Efficacy and safety evaluation of plasma-derived human coagulation factor Ⅷ in patients with hemophilia A / 中国输血杂志

【Objective】 To evaluate the efficacy and safety of plasma-derived human coagulation factor Ⅷ (FⅧ) in the treatment of patients with hemophilia A. 【Methods】 A multi-center and open, SAT(single-arm trials) clinical study was conducted. A total of 54 subjects with hemophilia A were enrolled in 5 research centers. FⅧ was injected according to the subjects' weight, severity of disease and other factors, and the transfusion efficiency of FⅧ activity at 10 min after the first infusion of the first bleeding event was taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs within 24 h after the first infusion of the first bleeding event were the secondary efficacy indexes. The pathogenic microbial indexes and FⅧ inhibitors were detected on 90(th) and 180(th) day after treatment. 【Results】 The transfusion efficiency of FⅧ activity of 54 subjects at 10 min after the first infusion was 171.9% on average, with median of 169.5%, both higher than the target value of 100%. Within 24 h after the first infusion, the improvement of bleeding symptoms and signs of the subjects were scored, among which 19 cases (35.2%) were "obvious", 35 cases (64.8%) were "good", and the total clinical effective rate reached 100%. Five subjects (9.3%) had six drug-related adverse events. On 90(th) and 180(th) day after treatment, hepatitis B surface antigen, hepatitis C antibody, HIV antibody, treponema pallidum antibody and FⅧ inhibitors were detected, and no negative to positive cases were found. 【Conclusion】 After infusion, the FⅧ preparation can significantly improve the FⅧ activity level in hemophilia A patients in a short period of time, which has high infusion efficiency and can achieve better treatment efficacy, and can also effectively control and relieve bleeding symptoms and signs, with good overall safety.

Therapeutic effect and prognosis of PKP in patients with diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures / 中华内分泌外科杂志

Objective:To investigate the therapeutic effect and prognosis of percutaneous balloon kyphoplasty (PKP) for diabetic patients with osteoporotic thoracolumbar compression fractures.Methods:A total of 105 patients with diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures who received diagnosis and treatment in our hospital from May. 2017 to Feb. 2020, who were followed up to Mar. 2022 were selected as the research subjects, and all were treated with PKP. Time, intraoperative blood loss, hospital stay, incidence of secondary vertebral fracture, anterior height of injured vertebral body, Sagittal kyphosis Cobb angle, VAS score, and ODI index were investigated. The patients were divided into good prognosis group ( n=82) and poor prognosis group ( n=23) according to the presence or absence of secondary vertebral fractures during the follow-up period. Binary Logistic regression model was used to analyze the risk factors affecting the prognosis. Results:After PKP treatment, the efficiency of all 105 patients was 87.62% and the incidence of secondary vertebral fracture was 21.90%. The operative time was (83.52±16.85) min, the intraoperative blood loss was (32.11±1.52) ml, and the length of hospital stay was (10.62±1.65) d. The height of the anterior edge of the injured vertebra was (24.62±5.16) mm and (24.67±5.03) mm at the last follow-up and 3 months after surgery, respectively, higher than that before surgery ( t=15.21, 15.63, P=0.000). The Cobb angle of sagittal kyphosis was (10.03±1.27) ° and (10.10±1.25) °, respectively, and the VAS score was (3.11±0.52) and (1.00±0.11) points, respectively, 3 months after surgery and at the last follow-up. The ODI indexes were (11.25±2.85) % and (5.32±1.01) %, respectively, lower than those before surgery ( t3 months after surgery=28.84, 18.17, 29.21, tlast follow-up=25.68, 27.49, 42.78, P=0.000). There were significant differences in age, BMD, bone cement leakage, bone cement distribution and use of anti-osteoporosis drugs between the good prognosis group and the poor prognosis group ( t=4.03, 5.22, χ2=12.50, 22.694, 26.22, P=0.000). Logistic regression analysis showed that age ( OR=1.309, 95%CI=1.134-1.511, P=0.000), BMD ( OR=126.660, 95%CI=13.376-1199.376, P=0.000), bone cement leakage ( OR=4.698, 95%CI=1.306-16.902, P=0.018), dense distribution of bone cement ( OR=9.697, 95%CI=2.679-34.869, P=0.001), no use of anti-osteoporosis drugs ( OR=7.586, 95%CI=2.197-26.193, P=0.001) was an independent risk factor for the prognosis of patients with diabetes complicated with osteoporotic thoracolumbar compression fracture. Conclusion:PKP has a high rate of excellence in the treatment of diabetes mellitus complicated with osteoporotic thoracolumbar compression fractures, but factors such as age, BMD, bone cement leakage, bone cement dense distribution, and no postoperative use of anti-osteoporotic drugs will increase risks of secondary fractures, which in turn affects their prognosis.

