ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

Objective To investigate the occurrence of intraoperative frozen section(FS)pathology unclear diagnosis in thyroid carcinoma,seeking clinical factors affecting the pathological accuracy of FS.Methods Retrospective analysis of thyroid cancer patients who underwent surgical treatment at People's Hospital of Daxing District in Beijing from August 2016 to December 2019.Target nodules were divided into FS clear diagnosis group and unclear diagnosis group(including delayed diagnosis group,misdiagnosis group,accidental diagnosis group)according to the results of FS and paraffin section pathological examination.The general information,laboratory test,result of color ultrasound and pathological types between FS clear diagnosis group and unclear diagnosis group were compared.Results A total of 336 cancer nodules were included.The quantity and proportion of cancer nodules in clear diagnosis group,delayed diagnosis group,misdiagnosis group and accidental diagnosis group were respectively 266(79.17%),28(8.33%),21(6.25%)and 21(6.25%).In the delayed diagnosis group,"no exception"thyroid cancer was the most frequently used.Compared to clear diagnosis group,the maximum diameter of cancer nodules in delayed diagnosis group,misdiagnosis group,accidental diagnosis group were smaller(P<0.05);In the delayed diagnosis group,the proportion of aspect ratio>1 was higher(P=0.017),and the proportion of microcalification was lower(P=0.002).In the misdiagnosis group,thyroid peroxidase antibody level was higher(P=0.002).Conclusion Clinical doctors should be familiar with commonly used diagnostic terms for delayed diagnosis and misdiagnosis.When making treatment decisions,full consideration should be given to the possibility of difficult to diagnose diagnosis,especially for patients with small nodules and concurrent chronic lymphocytic thyroiditis.

Primary hypertrophic osteoarthropathy(PHO)is a rare disease also known as pachydermo-periostosis.We reported a painless case whose diagnosis was confirmed by genetic test.A 24-year-old male presented a series of symptoms that first began at 14.He suffered from progressive clubbed-fingers accompa-nied by swelling of the wrist and ankle joints.Facial skin concentric thickening and alar nose broadening ap-peared simultaneously and increased progressively.He was also prone to acne and hyperhidrosis.X-rays showed thickening of the metacarpal and phalangeal bones,as well as symmetrical periosteal ossification of both the tibia and fibula.Clinical diagnosis of PHO is difficult because of the variable features.With acromeg-aly excluded,the diagnosis was confirmed by a genetic test.Whole exome sequencing revealed a heterozygous SLCO2A1 c.611C＞T(p.Ser204Lue)and SLCO2A1 c.1602C＞A(p.Asn534Lys)mutation from each par-ent.It suggests that primary hypertrophic osteoarthropathy should be considered for young limb hypertrophic patients especially when periosteal thickening signs were showed in X-ray.A confirmatory diagnosis can be made through the genetic test.

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Benzofurans/therapeutic use* ; Double-Blind Method ; Treatment Outcome

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Paraneoplastic neurological syndromes (PNS) are heterogeneous disorders caused by autoimmune responses of cancer, which can affect any part of the nervous system. Anti-amphiphysin antibody is one of the high-risk PNS antibodies, which is usually associated with small cell lung cancer and breast cancer. However, extrapulmonary neuroendocrine carcinoma is rare in patients with anti-amphiphysin antibody. A case of anti-amphiphysin-associated paraneoplastic brainstem encephalitis with esophageal neuroendocrine carcinoma is reported. The tumor was detected by fluorine 18 fluorodeoxyglucose positron emission tomography and pathologically confirmed by gastroscopic biopsy. The patient′s neurological symptoms were partially improved after treatment of intravenous immunoglobulin and glucocorticoids. However, the disease prognosis is closely related to the accompanying tumor.

Objective:To understand the characters of norovirus infection in children with acute diarrhea in Beijing from 2014 to 2019.Methods:Fecal specimens were collected from children with acute diarrhea visiting the hospital affiliated to the Capital Institute of Pediatrics from April 2014 to December 2019 for norovirus screening by reverse transcription-polymerase chain reaction (RT-PCR). Then RdRp gene and VP1 gene of norovirus (NoV) were amplified and sequenced from positive specimens and then genotyped by Norovirus Genotyping Tool 2.0.Results:Fecal specimens were collected from 2 577 cases with acute diarrhea and tested for NoV RNA in this study, of which 484 cases (18.78%, 484/2 577) were positive for NoV. NoV infection can occur all year round, with obvious seasonal distribution, the epidemic peak is in autumn and winter. There was no gender difference in the detection of NoV ( χ2=1.77, P=0.183). 399 specimens genotyped by VP1 gene with 98.25% (392/399) being GII and GII.4 Sydney as the mainly genotype (52.13%, 208/399), followed by GII.3 (19.8%, 79/399) and GII.2 (18.5%, 74/399). Then 267 specimens also were genotyped by RdRp region, which revealed that the main genotype was GII.P31 (57.3 %, 153/267), followed by GII.P12 (15.36%, 41/267) and GII.P16 (14.98 %, 40/267). Dual-typing revealed that various combination strains, GII.4 Sydney[P31] (53.18%, 142/267) as the major combination, followed by GII.3[P12] and GII.2[P16] (15.36%, 41/267 and 10.49%, 28/267). While GII.3[P12] showed a downward trend, GII.4 Sydney[P16] increased gradually. Conclusions:Norovirus is an important pathogen of acute diarrhea in children in Beijing, from 2014 to 2019, with various prevalent genotypes.

