OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

The presence of high-level talents plays a crucial role in ensuring the successful establishment of national regional medical centers.It presents the high-level talent management experience of Henan Children's Hospital,aiming to facilitate the coordinated development of pediatrics in Central China.To address the practical challenges and difficulties encountered in high-level talent management within hospitals,lean talent management is achieved by standardizing the management structure,clarifying management objectives,refining the management mechanism,establishing a performance appraisal incentive system,and implementing an integrated'induction and utilization'management approach.These measures effectively facilitate the development of national children's regional medical centers.

Objective:To explore the clinical phenotypic features and genetic variation characteristics of children with epilepsy-aphasia spectrum due to GRIN2A gene variants confirmed by second-generation sequencing. Methods:The clinical data of 5 children with epilepsy-aphasia spectrum with epileptic onset diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University, from February 2019 to November 2022 were retrospectively analyzed. Whole-exome genome sequencing of the probands using a second-generation sequencing method confirmed that all 5 cases were children with the GRIN2A gene variant. The characteristics of the GRIN2A gene variants were analyzed. Results:Among the 5 children diagnosed with epileptic aphasia spectrum due to GRIN2A gene variants, the male-to-female ratio was 4∶1, and the age range of onset was 1.5-4.4 years. The clinical phenotype included seizures in all cases, language and intellectual developmental deficits in 4 cases, and attention deficit hyperactivity disorder in 3 cases. The seizures were manifested as focal seizures or secondary generalized seizures, and were effectively controlled with antiepileptic drugs. Among the 5 children, gene variant of case 1 was originated from a paternal heterozygous variant, and cases 2-5 had de novo variants, which were c.2107C>T (p.Gln703 *) nonsense variant, c.2284G>A (p.Gly762Arg) missense variant, c.2197del (p.Ala733Glnfs *3) shifted coding variant, c.2511G>A (p.Trp837 *) nonsense variant, and c.1651+1G>C shear site variant, respectively. None of the 5 loci were reported in the literature. Conclusions:Epilepsy-aphasia spectrum is an epilepsy syndrome with a complex onset, and may have different phenotypes at different genetic variant loci, with focal seizures or secondary generalized seizures, which can be effectively controlled with anti-seizure medication. The GRIN2A gene variant is the genetic etiology of the epileptic aphasia spectrum.

BACKGROUND:Stable intertrochanteric fractures can be treated by closed reduction and internal fixation,but there is no absolute advantage for unstable intertrochanteric fractures with osteoporosis. OBJECTIVE:To investigate the efficacy of arthroplasty in the treatment of unstable intertrochanteric fractures in the elderly with osteoporosis by comparing the indexes related to closed reduction internal fixation and arthroplasty. METHODS:Clinical data of 102 elderly patients with unstable intertrochanteric fractures of the femur treated in Affiliated Hospital of Qingdao University from January 2017 to January 2020 were retrospectively analyzed.Patients were divided into two groups according to the surgical method.In the Gamma3 group,62 cases received Gamma3 internal fixation system.In the joint replacement group,40 cases received an artificial femoral head replacement or total hip replacement.Surgical information,hospitalization,hip function,and postoperative complications were compared between the two groups. RESULTS AND CONCLUSION:(1)There were statistical differences between the Gamma3 group and the joint replacement group in weight-bearing time(P＜0.001),hospital stay(P＜0.05),intraoperative bleeding(P＜0.001),and length of surgery(P＜0.001).The mean weight-bearing time and hospital stay were shorter in the joint replacement group than in the Gamma3 group.Intraoperative bleeding and duration of surgery were better in the Gamma3 group than in the joint replacement group.(2)There was no significant difference in Harris hip score,subitem centesimal hip score,and postoperative complications 12 months after surgery in both groups(P=0.526,0.788,0.228).(3)It is indicated that arthroplasty has achieved better outcomes in the treatment of elderly unstable intertrochanteric fractures combined with osteoporosis,enabling early weight bearing and functional exercise.Careful selection of the appropriate patient and prosthesis type for arthroplasty will result in greater patient benefit.

