Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To explore the value of digital information line mark coplanar template (also referred to as the line mark template) in 125I radioactive seed implantation for the treatment of lung cancers. Methods:A retrospective analysis was conducted for 58 cases of lung cancers who were treated with template-assisted seed implantation in Oncology Department of the Second Hospital of Tianjin Medical University from Aug 2017 to May 2019.Line mark templates were adopted for 30 cases (the line mark template group) and general standard coplanar templates (also referred to as the general template) were used for 28 cases (the general template group). Pre-plan and post-implant parameters were compared, including the minimum prescription dose delivered to 90% of target volume ( D90), minimum peripheral dose (MPD), mean percentages of volume receiving 100%, 150% and 200% of the prescription doses ( V100, V150 and V200), external index (EI), conformity index (CI), and homogeneity index (HI) of target volume.The operation duration was also compared between the two groups. Results:There was no statistical difference between pre-plan and post-implant D90, MPD, V100, V150 and V200 in the line mark template group ( P>0.05). There was also no statistical difference between pre-plan and post-implant D90, MPD, V100, V150 and V200 of the general template group ( P>0.05). The operation duration of the line mark template group and the general template group was (44.3±12.4) and (60.0±12.8) min, respectively ( t=-3.03, P<0.05). Conclusions:The use of template-assisted seed implantation can accurately achieve preoperative planning, while the line mark template shortens the operation duration and thus improves the tolerance of patients.

Objective:To evaluate the pre- and post-implantation dosimetric consistency and efficacy of CT-guided 125I radioactive seed implantation for the treatment of the local recurrence of lung cancers under the assistance of a universal coplanar template (also referred to as the universal template). Methods:This study involved 38 patients with a local recurrence of non-small cell lung cancers who received universal template-assisted 125I radioactive seed implantation in the Second Hospital of Tianjin Medical University from Jan 2009 to Dec 2015.Preoperative planning was carried out before implantation, and the prescription dose was 110 Gy.The paired T-test was adopted for cooperation between intraoperative verification result and pre-plan values of the dosimetric parameters including minimum peripheral dose (MPD), the minimum prescription doses delivered to 90% and 100% of the target volume ( D90 and D100), conformity index (CI), external index (EI), and homogeneity index (HI). The efficacy was evaluated at the 6th month after implantation according to the RECIST 1.1 (Response Evaluation Criteria in Solid Tumors). Results:All patients successively received the seed implantation.The pre-plan and post-implant dosimetric parameters were as follows: MPD (222.7±26.2), (227.74±29.8) Gy; D90(130.8±13.6), (134.8±12.8) Gy; D100 (106.4±10.6), (110.7±11.8) Gy, CI ( 0.75±0.06), (0.74±0.04), EI(22.7±5.8)%, (24.3±4.8)%; HI(36.8±4.7)%, (37.2±5.3)%, the mean irradiation dose of hearts (19.3±7.2), (21.3±6.8) Gy( P> 0.05). The median follow-up period was 22.5 months (8-98 months). The median survival was 21 months (95% CI, 7.4-34.6), and the 2-year overall survival (OS), progression-free survival (PFS), and local control (LC) rate were 47.4%, 39.5%, and 83.5%, respectively. Conclusions:The universal template-assisted and CT-guided 125I radioactive seed implantation in the treatment of postoperative local recurrence of non-small cell lung cancers can achieve the goal of the preoperative TPS planning during the operation and achieve good efficacy.It is a minimally invasive, accurate, safe and effective therapy.

