Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Objective:To apply digital analysis to quantify hyperechogenicity of substantia nigra, and explore its clinical value for diagnosis of Parkinson′s disease (PD).Methods:The cross-sectional study included 652 PD patients (PD group) and 99 healthy controls (healthy control group) from November 2017 to October 2020 in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology. All subjects underwent transcranial sonography. The diagnostic accuracy of substantia nigra hyperechogenicity using digital analysis was compared with that in a manual measurement in PD. Furthermore, the receiver operating characteristic (ROC) curve analysis was applied to explore its diagnosis value in PD.Results:There were 482 subjects including 400 in the PD group and 82 in the healthy control group, whose quantified results of substantia nigra hyperechogenicity could be used for analysis. The ROC analysis showed that the area under the curve of the quantified larger substantia nigra hyperechoic region detection for diagnosing PD was 0.858 (95% CI 0.805-0.910), the sensitivity was 87.8%, and the specificity was 73.2%, consistent with that of doctors (area under the curve: 0.884). Further more, among these PD patients, there was no correlation between larger substantia nigra hyperechogenicity and age, age of onset, course of disease, non-motor symptoms, and motor symptoms (all P>0.05). Conclusions:Digital analysis was used to quantify the changes in substantia nigra hyperechogenicity in this seudy. The results showed that diagnostic accuracy for PD based on digital analysis was consistent with that of experienced clinicians.

Objective:To compare the safety and efficacy of high-dose- rate interstitial brachytherapy and particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases in the field after external radiotherapy.Methods:Clinical data of 42 patients with residual or newly metastatic pelvic lymph nodes after radiotherapy at Cangzhou Integrated Traditional Chinese and Western Medicine Hospital who met the inclusion criteria from January 2017 to April 2020 were retrospectively analyzed. Among them, 12 patients were male and 30 females, aged 39-82 years, (61.6±9.64) years on average. According to the treatment method, all patients were divided into the high-dose-rate interstitial brachytherapy group ( n=18) and particle implantation radiotherapy group ( n=24). During 3-year follow-up, the local control rate (LCR), incidence of complications and overall survival (OS) were compared between two groups. Age and operation time conforming to normal distribution were analyzed by t-test. The remaining indexes were analyzed by the Chi-square test or Fisher's exact test. The OS and LCR were calculated by Kaplan-Meier method. Results:There was no significant difference in baseline data between two groups (all P>0.05). The operation time in the high-dose- rate interstitial brachytherapy group was longer than that in the particle implantation radiotherapy group [(66.39±11.07) : (45.75±9.19) min, P<0.001]. During subsequent follow-up, there was no significant difference in the LCR between two groups (1-year LCR 88.9% vs. 87.5%, P=0.927; 2-year LCR 72.2% vs. 62.5%, P=0.874). There was no significant difference in the median OS between two groups (31.6 vs. 29.8 months, P=0.798). There was no significant difference in the incidence of early complications between two groups [ (4/18) vs. 5/24 (20.8%), P=1.000]. No late complications observed. Conclusion:High-dose- rate interstitial brachytherapy yields equivalent efficacy and safety to particle implantation radiotherapy in the treatment of lymph nodes with pelvic metastases.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To analyze the prognosis and risk factors for brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete resection, aiming to identify those most likely to benefit from prophylactic cranial irradiation (PCI).Methods:Clinical data of 94 patients with LS-SCLC treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from January 2005 to December 2018 who underwent complete resection were retrospectively analyzed, including 31 cases treated with PCI and 63 without PCI. Prognostic factors and risk factors of BM were analyzed by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. Independent risk factors of overall survival (OS) and BM were assessed by multivariate Cox regression model.Results:The 2-year and 5-year OS rates were 80.6% and 61.3% in the PCI group, and 61.9% and 46.0% in the non-PCI group, respectively ( P=0.001). The 2-year and 5-year brain metastasis-free survival (BMFS) rates were 80.6% and 54.8% in the PCI group, and 57.1% and 42.9% in the non-PCI group, respectively ( P=0.045). The 2-year and 5-year progression-free survival (PFS) rates were 71.0% and 48.4% in the PCI group, and 49.2% and 34.9% in the non-PCI group, respectively ( P=0.016). PCI could improve OS in patients with pII/III stage LS-SCLC ( P=0.039, P=0.013), but the OS benefit in patients with pI stage LS-SCLC was not significant ( P=0.167). BM occurred in 3 patients (9.7%) in the PCI group, which was significantly lower than that in the non-PCI group ( n=17, 27.0%; P=0.044); there was no significant difference in the BM rate of patients with pI and pII stage LS-SCLC between PCI and non-PCI groups ( P=0.285, P=0.468); and the BM rate of patients with pIII stage LS-SCLC in the PCI group was significantly lower than that in the non-PCI group ( P=0.041). Multivariate analysis showed age ≥60 ( HR=2.803, P=0.001), BM ( HR=2.239, P=0.022), no PCI ( HR=0.341, P=0.004) and pathological stage pII/III ( HR=4.963, P=0.002) were the independent high-risk factors affecting OS; and pathological stage pII/III ( HR=11.665, P=0.007) was an independent high-risk factor affecting BM. Conclusions:LS-SCLC patients with pII-III stage have a higher risk of developing BM and poor prognosis after complete resection, and should receive PCI treatment. However, LS-SCLC patients with pI stage may not benefit significantly.