Objective: To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.

Objective:To investigate the predictive value of inflammatory and nutritional indices for postoperative survival of elderly patients with esophageal squamous carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 130 elderly patients with esophageal squamous carcinoma who were admitted to Sichuan Cancer Hospital from January 2019 to April 2020 were collected. There were 102 males and 28 females, aged (70±4)years. Mea-surement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Receiver opera-ting characteristic (ROC) curves were plotted. The area under the curve (AUC) and optimal cut-off values were calculated. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Postoperative survival of elderly patients with esophageal squamous carcinoma predicted by inflammatory and multitional indices. Results of ROC curves analysis showed that the best cut-off values of preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI) for predicting postoperative survival of elderly patients with esophageal squamous carcinoma were 470.71×10 9/L, 1.11, 2.07, 136.24, and 46.28, respectively. (2) Risk factors analysis of postoperative survival of elderly patients with esophageal squamous carcinoma. Results of multivariate analysis showed that preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI<46.28, score of preoperative patient-generated subjective global assessment (PG-SGA) ≥4, postoperative pathological stage Ⅳ and post-operative complications were independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma ( hazard ratio=3.30, 2.50, 0.36, 4.86, 1.57, 1.97, 95% confidence interval as 1.10?9.88, 1.07?5.88, 0.16?0.81, 1.13?20.87, 1.20?2.06, 1.02?3.82, P<0.05). (3) Follow-up. All the 130 patients were followed up for 39(range, 1?60)months. Of the 130 patients, 81 cases survived, 49 cases died, and the median overall survival time was not reached. The 1- and 3-year survival rates of the 130 patients were 83.85% and 54.62%, respectively. ① The median overall survival time was 25(0,43)months for patients with SII ≥470.71×10 9/L, and unreached for patients with SII <470.71×10 9/L, showing a significant difference between them ( χ2=60.59, P<0.05). ② The median overall survival time was 26(0,44)months for patients with SIRI ≥1.11, and unreached for patients with SIRI <1.11, showing a significant difference between them ( χ2=45.57, P<0.05). ③ The median overall survival time was unreached for patients with PNI ≥46.28, and 38(0,47)months for patients with PNI <46.28, showing a significant difference between them ( χ2=12.53, P<0.05). ④ The median overall survival time was unreached for patients with PG-SGA <4 and ≥4, showing a signifi-cant difference between them ( χ2=14.41, P<0.05). ⑤ The median overall survival time was 25(1,47)months for patients in pathological stage Ⅲ, 12(1,32)months for patients in stage Ⅳ, and unreached for patients in stage 0, Ⅰ, Ⅱ, respectively, showing a significant difference among them ( χ2=58.75, P<0.05). ⑥ The median overall survival time was 33(1,47)months for patients with postoperative complication, and unreached for patients without postoperative complication, showing a significant difference between them ( χ2=14.27, P<0.05). Conclusions:Preoperative SII, SIRI and PNI have good predictive value for postoperative survival in elderly patients with esophageal squamous carcinoma. Preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI <46.28, score of preoperative PG-SGA ≥4, postoperative pathological stage Ⅳ, and postoperative complications are independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma. Patients with preoperative SII <470.71×10 9/L, preoperative SIRI <1.11, preoperative PNI >46.28, score of preoperative PG-SGA <4, postoperative pathological stage 0, Ⅰ, Ⅱ, and non post-operative complications have better survival.

