AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Neurons ; Phosphatidylinositol 3-Kinases

Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.

Objective:To evaluate the feasibility and safety of carbon ion radiotherapy (CIRT) in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials.Methods:Clinical stage T 2-3 patients with muscle-invasive bladder cancer (without distant metastasis) were studied. A three-fraction treatment was applied, including the local irradiation with the dose from 12 Gy to 24 Gy and 11 fractions of whole-bladder irradiation with a dose of 44 Gy. The carbon ion irradiation dose is determined with relative biological effectiveness (RBE) of 3.0. The total dose for bladder tumor was 56-68 Gy in 14 fractions. The primary endpoints included tumor treatment-related side effects, dose-limiting toxicity (DLT) responses, and local control (LC) rate, and the secondary endpoints included progression-free survival (PFS). Results:Nine patients received CIRT of various doses in the clinical trials, with the dose gradually increasing to 68 Gy. The patients did not suffer from DLT response, acute adverse effects of radiation therapy of grade ≥3, and late radiation adverse reactions during follow-up. When the dose to the tumor reached 68 Gy, there were 2 cases of grade 2 acute urogenital tract reaction and 1 case of acute lower gastrointestinal tract symptom. For the group with a dose above 62 Gy, three cases of grade 1 late radiation bladder reaction were observed and their symptoms included urinary frequency and microscopic hematuria. At the end of treatment, hematuria disappeared, dysuria was relieved, and urine red blood cell value significantly decreased for all the patients. Three months and six months after treatment, the LC rates were 100% and 88.9%, respectively, and the objective response rates were both 88.9%. One patient developed local recurrence and was treated with salvage surgery six months after treatment.Conclusions:The preliminary efficacy observation of CIRT in the treatment of muscle-invasive bladder cancer showed significant short-term efficacy, obvious symptom relief, and good tolerability for patients, without DLT. Therefore, CIRT is safe and feasible.

OBJECTIVE: To explore the mediating effect of experiential avoidance on neurosis and posttraumatic stress response in firefighters. METHODS: A cluster random sampling method was used to select 275 male firefighters from 26 Fire Alarm squadrons in a province of China.The Neuroticism subscale of Eysenck Personality Questionnaire Short Scale, the Acceptance and Action Questionnaire-Second Edition, and the Impact of Event Scale were used to investigate the relationship of neurosis, experiential avoidance and posttraumatic stress response. RESULTS: The median score of neurosis, experiential avoidance and posttraumatic stress response was 5, 21 and 15, respectively. Both neurosis and experiential avoidance were positively correlated with posttraumatic stress syndromes(Spearman correlation coefficient were 0.45 and 0.45, P<0.01). The total effect of neurosis on posttraumatic stress response in firefighters was 0.57. The intermediary role of experiential avoidance on neurosis and posttraumatic stress response was 0.19, accounting for 33.33% of the total effect. CONCLUSION: Experiential avoidance plays a partial positive mediating role between neurosis and posttraumatic stress response in firefighters.

Objective To investigate the influence of two different mechanical ventilation modes of bi-level positive airway pressure ventilation(BIPAP)and synchronized intermittent ventilation (SIMV)on the respiratory function and clinical curative effect in children patients with severe hand foot and mouth disease(HFMD)complicating neurogenic pulmonary edema.Methods Thirty children patients with severe HFMD complicating neurogenic pulmonary edema receiving mechanical ventilation were divided into the SIMV group (control group)and BIPAP group (experimental group).The lung protective ventilation strategy was applied in both groups.After 30 min use of SIMV and positive end expiratory pressure (PEEP)ventilation,the experimental group changed to use the BIPAP ventilation mode,while the control group still used the initial parameters.The airway peak pressure,alveolar plat-form (Pplat)pressure,lung compliance,pH value,arterial blood CO2 partial pressure (PaCO2 )and oxygenation index (PaO2/FiO2 )at 0 h (baseline value),24,48,72 h after mechanical ventilation were monitored.Besides,the duration of mechanical ventila-tion,28 d mortality rate and the length of ICU stay were observed.Results Thirty children patients smoothly spent their acute re-spiratory failure period.One case in each group during the later period of treatment was transferred to the other hospital for contin-uous therapy.Among them the transferred case in the control group finally died due to give up treatment.The rest 28 cases all were cured and discharged from hospital.The 28 d mortality rates in the two groups were 6.67% and 0% respectively,with no statistical difference (P >0.05).Compared with the control group,the airway peak pressure,Pplat and PaCO2 after mechanical ventilation for 24,48,72 h in the experimental group were significantly decreased(P <0.05);the lung compliance and PaO2/ FiO2 improvement was significantly higher than that in the control group(P <0.05);meanwhile the duration of mechanical ventilation and the length of ICU stay in the experimental group were shorter than those in the control group (P <0.05).Conclusion The BIPAP mode used in the mechanical ventilation therapy of the children patients with severe HFMD complicating neurogenic pulmonary edema can pro-vide better effective ventilation,improve oxygenation and respiratory function,and shorten the duration of mechanical ventilation.