Efficacy and safety of flumatinib in treatment of imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of flumatinib in the treatment of imatinib-resistant or imatinib-intolerant patients with chronic phase chronic myelogenous leukemia (CML-CP).Methods:The clinical data of 9 CML-CP patients who received flumatinib after imatinib resistance or intolerance in Jining No. 1 People's Hospital from April 2020 to May 2021 were retrospectively analyzed. Patients were evaluated for the hematologic, cytogenetic and molecular responses, progression-free survival (PFS), event-free survival (EFS), and adverse reactions.Results:Among 9 CML-CP patients, there were 4 imatinib-resistant patients and 5 imatinib-intolerant patients. The median duration of flumatinib exposure was 17 months (1-25 months). Except for 1 case who discontinued flumatinib early due to grade 4 thrombocytopenia and other adverse reactions, 7 of the remaining 8 cases achieved the best response at 3, 6 and 12 months of flumatinib therapy. By the end of follow-up in April 2022, 7, 7 and 6 patients achieved complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response 4.5 (MR4.5), respectively. The median time to achieving CCyR, MMR and MR4.5 was 4.5 months (3-6 months), 12 months (3-12 months) and 15 months (3-21 months), respectively. Within 17 months (11-25 months) of follow-up, 7 of the 9 patients had EFS and 8 patients with continuous flumatinib had PFS. Among 9 patients treated with flumatinib, hematologic adverse reactions were observed in 6 cases, and grade 3-4 hematologic adverse reactions occurred in 2 cases. Non-hematologic reactions events mainly included diarrhea (4 cases), muscle ache (2 cases), fatigue (2 cases) and liver damage (2 cases), which were all grade 1-2.Conclusions:Flumatinib is effective and well tolerated in the treatment of imatinib-resistant or imatinib-intolerant CML-CP patients.

Microplastics pollution in the Yellow River basin: current status and control strategy / 生物工程学报

Microplastics pollution has attracted worldwide attention. Compared with the status quo of microplastics pollution in marine environment and other major rivers and lakes, the relevant data of the Yellow River basin is relatively inadequate. The abundance, types, and spatial distribution characteristics of microplastic pollution in the sediments and surface water of the Yellow River basin were reviewed. Meanwhile, the status of microplastic pollution in the national central city and Yellow River Delta wetland was discussed, and the corresponding prevention and control measures were put forward. The results showed that the spatial distribution of microplastics pollution in sediments and surface water of the Yellow River basin increased from upstream to downstream, especially in the Yellow River Delta wetland. There are obvious differences between the types of microplastics in sediment and surface water in the Yellow River basin, which is mainly related to the materials of microplastics. Compared with similar regions in China, the microplastics pollution levels in national key cities and national wetland parks in the Yellow River basin are in the medium to high degree, which should be taken seriously. Plastics exposure through various ways will cause serious impact on aquaculture and human health in the Yellow River beach area. To control microplastic pollution in the Yellow River basin, it is necessary to improve the relevant production standards, laws and regulations, and improve the capacity of biodegradable microplastics and the degradation capacity of plastic wastes.

Clinical characteristics of acute myeloid leukemia patients with TET2 gene mutation and effects of TET2 mutation on therapeutic efficacy and prognosis / 白血病·淋巴瘤