Objective:To study the feasibility of domestic flow diverter(TFD) for the treatment of unruptured internal carotid artery small- and medium-sized wide-neck aneurysms.Methods:This is a retrospective case series study.The study retrospectively evaluated consecutive 54 patients with unruptured intracranial small- and medium-sized wide-neck aneurysms treated with TFD in the Department of Cerebrovascular Disease,the Second Affiliated Hospital of Kunming Medical University between October 2019 and January 2024. There were 11 males and 43 females, and the age of patients was (54.9±9.6) years (range:36 to 74 years). There were 63 aneurysms in 54 patients,6 of which were tandem multiple small aneurysms. One case had saccular aneurysms of bilateral internal carotid artery. The maximum diameter of aneurysm was (4.1±0.8) mm (range: 1.5 to 10.0 mm).The ratio of the maximum diameter of the aneurysm to the neck width diameter was 1.3±0.4 (range:0.4 to 2.4). The surgical and follow-up data were collected. The aneurysm embolization rate at the immediate operation and follow-up,and the complications were analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade D as complete occlusion and grade C and above (C1,C2,C3 and D) as successful occlusion. Clinical outcomes of all patients were evaluated by modified Rankin scale(mRS).Results:For 63 aneurysms, 48 aneurysms were treated with TFD alone,and 15 aneurysms were treated with a combination of TFD and coiling. The immediate postoperative successful occlusion rate was 14.3% (9/63) and the complete occlusion rate was 3.2% (2/63). Follow-up results were obtained for all of the patients. The follow-up time ( M(IQR)) was 124 (182) days (range: 85 to 754 days). The time to aneurysm successful occlusion was 140.5 (151.5) days (range: 85 to 308 days). At final follow-up,the successful aneurysm occlusion rate was 68.3% (43/63) and the complete occlusion rate was 58.7% (37/63). The complete occlusion rate of the TFD group was 50.0% (24/48) and the TFD+coiling group was 13/15. All patients had no aneurysm rupture,ischemic complications and no recurrence of the aneurysm needed to retreatment during the intraoperative and follow-up period. A total of 3 mild haemorrhagic complications which were related to dual-antiplatelet agents. Twelve patients had asymptomatic mild-moderate stent stenosis. TFD covered 66 branch vessels totally. Only 6 branches were affected by the time of the last follow-up and none of the patients had relevant ischaemic symptoms. All of 54 patients were evaluated as mRS score<2 points at the last follow-up. Conclusion:Using TFD to treat internal carotid artery unruptured small and medium-sized wide-neck aneurysms can simplify the surgical procedure with low complication rate, which is a clinically optional treatment approach.

Objective:To study the feasibility of domestic flow diverter(TFD) for the treatment of unruptured internal carotid artery small- and medium-sized wide-neck aneurysms.Methods:This is a retrospective case series study.The study retrospectively evaluated consecutive 54 patients with unruptured intracranial small- and medium-sized wide-neck aneurysms treated with TFD in the Department of Cerebrovascular Disease,the Second Affiliated Hospital of Kunming Medical University between October 2019 and January 2024. There were 11 males and 43 females, and the age of patients was (54.9±9.6) years (range:36 to 74 years). There were 63 aneurysms in 54 patients,6 of which were tandem multiple small aneurysms. One case had saccular aneurysms of bilateral internal carotid artery. The maximum diameter of aneurysm was (4.1±0.8) mm (range: 1.5 to 10.0 mm).The ratio of the maximum diameter of the aneurysm to the neck width diameter was 1.3±0.4 (range:0.4 to 2.4). The surgical and follow-up data were collected. The aneurysm embolization rate at the immediate operation and follow-up,and the complications were analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade D as complete occlusion and grade C and above (C1,C2,C3 and D) as successful occlusion. Clinical outcomes of all patients were evaluated by modified Rankin scale(mRS).Results:For 63 aneurysms, 48 aneurysms were treated with TFD alone,and 15 aneurysms were treated with a combination of TFD and coiling. The immediate postoperative successful occlusion rate was 14.3% (9/63) and the complete occlusion rate was 3.2% (2/63). Follow-up results were obtained for all of the patients. The follow-up time ( M(IQR)) was 124 (182) days (range: 85 to 754 days). The time to aneurysm successful occlusion was 140.5 (151.5) days (range: 85 to 308 days). At final follow-up,the successful aneurysm occlusion rate was 68.3% (43/63) and the complete occlusion rate was 58.7% (37/63). The complete occlusion rate of the TFD group was 50.0% (24/48) and the TFD+coiling group was 13/15. All patients had no aneurysm rupture,ischemic complications and no recurrence of the aneurysm needed to retreatment during the intraoperative and follow-up period. A total of 3 mild haemorrhagic complications which were related to dual-antiplatelet agents. Twelve patients had asymptomatic mild-moderate stent stenosis. TFD covered 66 branch vessels totally. Only 6 branches were affected by the time of the last follow-up and none of the patients had relevant ischaemic symptoms. All of 54 patients were evaluated as mRS score<2 points at the last follow-up. Conclusion:Using TFD to treat internal carotid artery unruptured small and medium-sized wide-neck aneurysms can simplify the surgical procedure with low complication rate, which is a clinically optional treatment approach.

