It has demonstrated histone deacetylase inhibitor to be protective in preclinical and early clinical studies for the therapy of cancer,central nervous system degenerative diseases and immune system diseases.Strikingly,Recent studies have shown that it has emerged as a potent prosurvival and anti-inflammatory drug,offering new lines of therapeutic intervention for sepsis shock,and can reverse the changes of genes expression at the molecular level,caused by sepsis shock and its follow-up of fluid resuscitation.What' s more,it has slight impact on hemodynamics,ultimately alleviates lesions to systemic inflammatory response syndrome and multiple organ failure syndrome and simultaneously lays a good foundation to win the golden time for treatment.On the other hand,with the development of second hit theory,it will also set up a bridge between hemorrhagic shock and septic shock,resulting in expansioning the breadth and depth of understanding of shock.In brief,histone deacetylase inhibitors are the extension and challenges of the traditional therapy of anti-sepsis shock.

Objective To explore the pathogenesis of acute lung injury in rats suffering hemorrhagic shock at plateau.Methods Seventy-two male Wistar rats, weighing 280-320 g, were randomized into 6 groups (n=12): sham group (group Sham), hemorrhagic shock for 15 min (group HS15), hemorrhagic shock for 30 min group (group HS30), hemorrhagic shock for 45 min group (group HS45), hemorrhagic shock for 60 min group (group HS60) and 90 min group (group HS90).Hemorrhagic shock model of Wistar rats was reproduced at plateau.The rats were only anesthetized, no shock and were sacrificed after 90 min in group Sham.The other groups were different in bleeding time and then were respectively sacrificed at 15, 30, 45, 60 and 90 min after shock.The pathological changes in the lungs were observed with light microscope.Wet to dry weight ratio (W/D), lung permeability index (LPI), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and superoxide dismutase (SOD) in lung were measured.Enzyme-linked immunosorbent assay was used to detect the TNF-α and IL-10 in lung tissue, the expression and distribution of claudin-3 and claudin-4 in lung tissue was verified by immunohistochemistry method.Results Compared with group Sham, shock causes acute lung injury at different degree, and was positively correlated with the duration of shock, during the period of 15 to 30 min, it merely rendered a slight change in lung W/D, LPI, MPO, MDA, TNF-α, T-SOD and IL-10.Subsequently, along with time prolonged, lung W/D, neutrophils in BALF, LPI, MPO, MDA, TNF-α were significantly elevated, while T-SOD and IL-10 were notably reduced (P<0.05).Immunohistochemical results showed that claudin-3 and claudin-4 expression in lung epithelial cells and endothelial cells expressed at low levels and dislocated (P<0.05).Conclusion After a short time compensatory lesions, the change of rats' hemodynamic stability suffering severe hemorrhagic shock showed a spiral downward.Along with the extension of the shock, hemorrhagic shock at plateau results into the disturbance of inflammatory response and oxidative stress, the loss of claudin-3 and claudin-4 in lung epithelial cells, which triggers the acute lung injury.

Sixty patients with piriformis syndrome were treated mainly by electroacupunture, Tuina plus TDP irradiation. After 10 treatments, among 60 patients, 41 cases were cured and 19 cases were improved.

