Objective To observe the protective effects of Yiqi Jiedu Decoction on ionizing radiation-induced small intestinal functional injury in mice,and explore whether it alleviates such injury by inhibiting small intestinal ferroptosis,thereby providing scientific support for the discovery and development of intestinal radiation protection drugs in aerospace medicine.Methods A total of 378 male Balb/c mice were randomly divided into 7 groups:blank control group,model group,positive drug group,high-dose Yiqi Jiedu Decoction group,low-dose Yiqi Jiedu Decoction group,Liproxstatin-1 pre-irradiation administration group,and Liproxstatin-1 post-irradiation administration group,with 54 mice in each group.Each group was further divided into 3 batches,with 18 mice per batch.Seven days after preventive administration,all groups except the blank control group were subjected to a single whole-body irradiation with 2.0 Gy 60Co γ-rays.The general condition and morphological structure of the small intestine were observed at 1,3,and 7 days post-irradiation.The small intestinal charcoal propulsion rate,serum D-xylose content,and lactic acid content were measured,along with the levels of Fe,LPO,MDA,GSH,and SOD activity in the small intestine.Results Yiqi Jiedu Decoction could mitigate the decrease in body weight of mice after 2.0 Gy 60Co γ-ray irradiation,improve the morphological structure of the small intestine,reduce the small intestine charcoal propulsion rate,increase serum D-xylose levels,and decrease total serum lactate levels.It also alleviated mitochondrial shrinkage in the small intestine and reduced the contents of Fe and MDA in small intestine tissues.Conclusion Yiqi Jiedu Decoction may alleviate ionizing radiation-induced small intestinal functional injury by inhibiting ferroptosis in the small intestine,providing a new strategy for intestinal radiation injury in deep space exploration missions such as manned spaceflight.

Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To investigate the effect of ligation methods of inferior mesenteric artery (IMA) on preserving left colic artery (LCA) in laparoscopic radical resection of rectal cancer.Methods:The prospective randomized controlled study was conducted. The clinical data of 864 patients who underwent laparoscopic radical resection of rectal cancer at Renji Hospital of Shanghai Jiaotong University School of Medicine from January 2020 to December 2024 were selected. Patients were randomly divided into the low ligation group and high ligation group using a random number table. Patients of the low ligation group underwent laparoscopic radical resection of rectal cancer with preserving LCA by low ligation of IMA and apical lymph node dissection, and patients of the high ligation group underwent laparoscopic radical resection of rectal cancer with traditional high ligation of IMA. Observation indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postoperative pathological examination; (4) postoperative recovery. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric test. Results:(1) Grouping of the enrolled patients. A total of 864 patients with rectal cancer who underwent laparoscopic radical resection of rectal cancer were screened for eligibility, including 410 males and 454 females, aged (63±11)years. All 864 patients were randomly divided into the low ligation group and high ligation group, with 432 patients in each group. There was no significant difference in gender, age, body mass index, carcinoembryonic antigen, distance from tumor to anal margin, diabetes, hypertension, neoadjuvant radiochemotherapy, IMA subtypes and IMA length between the two groups ( P>0.05), ensuring comparability. (2) Intraoperative conditions. All patients of the two groups successfully completed surgery, with no errors in blood vessel ligation during operation or conversion to open surgery. There was a significant difference in time of IMA dissection between the low ligation group and high ligation group [(31±11)minutes vs. (28±9)minutes, t=4.39, P<0.05], and there was no significant difference in total operation time, volume of intra-operative blood loss or prophylactic stoma rate between the two groups ( P>0.05). (3) Postopera-tive pathological examination. There was a significant difference in the number of lymph node dissected between the low ligation group and high ligation group (1.8±1.4 vs. 1.5±1.4, t=2.51, P<0.05), and there was no significant difference in tumor diameter, the total number of lymph node dissected, total lymph node positive status, No.253 lymph node positive status, TNM staging between the two groups ( P>0.05). (4) Postoperative recovery. The time to postoperative first flatus and the number of anastomotic leakage of patients in the low ligation group were (74±22)hours and 16 cases, versus (78±20)hours and 31 cases in the high ligation group, respectively, showing significant differences in the above indicators between the two groups ( t=2.52, χ2=5.06, P<0.05). There was no significant difference in the time to postoperative initial liquid food intake, duration of post-operative hospital stay, duration of abdominal drainage tube indwelling, duration of anal tube indwelling, postoperative wound infection, pulmonary infection, intestinal obstruction, or urinary dysfunction between the two groups ( P>0.05). None of patients in the two groups had readmission or death during the postoperative 30 days. Conclusion:Low ligation of IMA in laparoscopic radical resection of rectal cancer can guide precise LCA preservation, which is beneficial for accelerating the recovery of intestinal function and reducing the incidence of anastomotic leakage.

