OBJECTIVE To provide evidence for the safe clinical application of Trastuzumab for injection. METHODS Reports of adverse drug reaction （ADR） related to Trastuzumab for injection submitted in Beijing from June 2018 to May 2023 were collected. Statistical analyses were performed using SPSS 25.0 software. The gender and age of patients with ADRs， outcome， types of cancer， and the time of onset， severity， affected organs/systems of ADRs were included for analyses. The univariate Logistic regression analysis was conducted on patient fever and ADR prognosis. RESULTS A total of 195 patients with 318 instances of ADRs were included in the study. Women （87.69%） and patients aged 60-69 （33.85%） were more likely to experience ADRs. Breast cancer dominated （86.67%） in terms of cancer types； in terms of outcomes， most patients （67.69%） showed improvement， and some patients （27.69%） achieved full recovery. Overall， 68.72% of ADRs mainly occurred on the day of medication， and 95.38% of ADRs were of “moderate” severity. The most affected organs/systems were general diseases and various reactions at the administration site （40.57%）， with chills （18.87%） and fever （18.24%） being the most common. Univariate Logistic regression analysis showed that fever mostly occurred within 1 day of medication （OR＝5.63， 95%CI was 2.26-14.02， P＜ 0.001）. The time of onset of ADR greater than 1 day was a risk factor for poor ADR prognosis （OR＝20.08， 95%CI was 2.45- 164.43， P＝0.005）， mainly manifesting as bone marrow suppression and liver function abnormalities. Neutrophilia， cardiorespiratory arrest， and mixed liver damage were new ADRs not recorded in the drug’s instructions. CONCLUSION Women and patients aged ≥60 are high-risk groups for ADRs of Trastuzumab for injection. Chills and fever remain the most common ADRs of this drug， and these symptoms mostly occur within 1 day of medication， which have better prognoses. Close attention should be paid to the patient’s temperature changes on the day of drug infusion， with timely intervention. Regular monitoring of the patient’s hematological indicators is necessary to detect any bone marrow suppression and liver function abnormalities after medication.

Objective:To summarize the clinical features, electroencephalogram (EEG) and magnetoencephalogram (MEG) of patients with pure paroxysmal kinesigenic dyskinesia (PKD) and PKD with epilepsy, so as to better distinguish them and guide the treatments.Methods:The clinical data of 200 patients diagnosed with PKD in the Outpatient Department of Xuanwu Hospital, Capital Medical University from 2000 to 2023 were analyzed retrospectively. The patients were divided into 2 groups: pure PKD (174 cases) and PKD with epilepsy (26 cases) according to whether accompanied by epilepsy. The differences in clinical features, drug therapy, EEG and MEG were compared between the 2 groups.Results:The clinical features of the 2 groups were essentially similar, and the proportion of PKD dyskinesia induced by emotional stress in the pure PKD group (54/174, 31.03%) was higher than that in the PKD with epilepsy group (2/26, 7.69%; χ 2=5.010, P=0.025). In terms of pharmacological response, carbamazepine was the most commonly used medication in both groups, but patients with PKD with epilepsy may need a higher therapeutic dosages (0.2-0.4 g/d, and gradually increased to 0.8 g/d) to effectively manage both dyskinesia and seizures. Regarding the EEG and MEG, the proportion of EEG abnormalities was higher in PKD patients with epilepsy, mainly manifested as focal spikes [1/70(1.43%) vs 9/21(42.86%), χ 2=24.268, P<0.001], together with aberrant MEG discharge (4/18 vs 3/5, χ 2=1.155, P=0.282). The MEG dipoles were mainly distributed in the brain regions close to the frontal lobe and central region. Conclusions:The clinical manifestations of motor symptoms of pure PKD and PKD with epilepsy are similar, and carbamazepine remains the most effective treatment. PKD patients with epilepsy have a higher proportion of abnormal EEG, mainly manifested as focal spikes, and are more likely to show abnormal discharge of MEG, which could be used to distinguish them.

