OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

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

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

This paper aimed to predict the active ingredients and action targets of Compound Uncaria Hypotensive Tablet for hypertension based on network pharmacology, and discuss its possible "multi-components, multi-targets, and multi-pathways" mechanism for treatment of hypertension. The integrative pharmacological platform of traditional Chinese medicine (TCM-IP) was used to construct the component target-disease target network of Compound Uncaria Hypotensive Tablet, and the internet analysis method was used to screen the key nodes, on which the pathway enrichment analysis was carried out to explore its possible biological process in the treatment of hypertension. Target network analysis showed that, 35 predicted active ingredients of Compound Uncaria Hypotensive Tablet had a strong interaction with the prostaglandin endogenous peroxidase synthase (PTGS1, PTGS2), ATP synthetase (ATP1A1, ATP5A1, ATP5C1, ATP5B) and other 29 major proteins. Network enriched analysis showed that Compound Uncaria Hypotensive Tablet participated in the regulation of hypertension in different processes of pathology, through 15 pathways such as regulating blood pressure, G protein coupled receptor activation, adrenergic myocardial cell signal transduction and platelet activation. This study revealed the potential active compounds and possible mechanism of Compound Uncaria Hypotensive Tablet for treatment of hypertension, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Compound Uncaria Hypotensive Tablet.

BACKGROUND: Previous studies have found that polygonatum sibiricum polysaccharide (PSP) exhibits anti-osteoporosis effect, but its therapeutic effect in ovariectomized osteoporotic rats and the molecular mechanisms are poorly understood. OBJECTIVE: To investigate the effect of administration of PSP on the bone microstructure, bone mineral density as well as osteoblast- and osteoclast-related gene expression in rats. METHODS: Twenty-five infertile female Sprague-Dawley rats aged 3 months were randomly allotted into five groups (n=5 per group): sham operation (same volume normal saline), model, zoledronate (0.2 mg/kg?d), high-dose PSP (800 mg/kg?d) and medium-dose PSP (400 mg/kg?d) groups. All rats were subjected to ovariectomy except sham operation group. The administration was intragastrically given every 2 days beginning at 7 days after modeling and lasted 12 weeks. Then, the rats were sacrificed, and the uterus was weighed. The bilateral tibias were removed, one side for histomorphometric analysis by micro-CT, and the other one for RNA detection by qualified PCR. RESULTS AND CONCLUSION: Compared with the sham operation group, the rat body mass in the model group was significantly increased and the weight of uterus was significantly decreased (P < 0.05). Compared with the model group, zoledronate and high-dose PSP could significantly alleviate the excessive increase in body mass (P < 0.05). The bone mineral density in the model group was decreased by 63% compared with the sham operation group (P < 0.01), Compared with the model group, after 12-week high-dose PSP and zoledronate administration, the bone mineral density was increased by 44% and 38%, respectively (P < 0.01); the trabecular bone volume fraction and trabecular number rose significantly(P<0.05),while the trabecular separation decreased significantly(P<0.05).In vivo,PSP could significantly promote the expression levels of osteoblast-related genes (alkaline phosphatase, RUNX2, Col1a1 and osteocalcin), and significantly inhibit the expression levels of osteoblast-related genes (ACP5 and CTSK) (P < 0.05). These results imply that high-dose PSP can reduce bone loss and decrease of bone mineral density, improve the destruction of bone microstructure, as well as promote osteoblast-related genes but inhibit osteoclast-related gene mRNA expression in the ovariectomized rats.

Objective To observe whether the classic drug-resistant mutations can be induced in various concentrations of adefovir (ADV)-treated HepG2.2.15 cells persistently and explore the mechanism for emergence of drug resistance.Methods HepG2.2.15 cells were cultured continually in 12-well plates with medium containing 0,0.01,0.1,1.0μmol/L concentration of ADV,and passaged every 3 days up to the 110th generations.The intracellular and supernatant HBV DNA was extracted every 10 generations.Intracellular HBV cccDNA was amplified by plasmid-safe ATP dependent DNase (PSAD) digestion in combination with rolling circle amplification and gap-spanning semi-nested PCR assay.And the RT region of supernatant HBV DNA was amplified by one-tube nested PCR assay.Then the classic drug-resistant mutations of the RT region of intracellular cccDNA and supernatant HBV DNA were analyzed using direct PCR sequencing combined with clonal sequencing (more than 20 clones/sample).Results HBV DNA stably replicated in ADV-untreated cells (control group).The intracellular total DNA and cccDNA levels,supernatant HBV DNA level decreased continuously with the prolonged ADV culture duration in 0.01 μmol/L and 0.1μmol/L ADV group.Drug resistant mutations were not detected up to the 110th generation in 0.01 μmol/L ADV group;while rtA181V+N236T mutations were detected at the110th generation in 0.1μmol/L ADV group.The 1.0μmol/L ADV group was ceased of culture at the 15th generation due to inhibited cell growth.Conclusion HBV cccDNA exists in HepG2.2.15 cells,and the classical drug-resistant mutations of rtA181V+N236T could be induced by proper concentration of ADV.

Background: Transarterial chemoembolization (TACE) is recommended as the standard care for unresectable hepa-tocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage A–B. However, the efficacy of TACE on large (≥ 10 cm) stage A–B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy (HAIC) might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC. Methods: A prospective, non-randomized, phase Ⅱ study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen (oxaliplatin, 85 mg/m2intra-arterial infusion; leucovorin, 400 mg/m2intra-arterial infusion; and fluorouracil, 400 mg/m2bolus infusion and 2400 mg/m2continuous infusion) every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression (TTP), and safety were assessed. Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group (52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months (hazard radio [HR] = 2.35, 95% confidence interval [CI] = 1.16–4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection (10 vs. 3, P = 0.033). The proportions of grade 3–4 adverse events (AE) and serious adverse events (SAE) were lower in the HAIC group than in the TACE group (grade 3–4 AEs: 13 vs. 27, P = 0.007; SAEs: 6 vs. 15, P = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent (10 vs. 2, P = 0.026). Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

OBJECTIVETo investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD).

METHODSPatients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score.

RESULTSEighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%.

CONCLUSIONSAutologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.

Adult ; Aged ; Disease-Free Survival ; End Stage Liver Disease ; pathology ; therapy ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver Function Tests ; Male ; Middle Aged ; Portal Vein ; Prospective Studies ; Treatment Outcome