OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To investigate the distribution and characteristics of gene mutations in osteosarcoma, and to analyze the frequency and types of detectable mutations, and to identify potential targets for individualized treatment of osteosarcoma. Methods: The fresh tissue or paraffin-embedded tissue samples of 64 cases of osteosarcoma that were surgically resected or biopsied and then subject to next generation sequencing, were collected from Beijing Jishuitan Hospital, China from November 2018 to December 2021. The tumor DNA was extracted to detect the somatic and germline mutations using targeted sequencing technology. Results: Among the 64 patients, 41 were males and 23 were females. The patient age ranged from 6 to 65 years with a median age of 17 years, including 36 children (under 18 years old) and 28 adults. There were 52 cases of conventional osteosarcoma, 3 cases of telangiectatic osteosarcoma, 7 cases of secondary osteosarcoma, and 2 cases of parosteosarcoma. The detection rate of gene mutations was overall 84.4% (54/64). There were 324 variations in 180 mutated genes, including 125 genes with copy number variations, 109 single nucleotide variants, 83 insertions or deletions, and 7 gene fusions. The most common mutated genes were TP53, VEGFA, CCND3, ATRX, MYC, RB1, PTEN, GLI1, CDK4 and PTPRD. Among them, TP53 had the highest mutation rate (21/64, 32.8%), single nucleotide variant was the main mutation type (14/23, 60.9%), and 2 cases carried the TP53 germline mutation. VEGFA and CCND3 showed copy number amplification simultaneously in 7 cases. Conclusions: The high-frequency mutation of TP53 suggests that it plays an important role in the pathogenesis and development of osteosarcoma. VEGFA, CCND3 and ATRX are mutated genes in osteosarcoma and worthy of further studies. Combination of pathologic diagnosis and next generation sequencing with clinical practice can guide individualized treatment for patients with refractory, recurrent and metastatic osteosarcoma.
Adult ; Male ; Child ; Female ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Aged ; DNA Copy Number Variations ; Osteosarcoma/pathology* ; Mutation ; DNA, Neoplasm ; High-Throughput Nucleotide Sequencing ; Bone Neoplasms/pathology* ; Nucleotides

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To trace and characterize the whole genome of SARS-CoV-2 of confirmed cases in the outbreak of COVID-19 on July 31, 2021 in Henan Province. Method: Genome-wide sequencing and comparative analysis were performed on positive nucleic acid samples of SARS-CoV-2 from 167 local cases related to the epidemic on July 31, 2021, to analyze the consistency and evolution of the whole genome sequence of virus. Results: Through high-throughput sequencing, a total of 106 cases of SARS-CoV-2 whole genome sequences were obtained. The results of genome analysis showed that the whole genome sequences of 106 cases belonged to the VOC/Delta variant strain (B.1.617.2 clade), and the whole genome sequences of 106 cases were shared with the genomes of 3 imported cases from Myanmar admitted to a hospital in Zhengzhou. On the basis of 45 nucleotide sites, 1-5 nucleotide variation sites were added, and the genome sequence was highly homologous. Conclusion: Combined with the comprehensive analysis of viral genomics, transmission path simulation experiments and epidemiology, it is determined that the local new epidemic in Henan Province is caused by imported cases in the nosocomial area, and the spillover has caused localized infection in the community. At the same time, it spills over to some provincial cities and results in localized clustered epidemics.
Humans ; COVID-19 ; SARS-CoV-2/genetics* ; Genome, Viral ; Epidemics ; Phylogeny

Objective: We investigated changes in the intestinal flora of children with Mycoplasma pneumoniae pneumonia (MPP). Methods: Between September 2019 and November 2019, stool samples from 14 children with MPP from The Fourth Hospital of Baotou city, Inner Mongolia Autonomous Region, were collected and divided into general treatment (AF) and probiotic (AFY) groups, according to the treatment of "combined Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus tablets live". High-throughput 16S rDNA sequencing was used to identify intestinal flora. Results: Intestinal flora abundance and diversity in children with MPP were decreased. Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls ( P < 0.05). When compared with healthy controls, the proportion of Enterorhabdus was lower in the AF group, while the proportion of Lachnoclostridium was higher ( P < 0.05). The proportion of Bifidobacteria and Akkermansia was lower in the AFY group but Enterococcus, Lachnoclostridium, Roseburia, and Erysipelatoclostridium proportions were higher. The proportion of Escherichia coli- Shigella in the AFY group after treatment was decreased ( P < 0.05). Conclusions The intestinal flora of children with MPP is disturbed, manifested as decreased abundance and diversity, and decreased Bifidobacteria. Our probiotic mixture partly improved intestinal flora disorders.
Child ; DNA, Ribosomal ; Escherichia coli ; Gastrointestinal Microbiome ; Humans ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma ; Technology