Objective:To evaluate the effect of individualized blood pressure management on postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.Methods:One hundred and sixty elderly hypertensive patients of both sexes, aged 60-80 yr, with body mass index of 19-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection for gastrointestinal tumor under general anesthesia, were divided into 2 groups ( n=80 each) using a random number table method: standardized blood pressure management group (group S) and individualized blood pressure management group (group I). Combined intravenous-inhalational anesthesia was performed, and BIS values were maintained at 40-60 and heart rate at 50-100 times/min during surgery in both groups. In group S, intraoperative systolic blood pressure was maintained above 90 mmHg with a decrease of less than 30% of the baseline value, while intraoperative fluctuation of systolic blood pressure was maintained less than 10% of the baseline value in group I. The use of vasoactive agents, numerical rating scale scores within 3 days after operation, and length of hospital stay were recorded. Postoperative delirium was evaluated by Confusion Assessment Method within 5 days after surgery. Results:Compared with group S, the intraoperative usage rate of norepinephrine was significantly increased, the incidence of postoperative delirium was reduced( P<0.05), and no significant change was found in the numerical rating scale scores and length of hospital stay in group I ( P>0.05). Conclusions:Individualized blood pressure management can reduce the development of postoperative delirium in elderly hypertensive patients undergoing radical resection for gastrointestinal tumor.

Objective To analyze the epidemiological characteristics of measles cases with immunization history of measles-containing vaccine (MCV), and to provide a basis for improving measles prevention and control measures. Methods Data were collected through the measles surveillance system and the immunization program information management system. Data were analyzed by descriptive epidemiological methods. Results A total of 9 164 cases of measles were reported in Liaoning Province during 2014-2021, of which the cases of measles with immunization history of 1 dose MCV accounted for 5.64%, and ≥ 2 doses accounted for 3.60%. There was a statistically significant difference in the immunization proportion among different years (χ²=184.534, P<0.001). The cumulative inoculation rate of measles cases was 23.85%, the immunization rates among different groups varied from 3.57% to 35.94%, and the differences were statistically significant (χ²=109.448, P<0.001). There was a statistically significant difference between 2-6 years old and 7-14 years old in the immunization rate of 1 dose and ≥ 2 doses (χ²=4.147, P<0.05). The onset time of most cases was over 2 weeks after the last dose of MCV vaccination, accounting for 82.06%. The incidence rates of fever, cough, catarrh symptoms, conjunctivitis, lymph node enlargement and articular pain were all significantly lower in the cases with immunization history than those in the patients without a history of MCV immunization (P<0.05). Conclusion The cases with immunization history account for a certain proportion in measles cases, mainly secondary vaccination failure. The incidence rate of fever, cough, catarrhal symptoms, conjunctivitis, Koch's patches, lymphadenopathy, joint pain, and other clinical symptoms in measles patients with a history of MCV immunization is lower than that in patients without immunization history. Inoculation of MCV is of great significance in relieving clinical symptoms. It is necessary to inoculate two doses of MCV in time for measles prevention and control.

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.
Child ; Child, Preschool ; Humans ; Male ; Cafe-au-Lait Spots ; Computational Biology ; Genetic Testing ; Genomics ; Intellectual Disability/genetics* ; Mutation

Objective To understand the epidemiological characteristics of rubella in Liaoning Province in 2019,and analyze the epidemiological characteristics of rubella virus genotypes and gene subtypes at molecular level.Methods By collecting the incidence data of rubella in Liaoning Province in 2019 from the national notifiable infectious diseases reporting system,the epidemiological characteristics of rubella were analyzed.At the same time,the measles/rubella laboratory network of Liaoning Province was used to collect throat swab samples from suspected rubella outbreaks and sporadic cases.After three generations of blind transmission of positive samples,rubella virus isolates were obtained.Viral nucleic acid was extracted,amplified and the 739 bp nucleotide fragment sequence of E1 gene of positive rubella virus isolates was determined.The phylogenetic tree was constructed with the genotype reference strain sequences recommended by WHO and the published gene subtype reference strain sequences.The genotypes and subtypes were compared and the amino acid variation sites were analyzed.Results The reported incidence of rubella in Liaoning Province in 2019 was 0.927/100 000,which showed an obvious trend of recovery after a significant decrease in the incidence of rubella from 2017 to 2018,and the age of rubella patients was mainly 15 to 19 years old.A total of 55 rubella virus strains were isolated from 7 cities in Liaoning Province in 2019.Sequence phylogenetic analysis showed that all rubella isolates belonged to 1E-L2 gene subtype,which was also the dominant gene subtype of rubella epidemic in China.The nucleotide and amino acid homology among the strains were 99.051%～99.864% and 98.780%～100% respectively.Compared with the BRD-Ⅱ vaccine strain,the rubella isolates mainly showed A333T mutation and showed highly conserved amino acid sequence.Conclusion The 2019 rubella isolates in Liaoning Province were all 1E-L2 gene subtypes,which led to the resurgence of rubella epidemic.Therefore,molecular epidemiological surveillance of rubella virus should be further strengthened to provide a basis for the formulation and elimination of rubella prevention and control measures in Liaoning Province.

