A Comparison of Clinical Prognostic Indices in Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with a Pegylated Liposomal Doxorubicin Combination Regimen in China.

Background: There is no consensus regarding the risk stratification scores for elderly patients with diffuse large B-cell lymphoma (DLBCL). We aimed to compare the prognostic predictive ability of the current clinical scoring indices in DLBCL elderly patients treated with the R-CODP regimen (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone). Methods: We retrospectively collected the data of elderly DLBCL patients who received the R-CODP regimen as the first-line treatment. The efficacy of the regimen was evaluated. The Akaike information criteria (AIC), concordance index (C-index), and integrated discrimination improvement (IDI) were used to assess the fitness and prognostic performance of the current clinical prognostic indices. Results: In the total of 158 patients enrolled, the median follow-up time was 6.7 years (95% CI: 6.3-7.9), and the 5-year OS was 52.8% (95% CI: 45.5%-61.2%). The International Prognostic Index (IPI), National Comprehensive Cancer Network-IPI (NCCN-IPI), and Elderly International Prognostic Index (E-IPI) were all significantly associated with OS (P < 0.001 for all). However, no significance was observed in 5-year OS in the low- vs low-intermediate-risk groups for IPI (P = 0.377), NCCN-IPI (P = 0.238), and E-IPI (P = 0.080). Compared with the IPI and NCCN-IPI, the E-IPI had the lowest AIC value of 747.5 and the highest C-index of 0.692. For predicting 5-year mortality, the E-IPI showed better performance (AUC: 0.715 for E-IPI vs 0.676 for IPI, P = 0.036), with the IDI of 6.29% (95% CI: 3.71%-8.88%, P < 0.001) and 4.80% (95% CI: 1.32%-8.28%, P = 0.007) compared to the IPI and NCCN-IPI, respectively. Conclusion: The E-IPI might be a better prognostic prediction model in Chinese DLBCL generics treated with R-CODP for predicting 5-year mortality. However, the IPI, NCCN-IPI, and E-IPI did not seem to be able to distinguish patients with a favorable prognosis well.

The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro.

Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 µM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form ß of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1ß and TNF-α in serum. In conclusion, oral administration of crystal form ß of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.

Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.

Total Saikosaponins of Bupleurum yinchowense reduces depressive, anxiety-like behavior and increases synaptic proteins expression in chronic corticosterine-treated mice.

BACKGROUND: Bupleurum yinchowense Shan et Y. Li is widely used to treat depressive and anxiety disorders for hundreds of years in China. Total saikosaponins (TSS) is the major ingredient of Bupleurum yinchowense. A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and subsequent mammalian target of rapamycin (mTOR) signaling is responsible for synaptic maturation and may contribution to the synaptic alteration underlying depression. The aim of the study was to investigate the antidepressant-like and anxiolytic effect of TSS in chronic corticosterone-treated mice. The effect of TSS on synaptic proteins expression and AMPA receptor-mTOR signaling pathway alteration was also evaluated. METHODS: Dose-response effect of TSS (12.5, 25, 50 mg/kg) was investigated in forced swim test (FST) in ICR male mice. In the chronic corticosterine-treated model, TSS was given intragastrically once a day for 2 weeks and continued through the behavior testing period. Behavior tests and AMPA receptor related signaling pathway were investigated. RESULTS: TSS (25 and 50 mg/kg) decreased the immobility time in the FST when compared with the control group. TSS (25 mg/kg) showed antidepressant-like and anxiolytic effects in the chronic corticosterone treatment model in mice. TSS increased hippocampal synaptic proteins (synapsin-1 and postsynaptic density protein 95) expression. Immunohistochemistry analysis showed that TSS significantly increased the synapsin-1 expression in CA3 of hippocampus. TSS also increased hippocampal phosphorylation expression of GluR1 Ser 845 (AMPA receptor subunit) and its downstream regulators extracellular signaling-regulated kinase (ERK), protein kinase B (Akt) and mTOR. CONCLUSION: TSS produces antidepressant-like and anxiolytic effects and increases synaptic proteins expression which may be mediated by induction of AMPA receptor and subsequent mTOR signaling pathway.

Effects of 630 nm Red and 460 nm Blue Light Emitting Diode Irradiation on Healing of the Skin Wound in Japanese Big-ear White Rabbit.

