Objective To investigate the effect of exogenous hydrogen sulfide (H2S) on intestinal mucosal barrier after cardiopulmonary resuscitation (CPR) in cardiac arrest (CA) rabbits. Methods Forty-four male New Zealand rabbits were divided into sham operation group (Sham group, n = 12), post-cardiac arrest syndrome (PCAS) group (n = 16) and H2S intervention group (PCAS+NaHS, n = 16) according to random number table method. The rabbit model of PCAS was established by tracheal clamping and suffocation, and CPR was started at 5 minutes after CA. However, Sham group did not clamp the tracheal intubation after anesthesia, and the other operations were the same as those in PCAS group. In the PCAS+NaHS group, a bolus of NaHS (0.5 mg/kg), a H2S donor, was injected via era vein 1 minute before the start of CPR, followed by a continuous injection of NaHS (1.5 mg·kg-1·h-1) for 3 hours, while the rabbits in other group were intravenously injected with the same volume of normal saline (NaCl 0.9%). Intestinal and portal vein blood samples were collected 24 hours after return of spontaneous circulation (ROSC). The level of serum fluorescein isothiocyanate-dextran (FD-4) was detected by fluorescein isothiocyanate (FITC) labeling method to reflect intestinal mucosal permeability. After hematoxylin-eosin (HE) staining of small intestine tissues, the morphological changes of mucosa were observed under light microscope, and the intestinal mucosa injury score was calculated. The expression of tight junction protein ZO-1 in intestinal mucosa was detected by immunohistochemistry. The content of malondialdehyde (MDA) in small intestinal tissue was determined by thiobarbituric acid chromogenic method, the activity of superoxide dismutase (SOD) was determined by xanthine oxidation method, and the level of myeloperoxidase (MPO) was determined by double antibody sandwich enzyme linked immunosorbent assay (ELISA) to reflect the oxidative stress and inflammatory reaction in small intestinal tissue. The expression of apoptosis protein (caspase-3) and autophagy related protein (Beclin-1, LC3) in small intestine tissue was detected by Western Blot. Results 12, 13 and 14 animals were successfully resuscitated in Sham group, PCAS group and PCAS+NaHS group respectively, while 12 animals in each group survived to the end of experiment. Compared with Sham group, the level of FD-4 in portal vein serum was significantly increased in PCAS group (mg/L: 11.95±0.59 vs. 1.43±0.48, P < 0.05), the pathological injury and inflammation infiltration were obviously aggravated under light microscope, the score of small intestine injury was significantly increased (4.21±0.37 vs. 0.36±0.18, P < 0.05), the expression of tight junction protein ZO-1 in the intestine was visibly down-regulated detected by immunohistochemistry, MDA content and MPO activity were significantly increased [MDA (nmol/mg): 3.65±0.32 vs. 1.54±0.24, MPO (U/g): 362±35 vs. 134±18, both P < 0.05], while SOD activity was significantly decreased (U/mg:78.84±7.49 vs. 115.48±8.48, P < 0.05), the expression levels of cleaved capase-3, Beclin-1 and LC3 proteins in the intestine were significantly increased (caspase-3/β-actin: 1.11±0.08 vs. 0.21±0.02, Beclin-1/β-actin: 2.08±0.11 vs. 0.42±0.03, LC3/β-actin: 1.05±0.07 vs. 0.37±0.05, LC3-Ⅱ/ LC3-Ⅰ: 1.28±0.14 vs. 0.17±0.02, all P < 0.05). Compared with PCAS group, the portal vein serum FD-4 level in PCAS+NAHS group was significantly decreased (mg/L:5.59±0.48 vs. 11.95±0.59, P < 0.05), the intestinal mucosal pathological injury and inflammatory cell infiltration were significantly decreased, the score of small intestine injury was significantly decreased (2.18±0.47 vs. 4.21±0.37, P <0.05), the expression of ZO-1 in intestine was significantly increased, MDA content and MPO activity in intestine were significantly decreased [MDA (nmol/mg): 2.65±0.31 vs. 3.65±0.32, MPO (U/g): 251±21 vs. 362±35, both P < 0.05], while SOD activity was significantly increased (U/mg: 96.86±7.52 vs. 78.84±7.49, P < 0.05), while the expression of activated caspase-3, Beclin-1 and LC3 proteins was significantly decreased (caspase-3/β-actin: 0.72±0.06 vs. 1.11±0.08, Beclin-1/β-actin: 0.96±0.08 vs. 2.08±0.11, LC3/β-actin: 0.72±0.06 vs. 1.05±0.07, LC3-Ⅱ/ LC3-Ⅰ:0.83±0.09 vs. 1.28±0.14, all P < 0.05). Conclusion H2S has a protective effect on intestinal mucosal injury induced by CA/CPR, which may be related to tight junction protein ZO-1 up-regulation, oxidative stress alleviation, inflammation reduction, apoptosis and autophagy inhibition.

Objective: To investigate the clinical characteristics, diagnosis, treatment and prognosis of therapy-related myeloid neoplasms (t-MNs) after successful treatment for acute promyelocytic leukemia (APL) . Methods: Clinical data of 4 patients, diagnosed as t-MNs secondary to APL at Hematology Hospital of Chinese Academy of Medical Sciences from October 2012 to January 2019, were collected retrospectively. T-MNs related literature was reviewed. Results: The 4 cases were all females, with the median age 42 (range 40-53) years old at the diagnosis of APL. Regarding the induction and consolidation regimens, 3 patients received all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) combined with anthracycline/anthraquinone and/or cytosine. One patient only received ATRA and other auxiliary drugs. Alkylating agents were not administrated. The 4 patients developed t-MNs 40 to 43 months after complete remission (CR) of APL, including 1 case of therapy-related myelodysplastic syndrome (t-MDS) and 3 cases of acute myeloid leukemia (t-AML) . The PML-RARα fusion genes were all negative when t-MNs developed. The three patients with t-AML were treated with 3 to 4 re-induction regimens, one of whom underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after complete remission (CR) . One patient with t-MDS received hypomethylating agents. After a median follow-up of 54.5 (48-62) months, 2 patients with t-AML died, the median overall survival after t-MN was 12 (5-18) months. From 1989 to 2018, a total of 63 t-MN cases were reported in the literature. Therefore, 67 cases were analyzed when four patients in our center were added, including 27 males and 40 females with median age 52.5 (15-76) years. The median latency was 39 (12-126) months and the median overall survival after diagnosis of t-MN was 10 (1-39) months. Conclusions Although rare, t-MNs may occur after successful control of APL. There are no existing guidelines for prevention and treatment of t-MNs, which have very poor prognosis. If cytopenia or other abnormalities of peripheral blood cells develop after 3 years of APL, t-MNs should be considered as a differential diagnosis.