SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

Characterization of a New Laccase from Vibrio sp. with pH-stability, Salt-tolerance, and Decolorization Ability.

Laccases have been widely used for fruit juice clarification, food modification, and paper pulp delignification. In addition, laccases exhibit remarkable performance in the degradation of toxic substances, including pesticides, organic synthetic dyes, antibiotics, and organic pollutants. Thus, the screening and development of robust laccases has attracted significant attention. In this study, Vibrio sp. LA is a strain capable of producing cold-adapted laccases. The laccase coding gene L01 was cloned from this strain and expressed in Yarrowia lipolytica, a host with good secretion ability. The secreted L01 (approximate MW of 56,000 Da) had the activity and specific activity of 18.6 U/mL and 98.6 U/mg toward ABTS, respectively. The highest activity occurred at 35 °C. At 20 °C, L01 activity was over 70% of the maximum activity in pH conditions ranging from 4.5-10.0. Several synthetic dyes were efficiently degraded by L01. Owing to its robustness, salt tolerance, and pH stability, L01 is a promising catalytic tool for potential industrial applications.

Genomic prediction of pig growth traits based on machine learning.

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.

Copper-Catalyzed Difluoroalkylation Reaction.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

Kinase Partner Protein Plays a Key Role in Controlling the Speed and Shape of Pollen Tube Growth in Tomato.

The rapid and responsive growth of a pollen tube requires delicate coordination of membrane receptor signaling, Rho-of-Plants (ROP) GTPase activity switching, and actin cytoskeleton assembly. The tomato (Solanum lycopersicum) kinase partner protein (KPP), is a ROP guanine nucleotide exchange factor (GEF) that activates ROP GTPases and interacts with the tomato pollen receptor kinases LePRK1 and LePRK2. It remains unclear how KPP relays signals from plasma membrane-localized LePRKs to ROP switches and other cellular machineries to modulate pollen tube growth. Here, we biochemically verified KPP's activity on ROP4 and showed that KPP RNA interference transgenic pollen tubes grew slower while KPP-overexpressing pollen tubes grew faster, suggesting that KPP functions as a rheostat for speed control in LePRK2-mediated pollen tube growth. The N terminus of KPP is required for self-inhibition of its ROPGEF activity, and expression of truncated KPP lacking the N terminus caused pollen tube tip enlargement. The C-terminus of KPP is required for its interaction with LePRK1 and LePRK2, and the expression of a truncated KPP lacking the C-terminus triggered pollen tube bifurcation. Furthermore, coexpression assays showed that self-associated KPP recruited actin-nucleating Actin-Related Protein2/3 (ARP2/3) complexes to the tip membrane. Interfering with ARP2/3 activity reduced the pollen tube abnormalities caused by overexpressing KPP fragments. In conclusion, KPP plays a key role in pollen tube speed and shape control by recruiting the branched actin nucleator ARP2/3 complex and an actin bundler to the membrane-localized receptors LePRK1 and LePRK2.

Overexpression of the tomato pollen receptor kinase LePRK1 rewires pollen tube growth to a blebbing mode.

The tubular growth of a pollen tube cell is crucial for the sexual reproduction of flowering plants. LePRK1 is a pollen-specific and plasma membrane-localized receptor-like kinase from tomato (Solanum lycopersicum). LePRK1 interacts with another receptor, LePRK2, and with KINASE PARTNER PROTEIN (KPP), a Rop guanine nucleotide exchange factor. Here, we show that pollen tubes overexpressing LePRK1 or a truncated LePRK1 lacking its extracellular domain (LePRK1ΔECD) have enlarged tips but also extend their leading edges by producing "blebs." Coexpression of LePRK1 and tomato PLIM2a, an actin bundling protein that interacts with KPP in a Ca(2+)-responsive manner, suppressed these LePRK1 overexpression phenotypes, whereas pollen tubes coexpressing KPP, LePRK1, and PLIM2a resumed the blebbing growth mode. We conclude that overexpression of LePRK1 or LePRK1ΔECD rewires pollen tube growth to a blebbing mode, through KPP- and PLIM2a-mediated bundling of actin filaments from tip plasma membranes. Arabidopsis thaliana pollen tubes expressing LePRK1ΔECD also grew by blebbing. Our results exposed a hidden capability of the pollen tube cell: upon overexpression of a single membrane-localized molecule, LePRK1 or LePRK1ΔECD, it can switch to an alternative mechanism for extension of the leading edge that is analogous to the blebbing growth mode reported for Dictyostelium and for Drosophila melanogaster stem cells.

