OBJECTIVE: To investigate the effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the surgical efficacy of short-segment percutaneous pedicle screw fixation for thoracolumbar burst fractures with high rate of spinal canal encroachment. METHODS: From January 2016 to January 2022, 38 patients with thoracolumbar burst fractures with high rate of spinal canal encroachment (spinal canal encroachment rate >40%, complete posterior longitudinal ligament, no flipping bone block in the posterior marginal of the vertebra) without spinal cord injury who were were treated with short-segment percutaneous pedicle screw fixation were retrospectively analyzed. During the operation, 18 cases were used distraction-reduction first and then intermediate instrumentation on injured vertebral and sequential distraction-reduction again(the distraction-reduction first group) including 8 females and 10 males with a mean age of 46.5 (38.5, 50.0) years old, and the other 20 cases were used intermediate instrumentation on injured vertebral first and then direct distraction-reduction(the intermediate instrumentation first group) including 10 males and 10 females with a mean age of 46.0 (35.8, 50.8) years. The anterior height ratio of the injured vertebra, local Cobb's angle of the injured vertebrae, the spinal canal encroachment rate, and the improvement rate of spinal canal encroachment were compared and evaluated. RESULTS: All patients were followed up for more than 1 year, and no complications such as spinal cord and root injury, screw loosening and screw rod fracture were found. The anterior height ratio of the injured vertebra, local Cobb' angle of the injured vertebra in the two groups were significantly improved compared with preoperative data(P<0.05), and those at 3 months and 1 year after operation was lost compared with that at the previous time point(P<0.05). Although the spinal canal encroachment rate of the two groups 1 day and 1 year after operation was improved compared with that before operation(P<0.05), the improvement of spinal canal volume in the distraction-reduction first group was significantly better than that in the intermediate instrumentation first group (P<0.01). CONCLUSION In the treatment of patients with thoracolumbar fractures with high rate of spinal canal encroachment, short-segment percutaneous pedicle screw internal fixation with distraction-reduction first and then intermediate instrumentation and sequential distraction-reduction again can more effectively reduce the bony encroachment in the spinal canal and achieve indirect decompression effect better.
Humans ; Female ; Male ; Adult ; Middle Aged ; Spinal Fractures/surgery* ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Fracture Fixation, Internal/instrumentation* ; Pedicle Screws ; Retrospective Studies ; Spinal Canal/surgery*

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Janus kinase (JAK) and histone deacetylase (HDAC) referred to as crucial targets in autoimmune diseases and cancers have achieved quite success in the treatment of these diseases. Until now, several JAK and HDAC inhibitors have been approved. Recently, developing single multi-targeting inhibitors including JAK/HDAC dual inhibitors based on network pharmacology has made significant progress in improving therapeutic efficacy, reducing toxic and side effects, and overcoming drug resistance. In this review, we summarize novel JAK/HDAC dual inhibitors as well as JAK/HDAC-based triple-targeting inhibitors, in order to provide reference for the discovery of novel JAK/HDAC dual inhibitor.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC₈₀ = 32 μg·mL^-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Protein-protein interaction (PPI) plays an important role in the regulation of life. Most of the PPI interfaces are large and discontinuous, and it is difficult for small molecules to specifically bind to them. Peptides are critical in PPI surface interactions due to their higher affinity and specificity. However, peptides have some defects such as easy hydrolysis by protease and poor membrane permeability. Due to good biocompatibility and chemical diversity, cyclic peptides play an important role in drug discovery. Therefore, the development of efficient cyclic peptide construction methods has become a frontier issue in peptide drug research. In recent years, a series of new progresses have been made in the synthesis strategy and the application of cyclic peptides, providing powerful technical tools for the research and development of cyclic peptide drugs. In this review, the synthesis strategies of cyclic peptides and their application will be reviewed from four aspects: synthesis strategies, property improvement, biological activity and prospect.