Objective To observe the effects of 630 nm red light and 460 nm blue light emitting diode irradiation on the healing of skin wounds in Japanese big-ear white rabbits. Methods The skin wound model was established with 8 Japanese big-ear white rabbits. Three parts of vulnus in each rabbit were used:two parts of vulnus were irradiated vertically by red and blue LED light,respectively(15 min/time),and the distance between lights and wounds was 15 cm;the 3rd part of the wound was used as a control. On the 21st day of the wounds exposure to light,the number of healing wounds and the percentage of healing area were recorded and the treatment effect of these two light sources was compared. HE staining was used to analyze the newborn tissue structure. Masson staining was used to observe the proliferation of skin collagen fibers. Immuohistochemical staining was used to analyze fibroblast growth factor(FGF),epidermal growth factor(EGF),endothelial growth factor(CD31),proliferating cell nuclear antigen(Ki-67),and inflammatory cytokines(CD68)infiltration in the skin. Results The healing rate in the red light,blue light,and control groups was 50.0%(4/8),25.0%(2/8),and 12.5%(1/8),respectively. Since the 12th day after modeling,the healing area percentage in the red light group was significantly higher than those in the blue light and control groups(P<0.05,P<0.01). On the 21st day after modeling,the skin thickness of the red light group was(2.95±0.34)mm,which was significantly higher than that in control group [(2.52±0.42)mm;F=3.182,P=0.016)]. The average optical density of collagen fibers was 0.15±0.03 in red light group,which was significantly higher than that of the blue light group(0.09±0.01;F=7.316,P=0.012)and control(0.07±0.01;F=7.316,P=0.003). The results of immunohistochemistry showed the expression levels of EGF,FGF,CD31 antigen,and Ki-67 in the red light group were significantly higher than those in the blue light and control groups,whereas the CD68 expression was significantly lower(P<0.05 or P<0.01). Conclusion LED red light irradiation can promote the healing of skin wounds in Japanese big-ear white rabbits,which may be achieved by the effect of red light irradiation in stimulating the proliferation of skin epidermal cells,vascular endothelial cells,and fiberous tissue.

The Histopathological Investigation of Red and Blue Light Emitting Diode on Treating Skin Wounds in Japanese Big-Ear White Rabbit.

The biological effects of different wavelengths of light emitting diode (LED) light tend to vary from each other. Research into use of photobiomodulation for treatment of skin wounds and the underlying mechanisms has been largely lacking. We explored the histopathological basis of the therapeutic effect of photobiomodulation and the relation between duration of exposure and photobiomodulation effect of different wavelengths of LED in a Japanese big-ear white rabbit skin-wound model. Skin wound model was established in 16 rabbits (three wounds per rabbit: one served as control, the other two wounds were irradiated by red and blue LED lights, respectively). Rabbits were then divided into 2 equal groups based on the duration of exposure to LED lights (15 and 30 min/exposure). The number of wounds that showed healing and the percentage of healed wound area were recorded. Histopathological examination and skin expression levels of fibroblast growth factor (FGF), epidermal growth factor (EGF), endothelial marker (CD31), proliferating cell nuclear antigen (Ki67) and macrophagocyte (CD68) infiltration, and the proliferation of skin collagen fibers was assessed. On days 16 and 17 of irradiation, the healing rates in red (15 min and 30 min) and blue (15 min and 30 min) groups were 50%, 37.5%, 25% and 37.5%, respectively, while the healing rate in the control group was 12.5%. The percentage healed area in the red light groups was significantly higher than those in other groups. Collagen fiber and skin thickness were significantly increased in both red light groups; expression of EGF, FGF, CD31 and Ki67 in the red light groups was significantly higher than those in other groups; the expression of FGF in red (30 min) group was not significantly different from that in the blue light and control groups. The effect of blue light on wound healing was poorer than that of red light. Red light appeared to hasten wound healing by promoting fibrous tissue, epidermal and endothelial cell proliferation. An increase in the exposure time to 30 min did not confer any additional benefit in both red and blue light groups. This study provides a theoretical basis for the potential therapeutic application of LED light in clinical settings.

Hemagglutinin amino acids related to receptor specificity could affect the protection efficacy of H5N1 and H7N9 avian influenza virus vaccines in mice.

The continuous and sporadic human transmission of highly pathogenic avian H5N1 and H7N9 influenza viruses illustrates the urgent need for efficacious vaccines. However, all tested vaccines for the H5N1 and H7N9 viruses appear to be poorly immunogenic in mammals. In this study, a series of vaccines was produced using reverse genetic techniques that possess HA and NA genes from the H5N1 virus in the genetic background of the high-yield strain A/PR/8/34 (H1N1). Meanwhile, a group of H7N9 VLP vaccines that contain HA from H7N9 and NA and M1 from A/PR/8/34 (H1N1) was also produced. The HA amino acids of both the H5N1 and H7N9 vaccines differed at residues 226 and 228, both of which are critical for receptor specificity for an avian or mammalian host. Mice received two doses (3µg of HA each) of each vaccine and were challenged with lethal doses of wild type H5N1 or H7N9 viruses. The results showed that a recombinant H5N1 vaccine in which the HA amino acid G228 (avian specificity) was converted to S228 (mammalian specificity) resulted in higher HI titers, a lower viral titer in the lungs, and 100% protection in mice. However, a H7N9 VLP vaccine that contains L226 (mammalian specificity) and G228 (avian specificity) in HA showed better immunogenicity and protection efficacy in mice than VLP containing HA with either L226+S228 or Q226+S228. This observation indicated that specific HA residues could enhance a vaccine's protection efficacy and HA glycoproteins with both avian-type and human-type receptor specificities may produce better pandemic influenza vaccines for humans.

Effect of Polysaccharide from Cordyceps militaris (Ascomycetes) on Physical Fatigue Induced by Forced Swimming.

