ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective To investigate the effects and mechanisms of silica dust on the apoptosis of alveolar epithelial cell (AEC) through in vitro and animal experiments. Methods i) In vitro experiment. A549 cells were stimulated with 100 mg/L silica suspension for 0, 12, 24 and 48 hours. The cell apoptosis rate was detected by flow cytometry. ii) Animal experiment. Specific pathogen-free male C57BL/6 mice were randomly divided into control, 14-day, 28-day, and 56-day groups, with five mice in each group. The mice in the control group were sacrificed at 56 days after being treated with 40.0 μL 0.9% sodium chloride solution, and the mice in the last three groups were sacrificed at 14, 28 and 56 days after being treated with 40.0 μL silica suspension with a mass concentration of 125 g/L via tracheal exposure method. The lung tissues of mice were collected to measure lung organ coefficients. Masson staining was used to detect the degree of pulmonary fibrosis, and Ashcroft scores were evaluated. The apoptosis of AEC in mice was observed by TUNEL immunofluorescence assay. iii) The mRNA relative expression of apoptosis-related genes in A549 cells and mouse lung tissue was detected using reverse transcription and real-time fluorescence quantitative polymerase chain reaction. Results i) In vitro experiment. The apoptosis rate of A549 cells increased with longer silica exposure (all P<0.05). The relative expression of B cell lymphoma-2 (BCL-2) mRNA in A549 cells in 24 h group and 48 h group decreased (both P<0.05), and the relative expression of BCL-2 associated X protein (BAX) mRNA increased (both P<0.05), compared with 0 h group. The mRNA relative expression of caspase (CASP) -3 and CASP-9 in A549 cells increased with longer silica exposure (all P<0.05). ii) Animal experiment. The lung organ coefficients and Ashcroft score in mice progressively increased (all P<0.05), the degree of pulmonary fibrosis was gradually aggravated, and TUNEL positive cells in lung tissue were gradually increased, while Bax, Casp-3 and Casp-9 mRNA relative expression increased with longer silica exposure (all P<0.05). Conclusion Silica dust may cause pulmonary fibrosis by inducing apoptosis of AEC, with a time-dependent effect. The mechanism may be related to the effect of silica dust on mitochondrial apoptosis through Bcl-2/Bax/Caspase-3 signaling pathway.

OBJECTIVES: The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells. METHODS: Gastric cancer MKN45 cells were treated with PEG-MTPABZ-PyC. A high-content live-cell imaging system was used to assess the cellular uptake kinetics and subcellular localization of the photosensitizer. The cytotoxic effects of PEG-MTPABZ-PyC-mediated photodynamic therapy were examined using the cell counting kit-8 (CCK-8) assay and flow cytometry, while the intrinsic cytotoxicity of the photosensitizer alone was verified by the CCK-8 assay. Intracellular reactive oxygen species (ROS) generation after photodynamic therapy was detected using 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). RESULTS: PEG-MTPABZ-PyC alone exhibited no cytotoxicity toward MKN45 cells, indicating excellent cytocompatibility. The compound efficiently entered cells within 6 hours and localized predominantly in lysosomes. Upon light irradiation, PEG-MTPABZ-PyC-mediated photodynamic therapy induced significant cytotoxicity compared with the control group (P<0.05) and generated abundant intracellular ROS. CONCLUSIONS The novel photosensitizer PEG-MTPABZ-PyC demonstrates potent photodynamic cytotoxicity against gastric cancer cells, showing promising potential for further development in gastric cancer photodynamic therapy.
Humans ; Stomach Neoplasms/drug therapy* ; Photochemotherapy/methods* ; Photosensitizing Agents/pharmacology* ; Cell Line, Tumor ; Polyethylene Glycols/chemistry* ; Reactive Oxygen Species/metabolism* ; Mesoporphyrins/pharmacology*

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective To establish an HPLC-based method for the determination of α-obscurine,ferulic acid,hydroxysafflower yellow A,benzoylneaconitine,benzoylaconitine,periplosin,4-methoxysalicylsalicylate,kaempferol and oleanolic acid simultaneously in Shujin Tongluo Black Plaster.Methods HPLC method was used to determine the 9 components in Shujin Tongluo Black Plaster simultaneously.The 70%methanol extracts were analyzed using Waters SunFire C18 chromatography column(4.6 mm×250 mm,5 μm),in mobile phase containing acetonitrile-0.2%phosphoric acid solution for gradient elution with volume flow rate of 1.0 mL/min;column temperature was set at 25℃;detection wavelength was set at 230 nm.Results The 9 components had good linear relationship in their respective ranges(r≥0.999 7).The average recoveries were between 98.06%-100.56%and RSD was between 0.48%-2.56%,respectively.Conclusion The method has the advantage of repeatability,simple and fast,and can be used as the quality control of Shujin Tongluo Black Plaster.