Objective:To analyze the efficacy and safety of radioactive 125I seed implantation in the treatment of unresectable early-stage non-small cell lung cancer (NSCLC), in order to provide data for clinical practice and relevant research. Methods:A retrospective study was conducted on the data of 39 patients with early-stage NSCLC who received CT-guided radioactive 125I seed implantation from Dec 2010 to Dec 2018 in multiple hospitals.The seed implantation process consisted of preoperative planning and design, CT-guided puncture, seed implantation, and postoperative evaluation and dose verification.The efficacy and complications of the treatment were analyzed.The clinical efficacy was evaluated by adopting the Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) and the adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results:All the patients were 70 years old on average (51-85). The median lesion diameter was 2.7 cm (1.1-6.0 cm), the median seed activity was 0.7 mCi (0.6-0.8 mCi), while the median follow-up duration was 29 months (3-97 months). Meanwhile, the 1-, 3-, and 5-year overall local control rates were 89.5%, 79%, and 79%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 74.8%, and 49.9%, respectively.Local recurrence and distant metastasis were the main causes of failure, accounting for 17.9% (7 cases) each.The incidence of pneumothorax was 56.4% (22 cases), among which nine cases (23.1%) required invasive closed thoracic drainage.Only 1 case of grade-2 radiation pneumonia (2.6%) was observed, with no other adverse reactions such as dermatoses, esophagitis, or myelitis being discovered.As indicated by univariate analysis, the patients with KPS scores of 80-90, pathological type of adenocarcinoma, T stage of T 1-2, and D90>180 Gy exhibited better local control ( χ2=6.202, P<0.05). Meanwhile, high D90 was also associated with a higher survival rate ( χ2=6.907, P<0.05). Conclusions:Radioactive 125I seed implantation is a safe and effective treatment for unresectable early-stage NSCLC.In cases where external beam radiotherapy is not available, radioactive 125I seed implantation can be considered as one of the treatment options.Pneumothorax is the most common complication of radioactive 125I seed implantation, and adenocarcinoma (pathological type) and higher values of D90 are predictors of better local control.

Objective:To investigate the feasibility, efficacy, and safety of CT- and bronchoscopy-guided 125I seed implantation in the treatment of central lung cancer complicated with atelectasis. Methods:Retrospective analysis was conducted on twenty-nine patients who were treated from May 2016 to Oct 2019 in the Second Hospital of Tianjin Medical University for central non-small-cell lung carcinoma complicated with pulmonary atelectasis that was inoperable due to medical reasons. 125I seeds were implanted into the trachea under the guidance of bronchoscopy first.The 125I seeds were then implanted into the hilum of the lungs by percutaneous puncture under the guidance of the CT and template.The seed activity was 18.5-29.6 MBq, and the prescription dose was 120 Gy.TPS planning and quality verification were performed before and after the operations.The rate of atelectasis recanalization, the satisfactory rate of dose verification, the improvement of dyspnea index, the survival time, and the adverse events during and after operation were observed. Results:All 29 patients with lung cancer complicated with atelectasis successfully completed the seed implantation, and the satisfactory rate of quality verification was 93.1%.The rate of atelectasis recanalization at 2, 6, 12, 18, and 24 months was 93.1%, 89.7%, 78.6%, 76.2%, and 60%, respectively.Their dyspnea and anoxia symptoms were significantly relieved in 5-28 months after treatment.The results showed that the patients′ dyspnea index was 2.8-0.8 before treatment and 1.4-0.9 after treatment.The median follow-up period was 20 months and median survival was 21 months.Adverse events associated with the radiation therapy included pneumothorax, hemoptysis, cough, fever, and particle displacement.No level-3 or more serious adverse events occurred.Conclusions:The CT- and bronchoscopy-guided 125I seed implantation is a safe and effective therapy option for the treatment of central non-small-cell lung carcinoma associated with atelectasis.It contributes to a high rate of local recanalization, and can rapidly improve clinical conditions and quality of life of the patients with few adverse reactions.