Cordyceps militaris is the one of the most important medicinal mushrooms, widely used in East Asian countries. Polysaccharide is considered to be the principal active component in C. militaris and has a wide range of biological and pharmacological properties. This study was undertaken to investigate the effect of polysaccharide from C. militaris (PCM) on physical fatigue induced in animals through a forced swimming test. The mice were divided into 4 groups receiving 28 days' treatment with drinking water (exercise control) or low-, medium-, and high-dose PCM (40, 80, and 160 mg/kg/day, respectively). After 28 days, the mice were subjected to the forced swimming test; the exhaustive swimming time was measured and fatigue-related biochemical parameters, including serum lactic acid, urea nitrogen, creatine kinase, alanine aminotransferase, aspartate aminotransferase, superoxide dismutase, glutathi- one peroxidase, catalase, malondialdehyde, liver glycogen, and muscle glycogen, were analyzed. The results showed that PCM could significantly prolong the exhaustive swimming time of mice; decrease concentrations of serum lactic acid, urea nitrogen, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde; and increase liver and muscle glycogen contents and the concentrations of serum superoxide dismutase, glutathione per- oxidase, and catalase. The data suggest that PCM has an antifatigue effect, and it might become a new functional food or medicine for fatigue resistance.

[Discussion on releasing price of Chinese patent medicine to market economy to achieve sustainable development].

OBJECTIVE: To analyze costs of the traditional Chinese medicine industry focusing on production costs. METHOD: Data of 50 planted Chinese herbal medicines and 50 wild Chinese herbal medicines were summarized and analyzed to see the changes of price of Chinese herbal medicines. RESULT: The derivative problems of limited price were analyzed by crude drug, quality of Chinese medicine and sustainable utilization of resource. CONCLUSION: The price of Chinese medicine shall be adapted to sustainable development of market economy.

Total saponin from root of Actinidia valvata Dunn prevents the metastasis of human hepatocellular carcinoma cells.

OBJECTIVE: To extract the active component from the root of Actinidia valvata Dunn and to investigate the effects on hepatocellular carcinoma (HCC) cells in vitro. METHODS: Total saponin was extracted from the root of A. valvata (TSAVD). HCC cells, such as BEL-7402, HepG2, PLC, SMMC-7721, MHCC-97-H, and MHCC-97-L, were treated with TSAVD in 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide (MTT) assay. BEL-7402 and MHCC-97-H cells were also treated respectively with TSAVD at different concentrations for 24 h in wound healing and adhesion assays, and the effects of TSAVD on BEL-7402 and MHCC-97-H cells mobility and adhesion abilities were observed. Meanwhile, the effects of TSAVD on invasion and migration of BEL-7402 and MHCC-97-H cells were also investigated by transwell chamber in invasion and migration assays. RESULTS: TSAVD at 1.5 mg/mL inhibited BEL-7402 cell proliferation with inhibition ratios (IRs) of 61.08%, 74.12%, 84.55% at 24, 48, and 72 h, respectively. Meanwhile, TSAVD inhibited MHCC-97-H proliferation in a concentration-dependent manner from 1.5 to 0.5 mg/mL, with the IR of 36% at 1.5 mg/mL at 24 h. For SMMC-7721, PLC, and HepG2, the IR was lower than 30% at 1.5 mg/mL at 24 h. In the wound healing assay, mobility abilities of BEL-7402 and MHCC-97-H cells in TSAVD treated groups were significantly weaker than those of the control group. After pretreatment for 24 h with TSAVD, adhesion abilities were reduced in both MHCC-97-H and BEL-7402 cells, with IRs of 48.50%±4.86% and 49.85%±5.25% at 200 µg/mL. The IRs of MHCC-97-H and BEL-7402 cells in the migration assay were 49.13%±2.91% and 79.37%±0.09% at 200 µg/mL. In the invasion assay, IRs were 69.78%±4.88% and 82.48%±0.25% at 200 µg/mL. CONCLUSIONS: Of all HCC cells, the highest inhibition by TSAVD was seen for BEL-7402 proliferation. TSAVD could restrain adhesion, invasion, mobility, and migration abilities of BEL-7402 and MHCC-97-H cells in vitro.

Corosolic acid induces apoptosis through mitochondrial pathway and caspase activation in human cervix adenocarcinoma HeLa cells.

We investigated the response of human cervix adenocarcinoma HeLa cells to Corosolic acid (CRA) treatment. Our results showed that CRA significantly inhibited cell viability in both a dose- and a time-dependent manner. CRA treatment induced S cell-cycle arrest and caused apoptotic death in HeLa cells. We found that CRA increased in Bax/Bcl-2 ratios by up-regulating Bax expression, disrupted mitochondrial membrane potential and triggered the release of cytochrome c from mitochondria into the cytoplasm. Moreover, CRA treatment triggered the activation of caspase-8, -9 and -3 in HeLa cells. All these results indicate that CRA-induced apoptosis is associated with the activation of caspases via a mitochondrial pathway. Taken together, we believe that CRA could have strong potentials for clinical application in treating human cervix adenocarcinoma and improving cancer chemotherapy.