OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of cinacalcet and etelcalcetide， to provide a reference for safe drug use in the clinic. METHODS ADE reports related to cinacalcet and etelcalcetide were extracted from the FDA Adverse Event Reporting System from January 1st， 2004 to June 30th， 2023 using the OpenVigil online tool. The Bayesian confidence propagation neural network method was adopted to detect the signals of ADE from the key organ systems. The signals were encoded according to the preferred term in the ADE terminology set of the Medical Dictionary for Regulatory Activities （26.0 edition）. RESULTS A total 41 709 and 1 710 ADE reports were extracted， and 29 and 45 safety signals were detected in key systems for cinacalcet and etelcalcetide， respectively； 20 and 36 positive signals were not included in the drug instructions. Hypocalcemia/decreased serum calcium， abnormal blood parathyroid hormone （PTH）/increased or decreased serum PTH were common ADEs of the two drugs， which were detected in the study. Among the signals not included in the drug instructions， new moderate and strong signals were detected， such as cinacalcet-induced calcification defense （metabolic and nutritional diseases）， bone starvation syndrome and high conversion bone diseases （musculoskeletal and connective tissue diseases） as well as etelcalcetide-induced sudden death， necrosis and treatment of non-responders （general disorders， administration site）， unstable angina pectoris， myocardial ischemia （cardiac diseases）， intestinal perforation， gastric antrum vasodilation and gastric ulcer （gastrointestinal diseases）. CONCLUSIONS In the clinical application of the two drugs， apart from the common ADEs such as hypocalcemia and abnormal blood PTH， the surveillance of some new potential ADEs should also be carried out， such as bone starvation syndrome， calcification defense， ventricular disease and other cinacalcet-induced ADEs， sudden death， myocardial ischemia， unstable angina pectoris， intestinal perforation， gastric ulcer and other etecalcetide-induced ADEs. If new ADEs appear， clinic should promptly assess the benefits and risks， and update the treatment plan and pharmacological monitoring plan to ensure the safety of patient medication.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

Objective:To evaluate the short-term efficacy and safety of Apollo stent in the treatment of symptomatic basilar artery stenosis.Methods:Patients with symptomatic basilar artery stenosis admitted to the Fourth Affiliated Hospital of China Medical University from January 2017 to May 2020 were selected and treated with Apollo stent implantation. The changes of clinical symptoms and the success rate of operation were evaluated. Postoperative complications included symptomatic intracranial hemorrhage, hyperperfusion, and new ischemic stroke, and follow-up results were evaluated 3 to 6 months later.Results:A total of 96 patients were included in this study, and all of them were confirmed by angiography to have severe basilar artery stenosis corresponding to the symptoms. Among them, 88 patients received stent implantation, with a success rate of 100%. Among the 88 patients, 86 received Apollo stent implantation, and 2 patients received self-Peng stent implantation. Among 86 patients with Apollo stent implantation, the lesions were located in the proximal segment in 73 cases (84.88%), in the middle segment in 10 cases (11.63%), and in the distal segment in 3 cases (3.49%). The degree of stenosis was (93.72±3.86)%, the length of stenosis was (8.50±2.65)mm, the residual stenosis rate was (1.76±4.87)%, and Mori type A lesions in 80 cases, type B lesions in 3 cases, and type C lesions in 3 cases. Among 86 patients with Apollo stent implantation, the incidence of perioperative neurological complications was 6.98%(6/86), including 1 case in the proximal part of the basilar artery (vascular rupture), 3 cases in the middle part of the basilar artery (perforating artery occlusion in 1 case, acute thrombosis artery occlusion in 2 cases), and 2 cases in the distal part (both acute vascular occlusion). Alteplase was injected into the microcatheter during the operation, and contact thrombolysis was performed. Immediately digital subtraction angiography (DSA) showed that the blood vessels were opened, and 1 case with neurological deficit was left. No hyperperfusion occurred in all patients. All patients were followed up for three months after operation. Among them, 58 patients had a good prognosis in the proximal segment of the basilar artery, 18 patients had a good prognosis in the middle segment, 4 patients had a good prognosis in the distal segment, and 6 patients had a bad prognosis (1 patient died). Postoperative stent restenosis occurred in 5 cases (5.81%), recurrent stroke in 3 cases (3.49%), and disabling stroke in 1 case (1.16%).Conclusions:Apollo stent is safe and effective in the treatment of symptomatic basilar artery stenosis, with good short-term prognosis, and long-term prognosis needs to be further studied.

