Early-stage neutralizing antibody level associated with the re-positive risk of Omicron SARS-CoV-2 RNA in patients recovered from COVID-19.

Post-discharge re-positivity of Omicron SARS-CoV-2 is challenging for the sufficient control of this pandemic. However, there are few studies about the risk of re-positivity. We aimed to explore the association of neutralizing antibodies (nAbs, AU/mL) with the incidence of re-positivity among patients recovered from COVID-19. A retrospective cohort study selected 318 Omicron-infected patients was conducted in China between December 2021 and April 2022. The peak value of nAb levels (nAb-peak) within 14 days of disease onset was defined as the baseline and was mainly used for the subsequent analyses. In the unadjusted, minimally adjusted, fully adjusted, and additionally adjusted for IgG models, a per-standard deviation (SD) increase in the nAb-peak values was significantly associated with a 59 %, 59 %, 50 %, and 75 % decreased risk of Omicron SARS-CoV-2 re-positivity during post-discharge surveillance, respectively. Stratified analyses showed no significant changes in the relationship between nAbs and re-positivity. Our study suggested that the increase in baseline nAb levels independently associated with a low risk of re-positivity in patients recovered from COVID-19.

Evaluation of the liver targeting and anti­liver cancer activity of artesunate­loaded and glycyrrhetinic acid­coated nanoparticles.

Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects in vivo. Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer.

Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.

Objective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents. Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed. Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 µM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice. Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.

[Clinical features of 19 children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 in Hangzhou, China]. / 杭州市19ä¾‹æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“å„¿ç«¥çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. RESULTS: Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. CONCLUSIONS: Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.

Mycobacterium tuberculosis bacteremia in a human immunodeficiency virus-negative patient with liver cirrhosis: A case report.

BACKGROUND: With the increasing prevalence of human immunodeficiency virus (HIV), the incidence of Mycobacterium tuberculosis (M. tuberculosis) bacteremia has also increased. As a common affliction of acquired immunodeficiency syndrome patients, M. tuberculosis infection is associated in these patients with severe sepsis and high mortality. In contrast, M. tuberculosis bacteremia is rarely seen in HIV-negative patients, and M. tuberculosis has never been reported from the blood of patients with liver cirrhosis. CASE SUMMARY: We evaluated a 55-year-old Chinese male patient who had been admitted to the hospital with abdominal distension of unknown cause of one-week duration, accompanied by diarrhea, shortness of breath, and occasional fever. Based on these indicators of abnormal inflammation and fever, we suspected the presence of an infection. Although evidence of microbial infection was not found in routine clinical tests and the patient did not show typical clinical symptoms of infection with M. tuberculosis, next-generation sequencing of blood samples nevertheless demonstrated the presence of M. tuberculosis, which was subsequently isolated from blood samples grown in conventional BacT/ALERT FA blood culture bottles. CONCLUSION: Our findings demonstrate that HIV-negative liver cirrhosis patients can also be infected with M. tuberculosis.

Design, synthesis, and biological evaluation of novel 3-(thiophen-2-ylthio)pyridine derivatives as potential multitarget anticancer agents.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.

[Expression of TGF-beta1/Smad protein in rat liver fibrosis model and the role of IFN-gamma].

OBJECTIVE: To study the impact of IFN-gamma on liver fibrosis and its possible mechanism. Thirty healthy male SD rats were randomly divided into two groups: fibrosis model group, IFN-gamma treatment group. Experimental liver fibrosis was induced by subcutaneous injection of CCl4. After 12-week-treatment, serum hyalurnic acid and TGF-beta1 was examined, histopathological changes and degrees of fibrosis were observed by optical microscopy. Meanwhile, the expression of TGF-beta1, TbetaR- I and Smad2/3 proteins was detected by immunohistochemistry and quantified by using computerized image analysis. RESULTS: (1) Pathological observation of hepatic specimens: histological examination showed that there were significant difference between normal group and fibrosis model group by comparing with the degrees of inflammation and fibrosis (P < 0.05). And the difference between fibrosis model group and IFN-gamma treatment group was significant (P < 0.05). (2) Changes of the hepatic fibrosis index (serum HA and TGF-beta1): the levels of serum HA, TGF-beta1 in fibrosis model group were higher than IFN-gamma treatment groups (P < 0.05). (3) Changes of gene protein levels about TGF-beta1/Smad: the expressions of TGF-beta1, TbetaR- I and Smad2/3 in rat hepatic tissue were detected with immunohistochemistry techniques. The expressions of the three items in model group were higher than normal group (P < 0.01). The difference between model group and IFN-gamma treatment group was significant (P < 0.05); CONCLUSION: IFN-gamma treatment group had significant results on treating experimental hepatic fibrosis. By the way of inhibiting expressions of TGF-beta1, TbetaR- I, Smad2/3, IFN-gamma treatment group exerted its anti-fibrosis effect.

