Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Helicobacter pylori(H.pylori)can colonize the gastric mucosa of humans and animals,leading to persistent infection,chronic inflammation,and tissue damage.To understand the preva-lence of H.pylori in dogs,this study designed specific primers targeting a unique region of the H.pylori virulence gene vacA and established a SYBR Green Ⅰ-based real-time PCR(qPCR)method.The specificity,sensitivity,and repeatability of this method were evaluated.Using the es-tablished method,alongside conventional PCR and H.pylori stool antigen(HpSA)detection,we conducted an epidemiological survey of H.pylori infection in pet dogs in urban Hangzhou.The re-sults showed that the standard curve demonstrated a good linear relationship within the concentra-tion range of 3.26×106 to 3.26×101 copies/μL.The method specifically detected H.pylori,with a minimum detection limit of 3.26×101 copies/μL.The intra-and inter-assay coefficients of variation ranged from 0.84％to 1.87％and 0.96％to 1.93％,respectively.Applying this method to canine fe-cal samples collected in Hangzhou from 2023 to 2024 revealed an overall H.pylori positive rate of 25.21％.In comparison,the detection rates by conventional PCR and HpSA were 10.68％and 8.97％,respectively.These results indicate that the established qPCR method is suitable for detec-ting H.pylori infection in dogs,providing a rapid,sensitive,specific,and reproducible quantitative detection method.Additionally,this study confirms the significant prevalence of H.pylori infection in household dogs.Given the widespread dissemination of H.pylori and its potential zoonotic risk,So recommend implementing risk communication and ongoing regional monitoring programs to protect the health of both humans and pets.

Helicobacter pylori(H.pylori)can colonize the gastric mucosa of humans and animals,leading to persistent infection,chronic inflammation,and tissue damage.To understand the preva-lence of H.pylori in dogs,this study designed specific primers targeting a unique region of the H.pylori virulence gene vacA and established a SYBR Green Ⅰ-based real-time PCR(qPCR)method.The specificity,sensitivity,and repeatability of this method were evaluated.Using the es-tablished method,alongside conventional PCR and H.pylori stool antigen(HpSA)detection,we conducted an epidemiological survey of H.pylori infection in pet dogs in urban Hangzhou.The re-sults showed that the standard curve demonstrated a good linear relationship within the concentra-tion range of 3.26×106 to 3.26×101 copies/μL.The method specifically detected H.pylori,with a minimum detection limit of 3.26×101 copies/μL.The intra-and inter-assay coefficients of variation ranged from 0.84％to 1.87％and 0.96％to 1.93％,respectively.Applying this method to canine fe-cal samples collected in Hangzhou from 2023 to 2024 revealed an overall H.pylori positive rate of 25.21％.In comparison,the detection rates by conventional PCR and HpSA were 10.68％and 8.97％,respectively.These results indicate that the established qPCR method is suitable for detec-ting H.pylori infection in dogs,providing a rapid,sensitive,specific,and reproducible quantitative detection method.Additionally,this study confirms the significant prevalence of H.pylori infection in household dogs.Given the widespread dissemination of H.pylori and its potential zoonotic risk,So recommend implementing risk communication and ongoing regional monitoring programs to protect the health of both humans and pets.

