Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology* ; Humans ; Acute Lung Injury/immunology* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.

OBJECTIVE To reveal the pharmacological mechanism of Sofren Injection in the treatment of Qi deficiency and blood stasis syndrome of angina pectoris in coronary heart disease,and to preliminarily verify the reliability of the prediction results by cell experiments.METHODS Firstly,we screened the main chemical components of Sofren injection and their targets from biomedical databases and literature.Then,using the DIAMOnD algorithm,we constructed the angina disease module by screening Qi deficiency and blood stasis syndrome-related genes from the GeneCards and MalaCards databases.Next,we conducted gene functional enrichment analysis of the core targets in the"angina pectoris-Qi deficiency and blood stasis-Sofren Injection"network to identify key pathways.Finally,we performed cell experiments to verify the effect of Sofren Injection on the expression of key pathway proteins in hypoxic H9C2 cardiomyocytes.RESULTS We identified 7 main chemical components of Sofren Injection,targeting a total of 362 genes.We screened 232 known angina pectoris-related genes and added 100 predicted genes by constructing the angina pectoris dis-ease module.A total of 2 960 genes related to Qi deficiency and blood stasis syndrome were obtained.Network topological analysis re-vealed 30 core targets for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syn-drome,including STAT3,EGFR,TNF,and IL-6.Gene functional enrichment analysis identified 82 pathways.Literature analysis combined with the results indicated that STAT3 and the JAK2/STAT3 pathway might be key pathways for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome.Cell experimental results showed significant de-creases in mRNA and protein expression of JAK2 and STAT3 in the SI group and the nicorandil group compared to the model group(P<0.05).CONCLUSION Disease module analysis and cell experiments confirm that STAT3 is a key gene in the pathological mecha-nism of coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome,and the JAK2/STAT3 pathway is a core pathway for Sofren Injection in treating this condition.This study demonstrates the effectiveness and novelty of combining disease mod-ule for mining the treatment of TCM formulas with specific disease and syndrome.

Objective:To evaluate the safety and efficacy of ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique for the treatment of complex encapsulated lesions.Methods:A total of 48 patients(48 lesions) with complex encapsulated lesions who underwent ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique at Xi′an Chest Hospital from January to October 2023 were retrospectively enrolled, including 39 cases of encapsulated abscess, 7 cases of encapsulated effusion, and 2 cases of encapsulated haematoma; the distribution of the bacterial flora of the abscesses were as follows: 24 cases of tuberculous abscess, 14 cases of bacterial abscess, 1 case of bacterial combined bacterial-fungal abscess, and 7 cases of encapsulated effusion were tuberculous pleurisy, and the clinical data were analysed retrospectively. The maximum upper and lower diameters, right and left diameters, and anterior and posterior diameters of the lesions were measured by ultrasound before and after the operation. The patients′ various biochemical indicators (C-reactive protein, white blood cell count, neutrophil count, erythrocyte sedimentation rate) were detected. The intraoperative and postoperative complications, postoperative outcomes, and postoperative clinical symptoms were recorded.Results:Of the 48 patients, 39 were cured and discharged after negative pressure suction and rotatory excision technique, and 9 patients were cured and discharged after surgical incision and drainage of the lesions. The overall effective rate of negative pressure suction and rotatory excision treatment reached 81.25%, and the average number of days of tube placement was (11.81±7.22) days, and the average number of days of follow-up was (35.77±19.39) days. Compared with preoperative values, the upper and lower diameters, the left and right diameters, and the anterior and posterior diameters of the lesions were all reduced after operation [5.80 (4.95, 7.95)cm vs 8.00 (6.00, 11.82)cm, 4.00 (3.25, 5.00)cm vs 5.85 (4.52, 7.65)cm, 1.80 (1.00, 2.90)cm vs 3.40 (2.50, 6.15)cm, all P<0.01]; and postoperative C-reactive protein, white blood cell count and neutrophil count all decreased (all P<0.05). Before operation there were 31 cases of local swelling, 16 cases of pain, 12 cases of activity limitation, 12 cases of fever, 7 cases of chest tightness, and 6 cases of shortness of breath, and during postoperative follow-up, there were 4 cases of local swelling, 5 cases of pain, and 4 cases of activity limitation. The symptoms of fever, chest tightness, and shortness of breath all disappeared, and there was a statistically significant difference between preoperation and postoperation (all P<0.05). There were no adverse events or complications associated with the intraoperative and postoperative follow-up of negative pressure suction and rotatory excision treatment. Conclusions:Ultrasound-guided percutaneous negative pressure suction and invasive rotatory excision technique for the treatment of complex encapsulated lesions can significantly reduce lesion size, reduce inflammatory response and improve patient symptoms, which is a safe, effective and minimally invasive technique.