Background::Epigenetics, and especially DNA methylation, contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). This study aimed to investigate the role of DNA methylation in SALS using whole blood of SALS patients.Methods::In total, 32 SALS patients and 32 healthy controls were enrolled in this study. DNA was isolated from whole blood collected from the participants. DNA methylation profiles were generated using Infinium MethylationEPIC BeadChip.Results::We identified 34 significant differentially methylated positions (DMPs) in whole blood from SALS patients, compared with the healthy controls. Of these DMPs, five were hypermethylated and 29 were hypomethylated; they corresponded to 13 genes. For the DMPs, ATAD3B and BLK were hypermethylated, whereas DDO, IQCE, ABCB1, DNAH9, FIGN, NRP1, TMEM87B, CCSAP, ST6GALNAC5, MYOM2, and RUSC1-AS1 were hypomethylated. We also identified 12 differentially methylated regions (DMRs), related to 12 genes (NWD1, LDHD, CIS, IQCE, TNF, PDE1C, LGALS1, CSNK1E, LRRC23, ENO2, ELOVL2, and ELOVL2-AS1). According to data from the Kyoto Encyclopedia of Genes and Genomes database, DNAH9 and TNF are involved in the amyotrophic lateral sclerosis (ALS) pathway. Correlation analysis between clinical features and DNA methylation profiling indicated that the methylation level of ELOVL2 and ARID1B was positively associated with the age of onset ( r = 0.86, adjust P = 0.001) and disease duration ( r = 0.83, adjust P = 0.01), respectively. Conclusions::We found aberrant methylation in DMP- and DMR-related genes, implying that many epigenetic alterations, such as the hypomethylation of DNAH9 and TNF, play important roles in ALS etiology. These findings can be helpful for developing new therapeutic interventions.

Objective:To investigate the prevalence and genetic characteristics of human adenovirus (HAdV) in healthy children and diarrheal children in Beijing.Methods:A total of 1 834 fecal samples were collected from diarrheal children younger than 6 years old in outpatients from January, 2015 to December, 2017 and from healthy children with the same age group from May, 2016 to February, 2017. The hexon and fiber genes of HAdV were detected for genotyping and the sequences analysis, respectively.Results:The detection rate of HAdVs in healthy children (1.5%, 8/536) was significantly lower than that in children with diarrhea (7.4%, 96/1 298) ( χ2=23.62, P<0.001). HAdV-41 was the dominant type detected both in the healthy children and diarrheal outpatients. There was no gender difference in HAdV-positive children with diarrhea. Except for newborns with no positive case, there was no difference in the detection rate of HAdV among the other age groups. There was no obvious seasonality of HAdV prevalence. Phylogenetic analysis showed that HAdV-41 strains circulating in Beijing belonged to three evolutionary branches, and strains with 15-amino acid truncated in the shaft of fiber were found. Conclusions:HAdV was one of the important pathogens causing diarrhea in children in Beijing from 2015 to 2017, with HAdV-41 as the predominant type.

Objective:To observe the clinical effect of integrated traditional Chinese and western medicine on brucellosis and its influence on humoral immune indexes.Methods:In October 2019, 169 cases of brucellosis hospitalized in Tianjin Second People's Hospital were selected as the research objects, and divided into two groups according to the random number method, 84 cases in the integrated treatment group and 85 cases in the western medicine treatment group. The western medicine treatment group was given antibiotics and other routine western medicine support treatment. The integrated treatment group was given traditional Chinese medicine for treatment based on syndrome differentiation, on the basis of western medicine treatment group, and 6 weeks was a course of treatment. The clinical efficacy and Traditional Chinese Medicine (TCM) syndrome scores were compared between the two groups of patients after treatment, and the changes in humoral immune indexes, biochemical, and liver and kidney functions of the patients before and after treatment were analyzed.Results:The total effective rate was 100.00% (84/84) in the integrated treatment group and 97.65% (83/85) in the western medicine treatment group. The difference was not statistically significant ( P>0.05) . The difference was not statistically significant ( P>0.05) . There was no statistically significant difference in TCM syndrome scores between the two groups before treatment ( P>0.05) , and the TCM syndrome scores after treatment were lower than before treatment ( P<0.05) . Among them, the TCM syndrome scores of the integrated treatment group were lower than those of the western medicine treatment group ( P<0.05) . There was no significant difference in IgG, IgA, IgM, C3, C4, miRNA-155, C-reactive protein (CRP) , erythrocyte sedimention rate (ESR) , alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the two groups before treatment ( P>0.05) . After treatment, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST were all lower than before treatment, and C3 and C4 complement levels were higher than before treatment ( P<0.05) . Among them, IgG, IgA, IgM, miRNA-155, CRP, ESR, ALT and AST in the integrative treatment group were all lower than the western medicine treatment group, while the C3 and C4 complement levels were higher than the western medicine treatment group ( P<0.05) . Conclusion:The treatment of brucellosis with integrated traditional Chinese and western medicine can significantly improve the TCM syndrome score and reduce the levels of CRP and ESR. The mechanism of action may be related to the regulation of the patient's humoral immunological indicators.