Objective: To verify the inhibitory effect of a carbon monoxide hemoglobin-based oxygen carrier (CO-HBOC) on the fibrotic process in mice with idiopathic pulmonary fibrosis (IPF), clarify its efficacy difference compared with hemoglobin-based oxygen carriers (HBOCs), and elucidate its mechanism of action via proteomic analysis. Methods: CO-HBOC was prepared using gas loading technology. An IPF mouse model was established and the mice were randomly divided into a normal saline control group, an HBOC treatment group, and a CO-HBOC treatment group. The fibrotic area percentage was analyzed using Micro-CT; the degree of inflammatory infiltration and fibrosis in lung tissue was assessed by pathological section staining (e.g., HE and Masson staining); and differentially expressed proteins in lung tissue of IPF mice after CO-HBOC treatment were screened using proteomic technology. Results: Micro-CT results showed that the mean fibrotic area percentage in the CO-HBOC treatment group on day 21 was (8.89±0.98)%, which was better than that of the HBOC group (16.5±1.732)% and the normal saline group (30.75±6.45)% (P<0.05). HE and Masson staining results showed that the CO-HBOC group had reduced inflammatory cell infiltration and significantly decreased collagen fiber deposition in lung tissue, with a mean pathological score of 3.33±0.58, which was lower than that of the normal saline control group (8.33±1.53)(P<0.05); the mean collagen-positive area percentage was (3.33±1.53)%, significantly lower than that of the normal saline control group (14.00±3.61)% (P<0.05). Proteomic analysis identified 330 differentially expressed proteins, which were mainly enriched in inflammatory response regulatory pathways (such as the complement and coagulation cascades), and the expression changes of complement proteins may be the core target of CO-HBOC's anti-fibrotic effects. Conclusion: CO-HBOC can inhibit inflammatory responses and regulate fibrosis-related signaling pathways, there-by effectively inhibiting the fibrotic process in IPF mice, with superior efficacy to HBOC. Its mechanism of action involves the regulation of complement cascade-related signaling pathways and complement protein expression, providing an experimental and theoretical basis for targeted therapy of IPF.

Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.

Objective To quantify the intraretinal fluid(IRF)volume in patients with diabetic macular edema(DME)using a deep learning-based three-dimensional segmentation model and to investigate the relationship of IRF volume with visual function and retinal biomarkers based on optical coherence tomography(OCT).Methods A total of 37 pa-tients(42 eyes)with DME who received treatment in the Ophthalmology Department of Sichuan Provincial People's Hospi-tal from July 2022 to September 2024 were prospectively included in this study.A three-dimensional segmentation model was used to automatically quantify the IRF volume within a 6 mm × 6 mm OCT scan at baseline and at the last follow-up.The correlation of visual acuity with IRF volume,central subfield thickness(CST),disorganization of the retinal inner lay-ers(DRIL),hyperreflective foci(HRF),external limiting membrane(ELM),ellipsoid zone(EZ),and vitreomacular in-terface abnormality(VMIA)was analyzed at baseline and the last follow-up.Additionally,the correlation of IRF volume with CST,DRIL,HRF,ELM,EZ,and VMIA was analyzed at both time points.Furthermore,the correlation of the visual acuity at the last follow-up with the IRF volume,CST,DRIL,HRF,ELM,EZ,and VMIA at baseline was analyzed.Results Compared with the baseline value,patients exhibited a significant increase in the best corrected visual acuity(BCVA)(logMAR),a significant decrease in the IRF volume and CST,a significant reduction in the HRF,a significant re-covery in the DRIL,ELM,and EZ(all P＜0.05),and no significant changes in the VMIA(P=1.000)at the last follow-up.At baseline,the BCVA was negatively correlated with the IRF volume,CST,DRIL,and HRF,but positively correlated with the ELM and EZ(all P＜0.05);there was no correlation between the BCVA and VMIA(P=0.069).At the last follow-up,the BCVA was negatively correlated with the DRIL,HRF,and VMIA,but positively correlated with the ELM and EZ(all P＜0.01);the BCVA did not correlate with the IRF volume and CST(P=0.419 and 0.994).At baseline,the IRF volume was positively correlated with the CST(P＜0.001)but negatively correlated with the ELM and EZ(P＜0.01);the IRF vol-ume did not correlate with the DRIL,HRF,and VMIA(all P＞0.05).At the last follow-up,the IRF volume was positively correlated with the CST and HRF(all P＜0.01);however,it was not correlated with the DRIL,ELM,EZ,and VMIA(all P＞0.05).The BCVA at the last follow-up was positively correlated with the BCVA,ELM,and EZ at baseline,but negative-ly correlated with the IRF volume,CST,DRIL,HRF,and VMIA at baseline(all P＜0.05).Conclusion The baseline IRF volume in DME patients is an important influencing factor of visual acuity at baseline and the last follow-up.Hence,the IRF volume may serve as a potential biomarker in the management of DME.

Objective To investigate the potential mechanism of action of polygonatum odoratum in treating Alzheimer's disease through the utilization of network pharmacology and molecular docking techniques.Methods The methods employed include target screening,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and molecular docking simulations to assess the binding interactions between the active compounds in polygonatum odoratum(POD)and the key target proteins associated with Alzheimer's disease.Subsequently,lipopolysaccharide(LPS)was used to induce an inflammatory cell model in BV2 microglial cells.After treating the cell model with POD extract for 24 hours,the cells were collected,and the expression of the target genes were detected by Real-time PCR.Results Eight active ingredients and 172 targets of POD were screened.The biological processes such as protein phosphorylation and signal transduction,protein binding and ATP binding were obtained by GO functional analysis.KEGG enrichment yielded PI3K/Akt,cAMP and other signaling pathways.The molecular docking result showed that the active ingredient of POD had well binding activity with epidermal growth factor receptor(EGFR),proto-oncogene tyrosine-protein kinase Src(SRC),tumor necrosis factor(TNF),STAT3.Through Real-time PCR experiments,the gene expressions of inducible nitric oxide synthase(iNOS),prostaglandin G/H synthase 2(PTGS2),interleukin(IL)-6,and IL-1β in the LPS-induced inflammatory cell model were significantly upregulated.After treating the inflammatory model with POD extract for 24 hours,the expression of TNF-α was significantly reduced,the expression of STAT3 was upregulated,there were no significant changes in the expressions of SRC and EGFR.Conclusion Network pharmacology suggests polygonatum odoratum's potential anti-Alzheimer's effects may be mediated through its interaction with targets such as EGFR,TNF,SRC,and STAT3.The experimental results suggest that polygonatum odoratum exerts an anti-inflammatory effect by acting on TNF-α,which may further alleviate the symptoms of Alzheimer's disease.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.