Objective:To investigate clinical features of adult patients with acute myeloid leukemia (AML) with TET2 gene mutation and effects of TET2 mutation on therapeutic efficacy and prognosis.Methods:A total of 123 newly diagnosed adult AML patients (except for acute promyelocytic leukemia) admitted to Jining No.1 People's Hospital from March 2017 to April 2021 were selected. Mutations of 24 AML-related genes including TET2 mutation were detected by using second-generation sequencing technology. Patients were divided into two groups according to the presence of TET2 mutation: TET2 mutation group and TET2 wild type group. The differences in clinicopathological characteristics, short-term efficacy and survival of both groups were compared.Results:Among 123 patients, TET2 mutation was detected in 28 cases (22.8%). Compared with TET2 wild type group, the patients were older [(59±15) years vs.(49±16) years, t = 2.984, P = 0.003], French-American-British (FAB) Corporative Group M 4 and M 5 subtypes were more common [75.0% (21/28) vs. 51.6% (49/95), χ2 = 4.838, P = 0.028], and the positive rate of CD34 in AML patients was lower in TET2 mutation group [46.4% (13/28) vs.72.6% (69/95), χ2 = 6.685, P = 0.010]. Moreover, TET2 mutation was more likely to be accompanied with ZRSR2 mutation [10.7% (3/28) vs. 1.1% (1/95), P = 0.037] and NPM1 mutation [35.7% (10/28) vs.17.9% (17/95), χ2 = 4.008, P = 0.045], but less likely to be accompanied with IDH1/2 mutation [0 vs.17.9% (17/95), P = 0.012]. However, there were no statistically significant differences in gender, peripheral blood leukocyte count at initial diagnosis, hemoglobin level, platelet count, bone marrow blasts ratio, cytogenetics and the European LeukemiaNet (ELN) risk stratification between the two groups (all P>0.05). In addition, there were no significant differences in the overall response rate (ORR) of 1 cycle chemotherapy [75.0% (12/16) vs. 66.7% (42/63), χ2 = 0.410, P = 0.522] and demethylation therapy [66.7% (4/6) vs. 44.4% (8/18), P = 0.640]. The difference in overall survival (OS) of both groups was not statistically significant [median OS time: 23 months (95% CI 5-41 months) vs. 35 months (95% CI 18-52 months, P = 0.498]. Conclusions:In AML patients, TET2 mutation is associated with advanced age, M 4 and M 5 subtypes, and low expression of CD34 on AML blasts. TET2 mutation is commonly accompanied by ZRSR2 and NPM1 mutation, but not IDH1 or IDH2 mutation. TET2 mutation may have no significant effects on therapeutic efficacy and survival in the whole cohort of AML patients without risk stratification.

Blood–brain barrier disruption caused by neonatal sevoflurane-induced depends on exposure time and is reversible in mice / 대한마취과학회지

No abstract available.

Expression of Tim-3 on natural killer cells in patients with acute myeloid leukemia and its clinical significance / 中华血液学杂志

Objective@#To investigate the expression characteristics of Tim-3 on natural killer (NK) cells of peripheral blood in patients with acute myeloid leukemia (AML) and its clinical significance.@*Methods@#Peripheral blood was obtained from 39 patients with newly diagnosed AML before intervention, with peripheral blood from 28 cases of healthy volunteers collected as normal control. Using CD3, CD56 and Tim-3 as markers, expression levels of Tim-3 on the peripheral blood NK cells were detected by immune fluorescence labeling and flow cytometry.@*Results@#The ratio of the peripheral blood CD3-CD56+ NK cells in newly diagnosed AML patients (5.74±5.31) %decreased significantly, compared with the normal control (12.55±6.33) % (t=4.596, P<0.001) . Tim-3 expression on the peripheral blood NK cells in newly diagnosed AML patients (42.67±19.08) % decreased significantly, compared with the normal control group (60.99±20.69) % (t=3.781, P<0.001) . CD3-CD56+NK cell ratio of peripheral blood in AML patients was significantly correlated with Chromosome karyotype (t=2.915, P<0.005) . Expression level of Tim-3 on NK cells in the peripheral blood of AML patients had significant correlation with ratio of CR and NCCN high risk group (P<0.05) .@*Conclusion@#The rate of NK cells in peripheral blood and the expression level of Tim-3 on NK cells in AML patients decreased significantly.The lower expression level of Tim-3 on NK cells correlate with prognosis of AML.

