Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

ObjectiveTo investigate the effect and potential mechanism of Zhishi Daozhi Formula （枳实导滞方， ZDF） on inflammation in rats with sepsis-induced gastrointestinal dysfunction based on the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB （TLR4/MyD88/NF‑κB） signaling pathway and intestinal flora. MethodsSixty SD rats were randomly divided into sham‑operation group， model group， ulinastatin group， and low‑， medium‑ and high‑dose ZDF groups， with 10 rats in each group. Except for the sham‑operation group， the rat model of sepsis‑induced gastrointestinal dysfunction was established by cecal ligation and puncture （CLP）. Three days before modeling and 12 h after modeling， the low-， medium- and high-dose ZDF groups were intragastrically administered with ZDF solution at doses of 3.80， 7.60 and 15.20 g·kg⁻¹·d⁻¹， respectively. The ulinastatin group received intraperitoneal injection of ulinastatin at 100,000 U/kg， while the sham-operation and model groups were given normal saline at 1 ml/100 g by gavage. All interventions were performed once daily for 4 consecutive days. Tow hours after the last intervention， gastric emptying rate and small intestinal propulsion rate were detected. Gastrointestinal function indicators including D‑lactic acid （D‑LA） and intestinal fatty acid binding protein （i‑FABP）， as well as inflammatory indicators including procalcitonin （PCT） and C‑reactive protein （CRP） were measured by ELISA 24 h after modeling. The counts of Escherichia coli， Bifidobacterium and Lactobacillus in the intestine were compared. The histopathological morphological changes of the rat intestinal mucosa were observed by HE staining. The protein and mRNA expressions of IκB kinase （Ikk）， TLR4， MyD88 and NF‑κB in ileal tissues were detected by western blot and qRT‑PCR， respectively. ResultsCompared to the sham-operation group， the model group showed decreased gastric emptying rate and small intestinal propulsion rate， increased intestinal Escherichia coli count， elevated serum D‑LA， i‑FABP， PCT and CRP levels， increased protein and mRNA expressions of Ikk， TLR4， MyD88 and NF-κB in ileal tissue， decreased counts of Lactobacillus and Bifidobacterium （P＜0.05）， accompanied by obvious pathological injury of ileal mucosa. Compared to the model group， all medication groups exhibited significant improvements in the above mentioned indicators and alleviated intestinal mucosal injury （P＜0.05）. Compared to the ulinastatin group， except for D-LA in the medium-dose ZDF group， the differences in the above indicators between the low- and medium-dose ZDF groups were statistically significant （P＜0.05）， while the differences between the high-dose ZDF group and the ulinastatin group were not statistically significant （P＞0.05）. With increasing dosage， the gastric emptying rate， small intestinal propulsion rate， Lactobacillus and Bifidobacterium counts in the rats of all three ZDF groups increased， while the levels of serum D-LA， PCT， CRP， and i-FABP， the protein levels of Ikk， TLR4， MyD88， and NF-κB in intestinal tissue， and the Escherichia coli count decreased （P＜0.05）. ConclusionZDF can ameliorate intestinal mucosal injury， maintain intestinal flora balance and inhibit inflammatory response in rats with sepsis‑induced gastrointestinal dysfunction， with the high-dose group showing the best efficacy， which may be achieved by down‑regulating the TLR4/MyD88/NF-κB signaling pathway.

Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Objective To investigate the molecular targets and signaling pathways involved in the therapeutic effects of Lishukang Capsule(LSK)in a rat model of high-altitude pulmonary edema(HAPE)using a proteomics-based approach.Methods A total of 60 male Wistar rats were randomly assigned to a control group,a HAPE model group,3 LSK treatment groups receiving low-,medium-,and high-dose LSK,respectively,and a Rhodiola rosea(also known as Hongjitian[HJT]in pinyin,a Chinese Romanization system)control group.After HAPE modeling,the pharmacodynamic effects were assessed and the optimal LSK dose was determined using HE stains,inflammatory cytokine quantification,lung tissue water content,and the protein concentration in bronchoalveolar lavage.Label free quantitative proteomic profiling was then applied to identify differentially expressed proteins(DEPs)in the optimal dose group,using a screening threshold of over 1.5-fold change and P<0.05.The selected DEPs were validated with Western blotting,followed by Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results The medium-dose LSK group exhibited significant anti-HAPE effects.Findings from the proteomic analysis revealed,in the comparison with the control group,267 DEPs were identified in the HAPE group.In the comparison with the HAPE group,225 DEPs were identified in the medium-dose LSK group.A total of 112 DEPs in the control group were normalized following LSK treatment in the medium-dose LSK group.In addition,GO enrichment analysis of proteins differentially expressed between the HAPE and LSK group showed that these DEPs were mainly enriched in 12 biological processes,2 cellular components,and 5 molecular functions.KEGG pathway analysis showed that LSK activated pathways associated with cell adhesion molecules,glycosaminoglycan biosynthesis,DNA replication/nucleotide excision repair,transcriptional dysregulation in cancer,and Herpes simplex virus type 1(HSV-1)infection,while inhibiting pathways associated with glycerophospholipid metabolism.Some differentially expressed proteins with potential functions were verified by Western blotting,including AGPAT5,NCAM1,SRSF3,and PLA2.These differentially expressed proteins were significantly expressed in the normal group,HAPE group,and LSK group,and the validation results were consistent with proteomic findings,indicating the high reliability of the proteomic results.Conclusion LSK exerts a significant protective effect against HAPE.Proteomic analysis suggests that its therapeutic action may be mediated through activating pathways involved in cell adhesion molecules,glycosaminoglycan biosynthesis,DNA replication/nucleotide excision repair,transcriptional dysregulation in cancer,and HSV-1 infection,alongside inhibition of pathways associated with glycerophospholipid metabolism.The key DEPs identified in these pathways may play crucial roles in the preventive and therapeutic effects of LSK on HAPE.

