Objective:To explore the clinical characteristics of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods:The clinical data of 24 patients with anti-CASPR2 encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. According to the age of first onset, the patients were divided into early onset group (10 cases, onset age<45 years) and late onset group (14 cases, onset age≥45 years). The clinical data including clinical manifestations, auxiliary examinations, and treatment response between these 2 groups were compared.Results:Among the 24 patients, there were 13 cases with epilepsy, 13 cases with cognitive decline, 13 cases with mental disorders, 14 cases with autonomic dysfunction, 8 cases with peripheral nerve hyperexcitability, 5 cases with Morvan syndrome, 5 cases with unstable walking, and 8 cases with sleep disorders. Among the 10 cases of the early onset group, 7 cases are females, and 8 cases showed epilepsy. The incidence rate of epilepsy in the early onset group was higher than that in the late onset group (5/14, Fisher exact probability, P=0.047). Among the 14 cases of the late onset group, 6 cases are females, 9 cases showed cognitive impairment and 8 cases presented with mental disorders. There were 6 cases with abnormal brain magnetic resonance imaging (MRI). The cerebrospinal fluid protein of the late onset group [0.37 (0.29, 0.58) g/L] was higher than that in the early onset group [0.22 (0.16, 0.30) g/L; Z=-2.667, P=0.008]. The modified Rankin Scale (mRS) scores before and after treatment were 3.29±0.83 and 1.50 (0.75, 2.25), which were higher than those in the early onset group [mRS scores before and after treatment were 2.10±0.99 and 0 (0, 1.00), t=-3.188, P=0.004; Z=-2.335, P=0.020]. Conclusions:There are various symptoms in patients with anti-CASPR2 encephalitis. The early onset patients are common in women, with a higher incidence of epilepsy. The late onset patients are common in males, with prominent manifestations of cognitive impairment and mental disorders, which have a greater impact on daily living abilities. And abnormal MRI findings are common, and the cerebrospinal fluid protein is higher in late onset patients. Anti-CASPR2 antibody may cause more severe immune damage to the nervous system in elderly patients.

Objective:To analyze the correlation between serum antibody titers of anti-contactin associated protein-like 2 (CASPR2) antibody and clinical features and prognosis in encephalitis.Methods:A retrospective analysis was conducted on the clinical data of 31 patients diagnosed with anti-CASPR2 antibody encephalitis at the First Affiliated Hospital of Zhengzhou University from January 2018 to April 2024. Patients were divided into low titer group (≤1∶32) and high titer group (>1∶32) based on serum anti-CASPR2 antibody titers, and their clinical characteristics, auxiliary examination results, and prognosis were compared between the two groups.Results:Among the 31 patients with anti CASPR2 antibody encephalitis (male∶female=1∶1.4), there were 16 cases in the low titer group and 15 cases in the high titer group; The age of patients in the high titer group was (33.9±17.9)years, which was lower than that of patients in the low titer group [(52.9±17.9)years], and the difference was statistically significant ( P=0.006). The proportion of patients with prodromal infection in the high titer group (6/15) was higher than that in the low titer group (1/16, P=0.037). There was no statistically significant difference in the cerebrospinal fluid related test results, imaging examination of intracranial abnormal lesions, abnormal electroencephalogram, serum abnormal tumor markers, and serum abnormal rheumatic immune indicators between the two groups of patients (all P>0.05). During hospitalization, one patient in the high titer group died; During the follow-up period, one patient died and three patients relapsed, all of whom were in the high titer group. During follow-up, the mRS scores of 6 patients ranged from 3 to 5 points (indicating functional impairment), with 4 cases in the high titer group and 2 cases in the low titer group. The proportion of patients with poor prognosis in the high titer group (9/15) was higher than that in the low titer group (2/16), and the difference was statistically significant ( P=0.021). Conclusions:Patients with high serum anti-CASPR2 antibody titers and encephalitis have a lower age of onset and are prone to pre infection triggers. High antibody titers may be associated with a higher risk of disease recurrence and poor prognosis for patients.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective:To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022.Methods:Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed.Results:A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024.Conclusion:The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Objective:To analyze the whole genome of Omicron variants causing the first local Omicron outbreak in Henan Province and to investigate the mutations in the SARS-CoV-2 genome for source tracing.Methods:Respiratory tract samples from COVID-19 cases in the Omicron outbreak in Henan Province from January 7 to 29, 2022 were subjected to whole-genome sequencing and sequence alignment analysis. Whole-genome identity, variations and evolution of the Omicron variants were analyzed.Results:Through high-throughput sequencing, the whole-genome sequences of SARS-CoV-2 were obtained from 120 cases, which accounted for 25.64% (120/468) of all COVID-19 cases in Anyang during the same period. Compared with the genome of Wuhan reference strain (NC_045512.2), there were 57-59 nucleotide mutation sites in the 120 whole genome sequences, and one or two nucleotide mutation sites were added to the shared 57 nucleotide sites. All of the 120 