Objective:To investigate the efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in treatment of inflammatory myofibroblastic tumor (IMT).Methods:The clinicopathological data of one recurrent abdominal IMT patient in Renmin Hospital of Wuhan University in 2018 were retrospectively analyzed. The clinicopathological and molecular characteristics, ALK-TKI treatment efficacy and prognosis of 41 patients with IMT reported in the literature from January 2010 to August 2020 were systematically reviewed.Results:This patient with abdominal IMT in Renmin Hospital of Wuhan University was a 27-year-old female who relapsed 2 months after surgery. Chemotherapy combined with bevacizumab was ineffective. After oral administration of crizotinib, the condition resolved after 1 month, and complete remission (CR) was achieved after 29 months. The median age of onset of 41 IMT cases reported in the literature was 22 years old (0-61 years old), of which 32 cases (78.0%) had multiple organ involvement, all of which had recurrence or metastasis. There were 38 cases of ALK mutation and 3 cases of TFG-ROS1 fusion gene-positive. Thirty-four patients treated with crizotinib in the first-line treatment of ALK-TKI, and the median resistance time of crizotinib was 8 months (2-48 months). The total clinical benefit rate of ALK-TKI was 85.3% (29/34), and 20 patients achieved CR. The median time for the first CR was 11 months (4-36 months), and the median duration time of medication for CR patients was 19.5 months (2-60 months). The median progression-free survival (PFS) time of 24 patients who underwent surgery and/or chemotherapy and radiotherapy was 4 months (1-45 months); after progression, ALK-TKI treatment was performed, and the median PFS time was 14 months (3-62 months).Conclusions:IMT is a true neoplasm with characteristics of recurrence and metastasis. Reasonable combination of ALK-TKI with surgery, radiotherapy and chemotherapy can improve the prognosis of IMT patients.

Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.

Objective: To analyze the genetic characterization of 2B genotype rubella virus strains first isolated in Liaoning province. Methods: Vero/Slam cells were used to isolate rubella viruses from throat swabs. Fragments of the E1 gene (739 nucleotides) were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the PCR products were sequenced and analyzed. The phylogenetic trees were constructed with rubella 2B genotypes reference strains. Results: RVi/Liaoning.CHN/13.18/1[2B] was isolateded from the case which had a history of international travel and probably imported from abroad. RVi/Liaoning.CHN/13.18/1[2B] was in the same 1ineage with RVs/Edinburgh.GBR/6.12[2B] and RVs/Kawasaki.JPN/17.11/1[2B], but far from the epidemic strains isolated in China in recent years. RVi/Liaoning.CHN/14.18/1[2B] belonged to the same lineage with rubella virus 2B genotype strains isolated in China from 2014 to 2015, and had the highest homology with RVi/Chouzhou.Anhui.CHN/17.15/2[2B] and RVi/Shaoyang.Zhejiang. CHN/13.13[2B]. Conclusions It was the first time to isolate the 2B genotype rubella virus in Liaoning province and the strain belonged to different 1ineage.

Objective: To analyze the gene characterization on the first imported D8 genotype measles virus in Liaoning province. Methods: In this study, Vero/Slam cells were used to isolate measles viruses from throat swabs. Fragments of the H gene (1854 nucleotides) and N gene (450 nucleotides) were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the PCR products were sequenced and analyzed. Results: The measles virus isolates and World Health Organization (WHO) D8 genotype reference strain (MVi/Manchester.GBR/30.94) belonged to the same branch in the genetic relationship tree. The nucleotide homology of the N and H gene was 98.9%. Phylogenetic trees were constructed with reference strains of the genotype D8 measles virus of China downloaded from GenBank. The result showed that the nucleotide similarities between the measles virus isolated in this study and the D8 genotype measles virus prevalent in Hong Kong from 2012 to 2016 and MVi/LosPatios.COL/11.18/D8 in Columbia was 100%. Conclusions It is the first time to do surveillance for the D8 genotype measles virus since measles virus surveillance was carried out. It was of great significance to accumulate the bases of measles virus molecular epidemiology in Liaoning province, and helpful to analyze and trace the transmission of measles virus in the whole country and the world.