ObjectiveTo explore the activating effects of ten important effective components in seven medicinal and edible substances on human pregnane X receptor （PXR）， including Glycyrrhizae Radix et Rhizoma （liquiritin and glycyrrhizic acid）， Houttuyniae Herba （quercetin and houttuyfonate）， Prunellae Spica （rosmarinic acid）， Cassiae Semen （aurantio-obtusin）， Poria （pachymic acid）， Lilii Bulbus （Lilium brownii saponin and colchicine）， and Lycii Fructus （Lycium barbarum polysaccharide） and screen potentially toxic components. MethodCell counting kit-8 （CCK-8） assay was used to investigate the cytotoxic effect of liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， pachymic acid， aurantio-obtusin， and colchicine （10， 20， and 50 μmol·L^-1）， and L. brownii saponin and L. barbarum polysaccharide （10， 20， and 50 mg·L^-1） on normal human hepatocyte cell line （L02）. The release of lactate dehydrogenase （LDH） in L02 cells after drug treatments was detected by the biochemical analyzer. The apoptosis induced by ten effective components was explored by Hoechst 33342 staining. The secreted luciferase reporter system was used to co-transfect the PXR expression vector and reporter gene vector containing cytochrome P450 3A4 （CYP3A4） transcriptional regulatory region into L02 cells， with 10 μmol·L^-1 rifampicin （RIF） as a positive control. After treated with liquiritin， glycyrrhizic acid， quercetin， houttuyfonate， rosmarinic acid， aurantio-obtusin， pachymic acid， and colchicine （5， 10， and 20 μmol·L^-1） and L. brownii saponin and L. barbarum polysaccharide （5， 10， and 20 mg·L^-1） for 24 h， the cells were tested for secreted luciferase activity. ResultCompared with the control group， colchicine， L. brownii saponin， and quercetin decreased the cell viability （P<0.05， P<0.01）. Compared with the control group， quercetin， rosmarinic acid， glycyrrhizic acid， colchicine， aurantio-obtusin， and pachymic acid increased the release rate of LDH in L02 cells （P<0.05， P<0.01）. The proportion of hyperchromatic nuclei increased gradually after rosmarinic acid， liquiritin， and L. barbarum polysaccharide treatments as compared with the control group （P<0.05， P<0.01）. In terms of co-transfection of pcDNA3.1-PXR and pGLuc-CYP3A4 into L02 cells， compared with the control group， aurantio-obtusin and pachymic acid showed activating effects on PXR （P<0.05）， whereas liquiritin and glycyrrhizic acid showed inhibitory effects （P<0.05）. ConclusionThe findings suggest that when medicinal and edible substances are taken for a long time， attention should be paid to their influence on drug-metabolizing enzymes and possible interactions， so as to improve their safety.

Objective:To evaluate the clinical efficacy and adverse events of 192Ir high-dose rate brachytherapy (HDR-BT) in the treatment of locally recurrent non-small cell lung cancer (NSCLC). Methods:Clinical data of 22 cases of recurrent NSCLC after radiotherapy admitted to our hospital from September 2013 to March 2018 were retrospectively analyzed. 192Ir HDR-BT was adopted for reradiotherapy. The prescription dose was 30Gy for 1 fraction. CT scan was reviewed every 1 month in the first 3 months after treatment and every 3 months after 3 months. Local control rate and adverse events were evaluated. The 1-and 2-year overall survival (OS) rates of re-treatment after relapse were calculated. Results:All the 22 patients completed the treatment successfully. The 1-, 3-and 6-month complete response (CR) rates were 9%, 14% and 14%, 82%, 82% and 82% for the partial response (PR) rates, 5%, 0% and 0% for the stable disease (SD) rates, 5%, 5% and 5% for the progressive disease (PD) rates, 91%, 96% and 96% for the objective response rates (ORR), respectively. The 1-and 2-year OS rates of re-treatment after relapse were 59% and 27%. Five patients (23%) experienced acute radiation-induced pneumonitis (3 cases of grade 1 and 2 cases of grade Ⅱ), 4 cases (18%) of radiation-induced bone marrow suppression (3 cases of grade I leukopenia and 1 case of grade I thrombocytopenia) and 1 case of postoperative pneumothorax. All these adverse events were mitigated after symptomatic treatment.Conclusion:192Ir HDR-BT is an efficacious and safe treatment of locally recurrent NSCLC.