Good outcome of severe lupus patients with high-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation: a 10-year follow-up study.

OBJECTIVES: This study aimed to examine the long-term efficacy, remission and survival of patients with severe systemic lupus erythematosus (SLE) after the combination treatment with high-dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (APBSCT). METHODS: Chinese patients with severe SLE receiving combination therapy with HDIT and APBSCT in Peking Union Medical College Hospital were enrolled from July 1999 to October 2005. Disease activity, treatment, and adverse effects of these patients were evaluated. The 10-year overall survival and 10-year remission survival were also analysed. RESULTS: Among the 27 patients, one patient failed to collect enough CD34+ cells and data was missing for two patients. In the end, 24 patients were included in the final analysis. After APBSCT, one patient died, two patients achieved partial remission and 21 (87.5%) achieved remission at 6 months. The median follow-up duration of the 23 patients was 120 months. Fourteen patients had completed a ten-year follow-up. The median proteinuria level of the 14 patients with LN with ten years of follow-up significantly decreased from 4.00 g/24 hours at pre-treatment to 0.00g/24 hours at year 5 and 0.00 g/24 hours at year 10 (both p=0.001). The 10-year overall survival rate and 10-year remission survival rate were both 86.0% (95% CI: 71.1-100.9%). After a median follow-up for 120 months, 16 patients (66.7%) remained in remission, 4 patients were lost to follow-up, 2 patients died and 1 patient remained active. CONCLUSIONS: The combination of HDIT and APBSCT may be an option to improve the survival of severe lupus patients.

Genetic analysis of porcine circovirus type 2 in China.

Porcine circovirus type 2 (PCV2) is the cause of postweaning multisystemic wasting syndrome (PMWS), which encompasses several distinct symptoms in pigs. PCV2 infection and clinical incidence of PMWS have increased in recent years, possibly due to shifts in viral populations and mutations. In this study, we identified PVC2 strains currently afflicting pig populations in mainland China, because this is a prerequisite for developing a specific vaccine to control the spread of PMWS. We collected 235 tissue samples from 16 provinces between 2014 and 2016. Of these, 152 samples were positive for PCV2. We compared the sequences we obtained for the PVC2 capsid gene, ORF2, to those of the Chinese PCV2 sequences deposited in GenBank between 2002 and 2016 (n = 648). Phylogenetic analyses demonstrated that the PCV2d genotype was the most prevalent strain in the sample population included in GenBank and among the positive samples from this study. We also found one PCV2c strain among the GenBank sequences. Furthermore, PCV2a-2F was the predominant genotype in the PCV2a cluster. Amino acid sequence comparisons demonstrated 70.8-100% identity within PCV ORF2 and several consistent mutations in ORF2. More interestingly, six isolates were classified as recombinant strains. Cumulatively, this study represents the first comprehensive description of PCV2 strains distribution, including recent samples, in Chinese porcine populations. We demonstrate the existence of high genetic variability among PVC2 strains and the ability of this virus to rapidly evolve.

Hepatic expression of transcription factors affecting developmental regulation of UGT1A1 in the Han Chinese population.