strains were VOC/Omicron (BA.1.1) variants and shared high homology. The whole-genome sequence obtained from the first case A contained 57 nucleotide mutation sites, while apart from the 57 identical nucleotide mutation sites, one specific mutation site (C1594T) was found in the whole-genome sequence obtained from the first case B, suggesting that the two cases were in the same transmission chain. After comparing with the database of domestic and imported cases by the Chinese Center for Disease Control and Prevention and the Henan Provincial Center for Disease Control and Prevention, it was found that the current outbreak was linked with the same transmission chain as the existing local epidemics in other provinces. Moreover, epidemiological investigation showed that on January 2, case A had come into contact with her cousin and his family who returned from an affected area outside the province.Conclusions:Based on the gene sequencing results and epidemiological investigation, the COVID-19 outbreak in Anyang city, Henan Province was a local epidemic and the source of it was a college student who returned to Anyang city from other province on December 28, 2021. These infections were linked to the same transmission chain as the existing local infection in other provinces.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective:To analyze the genome characteristics and variations in nucleotides and amino acids of SARS-CoV-2 causing an outbreak in Henan Province in November 2021 and perform the traceability analysis.Methods:In this study, throat swab specimens from cases in the acute phase were collected and tested for the nucleic acids of SARS-CoV-2 by real-time fluorescent RT-PCR. SARS-CoV-2 nucleic acid-positive samples were subjected to high-throughput genome sequencing and whole-genome alignment analysis.Results:The median Ct values of ORF1ab gene and N gene in 70 positive specimens was 26.41 (15.58 to 39.27) and 24.43 (12.04 to 39.74), respectively. Compared with the sequence of Wuhan-Hu(NC_045512) reference strain, 47 to 49 nucleotide mutations sharing 47 nucleotide mutation and 41 amino acid mutations were found in 63 strains of successfully sequenced SARS-CoV-2. Nine nucleotide mutations and 12 amino acid mutations were found in the spike protein. The index case shared 47 mutations with the Russian imported cases in Henan Province on October 14 and the local cases in Jiangxi Province in October. Moreover, their genomes were highly homologous and they all belonged to the Delta variant (AY.122 evolutionary branch).Conclusions:Continuous monitoring of imported COVID-19 cases and prolonging the period of quarantine were needed to reduce the risk of local outbreak and epidemic caused by imported COVID-19 cases. Analysis of the genomic characteristics of SARS-CoV-2 and the variations in nucleotides and amino acids was conducive to trace the origin of COVID-19 outbreak quickly and provide reference for precise control.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Objective: To investigate and analyze the clinical features, epidemiologic information and pathogenic characteristics of a rabies patient. Methods: Clinical data of the patient(boy) was collected and epidemiological survey was conducted, fluorescence quantitative reverse transcription-polymerase chain reaction (FQRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the samples of saliva, cerebrospinal fluid (CSF), skin tissue with hair follicle at the back of the neck for rabies laboratory diagnosis. Results: Early symptoms of the boy were vomiting, diarrhea, fever and irritability, followed by coma and death. The boy had nasal trauma one month ago and the domestic dog died of illness during the same period. He did not accept the rabies post-exposure prophylaxis (PEP). The result of the saliva sample was positive by FQRT-PCR. The predicted segments of the glycoprotein(G), nucleoprotein (N) genes of rabies virus were amplified from the positive saliva sample of the patient by RT-PCR. Compared with rabies virus strains in Henan province, the nucleotide homology and amino acid homology in G gene segment were 96.5%-98.8% and 96.5%-99.2% respectively. Conclusions The case was diagnosed in laboratory as rabies case. The pathogenic rabies virus strain was endemic in Henan province. The nasal trauma, the dead domestic dog were probably related to the infection of the boy.

Objective:To prepare and preliminarily identify the monoclonal antibodies(mAbs) specifically against 3D protein of Enterovirus 71(EV71),using bioinformatics to predict the epitopes of 3D,with HBc protein as a carrier.Methods: Artificial screening of 3D protein epitope sequences by bioinformatic method,inserted into the major immunodominant region(MIR) area of Hepatitis B virus core protein(HBc),to construct the recombinant protein.BALB/c mice were immunized with the recombinant virus like particles(VLPs),to prepare the mAbs against 3D protein of EV71.Affinity chromatography technology was used to purify the mAb.The indirect ELISA,ELISPOT,immunofluorescence and immunohistochemistry staining methods were used to identify the characteristic of the mAb.Results: We displayed 3D(aa34-43),3D(aa61-76) and 3D(aa151-164) epitopes by constructing fusion protein using HBc VLPs as a vector,after hybridization,one positive hybridoma cell line(3E1) was selected by ELISA.The isotype of 3E1 was IgG2a.The results of immunofluorescence and immunohistochemistry staining assay showed that the mAb 3E1 could specifically recognize EV71.Conclusion: The prepared mAb 3E1 can specifically recognizes the EV71,which laid the foundation for the detection of virus and further study on 3D protein,and verified the bioinformatics technology combined with HBc carrier displaying peptides could prepare mAb quickly and efficiently.