Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Establishment of a nomogram prediction model for intracranial hemorrhage risk after mechanical thrombectomy / 中国医师杂志

Objective:To establish a nomogram model for predicting the risk of intracranial hemorrhage in patients with acute cerebral infarction after mechanical thrombectomy.Methods:The clinical data of 251 patients with acute cerebral infarction who underwent mechanical thrombectomy in Shengjing Hospital Affiliated to China Medical University from January 2017 to December 2019 were retrospectively analyzed. Logistic regression model was used to analyze the independent risk factors of intracranial hemorrhage after mechanical thrombectomy. A nomogram prediction model based on independent risk factors was established to verify the prediction and accuracy of the model.Results:The analysis results of logistic regression model were as follows: age ( OR=1.303, 95% CI:1.184-1.433), the time from infarction to re-canalization ( OR=4.306, 95% CI:2.497-7.425), preoperative NISS score ( OR=7.584, 95% CI:2.221-25.900), preoperative computer tomography (CT) low-density lesions ( OR=7.954, 95% CI:1.176-53.792) were independent risk factors for intracranial hemorrhage after mechanical thrombectomy in patients with acute cerebral infarction ( P<0.05). Based on the above 4 independent risk factors, a nomogram predictive model of intracranial hemorrhage risk after mechanical thrombectomy was established. The Bootstrap internal verification method proved that the model had good prediction accuracy, and the receiver operating characteristic (ROC) curve analysis testified that area under curve (AUC) area was 0.966. Conclusions:The risk nomogram prediction model has good accuracy, discrimination and good prediction ability, which can improve the diagnostic efficacy of intracranial hemorrhage after mechanical thrombectomy in patients with acute cerebral infarction.

Effect of the structure and performance of tracheal intubation modelon teaching effect / 中华医学教育探索杂志

Objective To study the influence of the structure and performance of tracheal intuba-tion model on teaching effect. Methods Three models of tracheal intubation with different structures were named M1, M2 and M3. A total of 91 medical students of grade 5 were enrolled, divided randomly into group A, B and C after theoretical knowledge learning of 30 minutes and examination, rained respectively on the M1, M2 and M3 for 90 minutes, and then evaluated. The models were changed within the three groups and students were then trained and evaluated for the second time. Comparison of the results was performed among the three groups. After one month, group A, B and C received examination and evaluation again. Students and instructors were asked to fill in the rating scale for M1, M2 and M3. Results ①No statistically significant differences were found in the number (31, 28, 32), gender (male/female, 10/21, 9/19, 12/20) and the pre-training test score of the students among the three groups. ②The score of the first evaluation on M1 was significantly lower in group A than in group B and C, while the scores of the second and third examination were significantly higher in group A than in the other two groups. ③The score after one month was significantly higher in group A than in group B and C. ④M1 scores (4, 5; 4.63, 5) were significantly higher than those in group B (3, 4; 2, 2.5) and group C (2, 3; 2, 2.25). Conclusion The structure and performance of the training model of tracheal intubation can indeed influence the teaching effect.

Cytogenetic and molecular genetic analysis of the amniotic fluid cells of a fetus with pseudodicentric isochromosome 22 resulting in partial tetraploidy of 22q / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To diagnose chromosomal abnormalities in amniotic fluid cells by combining karyotyping and single nucleotide polymorphism array (SNP-array) analysis, and to explore the application of SNP-array in routine clinical practice.</p><p><b>METHODS</b>Conventional G banding was used to karyotype a fetal amniotic fluid sample and the corresponding peripheral blood samples from the parents, followed by SNP-array analysis of the fetal genomic DNA from the amniotic fluid.</p><p><b>RESULTS</b>The karyotype of the amniocytes was 47, XX, +mar. The marker chromosome was further identified as psu idic (22) (q11.2) by SNP-array analysis, revealing tetraploidy of a 1.7 Mb fragment in 22q11.1-q11.2 interval that involves the critical region for Cat eye syndrome.</p><p><b>CONCLUSION</b>A rare chromosomal abnormality was identified by combining conventional G banding and SNP-array. The high resolution SNP-array could provide more detailed information for determining the origin of chromosomal abnormalities.</p>

Treatment protocols of local-regional recurrence after breast cancer surgery / 国际肿瘤学杂志

Despite the deepening of research on breast cancer,improving of treatment techniques,there are still many patients will appear local-regional recurrence after surgery.For patients with local recurrence after radical mastectomy,according to whether the postoperative radiotherapy performed,prognosis and treatment protocols are absolutely different.As for patients with local recurrence after breast-conserving surgery,more and more studies have shown that lumpectomy (secondary breast conserving surgery) combined with brachytherapy can achieve a similar effect with radical surgery in recent years,so it is a worth considering treatment protocol.

Application of group feedback and formative assessment in the teaching of endotracheal intubation / 中华医学教育探索杂志

Objective To investigate the effect of group feedback and formative assessment respectively on teaching effectiveness of endotracheal intubation (ETI).Methods After atheoretical lecturing and theoretical test,eighty three undergraduates were randomized into concurrent-feedback group and groupfeedback group.ETIsimulation training was given respectively by providing concurrent or group feedback in the two groups,and then undergraduates received a skill assessment.After atheoretical lecturing and theoretical test,other 91 undergraduates were randomized into final-assessment group and formative-assessment group.ETIsimulationtraining and skill assessment were given in final-assessment group.Before training,first skill assessment was performed in formative-assessment group,and then feedback was delivered based on the assessment.After training,second skill assessment was given again.Skill assessment was evaluated using the criterion-based task specific checklist combined with global rating scale.t-test was used for comparison between groups.Results There was no statistical difference (P=0.212) in theoretical scores between group-feedback group,and concurrent-feedback group.Skill assessment score of group-feedback group (39.4 ± 4.9) was higher than that in concurrent-feedback group (35.4 ± 4.7),with statistical difference (P=0.000).There was no statistical difference (P=0.395) in theoretical scores between formative-assessment group and final-assessment group.Score of formative-assessment group (39.3 ± 6.2) was higher than that in final-assessment group (32.2 ± 2.4),with statistical difference (P=0.000).Conclusion Terminal feedback or formative assessment could enhance teaching effectiveness of endotracheal intubation among medical students.