PURPOSE: Complete or partial inactivity of UGT1A1, the unique enzyme responsible for bilirubin glucuronidation, is commonly associated with hyperbilirubinemia. We investigated the dynamic expression of UGT1A1, and that of the transcription factors (TFs) involved in its developmental regulation, during human hepatic growth in Han Chinese individuals. METHODS: Eighty-eight prenatal, pediatric, and adult liver samples were obtained from Han Chinese individuals. Quantitative real-time polymerase chain reaction was used to evaluate mRNA expression of UGT1A1 and TFs including PXR, CAR, HNF1A, HNF4A, PPARA, etc. UGT1A1 protein levels and metabolic activity were determined by western blotting and high-performance liquid chromatography. Direct sequencing was employed to genotype UGT1A1*6 (211G˃A) and UGT1A1*28 (TA6˃TA7) polymorphisms. RESULTS: UGT1A1 expression was minimal in prenatal samples, but significantly elevated during pediatric and adult stages. mRNA and protein levels and metabolic activity were prominently increased (120-, 20-, and 10-fold, respectively) in pediatric and adult livers compared to prenatal samples. Furthermore, expression did not differ appreciably between pediatric and adult periods. Dynamic expression of TFs, including PXR, CAR, HNF1A, HNF4A, and PPARA, was consistent with UGT1A1 levels at each developmental stage. A pronounced correlation between expression of these TFs and that of UGT1A1 (P < 0.001) was observed. Moreover, UGT1A1*6 and UGT1A1*28 polymorphisms reduced levels of UGT1A1 by up to 40-60 %. CONCLUSIONS: Hepatic expression of transcription factors is associated with developmental regulation of UGT1A1 in the Han Chinese population. Moreover, UGT1A1 polymorphisms are associated with reduced expression of UGT1A1 mRNA and protein, as well as enzyme activity.

Importation and Recombination Are Responsible for the Latest Emergence of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in China.

In China, a majority of the highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRSV) strains were seeded by the 2006 outbreak. However, the most recently emerged (2013-2014) HP-PRRSV strain has a very different genetic background. It is a NADC30-like PRRSV strain recently introduced from North America that has undergone genetic exchange with the classic HP-PRRSV strains in China. Subsequent isolation and characterization of this variant suggest high pathogenicity, so it merits special attention in control and vaccine strategies.

Clinical Features of Patients with Castleman's Disease Complicated Systemic Lupus Erythematosus.

Objective To investigate the clinical features of patients with Castleman's disease (CD) and systemic lupus erythematosus (SLE). Methods According to the diagnostic information between 1994 to 2014 extracted from the database of the Medical Record Department of Peking Union Medical College Hospital (PUMCH),patients with CD and SLE were included. A thorough literature review utilizing the key words of "Castleman's disease","systemic lupus erythematosus","SLE",and "lupus" was performed in PubMed during the same period. Cases with detailed clinical information were included while cases without detailed information were excluded from the analysis of this study. Results Nine patients worldwide were available for analysis [2 cases from PUMCH,accounted for 0.03%(2/6502) of all patients diagnosed as SLE and 1.0% (2/100) of patients diagnosed as CD during the same period] with a male-to-female ratio of2:7. The median age at diagnosis of CD was 39.0 years (range:21- 60 years). All patients were diagnosed as multicentric CD with generalized peripheral lymphadenopathy. Pathologic examination showed a balanced distribution:plasma cell variant:hyaline-vascular variant:mixed variant=3:3:3. Fever was the most common symptom (88.9%,8/9). Blood system was the most commonly involved system (88.9%,8/9) and kidneys were the most commonly involved organ (88.9%,8/9). Autoimmune thrombocytopenia (AITP) was observed in 55.6% (5/9) of patients,which was significantly higher than the general SLE patients (15.0%) (P<0.01). None of the 9 patients had evidence of central nervous system involvement. Conclusions CD complicated by SLE is a rare clinical condition. Compared to the general SLE population,this subgroup of patients may have higher rate of AITP and lower rate of central nervous system involvement.

Quality evaluation of peony seed oil spray-dried in different combinations of wall materials during encapsulation and storage.

This study aimed at evaluating the performance of peony seed oil microencapsulated by spray drying during encapsulation and storage. Four different combinations of gum arabic (GA), corn syrup (CS), whey protein concentrate (WPC) and sodium caseinate (CAS) were used to encapsulate peony seed oil. The best encapsulation efficiency was obtained for CAS/CS followed by the CAS/GA/CS combination with the encapsulation ratio of 93.71 and 92.80 %, respectively, while the lowest encapsulation efficiency was obtained for WPC/GA/CS (85.96 %). Scanning electron microscopy and confocal laser scanning microscopy revealed that the particles were spherical in shape and did not exhibit apparent cracks or fissures, and gum arabic was uniformly distributed across the wall of the microcapsules. Oxidative stability study indicated that the CAS/GA/CS combination presented the best protection against lipid oxidation and the smallest loss of polyunsaturated fatty acid content among all of the formulas as measured by gas chromatography. Therefore, CAS/GA/CS could be promising materials encapsulate peony seed oil with high encapsulation efficiency and minimal lipid oxidation.

