transfer surgery, and brain-computer interface systems. Here, we comprehensively review the neural mechanisms as well as translational applications of ipsilateral motor control upon rehabilitation after CNS injuries.
Animals ; Spinal Cord Injuries/therapy* ; Motor Neurons/physiology* ; Brain ; Stroke ; Recovery of Function/physiology*

Prognostication of coma patients after brain injury is important, yet challenging. In this study, we evaluated the predictive value of amplitude-integrated electroencephalography (aEEG) for neurological outcomes in coma patients. From January 2013 to January 2016, 128 coma patients after acute brain injury were prospectively enrolled and monitored with aEEG. The 6-month neurological outcome was evaluated using the Cerebral Performance Category Scale. aEEG monitoring commenced at a median of 7.5 days after coma onset. Continuous normal voltage predicted a good 6-month neurological outcome with a sensitivity of 93.6% and specificity of 85.2%. In contrast, continuous extremely low voltage, burst-suppression, or a flat tracing was correlated with poor 6-month neurological outcome with a sensitivity of 76.5% and specificity of 100%. In conclusion, aEEG is a promising predictor of 6-month neurological outcome for coma patients after acute brain injury.
Brain ; physiopathology ; Brain Injuries ; complications ; diagnosis ; physiopathology ; Coma ; diagnosis ; etiology ; physiopathology ; Electroencephalography ; methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neurophysiological Monitoring ; methods ; Prognosis ; Prospective Studies ; Sensitivity and Specificity ; Severity of Illness Index

Objective: To verify whether the enzymatic activity of kynureninase (KYNU) could be changed by the Arg188Gln (G/A) mutation. Methods: The total RNA of human hepatic tissue was extracted and the KYNU gene cDNA was amplified by RT-PCR. Primers were designed according to the sequences around the site Arg188Gln of KYNU gene and the Arg188Gln (G/A) mutant KYNU cDNA was generated by site-directed mutagenesis. Both the wild-type and mutant-type KYNU genes were subcloned into pcDNA vectors and the recombinant plasmids were constructed. After being transfected into human embryonic kidney 293 (HEK293) cells, the expression of KYNU recombinant plasmids were assessed by Western blot. The enzymatic activities of KYNU were detected by high performance liquid chromatography (HPLC). Results: The KYNU enzyme activities were expressed in both wild and mutant HEK293 cells. Michaelis constants (Km) of the wild and mutant KYNU were (9.833±0.513) μmol/L and (29.900±0.265) μmol/L, respectively (P<0.05). The maximum velocities (Vmax) of the wild and mutant KYNU were (0.700±0.096) nmol·mg^-1·min^-1 and (0.084±0.003) nmol·mg^-1·min^-1, respectively (P<0.05). Conclusion: Arg188Gln (G/A) mutation can decrease the enzymatic activity of KYNU.
Arginine ; genetics ; Enzyme Activation ; genetics ; HEK293 Cells ; Humans ; Hydrolases ; genetics ; metabolism ; Mutation ; Plasmids

Objective To evaluate the influence of dosage,operation method,adverse reaction of endoscopic photodynamic therapy (EPDT) on its therapeutic efficacy in rabbit models of in-situ rectal cancer,so as to provide preclinical basis of photodynamic therapy for rectal cancer.Methods 20 rabbits with in-situ VX2 rectal cancer were randomly divided into control group,PDT low dose group,intermediate dose group,and high dose group.At 24 h before PDT,photosensitizer (hermimether) was intravenously injected into rabbits.630 nm semiconductor laser was used as light source.The growth of the tumor was observed by conventional endoscopy and endoscopic ultrasonography,and the survival time,general conditions and adverse reactions were recorded.The histopathological changes were observed by hematoxylin-eosin staining.Results At 7 d after PDT,the total response rates of low dose,intermediate dose and high dose group respectively were 40％ (slight),80％ (60％ remarkable and 20％ slight),100％ (20％ remarkable and 80％ slight).The average survival times of the three groups were 14 d,10 d and 5 d,respectively.The main adverse reactions were inflammation,intestinal obstruction,intestinal peristalsis loss and death.Conclusions The dosage of PDT is an important factor to influence the curative effect.The appropriate dose of PDT will have a better effect on the treatment of rectal cancer.A thorough study of these problems is helpful to the clinical application of PDT in the treatment of rectal cancer.