AIM:To investigate whether hydrogen sulfide ( H2 S) protects the hearts against inflammatory re-sponses induced by acute myocardial ischemia in isolated rat hearts .METHODS: Rat acute myocardial ischemia injury was induced by ligation of the left anterior descending coronary artery for 4 h, and the normal perfusate was replaced with NaHS (5 μmol/L, 10μmol/L and 20 μmol/L) perfusate accordingly in NaHS groups 2 h after ischemia.The changes of cardiac function in the myocardial ischemic injury rats were observed .The mRNA expression of TNF-α, IL-1β, IL-6, IL-10 and ICAM-1 was detected by real-time PCR.The protein level of nuclear factor-κB ( NF-κB) in the myocardial tissues was detected by Western blotting .RESULTS:The cardiac function in ischemia group was lower than that in sham group (P<0.01).Compared with ischemia group, perfusion of NaHS resulted in the improvement of the cardiac function (P<0.05 or P<0.01).Compared with sham group, the mRNA expression of TNF-α, IL-1β, IL-6 and ICAM-1 in the cardiac tissues was significantly increased , and the mRNA expression of IL-10 in the cardiac tissues was significantly decreased in ischemia group (P<0.01).Compared with ischemia group , the perfusion of NaHS significantly decreased the mRNA ex-pression of TNF-α, IL-1β, IL-6 and ICAM-1 ( P<0.05 or P<0.01 ) .The perfusion of NaHS at concentrations of 10μmol/L and 20μmol/L significantly increased the mRNA expression of IL-10 (P<0.01).The protein level of NF-κB in ischemia group was markedly higher than that in sham group (P<0.01).Compared with ischemia group, the perfusion of NaHS at concentrations of 10 μmol/L and 20 μmol/L significantly decreased the expression of NF-κB ( P<0.05 or P<0.01).CONCLUSION:H2S protects the hearts against acute ischemia injury through inhibition of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression .

Aims To observe the changes of endoge-nous hydrogen sulfide/cystathionine-γ-lyase (H2 S/CSE)system and to study the effects of H2 S on cardiac function,H2 S/CSE and myocardial infarct volumes in acute myocardial ischemic injury in isolated hearts of rats.Methods The myocardial ischemic injury model was established by the ligation of coronary artery.The hemodynamic parameters,such as the left ventricular developed pressure (LVDP),±dp/dtmax and coronary arterial flow(CF),were respectively recorded to evalu-ate the cardiac function.The content of H2 S and the activity of CSE in cardiac tissue were detected respec-tively at each time point after ischemia.Infarct vol-umes in isolated rat hearts were determined by dual staining with Evans-blue and TTC.Results (1 )Com-pared with those of the sham group,LVDP,±dp/dtmax and CF were significantly decreased at 30 min,1,2,3, 4 h after ischemia(P<0.01),there were no statistical-ly significant differences in the content of H2 S and the activity of CSE in cardiac tissue at 3 0 min after ische-mia.But during the periods from 1 h to 4h after ische-mia,the content of H2 S and the activity of CSE in car-diac tissue were significantly decreased,the infarct volumes were greatly increased compared with those of the sham control group (P<0.05 or P<0.01 ).(2) Compared with those of the ischemia 4h group,LVDP, ±dp/dtmax and CF were significantly increased in the NaHS low,middle and high dose groups (P<0.05 or P<0.01),the content of H2S and the activity of CSE in cardiac tissue were significantly increased in the NaHS low,middle and high dose groups(P<0.05 or P<0.01 ),and the infarct volumes were significantly decreased in NaHS middle and high dose groups(P<0.01 ).Conclusion H2S and CSE are involved in myocardial ischemic injury in isolated hearts of rats. Administration of NaHS could enhance the activity of CSE,increase the content of H2 S,and reduce infarct volumes.It could be suggested that H2 S has cardiopro-tective effects on acute myocardial ischemic injury.

Aim To investigate whether hydrogen sul-fide ( H2 S ) inhibits cardiomyocyte apoptosis induced by acute myocardial ischemia in isolated perfused rat heart. Methods The myocardial ischemia injury model was replicated with Langendorff isolated perfused rat heart, and the left anterior descending coronary ar-tery was ligated for 4 h. 40 male SD rats were divided into five groups randomly: sham group, ischemia group, and NaHS groups (5,10,20μmol·L-1). The segmental heart samples were used for HE staining. Cardiomyocyte apoptosis was detected with TUNEL as-say. The expressions of caspase-3 and Cyt-C in hearts were determined with Western blot analysis. Results Myocardial cells were found to show serious disorder and coagulated zonal necrosis under light microscope, the apoptotic rate of cardiomyocytes and the expression of caspase-3 and Cyt-C were significantly increased af-ter ischemia for 4h. Perfusion of NaHS resulted in more clear cell morphology and milder pathologic chan-ges of myocardiocytes according to the HE staining a-nalysis, and the significant decrease of expression of Cyt-C. After perfusion of 10,20 μmol·L-1 NaHS,the apoptotic rate of cardiomyocytes and the expression of caspase-3 were significantly decreased. Conclusion H2 S has certain protective effects on acute myocardial ischemic injury in isolated perfused rat heart via inhibi-ting cardiomyocyte apoptosis.