Risk factors and precautions of inpatient suicide from the perspective of nurses: A qualitative study.

The risk factors and precautions of inpatient suicide were explored. Thirty suicide victims were drawn from the adverse event reports of suicidal act during hospitalization in a general hospital from 2008 to 2014. Data were gathered from the focus group interviews of twelve nurses who had experienced inpatient suicide. The data were analyzed by using analytical technique based on grounded theory, and software QSR NVIVO8 was used to aid the collation of data. Three main themes of risk factors about inpatient suicide emerged from the analysis: individual value, social factors and environmental factors. The individual value was categorized into different groups such as sense of guilt, hopelessness and low self-esteem. Social factors included two aspects of negative life events and social support. Three themes of precautions about inpatient suicide appeared in this study: evaluation, nursing and information exchange. Evaluation was elaborated from both physical and psychological assessments. This finding extends existing work of risk factors and precautions about inpatient suicide and brings new knowledge about the reasons why inpatients commit suicide.

[Prevalence and features of pathogenic bacteria in the department of hematology without bone marrow transplantation in Peking Union Medical College Hospital from 2010 to 2012].

OBJECTIVE: To investigate the incidence, pathogens, and clinical features of infection in consecutive cases from 2010 to 2012 in Peking Union Medical College Hospital. METHOD: The incidence, pathogen, treatment, and outcomes of patients with hematological diseases who had positive findings of bacterium in their samples from 2010 to 2012 were retrospectively analyzed. RESULTS: There were 449 positive samples (5.8%) from 4 890 patients during this period, among which 388 were proved to be with pathogenic bacteria. Samples separated from patients with community-aquired infections accounted for 8.4% of all positive samples. Most community-aquired infections were caused by Gram-negative bacteria (75%), although no multidrug-resistant bacteria was observed. Samples separated from patients with nosocomial infections accounted for 91.6% of all positive samples. Respiratory tract (49.4%) and peripheral blood (32.6%) were the most common samples with positive results. Skin soft tissues (10.4%), and urine (3.7%) were less common samples. Most of the pathogenic bacteria of the nosocomial infections were Gram-negative (66.9%). The most common Gram-negative bacteria included Escherichia coli (13.8%), Pseudomonas aeruginosa (12.1%), and Klebsiella pneumonia (12.1%), while Staphylococcus aureus (10.4%), Enterococcus faecium (7.0%), and Staphylococcus epidermidis (5.1%) were the most common Gram-positive bacteria. Gram-negative bacteria consisted of most of sputum samples and peripheral blood samples. Samples from the surface of skin wound and anal swab were composed largely by Gram-positive bacteria (63.8%). The detection rates of extended-spectrum beta-lactamase-producing Klebsiella pneumonia/Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis were 24.0%, 87.9% and 38.4%, respectively. The resistance to Acinetobacter baumannii was serious. Multidrug-resistant, extensive drug resistant and pan drug resistant A. baumannii acountted for 74% of all A. Baumannii infections. Stenotrophomonas maltophilia showed low resistance to sulfamethoxazole/trimethoprim, levofloxacin and minocycline. Also, 22 methicillin-resistant Staphylococcus aureus and 9 methicillin-resistant Staphylococcus Epidermidis were detected, which were only sensitive to vancomycin, teicoplanin, and linezolid. All patients were treated in the haematology wards and most of them were under agranulocytosis or immunosuppression. Finally, 22 patients reached clinical recovery through anti-infective therapy, whereas 49 patients died. Among those deaths, 42 patients attributed to severe infections and infection-associated complications. Fourteen of all the deaths might be infected with drug-resistance bacteria. There were 61 samples proved to be bacteria colonization. Nonfermenters such as Acinetobacter baumannii and Stenotrophomonas maltophilia made up for a large amount of bacteria colonization. CONCLUSIONS: The pathogens of nosocomial infections in the hematology ward are mainly Gram-negative bacteria. The incidences and pathogens vary from different infection sites. Nosocomial infection still has a higher mortality rate. Once nonfermenters are detected positive, the pathogenic or colonial bacteria should be distinguished.

