Objective:To investigate the anti-tumor effects and mechanisms of sonodynamic therapy (SDT) combined with anlotinib on non-small cell lung cancer (NSCLC). Methods:A549 and H1299 cells were used as the research models and the following groups were estab-lished:control,anlotinib,SDT,and SDT-anlotinib. Cell viability and migration ability were assessed using the CCK-8 and cell scratch assays. Additionally,flow cytometry was employed to determine reactive oxygen species (ROS)levels,apoptosis,and cell cycle;Western blot was performed to detect Caspase-3 and Cyclin D1 expression;and ROS elimination experiments were conducted to explore the mechanisms of co-mbined SDT and anlotinib treatment. Results:In comparison to the anlotinib group,the SDT-anlotinib group demonstrated a notable inhibi-tion in the proliferation of lung cancer cells[cell viability:A549:(49.96±4.82)％ vs. (86.79±2.64)％,P<0.01;H1299:(31.91±4.87)％ vs. (88.04±2.16)％,P<0.001]and migration[healing rate:A549:(4.23±0.17)％ vs. (14.28±0.05)％,P<0.05;H1299:(13.68±2.16)％ vs. (42.81±8.11)％,P<0.001]. Furthermore,the combination therapy group exhibited a notable induction of apoptosis[apoptosis rate:(12.58±0.815)％ vs. (8.43±0.56)％,P<0.05]. Mechanistic studies have demonstrated that anlotinib resistance is associated with ROS levels. Treatment with the ROS scavenger N-acetylcysteine (NAC) has been shown to decrease intracellular ROS content,increase the IC50 of anlotinib,and reduce sens-itivity. Intracellular ROS levels in tumor cells were significantly higher in SDT-anlotinib group compared to that in the anlotinib group[(934.14±2.01) vs. (166.75±1.45),P<0.001]. Additionally,Caspase-3 activation was observed,accompanied by a reduction in Cyclin D1 ex-pression. Conclusions:The combination of SDT and anlotinib exerted a pronounced anti-tumor effect. Activation of the ROS pathway led to the activation of Caspase-3 and the downregulation of Cyclin D1,resulting in the inhibition of lung cancer cell proliferation and the induction of apoptosis.

Objective:To investigate the anti-tumor effects and mechanisms of sonodynamic therapy (SDT) combined with anlotinib on non-small cell lung cancer (NSCLC). Methods:A549 and H1299 cells were used as the research models and the following groups were estab-lished:control,anlotinib,SDT,and SDT-anlotinib. Cell viability and migration ability were assessed using the CCK-8 and cell scratch assays. Additionally,flow cytometry was employed to determine reactive oxygen species (ROS)levels,apoptosis,and cell cycle;Western blot was performed to detect Caspase-3 and Cyclin D1 expression;and ROS elimination experiments were conducted to explore the mechanisms of co-mbined SDT and anlotinib treatment. Results:In comparison to the anlotinib group,the SDT-anlotinib group demonstrated a notable inhibi-tion in the proliferation of lung cancer cells[cell viability:A549:(49.96±4.82)％ vs. (86.79±2.64)％,P<0.01;H1299:(31.91±4.87)％ vs. (88.04±2.16)％,P<0.001]and migration[healing rate:A549:(4.23±0.17)％ vs. (14.28±0.05)％,P<0.05;H1299:(13.68±2.16)％ vs. (42.81±8.11)％,P<0.001]. Furthermore,the combination therapy group exhibited a notable induction of apoptosis[apoptosis rate:(12.58±0.815)％ vs. (8.43±0.56)％,P<0.05]. Mechanistic studies have demonstrated that anlotinib resistance is associated with ROS levels. Treatment with the ROS scavenger N-acetylcysteine (NAC) has been shown to decrease intracellular ROS content,increase the IC50 of anlotinib,and reduce sens-itivity. Intracellular ROS levels in tumor cells were significantly higher in SDT-anlotinib group compared to that in the anlotinib group[(934.14±2.01) vs. (166.75±1.45),P<0.001]. Additionally,Caspase-3 activation was observed,accompanied by a reduction in Cyclin D1 ex-pression. Conclusions:The combination of SDT and anlotinib exerted a pronounced anti-tumor effect. Activation of the ROS pathway led to the activation of Caspase-3 and the downregulation of Cyclin D1,resulting in the inhibition of lung cancer cell proliferation and the induction of apoptosis.