Objective:To explore the improvement and its mechanism of minocycline on sevoflurane anesthesia induced cognitive dysfunction in aged mice.Methods:Totally 75 aged clean-grade C57BL/6 mice were randomly divided into control (Con) group( n=25), sevoflurane (Sev) group( n=25) and sevoflurane + minocycline (Sev+ Min) group( n=25). Anesthetic injury was induced by 3% sevoflurane (2 h/d for 3 days) in Sev group. Minocycline (50 mg/kg) was injected intraperitoneally first, and then 3% sevoflurane (2 h/d for 3 days) anesthesia was performed in Sev+ Min group. Saline alone was injected intraperitoneally (once a day for 3 days) in Con group.The spatial memory function was detected by Morris water maze experiments. BrdU was used to label new neuron and the proliferation was observed by immunohistochemistry. The field excitatory postsynaptic potential (fEPSP) slope was measured in hippocampal dentate gyrus (DG) region of isolated brain slices by electricphysiological technique.The data were analyzed by repeated measures analysis of variance and SNK-q test using SPSS 21.0 software. Results:Results from positioning navigation experiment showed that the group×time interaction effect of mice was significant( F=15.65, P<0.01). On the 6th day after anesthesia, compared with Con group, the escape latency of the original platform in Sev group was significantly increased ( q=4.35, P<0.05) in space exploration experiment, while the target quadrant time ratio ( q=6.15, P<0.05))and the mean annulus crossings ( q=6.45, P<0.05) were significantly decreased. Compared with Sev group, the escape latency in Sev+ Min group was significantly decreased ( q=3.01, P<0.05), while the target quadrant time ratio ( q=3.21, P<0.05) and the mean annulus crossings ( q=3.48, P<0.05) were significantly increased. In immunohistochemistry experiment, the number of BrdU positive cells in Sev group was significantly reduced ((227.45±43.25), q=8.67, P<0.01) compared with Con group (355.87±62.58). Compared with Sev group, the number of BrdU positive cells in Sev+ Min group was significantly increased ((338.73±47.27), q=8.68, P<0.01). In electricphysiological test, the fEPSP slope after high frequency stimulation in Sev group ((126.83±25.67)%, q=6.18, P<0.01)) was significantly lower than that in Con group((214.38±43.42)%). In Sev+ Min group, the fEPSP slope was significantly higher ((178.49±32.67)%, q=3.64, P<0.05) than that in Sev group. Conclusion:Sevoflurane anesthesia can induce the short-term cognitive dysfunction in aged mice, and its mechanism is related to inhibiting neuron proliferation and synaptic plasticity. Minocycline can alleviate the damage caused by sevoflurane.

Objective To evaluate the clinical efficacy and prognostic factors of limited-stage small cell lung cancer ( LS-SCLC) treated with 125 I radioactive seed implantation guided by CT combined with systemic chemotherapy. Methods A total of 128 limited-stage small cell lung cancer patients were treated with 125 I radioactive seed implantation combined with chemotherapy from Jun 2008 to Jun 2012 in Tianjin Medical University Second Hospital. Theχ2 test was used to analyze the influencing factors of short-term efficacy. Survival rate was calculated by Kaplan-Meier method, single factor analysis was performed by Log-rank, and multivariate analysis was performed by Cox proportional hazard model. Results Totally 128 patients finished the treatment. The overall response rate was 86.7％ ( 111/128 ) after 6 months of treatment. The 1-, 2-and 3-year overall survival rate was 77.9％, 39.8％and 28.0％, respectively, and the median survival time was 21.0 months. The univariate analysis showed that the following factors were main prognostic factors:age, performance status ( PS) , hemoglobin≥120 g/L before treatment, smoking index, the maximum diameter of tumor, neuron-specific enolase before treatment, subscribe for prophylactic cranial irradiation ( PCI) , number of chemotherapy cycle, chemotherapy response, prescribed dose ( PD ) , postoperation dose covering 100％ volume ( D100 ) , remedial model. multivariate analysis revealed that age, PS, hemoglobin≥120 g/L before treatment and PD, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model were the independent prognostic factors for survival. 29 patients of 128 suffered from aerothorax and the incidence rate of aerothorax was 27.7％. Totally 16 patients occurred hemoptysis and theincidence rate was 12.5％. Conclusions 125 I radioactive seed implantation therapy showed good effecacy in the treatment of LS-SCLC. Age, PS, hemoglobin≥120 g/L before treatment, the maximum diameter of tumor, number of chemotherapy cycle, chemotherapy response, and remedial model might be the main prognostic factors for LS-SCLC patients.