Objective To explore the role of serum leucine-rich-alpha-2-glycoprotein1(LRG1),neopterin(NPT)and virus antibodies during the progression of viral meningitis(VM)and their value in evaluating the condition and predicting the prognosis of VM in children.Methods A total of 130 pediatric patients with VM admitted to Kaifeng Children's Hospital from August 2020 to February 2023 were selected as the observation group,and at the same time,another 130 pediatric patients with VM symptoms who were diagnosed as non central nervous system infectious diseases by lumbar puncture cerebrospinal fluid examination were selected as the control group.After admission,2 mL peripheral venous blood of children in the two groups was collected,and the levels of serum LRG1 and NPT were assessed by enzyme-linked immunosorbent assay.Before treatment,1 mL cerebrospinal fluid sample of children in the two groups was collected by lumbar puncture,and the host specific immuno-globulin G(IgG)against herpes simplex virus-I(HSV-I),cytomegalovirus(CMV),Epstein-Barr virus(EBV),and parain-fluenza virus(PIV)in cerebrospinal fluid was detected by enzyme-linked immunosorbent assay.The levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG were compared between the two groups.The VM children were then divided into the severe group(n=54)and mild group(n=76)according to the disease severity,and they were divided into the good prognosis group(n=37)and poor prognosis group(n=93)based on the prognosis.The levels of serum IRG1 and NPT and the positive rate of virus antibody IgG were compared in children with different disease severity and prognosis.The correlation of serum LRG1,NPT and virus antibody with the disease severity or disease progression for pediatric VM was analyzed,and their interactive effects on the disease progression of children with VM were analyzed.The predictive value of serum LRG1,NPT and virus antibody for pediatric VM outcome was analyzed by the receiver operating characteristic(ROC)curve.Results The levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the obser-vation group were significantly higher than those in the control group(P＜0.05);the levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the severe group were significantly higher than those in the mild group(P＜0.05);the levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the poor prognosis group were significantly higher than those in the good prognosis group(P＜0.05).High level of serum LRG1 with high positive rate of virus antibody IgG and high level of serum NPT with high positive rate of virus antibody IgG showed positive interactions in leading to poor prognosis in children with VM odds ratio(OR)=15.238,9.684).The submultiplicative models were applied for the high levels of serum LRG1 with high positive rate of virus antibody IgG(OR=15.238)and high levels of serum NPT with high positive rate of virus antibody IgG(OR=9.684).The area under the curve(AUC)for predicting poor prognosis in children with VM after 2 weeks of treatment by serum LRG1,NPT and virus antibody IgG were 0.786,0.794 and 0.919,respectively,and the AUC for the combined prediction of the three was 0.933;the AUC of LRG1,NPT and positive rate of virus antibody IgG for predicting poor prognosis in children with VM after 2 weeks of treatment was greater than that of the three alone(P＜0.05).Conclusion NPT and LRG1 may be involved in the development of VM.The levels of serum LRG1 and NPT are positively correlated with the severity and progression of VM.The levels of serum NPT and LRG1 and the positive rate of virus antibody IgG have certain value in the disease evaluation and prognosis prediction of VM,and the combination of the three has a higher predictive value for the prognosis of VM.There is a positive interaction between high LRG1 with high positive rate of virus antibody IgG,and high NPT with high positive rate of virus antibody IgG in children with VM.