Respiratory diseases(e.g.,lung inflammation and pulmonary fibrosis)are a serious threat to human health.Mitochondria,organelles unique to eukaryotic cells,not only have important functions in energy production,biosynthesis,and the maintenance of intracellular homeostasis but also act as diverse signaling organelles involved in inflammation,proliferation,differentiation,cell repair,and other processes.The mitochondrial quality control system involves mitochondrial biogenesis,dynamics,and autophagy.Certain pathological mechanisms of respiratory diseases,such as oxidative stress and inflammation,are closely related to the dysregulation of mitochondrial quality control systems.This paper summarizes the progress of research into mitochondrial quality control dysregulation in respiratory diseases(chronic obstructive pulmonary disease,pulmonary fibrosis,acute lung injury,asthma,and bacterial pneumonia)to explore new ideas for the prevention and treatment of respiratory diseases.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.

OBJECTIVE To reveal the pharmacological mechanism of Sofren Injection in the treatment of Qi deficiency and blood stasis syndrome of angina pectoris in coronary heart disease,and to preliminarily verify the reliability of the prediction results by cell experiments.METHODS Firstly,we screened the main chemical components of Sofren injection and their targets from biomedical databases and literature.Then,using the DIAMOnD algorithm,we constructed the angina disease module by screening Qi deficiency and blood stasis syndrome-related genes from the GeneCards and MalaCards databases.Next,we conducted gene functional enrichment analysis of the core targets in the"angina pectoris-Qi deficiency and blood stasis-Sofren Injection"network to identify key pathways.Finally,we performed cell experiments to verify the effect of Sofren Injection on the expression of key pathway proteins in hypoxic H9C2 cardiomyocytes.RESULTS We identified 7 main chemical components of Sofren Injection,targeting a total of 362 genes.We screened 232 known angina pectoris-related genes and added 100 predicted genes by constructing the angina pectoris dis-ease module.A total of 2 960 genes related to Qi deficiency and blood stasis syndrome were obtained.Network topological analysis re-vealed 30 core targets for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syn-drome,including STAT3,EGFR,TNF,and IL-6.Gene functional enrichment analysis identified 82 pathways.Literature analysis combined with the results indicated that STAT3 and the JAK2/STAT3 pathway might be key pathways for Sofren Injection in treating coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome.Cell experimental results showed significant de-creases in mRNA and protein expression of JAK2 and STAT3 in the SI group and the nicorandil group compared to the model group(P<0.05).CONCLUSION Disease module analysis and cell experiments confirm that STAT3 is a key gene in the pathological mecha-nism of coronary heart disease angina pectoris with Qi deficiency and blood stasis syndrome,and the JAK2/STAT3 pathway is a core pathway for Sofren Injection in treating this condition.This study demonstrates the effectiveness and novelty of combining disease mod-ule for mining the treatment of TCM formulas with specific disease and syndrome.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Objective To establish a method based on high performance liquid chromatography for the determination of 3-demethylcolchicine(3 DMC)in rat plasma and to study its pharmacokinetic behavior in rats.Methods The concentration of 3 DMC in rat plasma was determined by high performance liquid chromatography(HPLC).Plasma samples were precipitated by acetonitrile and supernatant was centrifuged for analysis.The determination conditions were as follows:The chromatography was performed on Alphasil VC-C18 column(4.6 mm × 150.0 mm,5.0 μm)with mobile phase consisted of water-acetonitrile-methanol(79∶16∶5),iso-elution at the flow rate of 0.8 mL·min-1.The detection wavelength was set at 240 nm,with polydacryin as the internal standard.The specificity,standard curve and lower limit of quantitation,precision and recovery,matrix effect and stability of the method were investigated.The rats were randomly divided into low,medium and high dose groups(1,2 and 4 mg·kg-1 3DMC were injected into the tail vein,respectively),and blood was collected from orbital venous plexus.The concentration of 3DMC in plasma samples was measured;the pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.0.Results 3DMC has a good linear relationship between 0.39 and 25.00 μg·mL-1,and its standard curve is y=5.96 × 10-2x+7.60 × 10-3(r=0.999 5).The lower limit of quantitation was 0.39 μg·mL-1,the intra-day and inter-day relative standard deviations were-5.08％to 0.75％,the recovery was 93.23％to 108.90％,the matrix effect was 94.88％to 104.00％,and the stability relative standard deviation(RSD)was less than 8.72％.All the results met the requirements.Pharmacokinetic parameters of low,medium and high dose groups:Cmax were(1.66±0.24),(4.36±0.78)and(9.73±1.42)mg·L-1,respectively;t1/2 were(0.31±0.02),(0.32±0.11)and(0.48±0.06)h,respectively;AUC0-t were(0.50±0.09),(1.53±0.16)and(2.67±0.11)mg·L-1·h,respectively.Conclusion The established method for the determination of 3DMC concentration in rat plasma is simple,specific and sensitive,and is suitable for the determination of 3DMC concentration and pharmacokinetic study in rat plasma.