ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Aromatic immunity in traditional Chinese medicine(TCM) is the medical knowledge accumulated in the process of people's struggling with diseases. It plays an important role in plague prevention, disease treatment, health preservation, and rehabilitation, and has profound TCM basic theoretical support and abundant modern scientific evidence. With the in-depth promotion of the Healthy China initiative and the succession of health needs in the post-COVID-19 era, how to practice the health concept of aromatic immunity in TCM and develop its health service resources with high quality has become an important proposition to be discussed urgently. This paper summarizes the cognitive process, puts forward the basic concept, discusses the scientific connotation and clinical application value, and looks forward to the future development trend of aromatic immunity in TCM, aiming to provide guidance for the development of great health products and promote the application of aromatic immunity in TCM in serving people's health.
Medicine, Chinese Traditional/methods* ; Humans ; COVID-19/immunology* ; China ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2

Objective:To explore the effect of preoperative visits based on lean management theory in the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery.Methods:According to the coin toss method,72 patients undergoing cardiopulmonary bypass surgery admitted to the Cardiothoracic Surgery Department of Chenzhou First People's Hospital from May 2024 to August 2024 were randomly divided into control group and observation group,with 36 cases in each group.The control group was given routine preoperative visits,and the observation group was given preoperative visits based on lean management theory on the basis of the control group.The psychological state,information demand level,vital signs and satisfaction of the patients were compared between the two groups 1 day before operation and when entering the room.Results:After intervention,the scores of State Anxiety Scale(S-AI)and Amsterdam Preoperative Anxiety and Information Scale(APAIS)were decreased in both groups,and the observation group were significantly lower than control group(P＜0.05).The vital signs(heart rate,systolic blood pressure and diastolic blood pressure)in observation group were lower than control group(P＜0.05).After intervention,the satisfaction of patients in observation group was significantly increased(P＜0.05).Conclusion:The implementation of preoperative visit based on lean management theory can help improve the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery,eliminate anxiety,provide patients with more targeted surgical information support for patients,stabilize patients 'vital signs,and improve patients' satisfaction.

Objective To investigate the role of peptidyl prolyl cis-trans isomerase 1(Pin1)in mediating stemness of tumor cells and the molecular mechanism of inducing epithelial-mesenchymal transition(EMT)in cervical cancer cells.Methods The Siha and Hele cells of Pin1 low-expression stable transfection uterine cervical neoplasm cell lines were constructed using lentivirus transfection technology and were divided into control group(shPin1-NON),knockdown group 1(shPin1-1)and knockdown group 2(shPin1-2).Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the expressions of Sex-determining region Y transcription factor 2(SOX2),Aldehyde dehydrogenase 1A1(ALDH1A1),and Cell adhesion molecule 44(CD44).The serum-free spheroidization method was used to induce cervical cancer spheroids,with the adherent culture of cervical cancer cells as a control.Subsequently,Western blotting and qRT-PCR were employed to detect the expression of SOX2,ALDH1A1 and CD44 in both spheroid cells and adherent cells.Spheroid formation assay was used to detect the spheroid formation of cervical cancer cells after Pin1 knockdown.Transwell assay was used to detect the migration and invasion abilities of cervical cancer cells following down-regulation of Pin1.Western blotting and qRT-PCR were used to detect the expression of E-cadherin and N-cadherin attribute proteins in cervical cancer cells after transfection with pin1 low expression lentivirus.Western blotting and qRT-PCR were also used to assess the effects of Pin1 low expression on the expression levels of key proteins(c-Jun and c-Fos)of the transcriptional complex of Activator protein 1(AP-1).Immunofluorescence combined with co-immunoprecipitation assays were conducted to detect the interaction and colocalization of Pin1 with c-Jun.Results In Siha and Hele cells,the mRNA and protein expression levels of Pin1,SOX2,ALDH1A1 and CD44 in shPin1-NON group were significantly higher than those in shPin1-1 group and shPin1-2 group(P<0.05).The expression levels of SOX2,ALDH1A1 and CD44 mRNA and protein in cervical cancer spheroid group were significantly higher than those in adherent cervical cancer cells(P<0.05).Compared with shPin1-NON group,the spheroidism and migration invasion abilities of shPin1-1 group and shPin1-2 group were significantly reduced(P<0.05).Compared with shPin1-NON group,the mRNA and protein expressions of E-cadherin in shPin1-1 and shPin1-2 groups were significantly increased(P<0.05),while the mRNA and protein expression levels of N-cadherin were significantly decreased(P<0.05).The mRNA and protein expression levels of c-Jun and c-Fos in shPin1-NON group were significantly higher than those in shPin1-1 group and shPin1-2 group(P<0.05).Conclusions Down-regulation of Pin1 can inhibit the stemness and migration invasion of cervical cancer cells,and Pin1 may mediate AP-1 to regulate the occurrence of stemness-induced epithelial-mesenchymal transition in cervical cancer cells.

Objective:To explore the effect of preoperative visits based on lean management theory in the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery.Methods:According to the coin toss method,72 patients undergoing cardiopulmonary bypass surgery admitted to the Cardiothoracic Surgery Department of Chenzhou First People's Hospital from May 2024 to August 2024 were randomly divided into control group and observation group,with 36 cases in each group.The control group was given routine preoperative visits,and the observation group was given preoperative visits based on lean management theory on the basis of the control group.The psychological state,information demand level,vital signs and satisfaction of the patients were compared between the two groups 1 day before operation and when entering the room.Results:After intervention,the scores of State Anxiety Scale(S-AI)and Amsterdam Preoperative Anxiety and Information Scale(APAIS)were decreased in both groups,and the observation group were significantly lower than control group(P＜0.05).The vital signs(heart rate,systolic blood pressure and diastolic blood pressure)in observation group were lower than control group(P＜0.05).After intervention,the satisfaction of patients in observation group was significantly increased(P＜0.05).Conclusion:The implementation of preoperative visit based on lean management theory can help improve the preoperative psychological state of patients undergoing cardiopulmonary bypass surgery,eliminate anxiety,provide patients with more targeted surgical information support for patients,stabilize patients 'vital signs,and improve patients' satisfaction.

AIM To investigate the protective effects of Didang Decoction-containing serum on rat glomerular endothelial cells(RGECs)following high glucose injury.METHODS Rats were given distilled water or Didang Decoction by gavage to prepare the blank serum or Didang Decoction-containing serum.CCK8 method was used to screen the glucose concentration for the modeling and serum concentration of the drug.The RGECs were divided into the blank group,the model group,Didang Decoction group(10%Didang Decoction medicated serum),Dapagliflozin group(normal serum+2 μmol/L Dapagliflozin)and Didang Decoction+Dapagliflozin group(10%Didang Decoction medicated serum+2 μmol/L Dapagliflozin).24 hrs after the drug treatment,the RGECs had their mRNA and protein expressions of Nrf2,HO-1 and NQO-1 detected by RT-qPCR method and Western blot method;their Nrf2 fluorescence expression detected by immunofluorescence method;and their SOD activity and MDA level detected by colorimetric method.RESULTS Compared with the blank group,the model group displayed decreased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.01),and increased MDA level(P＜0.01).Compared with the model group,the groups intervened with the drugs showed increased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.05,P＜0.01),and decreased MDA level(P＜0.01).CONCLUSION Didang Decoction-containing serum can protect RGECs from high glucose injury through activating the Nrf2 signaling pathway.