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.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Hypokalemia,a common clinical electrolyte disorder,can affect multiple systems and can be life-threatening in severe cases.Identifying the cause of hypokalemia is crucial for its prevention and treatment.However,the etiology of hypokalemia is complex and often requires detailed differential diagnosis.This article reports a rare clinical case of hypokalemia caused by long-term excessive consumption of strong tea and discusses its pathogenesis.The aim is to raise clinical awareness and understanding of the etiology of such cases of hypokalemia and reduce misdiagnosis and missed diagnosis.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Aim To explore the key components and mechanisms of Lizhong decoction in treating rats with cold-damp diarrhea based on network pharmacology,molecular docking technology and animal experiments.Methods By literature review and database collec-tion,the components of Lizhong decoction,therapeutic targets,and the mapping with diarrhea disease targets were conducted to construct an intersection target pro-tein-protein interaction network for screening core tar-gets,and GO and KEGG pathway enrichment analysis was performed to build an"active component-target-pathway"network,followed by molecular docking vali-dation.Forty-eight rats were randomly divided into the normal control group(K),model group(DG),Lizhong decoction group(LZDG),and Pulsatilla decoction group(BTDG).Subsequently,a rat cold-damp diar-rhea model was established using Senna combined with low-temperature high-humidity environment,and the rats were intervened with Lizhong decoction and Pul-satilla decoction.HE staining was used to detect path-ological changes in intestinal tissue,ELISA was em-ployed to measure the levels of peripheral blood IL-6,IL-10,IL-1 β,and TNF-α,and western blot was used to determine the expression of colon tight junction pro-teins.Results Network pharmacology initially identi-fied 125 compounds in Lizhong decoction,5 186 drug target components,438 disease targets,and 60"drug-disease"shared targets.GO and KEGG enrichment a-nalysis showed that signaling pathways such as IL-17 and TNF were highly enriched.Molecular docking in-dicated that the core components of the drug had good binding activity with corresponding key targets.Liz-hong decoction could effectively improve the clinical symptoms of rats with cold-damp diarrhea,and com-pared with the DG group,the diarrhea rate,diarrhea in-dex,and other related indicators also gradually de-creased to normal levels.Compared with the DG group,the LZDG group showed reduced inflammation levels and a recovery in energy metabolism levels.Conclusion It can regulate targets such as MMP9 and IL-17 signaling pathways through multi-components like Calycosin and formononetin to exert its therapeutic effect on cold-damp diarrhea.

Hypokalemia,a common clinical electrolyte disorder,can affect multiple systems and can be life-threatening in severe cases.Identifying the cause of hypokalemia is crucial for its prevention and treatment.However,the etiology of hypokalemia is complex and often requires detailed differential diagnosis.This article reports a rare clinical case of hypokalemia caused by long-term excessive consumption of strong tea and discusses its pathogenesis.The aim is to raise clinical awareness and understanding of the etiology of such cases of hypokalemia and reduce misdiagnosis and missed diagnosis.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.