Objective : To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway． Methods : Fifty female Wistar rats were randomly divided into Control group ，FA group，FA + MT 5 mg / kg group，FA + MT 10 mg / kg group and FA + MT 20 mg / kg group，with 10 rats in each group．Except for the Control group，all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model，and then treated with different MT doses for 14 d．The tainting was continued during the MT treatment．Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue，lung water content and lung coefficient were weighed and measured，glutathione ( GSH) ，superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ，and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ，in- terleukin (IL) -6，and IL-1 β concentrations，Western blot to detect the protein expression levels of Nrf2，heme ox- ygenase-1 (HO-1) ，nuclear factor-κB ( NF-κB) ，and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues，and quantitative polymerase chain reaction(qPCR) to detect the Nrf2，HO-1，and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels. Results : Compared with the control group，lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ，and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6，and IL-1 β levels were elevated (P＜0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P＜0. 05) ，and p-NF-κB protein expression levels were was ele- vated (P＜0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased，and the relative mRNA expression of Keap1 was elevated (P＜0. 05) ．Compared with the FA group，the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P＜0. 05) ，and the level of 8-OHdG was decreased (P＜0. 05) ; the levels of TNF-α , IL-6，and IL-1 β in the alveolar lavage fluid were de- creased (P＜0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P ＜0. 05) ．p-NF-κB protein expression level was decreased (P ＜0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P＜0. 05) ，and the relative mRNA expression level of Keap1 was decreased (P＜0. 05) in lung tissues，and all of them were in a dose-dependent manner． Conclusion MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.

Objective:To evaluate the reliability and validity of the Chinese version of the Edinburgh visual gait score (EVGS-CN) for children with cerebral palsy.Methods:The EVGS-CN was established following international guidelines for translation and cross-cultural validation of health status questionnaires. Videos of 30 children with cerebral palsy were assessed independently by six raters (with different levels of experience in gait analysis) using the EVGS-CN. Inter- and intra- observer reliability were evaluated using intraclass correlation coefficients (ICCs). The correlation analysis and group comparison were used to test the technique′s criteria-related validity, convergent validity, and discriminant validity.Results:The ICC values of the 17 items in the EVGS-CN ranged from 0.20 to 0.87 for inter-observer reliability, and from 0.41 to 0.90 for intra-observer reliability. Most items showed good inter- and intra-observer reliability among experienced raters, but only a moderate level when used by inexperienced raters. The EVGS-CN results were strongly correlated with those of physician rating scale (PRS) ( r=0.77, P≤0.001) and observational gait scale (OGS) ( r=-0.85, P≤0.001), moderately correlated with the total gross motor function measure-D/E (GMFM-D/E) score ( r=-0.55, P≤0.01), and strongly correlated with 10MWT times ( r=-0.69, P≤0.001) and timed up and go (TUG) times ( r=0.60, P≤0.001). Moreover, significant differences in average EVGS score were found between different gross motor function classification system (GMFCS) levels and between affected limbs on different sides. Conclusion:The EVGS-CN demonstrates satisfactory reliability and validity in evaluating children with cerebral palsy when it is used by an experienced or inexperienced rater.

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC₅₀) values of 3.22, 4.78, 8.90, and 4.31 μmol·L^-1, respectively.
Mice ; Animals ; Coumarins/chemistry* ; Rutaceae/chemistry* ; Anti-Inflammatory Agents/pharmacology* ; Plant Extracts/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure