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: To explore the effects of expanded frontal-parietal pedicled flap in reconstructing cervical scar contracture deformity in children after burns. Methods: A retrospective observational study was conducted. From January 2015 to December 2020, 18 male children with cervical scar contracture deformity after burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, aged 4 to 12 years, including 10 cases with degree Ⅱ cervical scar contracture deformity and 8 cases with degree Ⅲ scar contracture deformity, and were all reconstructed with expanded frontal-parietal pedicled flap. The surgery was performed in 3 stages. In the first stage, a cylindrical skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 300 to 500 mL was placed in the frontal-parietal region. The expansion time was 4 to 6 months with the total normal saline injection volume being 2.1 to 3.0 times of the rated capacity of expander. In the second stage, expander removal, scar excision, contracture release, and flap transfer were performed, with the flap areas of 18 cm×9 cm to 23 cm×13 cm and the secondary wound areas of 16 cm×8 cm to 21 cm×11 cm after scar excision and contracture release. After 3 to 4 weeks, in the third stage, the flap pedicle was cut off and restored. The rated volume of placed expander, total normal saline injection volume, type of vascular pedicle of flap, survival of flap and reconstruction of scar after the second stage surgery were recorded. The neck range of motion and cervico-mental angle were measured before surgery and one-year after surgery. The appearance of neck, occurrence of common complications in the donor and recipient sites of children, and satisfaction of children's families for treatment effects were followed up. Data were statistically analyzed with paired sample t test. Results: All the patients successfully completed the three stages of operation. The rated volume of implanted expander was 300 mL in 6 children, 400 mL in 9 children, and 500 mL in 3 children, with the volume of normal saline injection being 630 to 1 500 mL. The type of vascular pedicle of flap was double pedicle in 13 cases and was single pedicle in 5 cases. All the flaps in 17 children survived well, and the secondary wounds after neck scar excision and contracture release were all reconstructed in one procedure. In one case, the distal blood supply of the single pedicled flap was poor after the second stage surgery, with necrosis of about 2.5 cm in length. The distal necrotic tissue was removed on 10 days after the operation, and the wound was completely closed after the flap was repositioned. In the follow-up of 6 months to 3 years post operation, the cervical scar contracture deformity in 18 children was corrected without recurrence. The flap was not bloated, the texture was soft, and the appearances of chin and neck were good. The range of motion of cervical pre-buckling, extension, left flexion, and right flexion, and cervico-mental angle in one year after operation were improved compared with those before operation (with t values of 43.10, 22.64, 27.96, 20.59, and 88.42, respectively, P<0.01). The incision in the frontal donor site was located in the hairline, the scar was slight and concealed. No complication such as cranial depression was observed in expander placement site, and the children's families were satisfied with the result of reconstruction. Conclusions: Application of expanded frontal-parietal pedicled flap in reconstructing the cervical scar contracture deformity in children after burns can obviously improve the appearance and function of neck, with unlikely recurrence of postoperative scar contractures, thus it is an ideal method of reconstruction.
Burns/surgery* ; Child ; Cicatrix/surgery* ; Contracture/surgery* ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures/methods* ; Saline Solution ; Skin Transplantation ; Treatment Outcome

Actin-binding proteins (ABPs) are important components of the F-actin cytoskeleton and affect the dynamics of F-actin by promoting the polymerization and depolymerization of actin. Numerous studies have shown that F-actin and actin-binding proteins are involved in all stages of carcinogenesis. Our analysis of esophageal carcinoma proteomic data showed that the actin-binding protein EHD2 (E p s l 5 homology domain-containing protein 2) is expressed at low levels in esophageal squamous cell carcinoma tissues and patients with lower EHD2 expression had poorer prognosis. Previous studies have revealed that EHD2 is involved in the regulation of glucose metabolism, autophagy and tumor cell migration. However, the role and mechanism of EHD2 in esophageal squamous cell carcinoma progression remain unclear. This study aimed to explore the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. Immunofluorescence and cell fractionation analysis showed that EHD2 was not only localized in the cell membrane and cytoplasm, but also in the nucleus. Colony formation, EdU labeling and flow cytometry were used to determine the effect of EHD2 on the proliferation of esophageal squamous cell carcinoma. The results showed that overexpression of EHD2 and EHD2-3×NLS (nuclear localization signal) inhibited proliferation, cell cycle G