Objective:To evaluate clinical effect of deproteinized bovine bone for delayed implantation after fenestration.Methods:This trial is a continuation of a prospective clinical trial. From May 2011 to February 2015 in Department of Implantology, School of Stomatology, The Fourth Military Medical University after planting division of 55 cases of maxillary teeth missing area of residual alveolar bone height ≤5 mm patients. There were 21 female and 34 male patients, their average age were (55.2±7.1) years. A total of 62 side fenestration of maxillary sinus floor lift, clinical and imaging examination, evaluation of implant retention rate, complications, peripheral soft tissue health and marginal bone resorption.Results:A total of 82 implants were followed up in 41 patients. The average follow-up time was (51.8±14.3) months (36-78 months). The follow-up rate of the maxillary sinus was 75.8% (47/62), the follow-up rate of the implant was 73.9% (82/111), and the implant survival rate was 98.8% (81/82). The bone resorption results at the implant margins were (0.64±0.63) mm (-0.28 mm, 1.47 mm) in the near and (0.49±0.73) mm (-0.51 mm, 1.21 mm) in the far, the improved hemorrhage index was 0.46±0.72, the improved plaque index was 0.60±0.87, and the keratinized mucosa width was (2.14±1.22) mm. The incidence rate of peri-implant mucositis was 28.4% (23/81) among 23 implants, and there was no complication of peri-implant inflammation.Conclusions:This study shows that under the condition of insufficient sinus ridge spacing in the maxillary posterior area, it is feasible to use bovine bone alone to remove protein for delayed implantation of maxillary sinus floor elevation by windowing, and the clinical effect is reliable.

Objective To investigate the influencing factors and clinical significance of high-resolution magnetic renounce imaging (HR-MRI) plaque enhancement in patients with symptomatic intracranial atherosclerotic (ICAS) stenosis.Methods Patients with symptomatic ICAS stenosis confirmed by digital subtraction angiography and examined by HR-MRI were enrolled prospectively.The demographic data,vascular risk factors,laboratory tests,and imaging features of plaques were compared according to whether the plaques were enhanced or not.They were randomly divided into an ischemic stroke group and a transient ischemic attack (TIA) group according to the results of diffusion-weighted imaging.The relationship between plaque enhancement and ischemic stroke was analyzed.Results Thirty-fiwe patients with symptomatic ICAS stenosis were enrolled.Their mean age was 53 ± 13 years and 25 were males.There were 21 patientswith ischemic stroke and 14 patients with TIA;22 had plaque enhancement and 13 did not have.The leukocyte count ([7.50±2.30] × 109/L vs.[5.80± 1.00] × 109/L;t=2.487,P=0.018) and proportion of severe stenosis (86.4％ vs.53.8％;P =0.040) of the plaque enhancement group were significantly higher than those of the non-enhancement group.The proportion of smoking was significantly lower than the non-enhancement group (13.6％ vs.46.2％;P=0.050).The plaque enhancement rate of the ischemic stroke group was higher than that of the TIA group (71.4％ vs.50.0％;P =0.288),but there was no significant difference.Conclusions In patients with symptomatic ICAS,the degree of vascular stenosis and the leukocyte level were associated with plaque enhancement.In addition,there was no significant correlation between plaque enhancement and the occurrence of ischemic stroke in patients with symptomatic ICAS.

OBJECTIVE: To optimize reflux extraction technology of total flavonoids from the roots and stems of Angelica sinensis. METHODS: The reflux extraction technology of total flavonoids from the roots and stems of A. sinensis was optimized by Box-Behnken design-response methodology based on single factor test using volume fraction of extraction solvent ethanol, solide-liquid ration, extraction time, extraction times as investigation factors, the content of total flavonoids in extract as evaluation index. RESULTS: The optimal extraction technology of total flavonoids from the roots and stems of A. sinensis was that volume fractions of ethanol were 70％ and 50％; solid-liquid ratios were 1: 40 and 1: 30; extraction time were 1. 3 h and 1. 7 h; The number of extraction times is two times. In verification test, the contents of total flavonoids were 7. 253 6, 25. 144 1 mg/g (RSD= 1. 57％, 1. 49％, n = 3); relative errors of those to predicted value (6. 942 8, 25. 703 5 mg/g) were 4. 28％, 2. 24％. CONCLUSIONS: Optimized extraction technology for total flavonoids from the roots and stems of A. sinensis is simple, reproducible and predictable.