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

Structure of yeast sulfhydryl oxidase erv1 reveals electron transfer of the disulfide relay system in the mitochondrial intermembrane space.

The disulfide relay system in the mitochondrial intermembrane space drives the import of proteins with twin CX(9)C or twin CX(3)C motifs by an oxidative folding mechanism. This process requires disulfide bond transfer from oxidized Mia40 to a substrate protein. Reduced Mia40 is reoxidized/regenerated by the FAD-linked sulfhydryl oxidase Erv1 (EC 1.8.3.2). Full-length Erv1 consists of a flexible N-terminal shuttle domain (NTD) and a conserved C-terminal core domain (CTD). Here, we present crystal structures at 2.0 Å resolution of the CTD and at 3.0 Å resolution of a C30S/C133S double mutant of full-length Erv1 (Erv1FL). Similar to previous homologous structures, the CTD exists as a homodimer, with each subunit consisting of a conserved four-helix bundle that accommodates the isoalloxazine ring of FAD and an additional single-turn helix. The structure of Erv1FL enabled us to identify, for the first time, the three-dimensional structure of the Erv1NTD, which is an amphipathic helix flanked by two flexible loops. This structure also represents an intermediate state of electron transfer from the NTD to the CTD of another subunit. Comparative structural analysis revealed that the four-helix bundle of the CTD forms a wide platform for the electron donor NTD. Moreover, computational simulation combined with multiple-sequence alignment suggested that the amphipathic helix close to the shuttle redox enter is critical for the recognition of Mia40, the upstream electron donor. These findings provide structural insights into electron transfer from Mia40 via the shuttle domain of one subunit of Erv1 to the CTD of another Erv1 subunit.

Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China: a multicenter, randomized, open-label study.

BACKGROUND: Invasive fungal infection (IFI) is common in neutropenic patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is a broad-spectrum triazole antifungal drug with efficacy in prevention of IFI; however, it has not been previously studied as prophylaxis in a Chinese population. METHODS: This multicenter, randomized study in China enrolled AML and MDS patients with persistent chemotherapy-induced neutropenia. Prophylaxis with posaconazole or fluconazole was administered for a maximum of 12 weeks, or until patients recovered from neutropenia and achieved complete remission or an IFI occurred. The primary endpoint was incidence of proven, probable, or possible IFI during treatment. Clinical failure rate, all-cause mortality and time to first systemic antifungal treatment were secondary endpoints. RESULTS: Patients were randomized to receive posaconazole (n = 129) or fluconazole (n = 123); 117 patients in each group were included in the statistical analysis. The incidence of proven, probable or possible IFI was 9.4% (11/117) and 22.2% (26/117) in the posaconazole and fluconazole groups, respectively (p = 0.0114). The clinical failure rate was numerically lower in the posaconazole group (37/117 (31.6%; 95%CI: 23.3 - 40.9)) than in the fluconazole group (49/117 (41.88%; 95% CI: 32.8 - 51.4)) (p = 0.168). Patients receiving posaconazole had a later onset of first systematic antifungal treatment than those receiving fluconazole (p = 0.0139). The most common important adverse events were liver function abnormalities (11 patients (8.8%) on posaconazole and 6 (5.0%) on fluconazole (p = 0.221)). CONCLUSIONS: Posaconazole demonstrates efficacy as prophylaxis against IFI in high-risk neutropenic Chinese patients and is well tolerated during long-term use (ClinicalTrials. gov number, NCT00811928).

[The incidence of heparin-induced thrombocytopenia and positivity of antibody in patients treated with heparin preparations].