Objective:To evaluate the therapeutic effect of electroacupuncture on acute gastrointestinal injury (AGI) in patients with severe traumatic brain injury (sTBI).Methods:A prospective randomized controlled trial was conducted. 126 consecutively hospitalized patients with AGI after sTBI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine from January 2018 to December 2019 were enrolled. The patients were divided into observation group and control group by random number table. All the patients of two groups were given conventional treatment of western medicine for consecutive 7 days, including the treatments of primary diseases, indwelling nasogastric tube to extract gastric contents every 6 hours to determine gastric residual volume (GRV). When vital signs were basically stable, enteral nutrition (EN) was implemented and EN feeding amount and speed were adjusted according to GRV. On the basis of conventional western medicine treatment, the observation group was treated with electroacupuncture at Zusanli, Tianshu, Shangjuxu, Xiajuxu and Zhongwan, once in the morning and once in the evening, 30 minutes each time. The gastrointestinal function parameters including intra-abdominal pressure (IAP), serum diamine oxidase (DAO) and gastrointestinal failure (GIF) scores were observed before treatment and at day 3 and day 7 of treatment. The incidence of ICU hospital-acquired pneumonia (HAP-ICU), duration of mechanical ventilation (MV), length of ICU stay, 28-day mortality and adverse reactions of electroacupuncture were also observed in the two groups. Kaplan-Meier method was used for 28-day survival analysis.Results:During the 7-day treatment and observation, 26 cases of 126 patients withdrew from the study, and 100 cases were actually enrolled, 50 cases in the observation group and 50 cases in the control group. IAP and DAO at day 3 of treatment in both groups were significantly lower than those before treatment [control group: IAP (cmH 2O, 1 cmH 2O = 0.098 kPa) was 13.75±2.76 vs. 18.11±3.97, DAO (U/L) was 129.88±24.81 vs. 158.01±22.64; observation group: IAP (cmH 2O) was 13.56±2.19 vs. 18.50±3.54, DAO (U/L) was 129.11±29.32 vs. 159.36±28.65; all P < 0.01]. The gastrointestinal function parameters of the two groups improved gradually with the extension of treatment time, and the IAP, DAO and GIF scores at day 7 of treatment in the observation group were significantly lower than those in the control group [IAP (cmH 2O): 11.28±3.61 vs. 12.68±3.23, DAO (U/L): 49.69±17.56 vs. 57.27±20.15, GIF score: 2.02±0.74 vs. 2.40±0.70, all P < 0.05). The duration of MV and the length of ICU stay in the observation group were significantly shorter than those in the control group [duration of MV (days): 15.72±4.60 vs. 18.08±4.54, length of ICU stay (days): 16.76±4.68 vs. 19.26±5.42, both P < 0.05], and the incidence of ICU-HAP and 28-day mortality were significantly lowered (12.0% vs. 30.0%, 22.0% vs. 32.0%, both P < 0.05). Survival analysis showed that the 28-day cumulative survival rate in the observation group was significantly higher than that in the control group (86.4% vs. 76.1%; Log-Rank test: χ 2 = 37.954, P < 0.001). The patients in the observation group had no significant adverse reaction of electroacupuncture treatment. Conclusion:Electroacupuncture at corresponding acupoints can effectively improve gastrointestinal function in patients with AGI after sTBI, which is beneficial to shortening the length of ICU stay, promoting the recovery of the patients, and reducing the 28-day mortality.

