Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

To optimize the process of hydrogenation reduction in the synthesis of apremilast (APST), 3-nitrophthalic anhydride (4) and (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethanamine-(S)-2-acetamido-4-methylpentanoate (7) were used as starting materials to synthesize (S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-4-nitroisoindoline-1,3-dione (8) by amination.Then compound 8 was reduced to (S)-4-amino-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethyl) isoindoline-1,3-dione (9) with ammonium formate as hydrogen source and palladium hydroxide as catalyst.Finally, apremilast was obtained by the acetylation reaction with acetic anhydride.The structure of the products were verified by optical rotation, 1H NMR, 13C NMR, MS and elemental analysis.And the total yield of three steps was increased to 67.0%.The improved reduction process can avoid the special reaction of hydrogenation and pressurization, and reduce the safety risk and production costs with high commercial value.

Objective:To evaluate the clinical efficacy and changes between Dynesys and Posterior lumbar interbody fusion (PLIF) in the treatment of two-level lumbar degenerative disease.Methods:43 consecutive patients with lumbar degenerative disease were treated using the Dynesys or PLIF between June 2010 and June 2012. In all patients, 23patients were implanted Dynesys and other patients for PLIF. The follow-up period was at least 60 months. Used the Visual analogue scale (VAS) and Oswestry disability index (ODI) to evaluate the clinical outcomes. And during the follow-up period, collected the data for the intervertebral height and the range of motion (ROM), for the operation section and the upper adjacent vertebral. MRI and Grading Scale from the University of California at Los Angeles (UCLA) were used to define the change of intervertebral disc signal.Results:The ODI index and VAS score both improved significantly at the final follow-up evaluation ( P<0.05), as compared to the basal line values. And in terms of imaging, there were no significant difference in the vertebral height of the operation section and the upper adjacent vertebral. The range of motion (ROM) for the operative section in the group of PLIF was significantly lower than that in Dynesys group ( P<0.05). And when it comes to the upper adjacent vertebral space, it was higher at the same time ( P<0.05). According to the UCLA Grading Scale, there were 3 cases in the Dynesys group and 11 in the PLIF group had radiological adjacent degeneration, the difference was significant between two groups ( P<0.05). And when it comes to the second intension, there were 3 patients in PLIF groups (TLIF 1; PLIF 2) but only 1 in Dynesys groups. Conclusion:Dynesys and PLIF are both effective for lumbar degenerative disease and show good medium and long-term clinical and radiographic results. But when it comes the risks in developing ASD and the ROM of adjacent segments, Dynesys stabilization can be the better choice.

Objective To investigate the value of prothrombotic state (PTS) in prediction of perioperative cardiac events in elderly patients with coronary heart disease undergoing noncardiac surgery.Methods One-hundred and twenty-eight ASA physical status Ⅰ or Ⅱ elderly patients (NYHA class Ⅰ or Ⅱ) of both sexes,aged 6575 yr,undergoing elective abdominal surgery,were enrolled in the study.Total intravenous anesthesia was performed during surgery.Venous blood samples were collected for detection of the levels of D-dimer,thrombus precursor protein and P-selectin (molecular markers of PTS).Detection of PTS was based on the three indexes mentioned above.The patients were divided into 2 groups according to the cardiac events occurred during surgery and within 3 days after surgery:non-cardiac event group and cardiac event group.The general data of patients and each index during surgery were recorded.Logistic regression analysis was used to pick out the potential risk factors for cardiac events.Results Twenty-nine patients developed cardiac events.There was no significant difference in age,obesity,ratio of diabetes,duration of operation,and ratio of PTS between non-cardiac event and cardiac event groups (P ＜ 0.05 or 0.01).Logistic regression analysis showed that old age,diabetes,prolonged duration of operation,and PTS were independent risk factors for cardiac events (P ＜ 0.01).Conclusion PTS produces some value in prediction of perioperative cardiac events in elderly patients with coronary heart disease undergoing noncardiac surgery.