[The protective effect of N-acetylcysteine magnesium against liver cirrhosis with portal hypertension in rat].

OBJECTIVE: To study the effects of acetylcysteine magnesium on the vasoactive substances and hepatic fibrosis indexes in liver cirrhosis and portal hypertension of rats. METHODS: The rat liver cirrhosis model was made with 12 microg/kg dimethylnitrosamines. Then acetylcysteine magnesium was injected respectively with 25, 50, and 100 mg x kg(-1) dose daily into abdominal cavity. After 8 weeks treatment, pathological section, TGF-beta1, NO, TNOS and iNOS of hepatic tissue were detected to assess the effect of acetylcysteine magnesium against cirrhosis portal hypertension. RESULTS: After the DMNA modeling was completed, the HE and Sweet reticulocyte staining of liver pathological section showed that cirrhosis of the liver was in the III-IV phase, the infiltration of lymphocytes and formation of pseudolobuli in liver were alleviated in three acetylcysteine magnesium treatment groups (low, medium, and high dose), and the degree of liver fiber sclerosis in three groups was significantly lower than control group. Compared with control group, TGF-beta1, NO, TNOS and iNOS were significantly reduced in all treatment groups (P < 0.05). CONCLUSION: Acetylcysteine magnesium is probably a distinctive antioxidant which can remove various free radical in body and modulate ligand-dependent signal transduction and the growth of cell. It also have protection in the liver cirrhosis and portal hypertension of rats induced by dimethylnitrosamine.

[Relationship between intrauterine infection and the gene polymorphism of DC-SIGN/DC-SIGNR in the pregnant women of HBV positive].

OBJECTIVE: To investigate the influence of the individual genotype differences of DC-SIGN and DC-SIGNR on the mother-to-neonate intrauterine infection of HBV. METHODS: The genotypes of the gene DC-SIGN and DC-SIGNR in the pregnant women with HBV positive were detected by PCR and agarose gel electrophoresis. The significant difference of gene diversity of DC-SIGN and DC-SIGNR was analyzed by chi-square test. RESULTS: (1) All of 29 cases in intrauterine infection group were 7/7 DC-SIGN genotype. In the non-intrauterine infection group, 7/5 genotype were observed in 2 of 54 cases, and the other 52 cases were 7/7 genotype. The two groups was no significant difference (P = 0.54). (2) 29 cases of intrauterine infection group was observed 4 genotypes of DC-SIGNR such as 7/7, 7/5, 9/7 and 6/5, the genotype frequencies were 0.3793, 0.3448, 0.2414 and 0.0345 respectively. 54 cases of non-intrauterine infection group was found 6 genotypes such as 7/7, 7/5, 9/5, 9/7, 7/6 and 6/5, genotype frequencies were 0.5186, 0.1481, 0.0926, 0.1852, 0.0370 and 0.0185 respectively. The distribution of 7/5 genotype in the intrauterine infection group (29 cases) and the non-intrauterine infection group (54 cases) was statistically significant (P = 0.038) , and no significant difference was found in other genotypes between the two groups (P > 0.05). CONCLUSION: The gene DC-SIGN showed relatively little variation in the pregnant women infected with HBV. On the countrary, there were multiple genotypes of the gene DC-SIGNR in these women, and the genotype "7/5" of DC-SIGNR might be one of the susceptibility genes associated with intrauterine infection.

[Experimental study on intestinal bacterial translocation in acute hepatic failure in rats].

OBJECTIVE: To investigate if glutamine (Gln) reduces intestinal bacterial translocation in acute hepatic failure (AHF) in rats and its mechanisms. METHODS: Acute hepatic failure model in rat was established by intraperitoneal injection of galatosamine. The rats were randomly divided into 4 groups: the normal control group (A), prevention and treatment group (B), treatment group (C), and model group (D). The rats in groups A and D were fed with normal saline. Two days before intraperitoneal injection, the rats in group B were fed with Gln and those in group C were fed with Gln 24 hours after injection. After 4 days of treatment, the rats were sacrificed and pathological scores of liver were assessed. The percentage of intestinal bacterial transloaction and bacteria in mesenteric lymph nodes (MLN) were measured. The villus height, crypt depth of ileum mucosa were analyzed. The levels of serum diamine oxidase (DAO) were measured. RESULTS: The liver pathological scores of groups B and C were significantly lower than those of group D. The frequency of the bacteria found in MLN was significantly lower in group B compared with group D. The levels of DAO in blood were significantly lower in groups B and C than that of group D, and the level was significantly lower in group B than in group C. The villus height and crypt depth of the mucosa were significantly greater in group B and group C than in group D, and greater in group B than in group C. CONCLUSION: The results of the present study show that Gln can reduce the occurrence of the intestinal bacterial translocation in AHF in rats by improving the function of intestinal barrier.