OBJECTIVES: To investigate the incidence of the heparin-induced thrombocytopenia (HIT) and positivity of anti-heparin/platelet factor 4 complex antibody (HIT-antibody) in inpatients treated with heparin preparations. METHODS: A total of 197 consecutive patients, including 120 men and 77 women, who were treated with unfractioned heparin (UFH) or low molecular weight heparin (LMWH), were enrolled in this study. HIT-antibody was detected by enzyme-linked immunosorbent assay (ELISA). All patients were classified into subgroups based on "4Ts" (Pretest Clinical Scoring System) and types of underlying disorders. The incidence of HIT and positivity of HIT-antibody among different groups were analyzed. RESULTS: The overall incidence of HIT was 3.0% (6/197), and the positivity of HIT antibody was 12.2% (24/197). The positivity of HIT-antibody was 10.1% (18/178), 7.7% (1/13) and 83.3% (5/6) in low, moderate and high HIT probability group respectively. There were significant differences of HIT positivity and mean level of HIT-antibody between the high HIT probability group and the low or moderate HIT probability group (P = 0.000). Both the incidence of HIT and positivity of HIT-antibody were higher in surgical patients than in medical patients (5.8% vs 0.9%, P = 0.047 and 19.8% vs 6.3%, P = 0.004). CONCLUSIONS: The incidence of HIT and positivity of HIT-antibody were 3.0% and 12.2% respectively, both of which were related with the types of disorders. Detection of HIT-antibody has a better applicable value in patients with high HIT probability.

[Exploring the pathogenesis and therapy of liver cancer from "damp-heat insidious pathogen" to "cancer toxin"].

From a macro-level analysis of the attributes and pathogenic features of HBV, the main pathogenic factor for chronic liver diseases including viral hepatitis, cirrhosis, and liver cancer, the concept of damp-heat insidious pathogen was obtained, according to which, in-depth discussions were undertaken. Adopting syndrome typing of Wei (defense), qi (vital energy), Ying (nutrients), and blood, the pathogens leading to different syndromes as well as new products such as pathological "sputum", "stasis" in the disease process were understood, and then, the pathological "sputum" and "stasis", as the hub, playing a role in chronic lesions of the liver collateral were explained. Finally the pathological "sputum" and "stasis" blend and form cancer toxin. Through a comprehensive understanding of the development of chronic liver diseases, it is clear that damp-heat insidious pathogen, as its initiating factor, always exists in the whole process. We summed up heat clearing, dampness resolving, and detoxification was the principle for treating chronic liver disease.

Seasonal variation characteristics and influencing factors of dissolved organic carbon of soil water in permafrost peatlands of the Great Hing'an Mountains in summer and autumn.

Dissolved organic carbon (DOC) plays a crucial role in the assessment of greenhouse gas emission and carbon balance in peatlands. However, limited research has been conducted on the seasonal variations and properties of soil water DOC content at different depths in the permafrost peatlands of the Great Hing'an Mountains. In this study, we analyzed the seasonal patterns of soil water DOC contents (surface, 10 cm, 20 cm, 30 cm, 40 cm, and permafrost layer) the permafrost peatlands of the Great Hing'an Mountains (Tuqiang Forestry Bureau), and investigated the influencing factors, such as electrical conductivity, dissolved oxygen, HCO3- concentration, pH value, oxidation-reduction potential, and CO2 content. The stability of DOC was assessed by using UV-Vis spectrum. There were significant seasonal dynamics of DOC content in soil water, with higher contents in autumn and lower content in summer, ranging from 55.7 to 188.1 mg·L-1. There were significant differences in DOC content among different soil depths, with the highest levels detected in the permafrost layer. The DOC content showed a significantly positive correlation with pH value and electrical conductivity, while showed a significantly negative correlation with redox potential, HCO3- concentration, and dissolved oxygen content. Additionally, there was a significantly positive correlation between DOC and CO2 contents. The dissolved CO2 content in soil water increased with soil depth, with the highest content observed in the permafrost layer. Results of spectral analysis showed higher aromaticity in autumn compared to summer, indicating greater stability of DOC during the autumn season. Our results clarified the seasonal variations of soil water DOC in permafrost peatlands of the Great Hing'an Mountains and could provide important data to understand the carbon cycling in the region.