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.

Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

Objective:To investigate the influences of long non-coding RNA metastasis-associated lung adenocarcinoma tran-script 1(lncRNA MALAT1)/miR-876-5p/forkhead box protein M1(FOXM1)axis on TNF-α-induced proliferation,apoptosis and in-flammatory response of HaCaT cells.Methods:HaCaT cells were grouped into Ct group,Model group,si-NC group,si-MALAT1 group,mimic NC group,miR-876-5p mimic group,si-MALAT1+inhibitor NC group,and si-MALAT1+miR-876-5p inhibitor group.Except for the Ct group,cells in other groups were treated with 25 μg/L TNF-α to induce the in vitro cell model of psoriasis,and after 24 hours of TNF-α induction,the corresponding transfectants were transfected for 48 hours for subsequent experiments.qRT-PCR was applied to detect the expression of MALAT1 and miR-876-5p in cells;CCK-8 method and EdU staining were applied to detect cell pro-liferation;flow cytometry was applied to detect apoptosis;ELISA method was applied to detect the levels of IL-6,TNF-α,and IL-1β in cell supernatant;Western blot was applied to detect the protein expressions of FOXM1,proliferating cell nuclear antigen(PCNA),Bcl-2-associated X protein(Bax)and B-lymphocytoma-2(Bcl-2);dual-luciferase reporter gene assay was applied to verify the rela-tionship between MALAT1 and miR-876-5p,miR-876-5p and FOXM1;and RNA pull down experiments were applied to verify the re-lationship between MALAT1 and miR-876-5p.Results:Compared with the control group,the expressions of MALAT1 and FOXM1 protein expression in the experimental group were increased,and the expression of miR-876-5p was decreased(P<0.05);compared with Ct group,the expressions of MALAT1 and FOXM1 protein expression in HaCaT cells,A450 value,EdU positive rate,the levels of IL-6,TNF-α,IL-1β,and the protein expressions of PCNA and Bcl-2 in cell supernatant in Model group increased,the expression of miR-876-5p,apoptosis rate and the protein expression of Bax were decreased(P<0.05);silencing MALAT1 or overexpressing miR-876-5p could inhibit the proliferation and inflammatory response of HaCaT cells induced by TNF-α,and promote cell apoptosis;miR-876-5p inhibitor attenuated the inhibitory effects of silencing MALAT1 on TNF-α-induced HaCaT cell proliferation and inflammatory response,and the promotion on cell apoptosis;MALAT1 targeted and regulated the miR-876-5p/FOXM1 axis.Conclusion:Silencing MALAT1 may inhibit the expression of FOXM1 by up-regulating miR-876-5p,thereby inhibiting the proliferation and inflammatory re-sponse of HaCaT cells induced by TNF-α,and promoting cell apoptosis.

Objective To investigating the usage and changing trend of new anti-tumor drugs for respiratory system of 121 hospitals after the implementation of relevant policies insurance negotiation in China from 2019 to 2022,explore the development tendency of new anti-tumor drugs in hospitals under the medical reform policy and provide references for the rational use and standardized management of new anti-tumor drugs.Methods Based on the anti-tumour drug for respiratory system varieties in the Guidelines for the Clinical Application of Novel Anti-tumour Drugs Version 2022,descriptive statistical analysis was applied to retrieve data on the use of new anti-tumour drugs for respiratory system in 121 hospitals from 2019 to 2022,and drug dosage form,amount,drug frequency(DDDs),average daily cost(DDC)and drug ranking ratio(B/A)were statistically analyzed.Results The number of users and the proportion of new anti-tumour drugs for respiratory system used in 121 hospitals in China showed a year-on-year increasing trend from 2019 to 2022.In different cities of China,the drug use amount of Guangzhou,Beijing,Hangzhou and Zhengzhou was relatively large.In terms of drug use,small-molecule targeted drugs were still the main new anti-tumor drugs,while macromolecule targeted drugs showed a downward trend,and immunotherapy drugs showed a gradual upward trend.In terms of the amount of use,the top drugs in the four years were ecitinib,aletinib,gefitinib and oxitinib.The small molecule targeted drugs included in the national insurance negotiations showed increasing use and a decreasing amount of money spent.The ranking of DDDs was basically stable,with fluctuations in individual varieties.The DDC values of small molecule targeted drugs had significantly decreased,while the DDC values of immunotherapy drugs were relatively high.From 2021 to 2022,the B/A value of the novel anti-tumor drugs was most respiratory tumors was close to 1,and the varieties located at 0.8 to 1.2 accounted for 61.5％of the total drugs.Conclusion At present,the selection of new anti-tumor drugs for respiratory system is still dominated by small molecule targeted drugs and the use of immunotherapy drugs is increasing.The synchronization of the amount and frequency of most drugs has increased.The adjustment of the medical insurance catalog and the implementation of policies such as national negotiation effectively promote the decrease of the amount of drug use and the improvement of drug trend.

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.