Apocynin preserves glutamatergic neurons in the basolateral amygdala in mice with neonatal sevoflurane exposure / 대한마취과학회지

BACKGROUND: Neonatal exposure to anesthetics induces neuronal apoptosis and long-term cognitive dysfunction in rodents. We showed that the nicotinamide adenine dinucleotide phosphate-oxidase inhibitor apocynin not only reduces neurotoxicity by decreasing superoxide levels and preventing mitochondrial dysfunction but also improves long-term memory impairment in neonatal mice exposed to sevoflurane. We also found that after the contextual fear conditioning test, glutamatergic neurons expressed c-Fos (neural activation) regardless of previous exposure to sevoflurane. Moreover, there were fewer c-Fos-expressing glutamatergic neurons in the basolateral amygdala (BLA) after exposure to sevoflurane than after exposure to carrier gas. In this study, we investigated whether the administration of apocynin prior to sevoflurane exposure would preserve glutamatergic neurons in the BLA. METHODS: Apocynin (50 mg/kg) was injected intraperitoneally into six-day-old male mice 30 min before 6 h of exposure to 3% sevoflurane or carrier gas only. The mice were allowed to mature and then were subjected to the contextual fear conditioning test. The neural activation and neuron population in the BLA were investigated 2 h later. RESULTS: Administration of apocynin prior to neonatal sevoflurane exposure not only prevented learning deficits but also preserved c-Fos-expressing glutamatergic neurons in the BLA. CONCLUSIONS: Apocynin mitigates the cognitive impairment induced by neonatal sevoflurane exposure and preserves c-Fos-expressing glutamatergic neurons in the basolateral amygdala.

Therapeutic effects of intravenous administration of bone marrow stromal cells on sevoflurane-induced neuronal apoptosis and neuroinflammation in neonatal rats / 대한마취과학회지

BACKGROUND: Sevoflurane exposure during the early postnatal period causes neuroinflammation and neuronal apoptosis in rodents. Bone marrow stromal cells (BMSCs) have been shown to protect and repair the damaged central nervous system, for example in ischemic stroke models. In this study, we investigated whether intravenous administration of BMSCs ameliorated neurodegeneration, induced by sevoflurane exposure, in neonatal rats. METHODS: Sprague-Dawley rat pups (postnatal day 7) were exposed to 2% sevoflurane for 6 h (vehicle group, n = 7). BMSCs were administered 30 min after induction of sevoflurane anesthesia (BMSCs group, n = 7). The pups were exposed to carrier gas only, as a negative control (mock anesthesia group, n = 4). We assessed the therapeutic effects of BMSC treatment by measuring expression of the pro-inflammatory cytokine interleukin-6 (IL-6), and levels of cleaved caspase-3, in brain tissues immediately following sevoflurane anesthesia. RESULTS: Analysis of the cleaved caspase-3 bands revealed that levels of activated caspase-3 were elevated in the vehicle group compared with the mock anesthesia group, indicating that a single exposure to sevoflurane at subclinical concentrations can precipitate neuronal apoptosis. BMSC treatment did not suppress apoptosis induced by sevoflurane exposure (compared with the vehicle group). The vehicle group had higher proinflammatory cytokine IL-6 protein levels compared with the mock anesthesia group, indicating that sevoflurane exposure induces IL-6 expression. BMSC treatment suppressed sevoflurane-induced increases in IL-6 expression, indicating that these cells can inhibit the neuroinflammation induced by sevoflurane exposure (vehicle group vs. BMSC group). CONCLUSIONS: Intravenous administration of BMSCs reduces neuroinflammation, but does not attenuate apoptosis induced by sevoflurane exposure.

Observation on the craniocerebral injury of sheep by high explosive shell / 第三军医大学学报

Objective　To observe the characteristics and rules of craniocerebral injury resulting from a high explosive shell to provide the bases for treating explosive injury. Methods　A total of 36 sheep were distributed at the distance 6 to 48 m away from the explosive center and the shell was exploded electrically at 7 m above the earth. At the same time, the velocity of fragments and shock wave pressure were determined. Gross and pathological observations were performed after injury. Results　Among all sheep with fragment injury, craniocerebral injury was 32%. Their immediate death rate was 75% and all died 6 h later. The incidence rates of penetrating wound and blind wound were 75% and 25% respectively. Pollution of wound track was heavy. The percentage of head lost was 50% in sheep and 50% of injured animal suffered from comminuted fracture of skull base. Bleeding was found extensively on the surface of the cerebrum, even medulla oblongata was involved. Hemorrhage, edema, rupture of small blood vessels and degeneration of neuron were found at the regions 4 cm away from the wound tract with light microscopy. Combined blast injury was found and occurred most often in the abdomen and limbs, both accounting for 62.5%, and combined thoracic injury was the third, up to 50%. All the animals of craniocerebral injury combined with lung blast injury. Conclusion　High explosive shells destroy cranium badly and extensively. Many skulls are lost and the cranial base is readily fractured. The wound track is heavily polluted. Combined injury is more often occurred.