Investigation of a rare supernumerary i(Y)(q10) chromosome in a patient with premature ovarian failure / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the origin of a rare supernumerary chromosome in a patient with premature ovarian failure (POF), and to explore the relationship between this abnormal karyotype and pathogenesis of POF.</p><p><b>METHODS</b>GTG banding karyotyping, Q-banding and fluorescence in situ hybridization (FISH) were employed for the investigation.</p><p><b>RESULTS</b>The extra chromosome was identified as i(Y)(q10) by FISH with a panel of sex chromosome probes. The patient's karyotype was described as: 47,XX,+ ish mar i(Y)(q10) (DXZ1-, SRY-, DYZ3+, DYZ1++, wcpY+).</p><p><b>CONCLUSION</b>Co-occurrence of the supernumerary i(Y)(q10) with a female kryotype is extremely rare. This supernumerary chromosome may cause failure of X chromosomes synapsis during pachytene of meiosis I, which may trigger apoptosis of many oocytes and result in POF of the patient. Q-banding, FISH and multiple probes have been critical for accurate diagnosis of the unknown chromosome.</p>

The effect and safety of amlodipine besylate combined with benazepril in treatment of old patients with primary hypertension and left ventricular hypertrophy / 中国医师进修杂志

ObjectiveTo observe the effect of amlodipine besylate combined with benazepril in treatment of old patients with primary hypertension and left ventricular hypertrophy,and analyze the safety.MethodsOne hundred and eight old patients with primary hypertension and left ventricular hypertrophy were divided into observation group(54 cases) and control group(54 cases) by random digits table.The patients in observation group were treated with amlodipine besylate combined with benazepril and the patients in control group were only treated with amlodipine besylate.The levels of blood pressure,interventricular septal thickness(IVST),left ventricular posterior wall (LVPW),left ventricular end-diastolic dimension (LVEDD) and left ventficular mass index(LVMI) before and after treatment for 6 months were measured and compared between two groups.The adverse effects after treatment were compared too.ResultsAfter treatment,the levels of 24hSBP,24hDBP,IVST,LVPW,LVEDD and LVMI were significantly decreased in both groups (P ＜ 0.05).Moreover,the levels of 24hSBP,24hDBP,IVST,LVPW,LVEDD and LVMI after treatment in observation group were significantly lower than those in control group(P ＜ 0.05).There was 1 case ( 1.9％ ) of dry cough,2 cases (3.7％) of mild ankle edema in observation group,while only 2 cases (3.7％) of mild ankle edema in control group.There was no significant difference in adverse effects between two groups (P ＞ 0.05).ConclusionsCompared with amlodipine besylate single treatment,amlodipine besylate combined with benazepril in treatment of old patients with primary hypertension and left ventricular hypertrophy can more effectively control blood pressure and reverse left ventricular hypertrophy.The adverse effects are not increased,which can be applied in clinic.

Molecular and cytogenetic study on 5 cases with gonadal dysgenesis: clinical applications of fluorescence in situ hybridization(FISH) and BAC-FISH / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the applications of fluorescence in situ hybridization (FISH) in the diagnosis for the patients with gonadal dysgenesis.</p><p><b>METHODS</b>After routine gynecologic examination, ultrasonography and endocrine examination, 5 cases of gonadal dysgenesis and hypogonadism were analyzed by using chromosomal diagnoses including G-banding, Q-banding, multiplex FISH and BAC-FISH analyses.</p><p><b>RESULTS</b>Among the 5 cases of gonad agenesis patients, 2 were pure gonadal dysgenesis with 46, XY karyotype, 3 were mixed gonadal dysgenesis with mos 45, X/47, XXX; 45, X/46, XY or 46, X, der(Y) karyotype.</p><p><b>CONCLUSION</b>Sex chromosomal abnormalities resulted in gonadal dysgenesis symptoms. Applications of FISH and BAC-FISH analyses can correctly diagnose the sex chromosomal abnormalities for patients with gonad agenesis and provide accurate medical genetic data for clinical diagnosis and therapy.</p>

The double stapling technique in low anterior resection of rectal cancer / 中国普通外科杂志

Objective To investigate the outcome of low anterior resection of rectal cancer with double stapling technique.Methods A retrospective analysis of clinical records of 78 rectal cancer patients who had anal preservation operation using double stapling technique was performed.Results In all of the cases,the rectal closing and anastomosis were satisfactorily completed.All the resection margins were negative for tumor infiltration.There was no operative mortality or anastomosis leakage.Seventy-three(93.6%)cases were followed up for 9-65 months,pelvic recurrence occurred in 2 cases(2.7%),multiple metastasis of peritoneal cavity occurred in 1 case(1.4%),liver metastasis was found in 7 cases(9.6%),one patient suffered from local recurrence and Miles operation was performed 11 months later.Conclusions Double stapling technique can provide more chances for sphincter preservation operation in patients with lower rectal cancer.If the technique is properly used,it also may effectively reduce the rate of anastomosis leakage and other complications.