Objective:To compare the efficacy of pecto-intercostal fascial plane (PIFP) block versus transversus thoracic muscle plane (TTP) block under ultrasound guidance in coronary artery bypass grafting with general anesthesia.Methods:Ninety American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ patients of either sex, aged 50-79 yr, scheduled for elective coronary artery bypass grafting, were divided into 3 groups ( n=30 each) using a random number table method: PIFP block combined with general anesthesia group (PG group), TTP block combined with general anesthesia group (TG group), and general anesthesia group (G group). After anesthesia induction, bilateral PIFP block was performed under ultrasound guidance in group PG, TTP block was performed under ultrasound guidance in group TG. Three groups used the same general anesthesia method and patient-controlled intravenous analgesia after surgery. Visual analog scale scores (cough, position change, etc) at rest and during activity were recorded at 6, 12, 18 and 24 h after operation. The total consumption of intraoperative sufentanil, extubation time, length of stay in intensive care units, rate of rescue analgesia, effective pressing times of patient-controlled analgesia, incidence of postoperative nausea and vomiting, skin pruritus and nerve block-related adverse events were recorded. The operation time of nerve block was recorded and ultrasound-guided needle visibility score was assessed in PG group and TG group. Results:Compared with group G, the total consumption of intraoperative sufentanil was significantly reduced, the extubation time and length of stay in intensive care units were shortened, visual analog scale scores at rest and during activity were decreased at 6, 12 and 18 h after operation, the rate of rescue analgesia was decreased, and the effective pressing times of patient-controlled analgesia were decreased in group PG and group TG ( P<0.05), and no significant change was found in the aforementioned parameters in PG and TG groups ( P> 0.05). Compared with group TG, the operational time of nerve block was significantly shortened, and the ultrasound-guided needle visibility score was increased in group PG ( P<0.05). No nerve block-related adverse events were found in PG and TG groups. There was no significant difference in the incidence of postoperative nausea and vomiting and skin pruritus among the three groups ( P>0.05). Conclusions:PIFP block can provide good perioperative analgesia and promote the rapid recovery in the patients undergoing coronary artery bypass grafting with general anesthesia. Although the analgesic effect of PIFP blockade is similar to that of TTP blockade, PIFP blockade is more clinically valuable due to its simpler operation and less relative risk.

Objective:To evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.

ObjectiveTo analyze the exposure-response relationship of peripheral whole blood chromium level and lung function as well as genetic toxicity indicators in workers exposed to hexavalent chromium [Cr(Ⅵ)] compounds, and to propose a biological exposure limit of whole blood chromium for soluble Cr(Ⅵ) compounds-exposed workers. Methods A total of 515 workers from a dynamic occupational Cr(Ⅵ) compounds-exposed cohort in an enterprise from 2010 to 2017 were selected as the research subjects using a retrospective cohort study. A total of 918 followed-up results of research subjects and baseline data of a cohort were analyzed based on bibliometric analysis. The results include lung function tests, whole blood chromium level detected by inductively coupled plasma-mass spectrometry, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) detected by high performance liquid chromatography-tandem mass spectrometry, peripheral micronuclei frequency (MNF) detected by cytokinesis-block micronucleus assay, and mitochondrial DNA copy number (mtCN) detected by real-time fluorescence quantitative polymerase chain reaction. Results The results of bibliometric analysis showed that domestic and foreign studies on biological monitoring of Cr(Ⅵ) compounds increased year by year in the past 30 years, and whole blood chromium levels had a good correlation with the occupational Cr(Ⅵ) compounds exposure. The geometric mean of whole blood chromium levels in males and females among the occupational Cr(Ⅵ) compounds exposure cohort was 2.77 and 1.79 μg/L, respectively. A turning point appeared in 6.00 μg/L chromium in whole blood of the exposure-response curve of whole blood chromium levels with lung function indicators and genetic toxicity indicators. For each unit increase in the natural logarithm-transformed whole blood chromium level, the forced expiratory volume in one second (FEV₁) decreased by 0.05 L, the FEV₁/forced-vital-capacity decreased by 0.67%, the peak expiratory flow decreased by 0.15 L/s, the maximal mid-expiratory flow decreased by 0.09 L/s, the MNF increased by 0.149‰, the urinary 8-OHdG increased by 0.090 μg/g, and the mtCN increased by 0.013. When the whole blood chromium level was >6.00 μg/L, there was a significant increase in urinary 8-OHdG, MNF, and mtCN (all P<0.01). Conclusion The level of whole blood chromium can be used as a biomarker for occupational exposure to soluble Cr(Ⅵ) compounds. The preliminary biological exposure limit is set at 6.00 μg/L for whole blood chromium in workers exposed to soluble Cr(Ⅵ) compounds.

Objective:To develop the Surgical Readiness Scale for Female Patients with Stress Urinary Incontinence (SUI) and test its predictive performance.Methods:Based on the theory of "patient-centered" during the perioperative period, an initial scale was formed through literature review, semi-structured interviews, expert consultation, and pre-survey. From January 2021 to December 2022, convenience sampling was used to select 585 female SUI patients who underwent elective surgical treatment at the First Affiliated Hospital of Zhengzhou University as participants for a survey to test the reliability and validity of the scale.Results:A total of 585 questionnaires were distributed, and 560 valid questionnaires were collected, with a valid response rate of 95.73% (560/585). The Surgical Readiness Scale for Female Patients with SUI included four dimensions and 28 items. The content validity index of the scale was 0.975. Cronbach's α coefficient of the total scale was 0.909, and Cronbach's α coefficients of each dimension were 0.928, 0.822, 0.958, and 0.880, respectively. The total split-half reliability coefficient was 0.712, and the split-half reliability coefficients for each dimension were 0.921, 0.808, 0.941, and 0.841, respectively. Two exploratory factor analysis showed a cumulative variance contribution rate of 64.25%. Confirmatory factor analysis showed that the chi-square degree of freedom ratio was 1.680, the mean square root of asymptotic residuals was 0.056, the goodness of fit index was 0.840, the modified goodness of fit index was 0.811, and the comparative goodness of fit index was 0.944. The convergence validity and discriminant validity values were within a reasonable range, indicating good fit of the model.Conclusions:The Surgical Readiness Scale for Female Patients with SUI has good reliability and validity, and can be used as an effective evaluation tool for the surgical readiness of female SUI patients.

Objective:To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation.Methods:This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis.Results:Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions:The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.