Objective To evaluate cerebral perfusion through brain computed tomography perfusion imaging (CTP) in order to investigate the relationship between cerebral perfusion and vascular cognitive impairment (VCI).Methods A total of 103 patients with ischemic stroke were recruited, who received thrombolytic therapy and CTP test in the Fourth Affiliated Hospital of China Medical University from December, 2016 to May, 2017. The patients were divided into normal cognitive function group (control group, n=43), vascular cognitive impairment-no dementia group (VCIND group, n=48), and vascular dementia group (VD group, n=12) according to the degree of impairment in cognitive function after the assessment of Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). The characteristics of cerebral blood flow perfusion in region of interest of brain CTP were analyzed.Results There was difference in incidence of diabetes among three groups (χ2=7.556, P<0.05). The rate of diabetes was higher in VCIND group and VD group than in the control group. Age and diabetes were the independent risk factors for VCI (OR>1, P<0.05). There was difference in cerebral blood volume (CBV) in frontal lobe, temporal lobe, and parietal lobe among three groups (F>3.216, P<0.05). CBV in frontal lobe, temporal lobe, and parietal lobe reduced in VD group than in the control group (P<0.05), while CBV in frontal lobe and temporal lobe reduced in VD group than in VCIND group (P<0.05). There was difference in mean transit time (MTT) in left temporal lobe, left parietal lobe, and centrum semiovale among three groups, while there was difference in left occipital lobe in time to peak (TTP) among three groups (F>3.116, P<0.05). MTT and TTP were higher in VD group than in the control group and VCIND group (P<0.05). There was no difference in cerebral blood flow (CBF) in both left and right brain, and MTT and TTP in right brain among three groups (P>0.05). CBV in frontal lobe, parietal lobe and right temporal lobe demonstrated positive relationship with the scores of MMSE (r>0.203, P<0.05). CBV in parietal lobe and left frontal lobe also demonstrated positive relationship with the scores of CDT (r>0.214, P<0.05).Conclusion The cerebral blood flow perfusion reduced in different levels of VCI, especially in frontal lobe, temporal lobe and parietal lobe. Cerebral blood flow perfusion reduced with the progress of cognitive impairment, and the left hemisphere injured earlier than the right one. Brain CTP may be applied in the early recognition of VCI.

Hypoxia inducible factor-1αis a kind of hypoxia response factor. Acute cerebral ischemia and anoxia can induce up-regula-tion of hypoxia inducible factor-1α, and the downstream genes, which plays a role in both the energy metabolism and collateral circulation after cerebral ischemia. Neural stem and progenitor cells regeneration also benefit the functional outcome after ischemic stroke. Hypoxia in-ducible factor-1αmay induce proliferation and differentiation of neural stem and progenitor cells through Notch, Wnt/β-catenin pathways, etc., in the ischemic stroke model.

Objective To investigate whether apathy during the acute stage of stroke was related to glycated hemoglobin and homocysteine(Hcy) and functional disability,and to elucidate possible factors that are related to poststroke apathy (PSA).Methods Totally 298 patients with acute cerebral infarction who met the inclusion and exclusion criteria were recruited from the Fourth Affiliated Hospital of China Medical University.The control group of 298 volunteers was recruited from medical center in our hospital during the same period.The apathy scale (AS) was used to assess PSA within 2 weeks after stroke.Patients with an AS score≥ 14 points were defined as PSA,and the patients were divided into apathy group (A group) and non-apathy group (NA group) according to AS score.Modified Rankin Scale (mRS) was used to assess functional disability.Functional disability in daily living activities was assessed with the Barthel Index(BI).Serum levels of Hcy,glycated hemoglobin A1C (HbA1 c),lipid series and fibrinogen of patients were determined.Results The prevalence of PSA in patients was significantly higher than the control group (P ＜ 0.01).In the case group,A group had an older age,higher mRS score,higher Hcy level,lower educational level,lower BI score,and lower HbA1C level than the NA group(P ＜0.05).In the A group,the mRS score was positively correlated with the AS score(B =1.508,P =0.003),serum Hcy level was positively correlated with the AS score(B =0.170,P =0.013),the HbA1C level was negatively correlated with the AS score(B =-0.872,P =0.031).Conclusions The serum Hcy level,HbA1C level and functional disability are closely related to apathy during the acute stage of ischemic stroke.

Objective To analyze the characteristic changes of trace elements from Hedysari Radix in different months;To provide references for the choice of the best harvest periods. Methods Trace elements of Hedysari Radix from different months (June, July, August, September, October and November) were determined by atomic absorption spectroscopy and analyzed by single factors analysis of variance, correlation analysis, cluster analysis and factors analysis. Results There was obvious significance between the contents of Cu and Co (P<0.05), and there was obvious significance among the contents of Fe, Ca, Mn, Zn, Mg, Cr, Na, Li, Ni and K (P<0.01). The results of correlation analysis showed that months had positive correlation with Cu, had a negative correlation with Fe, Na, Mn, Cr and Li contents, and had significantly negative correlation with Ca, Mg contents. Mn, Cr, Ni, K and Na were the characteristics of trace elements from Hedysari Radix in different months. The different months samples could be divided into two categories of June, July, August, September samples (Ⅰ) and October, November samples (Ⅱ). Conclusion There is close relationship between the contents of trace elements from Hedysari Radix and months. The information and metabolic patterns of trace elements from Hedysari Radix in June, July, August, September (immature) samples are close or similar;the information of trace elements in October, November (nearly mature or maturing) samples are close or similar. Study on harvest times of Hedysari Radix by trace element as an indicator is with certain rationality.