Objective:To investigate the effect of ligation methods of inferior mesenteric artery (IMA) on preserving left colic artery (LCA) in laparoscopic radical resection of rectal cancer.Methods:The prospective randomized controlled study was conducted. The clinical data of 864 patients who underwent laparoscopic radical resection of rectal cancer at Renji Hospital of Shanghai Jiaotong University School of Medicine from January 2020 to December 2024 were selected. Patients were randomly divided into the low ligation group and high ligation group using a random number table. Patients of the low ligation group underwent laparoscopic radical resection of rectal cancer with preserving LCA by low ligation of IMA and apical lymph node dissection, and patients of the high ligation group underwent laparoscopic radical resection of rectal cancer with traditional high ligation of IMA. Observation indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postoperative pathological examination; (4) postoperative recovery. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the non-parametric test. Results:(1) Grouping of the enrolled patients. A total of 864 patients with rectal cancer who underwent laparoscopic radical resection of rectal cancer were screened for eligibility, including 410 males and 454 females, aged (63±11)years. All 864 patients were randomly divided into the low ligation group and high ligation group, with 432 patients in each group. There was no significant difference in gender, age, body mass index, carcinoembryonic antigen, distance from tumor to anal margin, diabetes, hypertension, neoadjuvant radiochemotherapy, IMA subtypes and IMA length between the two groups ( P>0.05), ensuring comparability. (2) Intraoperative conditions. All patients of the two groups successfully completed surgery, with no errors in blood vessel ligation during operation or conversion to open surgery. There was a significant difference in time of IMA dissection between the low ligation group and high ligation group [(31±11)minutes vs. (28±9)minutes, t=4.39, P<0.05], and there was no significant difference in total operation time, volume of intra-operative blood loss or prophylactic stoma rate between the two groups ( P>0.05). (3) Postopera-tive pathological examination. There was a significant difference in the number of lymph node dissected between the low ligation group and high ligation group (1.8±1.4 vs. 1.5±1.4, t=2.51, P<0.05), and there was no significant difference in tumor diameter, the total number of lymph node dissected, total lymph node positive status, No.253 lymph node positive status, TNM staging between the two groups ( P>0.05). (4) Postoperative recovery. The time to postoperative first flatus and the number of anastomotic leakage of patients in the low ligation group were (74±22)hours and 16 cases, versus (78±20)hours and 31 cases in the high ligation group, respectively, showing significant differences in the above indicators between the two groups ( t=2.52, χ2=5.06, P<0.05). There was no significant difference in the time to postoperative initial liquid food intake, duration of post-operative hospital stay, duration of abdominal drainage tube indwelling, duration of anal tube indwelling, postoperative wound infection, pulmonary infection, intestinal obstruction, or urinary dysfunction between the two groups ( P>0.05). None of patients in the two groups had readmission or death during the postoperative 30 days. Conclusion:Low ligation of IMA in laparoscopic radical resection of rectal cancer can guide precise LCA preservation, which is beneficial for accelerating the recovery of intestinal function and reducing the incidence of anastomotic leakage.

Objective To explore the effect of gender,training duration and type of sports on electro-cardiographic changes in Chinese elite athletes by performing electrocardiography(ECG).Methods A to-tal of 891 Chinese elite athletes who underwent ECG examinations between 2016 and 2019 were in-cluded in the study.The ECGs were divided into three groups according to the guidelines of the Euro-pean Society of Cardiology(ESC)in 2010:group 0(normal ECG),group 1(common and training-relat-ed ECG)and Group 2(uncommon and training-unrelated ECG).The effect of gender,training dura-tion(4 to 6 years,7 to 10 years and more than 11 years)and sports types(skill,strength,endur-ance and mixed categories)on the ECG changes was assessed.Results No significant differences were found in Group 2 in sex,training duration or sports types.However,the prevalence of common train-ing-related ECG changes was significantly higher in male athletes than in female athletes(58.9%vs.47.4%).Moreover,the highest prevalence was found in athletes with more than 11 years of training,significantly higher than those with 4-6 years of training(P<0.05).A highly significant difference was also observed among athletes of different sports(P<0.01),with the highest in those of the mixed cate-gory at 64.6%.Moreover,sinus bradycardia occurred with significantly higher incidence in athletes un-dertaking mixed and endurance training than others(P<0.05).Conclusion The training-related ECG changes of Chinese elite athletes is closely correlated to their gender,training duration and sports types.

Background::Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging).Methods::This prospective trial included patients with initial pre-NAC cT1–3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated.Results::A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30).Conclusions::In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%.Registration::chictr.org.cn, ChiCTR2100049093

Purpose: Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). Materials and Methods: The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. Results: Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). Conclusion Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimina-tion of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.