Aim To explore the roles and mechanisms of long non-coding RNA(lncRNA)AC087388.1 and poly(A)binding protein cytoplasmic 1(PABPC1)in esophageal squamous cell carcinoma(ESCC).Meth-ods The expression level of AC087388.1 in ESCC tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and fluorescence in situ hybridization experiments and its clinical relevance was analyzed.Cell counting kit-8(CCK-8),clone formation,scratch and Transwell inva-sion assays were used to detect the effects of knock-down of AC087388.1 on the cell viability,prolifera-tion,migratory,and invasion of ESCC cells respectively ability,and sub-localization in cells.RNA pull down and Western blot experiments were employed to verify the interaction between AC087388.1 and PABPC1 in ESCC cells.Salvage experiments were performed to detect the effect of AC087388.1 targeting PABPC1 on ESCC cells.Results AC087388.1 was highly ex-pressed in ESCC tissues and cells and positively corre-lated with clinical stage of ESCC patients,mainly local-ized in cytoplasm.Knockdown AC087388.1 inhibited ESCC cell viability,proliferation,migration and inva-sionability.PABPC1 was selected from the results of RNA Pull Down-MS experiments for subsequent experi-ments,and AC087388.1 was verified to bind to PAB-PC1 by RNA Pull Down and Western blot experiments.Overexpression of AC087388.1 was verified by rescue experiment to reverse the effects of knockdown of PAB-PC1 on ESCC cell viability,proliferation,migration and invasion.Conclusions High expression of AC087388.1 correlates with clinical stage and may be a risk factor for ESCC progression.AC087388.1 pro-motes the cell viability,proliferation,migration and in-vasive ability of ESCC cells by targeting PABPC1,which may be a novel biomarker for the diagnosis and treatment of ESCC.

OBJECTIVE:To systematically evaluate the correlation between phase angle and sarcopenia and its diagnostic indexes.METHODS:The PubMed,EMbase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect studies on the correlation between phase angle and sarcopenia and its diagnostic indexes from database inception to May 8,2024. Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 and Stata 14.0 software. RESULTS:A total of 50 eligible articles were included. Meta-analysis results showed that compared with the non-sarcopenic population,the phase angle was significantly reduced in sarcopenic patients[standardized mean difference (SMD)=-0.99,95％ confidence interval (CI) (-1.09,-0.90),P<0.00001]. The results of subgroup analysis indicated that the difference of phase angle was more significant in patients with severe sarcopenia and Asian sarcopenia. Moreover,reduction in the phase angle was more obvious in patients with malignant tumors and respiratory diseases with sarcopenia. And skeletal muscle mass index (Pearson's r=0.565,P<0.00001),grip strength (Pearson's r=0.446,P<0.00001),and gait speed (Pearson's r=0.405,P<0.00001) all showed a moderate positive correlation with phase angle. However,appendicular skeletal muscle mass index showed a very weak positive correlation with phase angle (Pearson's r=0.139,P=0.02). CONCLUSION:Phase angle has a significant difference between sarcopenia and non-sarcopenia population,and it is correlated with the diagnostic indexes of sarcopenia to different extents. It suggests that phase angle has some clinical values in the objective diagnosis of sarcopenia. However,the results may be influenced by some factors such as sarcopenia severity and detection instruments of phase angle. Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

Objective:To analyze the therapeutic effect of a virtual reality (VR)-based accommodation training device on accommodative excess visual fatigue.Methods:A case-control study was conducted.A total of 20 normal subjects (20 eyes) and 20 patients with accommodative excess visual fatigue (20 eyes) were recruited at Zhongshan Ophthalmic Center, Sun Yat-sen University between January and December 2022.The study consisted of two phases.In the first phase, the effect of watching videos with VR glass on the subjects' subjective and objective visual function was evaluated.Normal subjects wore VR device to watch a 2D video for 30 minutes, and assessments were performed before and after viewing.These assessments included binocular accommodation/convergence function (accommodation response, accommodative convergence to accommodation ratio [AC/A]), tear film function (first tear film break-up time), subjective symptoms (visual fatigue score), and basic visual health parameters including best corrected visual acuity (BCVA) and intraocular pressure (IOP).In the second phase, the improvement in subjective and objective visual fatigue metrics with the VR-based accommodation training device was investigated.Patients with visual fatigue were divided into a traditional training group using traditional flipper lenses and a VR training group using the VR accommodation training device, with 10 eyes in each group.The effects of the VR accommodation training device on indicators such as accommodative sensitivity, accommodation response, convergence function, visual fatigue score, acceptability score, system usability score, BCVA, and IOP were evaluated and compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.IIT2021007).Written informed consent was obtained from each subject.Results:In normal subjects, there was no statistically significant difference in first tear film break-up time, distance phoria, near phoria, AC/A, accommodative response, BCVA, or IOP before and after 30 minutes of continuous viewing of 2D video using VR glass ( t=1.155, 1.360, 4.479, 1.979, -1.249, -3.017, 2.211; all P>0.05).The visual fatigue score remained unchanged at (1.00±0.00) points before and after viewing.Among the subjects with visual fatigue, there were statistically significant differences in binocular accommodative sensitivity, dominant eye accommodative sensitivity, and BCVA before and after using the VR accommodation training device ( F=8.693, 4.078, 4.942; all P<0.05).Ocular accommodation sensitivity at 8 weeks after training was improved compared with 1 week after training, and BCVA at 4 weeks after training was improved compared with before training, and the differences were statistically significant (both P<0.05).In the VR training group, the average tear film break-up time, first tear film break-up time, and BCVA increased and the visual fatigue score decreased compared with before training, the differences were statistically significant (all P<0.05).In the traditional training group, the accommodation sensitivity of the dominant eye increased after training compared with before training, with a statistically significant difference ( P<0.05). Conclusions:Watching 2D videos with VR glass for 30 minutes does not induce subjective or objective symptoms of visual fatigue.The VR-based accommodation training paradigm effectively improves accommodative sensitivity and alleviates subjective symptoms of visual fatigue in individuals with accommodative excess visual fatigue.