Objective To discuss the influence of Tanshinone ⅡA on the tight junction protein of intestinal mucosal epithelial cells in rat severe septic models. Methods Seventy-five Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group and Tanshinone ⅡA injection high (20 mg/kg), medium (10 mg/kg) and low (5 mg/kg) dose groups, each group 15 rats. Sepsis rat models were established by cecal ligation and puncture (CLP) method, in sham operation group, only switched abdominal surgery was performed without CLP. In Tanshinone ⅡA injection groups, different doses of Tanshinone ⅡA were injected intraperitoneally after modeling for 10 minutes and 6 hours; in sham operation and model groups, equal volume of normal saline was injected intraperitoneally at the same times as above. After operation, 3 L/kg of normal saline was injected into the caudal vein in all rats for fluid resuscitation.Twelve hours after operation, the rats were killed, the abdominal lymph nodes, liver, spleen and kidney tissues were taken for bacterial culture and calculating the rate of bacterial translocation; under microscope, the histopathological changes of ileum mucosal tissues were examined and Chiu scoring was carried out; TdT-mediated dUTP nick end labeling (TUNEL) was applied to detect the ileum mucosal epithelial cell apoptosis and calculating the index (AI);fluorescence immunoassay and Western Blot methods were used to measure the contents and protein expression levels of tight junction protein, junctional adhesion molecule-1 (JAM), Claudin-1, Zonula occludens-1 (ZO-1), Occludin, c-Fos and Tryptase. Results ① In bacterial cultures of abdominal lymph node, liver, spleen and kidney, the positive rate of mesenteric lymph node was the highest, followed by liver and spleen, mainly Escherichia coli, Proteus mirabilis, etc. The highest positive rate of bacterial culture was in model group (38.8%), followed by low dose of Tanshinone ⅡA injection group (35.0%), and the lowest was 16.6% in high dose Tanshinone ⅡA injection group, the differences being statistically significant in comparisons between any pair of groups (all P < 0.05). ② Pathological examination showed that the pathological changes of ileum mucosa were obvious and the Chiu score (4.17±0.98 vs. 0) and AI (11.70±2.87 vs. 2.17±0.80) in model group were significantly higher than those in sham group (all P < 0.05); with the increase of dosage of Tanshinone ⅡA injection, the pathological changes of rat ileum mucosa were improved gradually, the Chiu score and AI were decreased gradually, and the degrees of decrease in high dose Tanshinone ⅡA group were more significant than those in model group (Chiu score: 1.12±0.79 vs. 4.17±0.98, AI: 3.65±1.98 vs. 11.70±2.87, both P < 0.05).③ Immunofluorescence staining showed that the positive staining of protein JAM, ZO-1 and c-Fos were all green in color, Claudin-1, Occludin and Tryptase were all red in color, the localizations of all of them were in the cytoplasm, the protein expression of JAM, Claudin-1, ZO-1, Occludin from strong to weak in turn were Sham group, high, medium, low dose Tanshinone ⅡA group and model group, the expression of c-Fos, Tryptase from strong to weak in turn were model group, low, medium, high dose Tanshinone ⅡA group and Sham group. ④ Western Blot showed that the expressions of ileum tissue JAM, Claudin-1, ZO-1 and Occludin in model group were all significantly lower than those of the sham group, while the expressions of c-Fos, Tryptase were obviously higher than those of the sham group, with the increase of dosage of Tanshinone ⅡA, the expressions of JAM, Claudin-1, ZO-1 and Occludin were increased gradually and the protein expressions of c-Fos and Tryptase were gradually decreased, and the changes in high dosage group of Tanshinone ⅡA were more significant than those in low and moderate groups [JAM (gray value): 25.39±1.82 vs. 12.41±1.34, 19.45±1.66, Claudin-1 (gray value): 28.44±1.56 vs.17.26±1.46, 21.23±1.34, ZO-1 (gray value): 28.84±1.59 vs. 16.45±1.21, 24.22±1.46, Occludin (gray value): 25.49±1.63 vs. 13.34±1.45, 19.45±1.37, c-Fos (gray value):15.76±1.36 vs. 27.84±1.36, 21.22±1.73, Tryptase (gray value): 14.44±1.41 vs. 28.14±1.38, 22.32±1.57], all the above comparisons of different dosage groups were statistically significant (all P < 0.05). Conclusion Tanshinone ⅡA injection may improve intestinal wall structure and reduce bacterial translocation by improving the intestinal mucosal tight junction protein in sepsis model rats, and this effect is positively correlated to Tanshinone ⅡA dosage.

ObjectiveTo investigate the influence of aging and castration on the density of andro gen receptor(AR) in the male rat heart. MethodsAR in the heart of rats aged 40d,90d(intact and castrated) and 2 years were demonstrated by means of immunohistochemical technique and the den sity of the positive staining was measured by using image analys is. The optical density of AR in the septum of the rats were analyzed by anova and doncan process of the SAS data analysis system. Re sultsOD(AR) of the group aged 2 years was higher than that of the groups aged 40d and 90d (0. 3550±0. 0077,0. 31080. 0264 and 0. 3149±0. 0200 respectively), thetwolattergroups showed similarly intensive staining, while the value of castrated group(0. 4136±0. 0320) was signif icantly greater than that of intact same aged group. Conclusion The development of sexual gland has little influence in the density of AR in the male rat heart during prepuberty to adult, both old age and castration increase the density of AR in the rat heart.