AIM: To investigate the effect of BCG + piroxicam versus BCG + gemcitabine in the prevention of postoperative recurrence in intermediate - to high-risk bladder cancer and the effect on serum albumin / globulin ratio (AGR) and paraoxonase 1 (PON1). METHODS: Eighty patients with medium-high risk bladder cancer in our hospital from October 2021 to April 2022 were randomly divided into two groups with 40 cases each. Both groups received transurethral resection of bladder tumor. The control group received postoperative bladder perfusion of pirubicin combined with BCG vaccine, and the study group received postoperative bladder perfusion of gemcitabine combined with BCG vaccine. The therapeutic effect, serum tumor markers secretory protein Dickkopf (DKK), bladder cancer specific nuclear matrix protein-1 (BLCA-1), β2-microglobulin (β2-MG), new angiogenesis factorsvascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), AGR and PON were compared between the two groups 1. Level, quality of lifeCore Quality of Life Questionnaire Scale (EORTC QLQ-C30), functional status Functional status Scoring Scale (KPS), adverse reactions, The recurrence rates at 1 year after surgery were compared between the two groups. RESULTS: The total effective rate of the study group was 92.50%(37/40) higher than that of the control group 75.00%(30/40) (P<0.05). The serum levels of DKK, BLCA-1, β2-MG, VEGF, FGF and AGR in the study group were lower than those in the control group at 1 month, 3 months and 6 months after surgery, while the level of PON1 was higher than that in the control group (P<0.05). The EORTC QLQC30 and KPS scores of the study group were higher than those of the control group at 1, 3 and 6 months after surgery (P<0.05). The incidence of nausea/vomiting, diarrhea, leukopenia and cystitis in the study group was lower than that in the control group (P<0.05). The recurrence rate of the study group 1 year and 2 years after surgery was lower than that of the control group (P<0.05). CONSLUSION: Compared with pirubicin combined with BCG vaccine, gemcitabine combined with BCG vaccine is more effective in the treatment of middle and high-risk bladder cancer, which can inhibit tumor angiogenesis, regulate AGR and PON1 levels, prevent postoperative recurrence, improve quality of life, improve functional status, and have higher safety.

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Objective:To study the effects of brachytherapy with 125I in the treatment of malignant adenogenous tumors invaded into cranial base area,and to evaluate the correlative factors of prognosis.Methods:24 patients with malignant adenogenous tumors invaded into cranial base area were treated by 125I seeds implanted into the tumors with the spacing of 1-1.5 cm and guided by CT,individual guide plate and navigation system respectively or in combination with the dose of 60-160 Gy.Survival rate,local recurrence rate,distant metastasis and safty of the treatment were evaluated.The correlative factors of prognosis included age,pathology diagnosis,diameter of the tumor,area of tumor invasion and history of radiotherapy were analyzed.Results:The follow-up time of the patients was 3-76 months and the median was 27 months.2 patients came up with radiotherapy reaction of level 4.The total survival rate was 41.7％,the local recurrence rate was 25.0％ and the distant metastasis rate was 37.5％.The cumulative survival rate of 1,3 and 5 years was 79％,67％ and 24％ respectively.Significant correlation was found between prognosis and local recurrence as well as the diameter of the tumor.Conclusion:125I brachytherapy provides a safe and feasible technique with minimal damage for treating malignant adenogenous tumors invaded into cranial base area.The prognosis is related to local recurrence and the diameter of the tumor.

Objective: To investigate clinical features of distant metastases from malignant salivary gland carcinomas after treated by 125I internal brachy therapy alone.Methods: Between 2002 and 2010, 43 patients with locally advanced unresectable or recurrent malignant salivary gland carcinomas were treated by 125I internal brachy therapy alone at Peking University School and Hospital of Stomatology.All of them had been follow-up at least 2 years.The primary sites of malignant salivary gland carcinomas were the parotid for 12 patients, infratemporal fossa for 9 patients, tongue for 7 patients, maxilla for 6 patients, parapharyngeal for 4 patients, floor of months for 3 patients, submandibular gland for 1 patient, and lip for 1 patient.The overall survival rate, local control rate, and distant metastases were retrospectively reviewed.Results: Distant metastases occurred in 23 of the 43 patients (53.5%).Distant metastases developed from 5 to 96 months, with an average interval of (27.0±23.7) months from the time of initial diagnosis, the mean interval was 21 months.The commonest site of distant metastases overall was the lung 69.6%(16/23).The most common pathological types of distant metastases were adenoid cystic carcinoma (14/23, 60.9%) and nonspecific adenocarcinoma (7/23, 30.4%).At the time of the last follow-up, 26 patients died, and 18 of them due to distant metastases (69.2%, 18/26).In the study, 27 patients got complete remission(CR), 12 got partial remission(PR) more than 50%, 2 less than 50%, and 2 patients were invalid.The effective rate (CR+ PR) was 90.7%.The 3 year loco-regional control rate and survival rate were 60.1%, 82.6%, respectively, and the 5 year's 53.4% and 56.0%.Conclusion: The 125I brachy therapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent malignant salivary gland carcinomas.However, further studies are needed with larger numbers of patients and for a longer follow-up assessment.Distant metastasis was the main cause of treatment failure, and the lung was the most common site of distant metastases.