Objective:To preliminarily evaluate the safety and efficacy of 3D printing template-assisted brachytherapy in the treatment of solitary metastatic lymph nodes adjacent to iliac vessels.Methods:Clinical data of 12 cases of para-iliac lymph node metastasis after radiotherapy admitted to our hospital from October 2018 to April 2020 were retrospectively analyzed. All patients received 3D printing template-assisted brachytherapy at a prescription dose of 20-30 Gy/fraction. CT scan was reviewed every 1 month in the first 3 months after treatment and every 3 months at 3 months after treatment.Local control rate, symptom relief rate and adverse events were evaluated.Results:All the 12 patients successfully completed the treatment and follow-up. At 1, 3 and 6 months after 3D printing template-assisted brachytherapy, 2, 2 and 3 patients obtained complete remission of lymph nodes, 9, 8 and 8 cases of partial remission, 1 case of stable disease and no case of disease progression. The symptoms were relieved in 10 patients. Acute radiation enteritis occurred in 2 patients and myelosuppression in 2 patients, which were mitigated after symptomatic treatment.Conclusion:3D printing template-assisted brachytherapy may be an efficacious and safe treatment of para-iliac lymph node metastasis, which yields tolerable adverse events.

Objective:To investigate the correlations of dynamic iodine nutrition status and thyroid function in pregnant women and newborns in Lingang of Shanghai, so as to provide an evidence for whether urine iodine testing and iodine supplementation should be carried out.Methods:A prospective study was conducted by randomly selecting pregnant women from October 2017 to October 2018 in Shanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health Sciences. The pregnant women were divided into early (5-12 weeks), middle (22-24 weeks), late pregnancy (36-37 weeks). Samples of serum and 24 hours urine were collected to test on thyrotropin (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroid peroxidase (TPOAb), anti-thyroglobulin (TgAb) and urinary iodine. TSH in neonatal heel blood was analyzed 72 h after birth (newborns from pregnant women in the late pregnancy). The differences of thyroid function of pregnant women with different pregnant periods and different urinary iodine levels were analyzed, as well as the neonatal TSH levels of pregnant women with different urinary iodine levels. Results:A total of 109, 90 and 54 cases of pregnant women in early, middle and late pregnancy were investigated and the medians of urinary iodine were 120.95, 136.30 and 116.80 μg/L, respectively. There was no significant difference in urinary iodine content among different pregnant periods( P > 0.05). The proportions of urinary iodine level less than 150 μg/L in early, middle and late pregnancy were 75.2% (82/109), 61.1% (55/90) and 59.3% (32/54), respectively. The median values of serum TSH in early, middle and late pregnancy were 1.81, 1.95 and 2.29 mU/L, mean values of FT 3 were (5.21 ± 0.84), (4.79 ± 0.72) and (4.13 ± 0.56)pmol/L, and means of FT 4 were (16.48 ± 2.58), (15.02 ± 2.78) and (13.31 ± 1.87) pmol/L, respectively. The FT 3 and FT 4 levels in the late pregnancy were lower than those in the early and middle pregnancy, while the TSH levels in the late pregnancy were higher than those in the early and middle pregnancy. There were no significant difference in serum FT 3, FT 4 and TSH levels among early, middle and late pregnancy under different urinary iodine levels. The median TSH of newborn heel blood was 1.48 mU/L. There was no statistically significant difference between the neonatal heel blood TSH level of pregnant women with urinary iodine < 150 μg/L [1.45(1.09, 2.23)mU/L] in late pregnancy and those with urinary iodine ≥150 μg/L [1.42 (1.14, 2.61) mU/L, Z=- 0.354, P > 0.05]. Conclusions:There is mild iodine deficiency in pregnant women in Lingang of Shanghai. However, due to the compensatory regulation, it has no significant effect on the thyroid function of mother and newborn. Monitoring of iodine nutrition of pregnant women should be carried out and iodine supplementation should be done scientifically and reasonably.