Objective To investigate the clinical efficacy of fasting nasogastric administration of sesame oil combined with multi-frequency vibrational abdominal massage in stroke patients with consti-pation undergoing nasogastric feeding.Methods A total of 50 stroke patients with nasogastric feeding were selected as study subjects and randomly divided into control group and study group,with 25 pa-tients in each group.The control group received routine nursing care plus multi-frequency vibrational abdominal massage,while the study group received fasting nasogastric administration of 20 mL of sesa-me oil on the basis of the control group's treatment.After 15 days of intervention,the defecation condi-tions[constipation clinical symptom score(CSS),stool consistency(Bristol stool scale),and stool volume]were compared between the two groups.Results After treatment,the CSS score in the study group was lower than that in the control group[(6.52±2.52)versus(12.64±3.32),P＜0.05].The normal stool consistency(types Ⅳ and Ⅴ on the Bristol stool scale)in the study group was higher than that in the control group(76.0％versus 8.0％,P＜0.05).The stool volume in the study group was higher than that in the control group[(303.00±93.79)g versus(196.40±60.27)g,P＜0.05].The total effective rate of defecation in the study group was 96.0％,which was higher than 32.0％in the control group(P＜0.05).The Patient Assessment of Constipation-Quality of Life(PAC-QOL)score in the study group was lower than that in the control group[(40.07±5.67)versus(63.07±7.46),P＜0.05].Conclusion Fasting nasogastric administration of sesame oil com-bined with multi-frequency vibrational abdominal massage can promote the recovery of intestinal function and improve constipation symptoms in stroke patients with nasogastric feeding.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective:To investigate the influence of four preoperative CT image characteristics on the outcome of thoracoscopic surgery for chronic tuberculous empyema.Methods:This is a retrospective cohort study. Two hundred and eleven patients of tuberculous empyema who underwent video-assisted thoracic surgery(VATS) decortication at the First Department of Surgery , Wuhan Pulmonary Hospital from June 2020 to June 2023 were retrospectively analyzed. There were 162 male cases and 49 female cases, with an age ( M (IQR)) of 33 (27) years (range: 8 to 76 years). Patients were divided into two groups according to whether low-density lines, mass-patchy density, pleural fusion were observed, and the lesion size. Compare the clinical indicators of two groups of cases. Using the rapeutic efficacy as the dependent variable and four CT features as covariates, cases with cure or improve were included in Logistic regression analysis to calculate OR (95% CI) values. Results:Preoperative chest CT images showed that 127 cases (60.2%) had low-density lines, 102 cases (48.3%) had mass-patchy density, and 88 cases (47.7%) had pleural fusion. The lesions spanned 2 to 11 intercostal spaces, with a median of 7 intercostal spaces. The lesion size was divided into two groups according to <7 intercostal spaces and ≥7 intercostal spaces, with 101 cases (47.9%) and 110 cases (52.1%), respectively. In the intra-group comparison, there were no difference in age, lesion location and pulmonary tuberculosis. In the comparison of gender, except that the proportion of female patients in the group with lesion size <7 intercostal spaces ( χ2=6.064, P=0.010) was higher than ≥7 intercostal spaces, there were no significant difference between other groups. In low-density lines group, there was no difference in the incidence of anemia and hypoproteinemia between the two groups. Compared with the non low-density line group, patients with low-density line group exhibited fewer cases of abnormal elevation in ESR and CRP was lower(all P<0.01), the period of preoperative treatment ( U=7 281.00, P<0.01) was longer than the non low-density line group, while the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy were all better than the non low-density line group(all P<0.05). In the comparison between the mass-patchy density group, there were fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP in the without mass-patchy density group(all P<0.05), and the period of preoperative treatmentwas shorter ( U=4 581.50, P=0.026), and the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration and therapeutic effect were better too(all P<0.05). In the grouping comparison of pleural fusion, there were no difference in cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP, and the period of preoperative treatment between the two groups; the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours, postoperative drainage duration, lung re-expansion duration, and therapeutic efficacy of the group without pleural fusion were better than the group with pleural fusion(all P<0.05). The group with <7 intercostal spaces had fewer cases of anemia, hypoproteinemia, abnormal elevation of ESR and CRP (all P<0.05), the period of preoperative treatment was longer ( U=4 295.00, P=0.004), the operation time, intraoperative hemorrhage, postoperative drainage at 72 hours,postoperative drainage duration, lung re-expansion duration and complications were less (all P<0.05), the therapeutic efficacy was better than the group with ≥7 intercostal spaces ( χ2=27.912, P<0.01). The Logistic regression analysis of cured and improved cases showed that mass-patchy density and lesion size were independent risk factors affecting the therapeutic efficacy (all P<0.05). Conclusions:For patients with CT images showing mass-patchy density, pleural fusion, and a large lesion size, the difficulty and risk of surgery may be relatively high.The preoperative CT images can provide objective reference for clinical preoperative evaluation.