Objective:To investigate clinical features of distant metastases ( DM ) and analyze clinico-pathologic risk factors associated with DM from salivary gland carcinomas after being treated by surgery combined with 125 I internal brachytherapy. Methods: Between October 2001 and March 2010, 197 pa-tients with salivary gland carcinoma were treated by surgery combined with 125 I internal brachytherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate clini-copathologic risk factors that might influence the risk of distant metastases. Results:DM occurred in 28 of 197 patients (14. 2%). The commonest site of distant metastases overall was the lung 89. 3% (25/28), followed by bones 17. 9% (5/28) and liver (4/28). DM developed after an average interval of (44. 2 ± 45. 8) months from the time of initial diagnosis, and the mean interval was 64 months. The average time to death after the diagnosis of DM was only (9. 7 ± 13. 4) months, and the mean time was 12 months. The 3-year locoregional control rate and survival rate were 90. 8%, and 87. 8% respectively,and the 5-year ones 84. 0% and 81. 0%, respectively. Univariate analyses revealed that the risk of distant metasta-ses was significantly influenced by locoregional tumor failure (F=26. 997,P<0. 01) and histologic dif-ferentiation (F=1. 592,P<0. 01). Multivariate analysis of freedom from distant metastases revealed that locoregional control (F=29. 332,P<0. 01) significantly influenced this end point. Conclusion: Sali-vary gland carcinoma could achieve high local control rate after being treated by surgery combined with 125 I internal brachytherapy, and the average interval from diagnosis to DM was prolonged, DM was signifi-cantly influenced bylocoregional control.

Objective To assess the value of the urine flow acceleration(UFA)versus maximum urinary flow rate (Qmax) for diagnosis of bladder outlet obstruction (BOO) in benign prostate hyperplasia (BPH).Methods A total of 50 men with BPH and 50 normal men were included in this study.Urodynamic examinations were performed in all patients according to the recommendations of the International Continence Society.Prostate volume,UFA and Qmax of each patient were analyzed and the results were compared between two groups.Results The UFA and Qmax of BPH group were much lower than that of the control group [(2.05±0.85)ml/s2 vs.(4.60±1.25)ml/s2 ; (8.50±1.05)ml/s vs.(13.00±3.35)ml/s,P＜0.05].The prostate volume in BPH group was increased compared with control group [(28.6±9.8) ml vs.(24.2±7.6)ml,P＜0.05].As diagnosis standard of UFA＜2.05 ml/s2 and Qmax＜ 10 ml/s,the sensitivity and specificity of UFA and Qmax in diagnosing BOO were (88％,75 ％)vs.(81％,63％).While compared with the result of P-Q chart,the Kappa values in correspondence analysis were 0.55 vs.0.35.The sensitivity,specificity and Kappa value of UFA in diagnosing BOO in BPHs were slightly higher than that of Qmax in comparison with the gold standard (BOO diagnosed by P-Q figure).Conclusions The UFA is a useful urodynamics parameter in diagnosing BOO of BPH.

Objective To compare differences of SRS-22 scores between male and female AIS patients.Methods From October 2007 to April 2009,298 AIS patients from 7 spine centers completed simplified Chinese edition of SRS-22 questionnaire,including 62 males and 236 females with an average age of 15.7 years old,and the average Cobb angle was 52.8°.Of 62 male patients,34 were from urban areas and 28 rural areas.Among 236 female patients,132 were from urban areas and 104 rural areas.A comparison was conducted in terms of age,Cobb angle,the ratio of urban population to rural population,and the scores of all domains and the subtotal scores of SRS-22 questionnaire between male and female patients.Results There was no difference of age,Cobb angle and the ratio of urban population to rural population between male and female patients(P＞0.05).The scores of four domains and subtotal scores of SRS-22 questionnaire were significantly higher in male patients when compared with female patients(P＜0.05).Conclusion Gender difference should be taken into the consideration when estimating the quality of life in AIS patients by SRS-22 questionnaire.The quality of life in male patients with AIS was better than that of female patients.