Objective To evaluate the effect of suberoylanilide hydroxamic acid (SAHA) on liver injury induced by lethal hemorrhagic shock in rats first entering high altitude.Methods Forty healthy male SpragueDawley rats,aged 2-3 months,weighing 240-280 g,transported from breeding grounds at an altitude of 1520 meters to the experimental station at an altitude of 3780 meters,were randomly divided into 4 groups (n =10each):sham operation group (group S),lethal hemorrhagic shock group (group LHS),normal saline group (group NS),and SAHA group.Anesthesia was induced with inhalation of 3% isoflurane and maintained with inhalation of 0.5%-1.0% isoflurane.Lethal hemorrhagic shock was induced by withdrawing blood from the femoral artery in groups LHS,NS and SAHA.Normal saline 0.25 ml and SAHA 7.5 mg/kg (0.25 ml) were injected intravenously over 2 min after completion of blood-letting in groups NS and SAHA,respectively.The survival rates with 3 h were recorded.Blood samples from femoral veins were taken before blood-letting,immediately after completion of blood-letting and at 3 h after completion of blood-letting (immediately after death if the survival time was less than 3 h) for determination of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) activities by the colorimetric method.Liver specimens were taken at 3 h after completion of blood-letting or immediately after death for examination of the pathological changes of the liver and for determination of c-Jun N-terminal kinase (JNK),phosphorylated-JNK (p-JNK) and caspase-3 expression and acetylation of H3K9 in liver tissues by Western blot.Results Compared with group S,the activities of serum AST,ALT and LDH were significantly increased in the other three groups (P ＜ 0.01).Compared with LHS and NS groups,the activities of serum AST,ALT and LDH were significantly decreased,the survival rate within 3 h and acetylation of H3K9 were increased,caspase-3 expression was down-regulated,and p-JNK/JNK ratio was decreased in group SAHA (P ＜ 0.05 or 0.01).The pathological changes of the liver were severe in LHS and NS groups and attenuated in SAHA group.Conclusion Administration of SAHA in early shock can significantly protect the liver after lethal hemorrhage in rats first entering high altitude,and increased acetylation of H3K9 and inhibition of the JNK/caspase-3 apoptotic pathway in liver tissues are involved in the mechanism.

Objective To compare the event-related potential(ERP) difference waveforms between attention deficit hyperactivity disorder (ADHD) children and normal children in the conflict task,and to investigate the neural mechanism of conflict monitoring of ADHD. Methods ERPs elicited by performing the spatial SimonStroop task were recorded in 32 children with ADHD and 32 normal children. The differences of ERP and behavior dren with ADHD(0.80±0. 11 ,0.87 ±0.08) were less than normal children (0.88 ±0.07,0.93 ±0. 04)in Sireaction time of ADHD group( (773.03 ±99.34)ms) in the Siin were longer than the control group( (737.21 ±81.40)ms) ,the differences had statistic significance (P＜0. 05). 2. ERP results:the amplitude of N2 of the children with ADHD in the four conditions were smaller than the control group, the difference in Siin had statistic sigof prefrontal and anterior cingulate cortex of ADHD were weaker than the control group. Conclusions The results suggest that, due to the inadequate allocation of attention resources of the children with ADHD, they have conflict monitoring function defects compare with normal children. The function defects of conflict information processing related brain areas may be the main neural mechanism. The result of the behavior and ERP can become the reference indicator for the early diagnosis and treatment of ADHD.

ObjectiveTo provide clues to find a biomarker for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression. Methods Surgical specimens were obtained from 87 patients with histopathologically proven malignant or benign lesions. The differential protein profiles of these malignant and benign specimens were detected using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting and immuno-histochemistry were used to validate the results. RT-PCR was used to detect the gene expression in the tissues. ResultsMrp14 was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. The result was further verified using Western blot and immuno-histochemistry. RT-PCR confirmed the overexpression of Mrpl4 at the gene level. Mrp14 is a potential biomarker for biliary tract neoplasms. ConclusionsThis is the first report which described the overexpression of Mrp14 in biliary tract neoplasms and further studies are needed to confirm our findings. Mrp14 may be a potential hiomarker for biliary tract neoplasms. It may provide important clues on the molecular mechanisms governing cancer progression.

Objective To investigate the clinincal curative effects of superficial palmar branch of radial artery (SPBRA) flaps with anastomosed accompanying vein repairing soft tissues defects in fingers.Methods From January,2016 to June,2017,10 cases with soft tissues defects received the operation of superficial palmar branch of radial artery flaps transplantation.In the process of operation,the superficial palmar branch of radial artery (SPBRA) was carefully separated,accompanying vein and superficial vein.The SPBRA was anastomosed with the proper digital artery,while the accompanying vein of superficial palmar branch and superficial vein were anastomosed with the palm vein.The nerve supplied this flap was anastomosed with the proper digital nerve.Mesured the range of motion and two-points discrimination of fingers with following-up.Regular followed-up was performed after operation.Results All patients were followed-up ranged from 6 to 24 months,averaged of 13.8 months.All flaps survived.The shape of flaps was plump and the two-points discriminations ranged from 8 to 12mm.Conclusion Using SPBRA flaps with anastomosed accompanying vein to repair soft tissues defects in fingers,there were minor damage to donor and recipient sites,and the shape and sense of recipient site was perfect.It is a promising treatment choice for patients with soft tissues defects in fingers.