Objective To compare the differences in setup error ( SE) assessment and correction between three-dimensional cone-beam computed tomography ( 3DCBCT ) and four-dimensional CBCT ( 4 DCBCT ) in breast irradiation patients during free breathing after breast-conserving surgery . Methods Twenty patients with breast cancer after breast-conserving surgery were recruited for external beam breast irradiation and 4DCBCT and 3DCBCT simulation. The target volumes were delineated. Volumetric modulated arc therapy plans were designed using the MONACO v510 treatment planning system. 3DCBCT and 4DCBCT images were collected alternately five times each before breast irradiation. The CT images were matched, and the interfraction SEs were acquired. After online setup correction, the residual errors were calculated, and the SEs, systematic errors, and random errors were compared. The paired t test was used for comparison between groups. Results The SEs acquired by 4DCBCT were significantly larger than those acquired by 3DCBCT in three directions ( P=0035, 0018, 0040 ) . After online setup correction, the random errors based on 3DCBCT were significantly smaller than those based on 4DCBCT in left-right and anterior-posterior ( AP ) directions ( 0.5± 039 mm vs. 0.7± 030 mm, P=0005;0.9± 109 mm vs. 1.2± 048 mm, P=0000) , and the residual errors based on 3DCBCT were also significantly smaller than those based on 4DCBCT in AP direction (0.2±033 mm vs. 0.6±063 mm, P=0000). The setup margins based on 4DCBCT was significantly larger than those based on 3DCBCT in AP direction both before and after online setup correction (P=0002). Conclusions Compared with 3DCBCT, 4DCBCT has more advantages in monitoring the SEs in three directions. Both 3DCBCT and 4DCBCT have similar efficacy in random error correction. The satisfying position repeatability and minimized target volume margins will be achieved by online setup correction.

Objective To compare the difference between volume computed tomography dose index (CTDIvol) and size-specific dose estimates (SSDE) in evaluating the radiation dose of abdominal CT scan.Methods Abdominal CT scan were performed on 180 patients with a Philips 256-slices spiral CT.The anterior-posterior dimension (AP) and lateral dimension (LAT) of each patients were measured at the level of left renal vein, and the effective diameter (ED) and SSDE were calculated with recorded CTDIvol Patients were categorized into 3 groups depending on body mass index (BMI): group A, BMI ＜ 20.0 kg/m2;group B, 20.0-24.9 kg/m2;group C, BMI ＞ 24.9 kg/m2.The differences between CTDIvoland SSDE of 180 patients and three different BMI groups were compared respectively.Results There was a significant difference between CTDIvol and SSDE of the 180 patients (t =-13.354, P ＜ 0.01), CTDIvol and SSDE were (9.91 ± 2.91) and (14.01 ± 2.82) mGy, respectively.For group A, CTDIvol and SSDE were (7.96 ± 1.83) and (12.83 ± 2.52) mGy, respectively (t =-8.417, P ＜ 0.01).Group B, CTDIvol and SSDE were (9.28 ± 1.76) and (13.62 ±2.18) mGy, respectively (t =-15.051, P ＜ 0.01).Group C, CTDIvol and SSDE were (12.19 ± 3.65) and (15.39 ± 3.47) mGy, respectively (t =-4.535, P ＜ 0.01).In addition, the mean percentage values of difference between CTDIvol and SSDE for the three groups were 62.83％, 47.80％, 28.40％, respectively, which meant CTDIvol underestimated the radiation dose compared to SSDE.With the BMI increasing, the values of difference between CTDIvol and SSDE decreased.Conclusions SSDE can be used to estimate the radiation dose of abdominal CT scan for a given size person.