This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics* ; Animals ; Tandem Mass Spectrometry ; Network Pharmacology ; Rats ; Chromatography, High Pressure Liquid ; Rats, Sprague-Dawley ; Male ; Idiopathic Pulmonary Fibrosis/metabolism* ; Humans ; Administration, Oral ; Protein Interaction Maps/drug effects* ; Signal Transduction/drug effects*

The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production. On the one hand, Rubicon, as a component of the phosphoinositide 3-kinase (PI3K) complex, interacts with different domains of vacuolar protein sorting 34 (Vps34), ultraviolet radiation resistance associated gene (UVRAG), guanosine triphosphate (GTP) kinase, and RAS oncogene family member 7 (Rab7) to mediate the inhibition of autophagy maturation; on the other hand, Rubicon inhibits the ubiquitination of nuclear factor κB essential modulator (NEMO) and the dimerization of interferon regulatory factor 3 (IRF3), thereby blocking the signal transduction related to IFN production. Research has revealed that various viruses, such as Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), Sendai virus (SeV), and hepatitis C virus (HCV), achieve innate immune evasion by regulating the expression or function of Rubicon. Rubicon is expected to be a new target for antiviral therapy.
Humans ; Autophagy/immunology* ; Immunity, Innate ; Interferons/immunology* ; Immune Evasion ; Animals ; Virus Diseases/virology* ; Signal Transduction ; Viruses/immunology* ; Intracellular Signaling Peptides and Proteins/immunology* ; Autophagy-Related Proteins

OBJECTIVE: To analyze the clinical features and laboratory characteristics of patients with cold agglutinin disease (CAD)/cold agglutinin syndrome (CAS) who were positive for acidified-serum lysis test (Ham test), and to compare them with Ham test negative CAD/CAS patients and paroxysmal nocturnal hemoglobinuria (PNH) patients, in order to provide references for the differential diagnosis of these diseases. METHODS: 53 patients diagnosed with CAD/CAS and 67 patients diagnosed with classic PNH in our hospital from January 2015 to December 2020 were retrospectively analyzed. The patients were grouped according to clinical diagnosis and results of cold agglutinin test (CAT), direct antiglobulin test (DAT), Ham test and PNH clone detection. The clinical and laboratory characteristics of each group were compared. RESULTS: The patients were grouped as follows: Ham^- CAD/CAS group, CAD/CAS patients negative for Ham test (n=36); Ham⁺ CAD/CAS group, CAD/CAS patients positive for Ham test (n=17); classic PNH group (n=67). Compared with the classic PNH group, the Ham⁺ CAD/CAS group had a higher median age (P =0.024), weaker positivity of Ham test, higher positive rates of CAT and DAT, and lower positive rate of PNH clone detection (all P <0.001). The proportions of patients with splenomegaly and cyanosis in Ham⁺ CAD/CAS group were significantly higher than those in classic PNH group (P =0.002 and P <0.001). Ham⁺ CAD/CAS group displayed lower red blood cell count (RBC) and lactate dehydrogenase (LDH) level (P =0.007 and P <0.001), and higher mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and indirect bilirubin (IBIL) level (P =0.003, P =0.004 and P =0.006) than those in classic PNH group. The levels of serum complement C3 and C4 in Ham⁺ CAD/CAS group were lower than those in classic PNH group (P =0.001 and P <0.001). The positive rate of urinary occult blood in Ham⁺ CAD/CAS group was lower than that in classic PNH group (P =0.010). The clinical and laboratory characteristics of Ham⁺ CAD/CAS group were similar to those of Ham^- CAD/CAS group, except for median age, hemoglobin (Hb), MCHC, mean corpuscular volume (MCV), reticulocyte ratio (Ret), Ham test results, DAT positive types, and proportion of splenomegaly. CONCLUSION Some clinical features and laboratory indicators of CAD/CAS patients with positive results of Ham test are different from those of classic PNH patients, but relatively similar to those of CAD/CAS patients with negative results of Ham test. These results may provide a reference for differential diagnosis of related diseases.
Humans ; Anemia, Hemolytic, Autoimmune/blood* ; Retrospective Studies ; Hemoglobinuria, Paroxysmal/diagnosis* ; Female ; Male ; Coombs Test ; Diagnosis, Differential ; Middle Aged ; Adult

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

POEMS syndrome is a rare plasma cell dysplasia. Its clinical manifestations include polyneuropathy, monoclonal protein, increased extravascular volume load, endocrinopathy, organomegaly and skin changes. The complex and atypical symptoms at presentation make early diagnosis challenging due to multiple system involvement. Peripheral neuropathy, limb numbness, is the most common initial symptom of this disease. However, case reports of increased extravascular volume load are rare. This article collected and analyzed the clinical data of two groups of patients with different initial symptoms (increased extravascular volume load and limb numbness). The clinical characteristics and treatment responses were summarized.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.