The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type Ⅰ collagen(COL Ⅰ), COL Ⅲ, transforming growth factor-β1(TGF-β1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL Ⅰ, COL Ⅲ, α-SMA, TGF-β1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.
NF-kappa B/metabolism* ; Hepatic Stellate Cells ; Transforming Growth Factor beta1/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; Isodon ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Toll-Like Receptor 4/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Lipopolysaccharides/pharmacology* ; Signal Transduction ; Colchicine/pharmacology* ; Caspases

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Colon cancer-related anemia (CCRA) is mainly caused by systemic inflammation, intestinal bleeding, iron deficiency and chemotherapy-induced myelosuppression in colon cancer. However, the best therapeutic schedule and related mechanism on CCRA were still uncertain. Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction (DBD), Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper. Here, CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p. oxaliplatin, rhEPO + DBD high dosage + Fe (EDF) and rhEPO + DBD high dosage (ED) groups had the best blood enrichment effect. Attractively, EDF group also showed antitumor activity. The sequencing results of gut microbiota showed that compared to P group, the relative abundances of Lachnospiraceae and opportunistic pathogen (Odoribacter) in ED and EDF groups were decreased. Interestingly, EDF also decreased the relative abundances of cancer-related bacteria (Helicobacter, Lactococcus, Alloprevotella) and imbalance-inducing bacteria (Escherichia-Shigella and Parabacteroides) and increased the relative abundances of butyrate-producing bacteria (Ruminococcaceae_UCG-014), however, ED showed the opposite effects to EDF, this might be the reason of the smaller tumor volume in EDF group. Our findings proposed the best treatment combination of DBD, rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.

Objective:To establish the sequence-related amplified polymorphism （SRAP）-polymerase chain reaction （PCR） system for Valeriana officinalis var. latifolia，so as to lay the theoretical and technical foundations for the breeding of V. officinalis var. latifolia. Method:Single factor test was applied to investigate the effects of Taq Mix dose，Mg²⁺ concentration，template DNA concentration，and Taq DNA polymerase content on SRAP-PCR amplification of V. officinalis var. latifolia，based on which the orthogonal experiments were performed to optimize the SRAP-PCR system for V. officinalis var. latifolia. The effective primers that could be used for genetic diversity studies of V. officinalis var. latifolia were selected under the optimal reaction condition. Result:The results of the single factor test showed that Taq Mix dose within the range of 8-11 μL resulted in better amplification. The addition of a low concentration of Mg²⁺，the medium to low concentrations of template DNA，or the low concentration of Taq DNA polymerase enhanced the amplification efficiency or richness. As demonstrated by the orthogonal experiments，the influencing degrees of related factors on SRAP-PCR amplification of V. officinalis var. latifolia were sorted in a descending order as follows： Taq Mix dose>Taq DNA polymerase content>Mg²⁺ concentration>template DNA concentration. The optimal reaction system for V. officinalis var. latifolia was determined to consist of 11 μL of Taq Mix，30 ng of template DNA，0.025 mmol·L^-1 Mg²⁺，1.5 U of Taq DNA polymerase，5 μmol·L^-1 forward primer，and 5 μmol·L^-1 reverse primer，which was supplemented to 20 μL with ddH₂O. The optimal annealing temperature was 36.8 ℃. A total of 17 pairs of effective primers with high band resolution and polymorphism were selected from 88 primer pairs for SRAP-PCR of V. officinalis var. latifolia. Conclusion:The established SRAP-PCR system for V. officinalis var. latifolia is stable， which can be used for genetic diversity studies of V. officinalis var. latifolia.

Background::Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods::In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results::Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy ( P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10 9/L (range 18-219) among patients who received rhTPO and 73 × 10 9/L (range 42-197) among those who received GCSF alone ( P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10 9/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10 9/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups ( P=0.362 and P=0.067, respectively). Conclusions::Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration::This trial has been registered in Clinicaltrials.gov as NCT03014102.

Background::Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods::In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results::Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy ( P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10 9/L (range 18-219) among patients who received rhTPO and 73 × 10 9/L (range 42-197) among those who received GCSF alone ( P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10 9/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10 9/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups ( P=0.362 and P=0.067, respectively). Conclusions::Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration::This trial has been registered in Clinicaltrials.gov as NCT03014102.

Objective:To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups.Results:A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, β 2-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group ( P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years ( P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group ( P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, β 2-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis ( P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma ( P<0.05 for both). Conclusions:The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

Objective:To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups.Results:A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, β 2-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group ( P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years ( P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group ( P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, β 2-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis ( P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma ( P<0.05 for both). Conclusions:The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.