Objective To investigate the effect of enhanced recovery after surgery (ERAS) on immune function and postoperative recovery in gastric cancer patients undergoing total laparoscopic radical gastrectomy.Methods Patients were randomly divided into ERAS group and control group.Blood CD4 +,CD8+,CD4 + CD25 +,C-reactive protein,postoperative recovery and complications were compared between the two groups.Results On day1,CD4 +,CD8 +,CD4 + CD25 + in the two groups were significantly lower than those before surgery (t =9.070,7.297,5.830,12.870,3.529,10.547,all P＜0.05).The ERAS group had higher CD8 +,CD4 + CD25 + levels than the control group (t =2.163,2.203,P ＜ 0.05).On day3,CD4 + CD25 + in ERAS group was not different from that before surgery (t =1.062,P ＞ 0.05) while the other indexes in the two groups raised but still were lower than preoperative level (t =3.322,5.015,3.418,9.912,all P ＜0.05);CD4 +,CDs +,CD4 + CD25 + in ERAS group were higher than control group (t =2.804,2.040,2.210,all P＜0.05).On day5,CD4+,CD4 + CD25+ in the two groups and CDs+ in ERAS group returned to the preoperative level,while CDs + of the control group was still lower than the preoperative level (t =6.862,P ＜0.05).On day1,3 and 5,the C-reactive protein levels of the two groups were higher than those before surgery(t=-13.338,-13.715,-11.319,-12.286,-13.182,-15.076,all P ＜ 0.05),and ERAS group were lower than the control group (t =-3.246,-2.100,-2.211,all P＜0.05).There was no mortality in neither groups.The time of passage gas by anus,defecation,getting out of bed,oral feeding,and postoperative hospital stay in the ERAS group were less than thoseinthecontrolgroup[(2.8±1.0)dvs.(3.9±0.9)d,t=-5.974;(3.8± 0.9)d vs.(4.3±1.0)d,t=-2.700;(19.1 ±4.0)hvs.(35.9±6.6)h,t=-16.045;(9.9 ±1.6)d vs.(11.5±2.0) d,t =-4.479,all P ＜ 0.05].Conclusions ERAS in the perioperative period of patients with total laparoscopic radical gastrectomy mitigates the stress on the cellular immune system,reduces inflammatory response,and help fast recover the postoperative gastrointestinal function.

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

AIM: To observe the effect of fudosteine on induced sputum cell components and lung function in patients with stable neutrophil-dominated COPD. METHODS: From October 2019 to October 2022, 53 patients with stable COPD were selected and divided into fudosteine group and placebo group. The placebo group was treated with routine treatment, and the fudosteine group was treated with fudosteine on the basis of routine treatment. The two groups were treated for 6 months. The clinical symptoms [Saint George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Modified British Medical Research Council Dyspnea scale (MMRC), Breathlessness, Cough, and Sputum Scale (BCSS)], lung function index, induced sputum cytology analysis and other related examination results were recorded in detail before and after treatment. RESULTS: (1) Compared with the baseline, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC (FEV1/FVC) of the two groups were improved after treatment, and the differences were statistically significant (P<0.05). However, after treatment, there was no significant difference in pulmonary function between the two groups except for the percentage of carbon monoxide diffusion in the predicted value (DLCO%pre) (DLCO%pre in the fudosteine group was higher than that in the placebo group). (2) After treatment, the total number of induced sputum cells and neutrophil counts in the fudosteine group were lower than those in the placebo group. Compared with the number of cells in each component at baseline, the total number of induced sputum cells and neutrophil count in the fudosteine group were significantly lower (P< 0.05). CONCLUSION: Fudosteine treatment in patients with stable neutrophil-dominated COPD can improve lung function, reduce the total number of induced sputum cells and the total number of neutrophils, thereby improving airway inflammation.