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.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

Damarane-type triterpene saponins are the main active ingredients in Gynostemma pentaphyllum (Thunb.) Makino. By using D101 macroporous adsorption resin and silica gel open-columns, C18 medium-pressure column chromatography, and preparative high performance liquid chromatography, we isolated four compounds from the leaves of G. pentaphyllum planted in Guangxi Zhuang Autonomous Region. Their structures were determined by comprehensive analyses of MS, NMR data and circular dichroism spectroscopy and identified as (3β,12β)-dihydroxy-25-peroxyhydrohydrodammarane-20,23-diene-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (1), (3β,12β,24S)-trihydroxydammarane-20,25-diene-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (2), (3β,20α)-dihydroxy-24-en-12β,22S-epoxydammarane-3-O-[β-D-glucopyranosyl(1→2)]-β-D-glucopyranoside (3), (3β,12β,20S)-trihydroxydammarane-24-en-3-O-[6-O-acetyl-β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→3)-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (4). Compounds 1-4 are new dammarane-type triterpene saponins.

Abstract: Objective　To investigate the clustered regularly interspaced short palindromic repeats (CRISPR) genotypes and regional distribution of Yersinia pestis strains in the natural plague foci of Hainan Tibetan Autonomous Prefecture of Qinghai Province (referred to as "Hainan prefecture") and provide a scientific basis for plague prevention and control in this area. Methods　A total of 36 representative Yersinia pestis strains, which were isolated from different host animals and insect vectors from 1954 to 2009 in Hainan Prefecture, were selected as experimental subjects. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three pairs of CRISPR primers (YPa, Ypb, YPc) were used for PCR amplification, sequencing and analysis of the DNA of the tested strains, respectively, as a means to identify the CRISPR genotypes of Yersinia pestis in Hainan Prefecture. Results　A total of 17 spacers were observed among 36 strains of Yersinia pestis, including 9 of YPa, 5 of YPb and 3 of YPc. All strains were divided into 5 CRISPR gene clusters (Cb2, Cb4 ', Ca7, Ca7 ', Ca35 ') and 6 genotypes (G1, G9, G22, G22-A1 ', G26-A1 ', G26-A1 'A4 -). The G26-a1 ' was the main genotype, which was distributed in Gonghe, Guide and Xinghai County, and the G22 is the second type, which was distributed in Gonghe and Guide County. Conclusions　The genetic polymorphism of CRISPR loci of Yersinia pestis strains in Hainan was high, and the regional distribution characteristics of Yersinia pestis strains with different genotypes were significant.

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

ObjectiveTo establish a model of inflammasome activation induced by psoralidin based on bone marrow-derived macrophages （BMDM） in mice， and to explore the immunomodulatory effects of psoralidin combined with echinatin. MethodLipopolysaccharide （LPS） and psoralidin were used to activate inflammasomes， and after 4 h LPS stimulation， echinatin （40 μmol·L^-1） was administered for pre-protection for 1 h， followed by stimulation with psoralidin （10， 20， 40 μmol·L^-1） for 4 h. The protein expression of Caspase-1 p20 in cell supernatant and precursor （pro）-Caspase-1 and pro-interleukin（IL）-1β in cell lysate were simultaneously detected by Western blot. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the content of IL-β and TNF-α in the supernatant of BMDM. ResultWestern blot revealed that compared with the conditions in the control group， the maturation of psoralidin-induced pro-Caspase-1 and the secretion of IL-1β was inhibited by echinatin （P<0.05，P<0.01）. ELISA showed that the production of IL-1β and TNF-α was enhanced by psoralidin of different concentrations （P<0.05，P<0.01） compared with the condition in the control group. In addition， compared with the psoralidin group， the psoralidin combined with echinatin group reduced the secretion of IL-1β and TNF-α （P<0.01）. ConclusionEchinatin could significantly inhibited the excessive immune-inflammatory response mediated by psoralidin， and thus achieve the effect of toxicity reduction. The present study explored the toxicity-reducing effect of psoralidin combined with echiantin， providing a basis for safe clinical application.

OBJECTIVES: The artificial intelligence-aided diagnosis model of rib fractures based on YOLOv3 algorithm was established and applied to practical case to explore the application advantages in rib fracture cases in forensic medicine. METHODS: DICOM format CT images of 884 cases with rib fractures caused by thoracic trauma were collected, and 801 of them were used as training and validation sets. A rib fracture diagnosis model based on YOLOv3 algorithm and Darknet53 as the backbone network was built. After the model was established, 83 cases were taken as the test set, and the precision rate, recall rate, F1-score and radiology interpretation time were calculated. The model was used to diagnose a practical case and compared with manual diagnosis. RESULTS: The established model was used to test 83 cases, the fracture precision rate of this model was 90.5%, the recall rate was 75.4%, F1-score was 0.82, the radiology interpretation time was 4.4 images per second and the identification time of each patient's data was 21 s, much faster than manual diagnosis. The recognition results of the model was consistent with that of the manual diagnosis. CONCLUSIONS The rib fracture diagnosis model in practical case based on YOLOv3 algorithm can quickly and accurately identify fractures, and the model is easy to operate. It can be used as an auxiliary diagnostic technique in forensic clinical identification.
Humans ; Rib Fractures/diagnostic imaging* ; Artificial Intelligence ; Thoracic Injuries ; Algorithms ; Radiography ; Retrospective Studies

The working principle and structural composition of the transcranial magnetic stimulator were introduced.The failures of the transcranial magnetic stimulator in some hospital were summarized from 2018 to 2022.The causes for common failures of the transcranial magnetic stimulator were analyzed with the fishbone diagram,and some suggestions were put forward on its daily utilization management.The maintenance thoughts for two common failures were described in detail including flow control alarm and no magnetic field output.References were provided for daily management and maintenance of the transcranial magnetic stimulator.[Chinese Medical Equipment Journal,2023,44(9):110-113]