As an interstitial brachytherapy,radioactive seed implantation could provide high doses in the local site and minimal doses at surrounding normal tissues.It has become one of the best choice for early stage prostate carcinoma.Radioactive seeds were implanted under the guidance by ultrasound,CT and MRI,featured with surgical and interventional treatment.Based on dosimetry for target and organs at risk,radioactive seed implantation is multiple disciplinary.In order to acquire the accurate and high quality seed implantation,it is necessary to set up a team including surgeons,radiation oncologists,interventional doctors and nuclear medicine doctors.The content of the consensus is as follows:radiation physics and dosimetry,indications,side-effects and 3 D-printing template work-follow.Despite the benefit of radioactive seed implantation for solid carcinoma,there still a compelling need for prospective randomized and stage Ⅲ clinical trials from multiple centers,so as to upgrade the evidencebased level,above all confirm the role of radioactive seed implantation in the comprehensive treatment of tumors.

Objective To explore the quality control and the short-term curative efficacy of 125Ⅰ radioactive seeds implantation in the treatment of spinal metastases by using co-planar template ( CPT ) assisted CT guidance. Methods Totally 12 cases of primary tumor were diagnosed by pathology, imaging changes for 16 lesions were consistent with the characteristics of spinal metastatic tumor. The prescription dose (PD) was 80 Gy, seed activity was 1. 48 × 107 -2. 59 × 107Bq(0. 4 -0. 7 mCi). According to preoperative plan, spinal metastases were treated with CPT assisted CT guided 125Ⅰ radioactive seeds implantation. The distribution of seeds was observed immediately after operation and the dose was assessed. Patients were followed up by CT to determine the change of tumor diameter and evaluate the efficacy. Follow-up time ranged from 3 to 29 months. And the improvement of pain was evaluated by pain grading. Results All of the 16 spinal metastases lesions were successfully implanted by the preoperative planning. After the implantation, quality verification showed the average dose of target region was (209. 21 ± 37. 16) Gy, D90 ( 115. 29 ± 7. 87 ) Gy, D100 ( 76. 59 ± 5. 53 ) Gy, V90 ( 99. 30 ± 0. 51 )%, V100 ( 98. 06 ± 1. 15 )%, conformal index (CI) 0. 981 ± 0. 012, external index (EI) 0. 012 ± 0. 007. And the average dose of the spinal cord was ( 30. 47 ± 4. 83 ) Gy. There was no significant difference in the mean dose between the target area and the spinal cord and the preoperative plan ( P>0. 05 ) . 3 months after surgery, among 16 spinal metastases lesions, complete response ( CR ) was 18. 8% ( 3/16 ) , PR ( partial response ) rate 62. 5% (10/16), PD(progressive disease) rate 6. 25%(1/16),SD(stable disease) rate 6. 25%(1/16), effective rate ( CR + PR ) 81. 3%. The were 3 cases in pain complete remission, 7 cases in partial remission, 2 cases in mild remission. The survival time range from 11 to 39 months. The median survival time was 24 months. No radiation damage of spinal cord was found. Conclusions CT guided CPT can be used to control the position and radiation dose of the seeds implantation before the operation, so as to achieve the objective of treating tumor with fewer complications and improvement of patients′tolerance.

Objective To investigate the feasibility of reducing CT scanning dose in the process of 125I radioactive seed implantation.Methods GEMS phantom and 062 M phantom were scanned using GE Lightspeed RT large hole CT with 120 kV,100 kV and 80 kV separately,and 150-10 mA (20 mA decreased progressively).The scanning dose,CT value and noise of the region of interest were recorded and the image quality was evaluated.Image signal-to-noise ratio (SNR) and contrast to noise ratio (CNR) values were calculated.Results With the decreasing of tube voltage and current,the SNR values were reduced accorgingly.The values had significant difference with those of standard images except the images acquired with 120 kV,150-70 mA and 100 kV,150-90 mA (t =-9.294-3.717,P ＜0.05).With the decreasing of the tube voltage and current,the CNR decreased significantly.The image quality was too low to evaluate while CNR lower than 2.The high contrast resolution of the CT images were not affected obviously with the tube voltage and current lowering.Conclusions In the process of 125I radioactive seed implantation,it is feasible to choose lower tube voltage and tube current(100 kV,70 mA) to scan the same area repeatedly except for the first scan with standard chest scanning parameters.The patient radiation dose has fallen dramatically.