Objective:Exploring the efficacy and safety of the combination of programmed cell death protein 1 (PD-1) inhibitors with chemotherapy for the treatment of local recurrence at the primary tumor site of esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy.Methods:Seventy-six patients with local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy, who were treated at the Cancer Hospital Affiliated with Nanjing Medical University from January 2019 to January 2024. All patients received treatment with a PD-1 inhibitor combined with chemotherapy, and the short-term efficacy, long-term efficacy, and adverse reactions were observed. Univariate and multivariate Cox regression models were employed to identify the factors influencing overall survival (OS) and after-recurrence survival (ARS).Results:Among the 76 patients, 7 achieved partial response, 35 had stable disease, and 34 experienced progressive disease. The objective response rate was 9.2% (7/76), and the disease control rate was 55.3% (42/76). With a median follow-up time of 23.1 months, 33 out of 76 patients died. The median survival time was 38.5 months (95% CI: 29.6-47.3 months); the 1-year, 2-year, and 3-year OS were 94.5%, 66.6%, and 51.7%, respectively. The median ARS was 14.7 months (95% CI: 10.4-19.1 months); the 6-month, 12-month, and 24-month ARS were 85.8%, 59.6%, and 25.7%, respectively. Univariate analysis showed that the initial radiation dose, the Eastern Cooperative Oncology Group (ECOG) performance status of patients after recurrence, the recurrence-free interval (RFI), and the approach to chemotherapy treatment following local esophageal recurrence were factors affecting OS and ARS ( P＜0.05). Multivariate analysis showed that initial radiotherapy dose ( HR=0.268, 95% CI: 0.100-0.720), the ECOG performance status after recurrence ( HR=4.106, 95% CI: 1.228-13.728), and RFI ( HR=0.248, 95% CI: 0.106-0.582) were independent prognostic factors for OS. Additionally, the initial radiation dose ( HR=0.289, 95% CI: 0.098-0.853) and the ECOG performance status after recurrence ( HR=5.143,95% CI:1.404-18.838) were independent prognostic factors for ARS. The incidence of treatment-related adverse-reactions was 85.5% (65/76). Grade 3 or higher treatment-related adverse reactions primarily included anemia in 4 cases, leukopenia in 8 cases, neutropenia in 9 cases, thrombocytopenia in 2 cases, liver function abnormalities in 4 cases, and elevated troponin T in 2 cases. There were no cases of treatment-related mortality. Conclusions:The combination of PD-1 inhibitors with chemotherapy is safe and effective for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy and can provide survival benefits for patients. This approach can be considered as a therapeutic option for local recurrence at the primary tumor site of ESCC following definitive chemoradiotherapy.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear. Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored. Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. Conclusions Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR₁, Rg₁, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Ginsenosides ; Saponins ; Chemometrics ; Panax notoginseng ; Cardiovascular Diseases ; Chromatography, Liquid ; Tandem Mass Spectrometry

Objective:To investigate the effect of pelvic floor muscle exercise (PFMT) combined with transcutaneous electrical nerve stimulation (TENS) on urinary incontinence after radical prostatectomy.Methods:A total of 120 patients with urinary incontinence after radical prostatectomy in Shuguang Hospital, Shanghai University of Traditional Chinese Medicine from July 2020 to June 2021 were retrospective selected and divided into control group and observation groupthe according to different treatment method, 60 cases in each group. The control group was treated with PFMT, and the observation group was treated with PFMT combined with TENS. Urodynamic indexes of 72 h urine pad usage, maximum urine flow rate, maximum cystometric capacity, maximum urethral closure pressure, abdominal leakage point pressure, ICI-Q-SF score and the clinical efficacy were compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:After treatment, the 72 h urine urine pad usage in the observation group [(1.95±1.13) pieces] was lower than that in the control group [(6.28±2.47) pieces], and the difference was statistically significant ( P<0.05). After treatment, the maximum flow rate [(13.92±2.53) mL/s], maximum cystometric capacity [(338.72±19.22) mL], maximum urethral closure pressure [(69.75±5.04) cmH 2O], abdominal leakage point pressure [(90.56±5.26) cmH 2O] in observation group after treatment were better than those in control group [(11.48±2.18) mL/s, (325.81±18.63) mL, (65.29±4.78) cmH 2O, (83.58±5.29) cmH 2O], the difference were statistically significant ( P<0.05). After treatment, the ICI-Q-SF score of the observation group [(5.97±1.82) points] was lower than that of the control group [(10.95±2.64) points], and the difference was statistically significant ( P<0.05); the clinical effective rate of observation group (93.33%) was higher than that of control group (78.33%), and the difference was statistically significant ( P<0.05). Conclusion:PFMT combined with TENS is better than PFMT alone in the treatment of postoperative urinary incontinence after radical prostatectomy.