AIM: To investigate the influences of electric stimulation applied during the absolute refractory period (ARP) on the cardiac function of normal rabbits and rabbits after myocardial infarction (MI) and to observe the regional effects of this electric stimulation. METHODS: 64 rabbits were randomly assigned to normal and MI groups and each group was then divided into the anterior and posterior groups. A thoracotomy was performed 4 weeks after MI in rabbits. One set of electrodes was inserted into the anterior and posterior wall of left ventricle of the anterior and posterior groups, respectively. Current pulses were delivered during the ARP (called CCM) during sinus rhythm in rabbits. The left ventricular systolic pressure (LVSP) and the left ventricular end diastolic pressure(LVEDP) as well as maximum positive and negative left ventricular pressure change (?dp/dt_(max)) were observed. RESULTS: In the normal and MI groups, LVSP, +dp/dt_(max) significantly increased, and LVEDP, -dp/dt_(max) were reduced during CCM stimulation compared with the baseline (P0.05). CONCLUSION: Electric stimulation delivered during the ARP significantly enhances the contractility and the relaxation of myocardium in normal rabbits and rabbits after MI, and the effects of CCM stimulation on heart are regional. [

We observed the effects of testosterone (T) on myosin ATPase activity and its isoenzyme distribution of noninfarcted myocardium in male infarcted rats. 21 days after myocardial infarction (MI), both myocardial fiber diameter and myosin ATPase activity were increased in T treated MI group when compared with that of the MI group (P

To determine the effects of long term captopril administration on cardiacmorphology and left ventricular function in rats with myocardial infarction, captopril wasadministered to rats 3 days after the begining of myocardial infarction and continued for35 days. Captopril lowened the ratio of left ventricular weight to body weight of bothrats with and without infarction, and also reduced volume, length and dimention of myo-cyte. Captopril had special effects on ventricular geometry in rats with infarction, whichresulted in decreased radius of left ventricular cavity. The cardiac index of captopril-treatedrats with infarction during baseline and a volume loading didn’t change, whereas the ra-dius of left ventricular cavity and LVEDP were decreased significantly, which indicated anincrease of the ejection fraction index. The results showed that long term administrationof captopril might be unfavoralle to compensary myocardial hypertrophy, but catdiacfunction was improved, which was ascribed to reduction of left ventricular cavity volumeand LVEDP.

AIM: To study the distribution, location and quantity of myocardial collagen(Col) in different phases after myocardial infarction(MI). METHODS: The method of immunohistochemical technique combined with automatic image analysis was used to investigate the changes of collagen Ⅰ and Ⅲ. RESULTS:Contents of Col Ⅰ, Col Ⅲ and the ratio of Ⅰ/Ⅲ were all increased in infarcted area (IA)after MI,and the increase of Col Ⅰ was higher, the collagen fibers still construct a network in acute phase, in chronic stage, all necrosis myocytes were replaced by collagen, the fibers were dense, and paralelled with cardiac cavity surface.In the septum,noninfarcted area, contents of collagen type Ⅰ and Ⅲ, the ratio of Ⅰ/Ⅲ were increased.In acute phase, the increase of type Ⅲ is dominant,with in chronic phase, type Ⅰ is. Right ventricle(RV) has no significant change in acute phase,untill chronic phase,it changed like septum,the increase in collgen is mainly type Ⅰ. CONCLUSION: The collgen remodeled after myocardial infarction were reparative fibrosis in IA phase, and reactive fibrosis in NIA phase. Remodeling occured later in RV than in septum.

To investigate the influences of bradykinin(BK)on left ventricular hypertrophy and cardiac function in angiotensin-converting enzyme inhibitor(ACEI) therapy in rats after myocardial infarction. METHODS: The effects of enalapril (500 ?g?kg -1 ?d -1 ), enalapril (500 ?g?kg -1 ?d -1 )with BKB 2 receptor antagonist (Hoe-140 500 ?g?kg -1 ?d -1 ), losartan(3 mg?kg -1 ?d -1 ) on left ventricular end-diastolic pressure (LVEDP), maximum positive left ventricular pressure change (+d p /d t max ) and LVW/BW as well as V(m)n of noinfarcted area were examined after 4 weeks treatment in rats after myocardial infarction. RESULTS: The values of LVEDP, LVW/BW and V(m)n of three treatment groups were higher than that of untreated MI group ( P