Metabolic reprogramming， as one of the core hallmarks of malignant tumors， plays a key role in the occurrence， development and treatment of breast cancer （BC）. Abnormal changes in glucose metabolism， amino acid metabolism， lipid metabolism， as well as the tricarboxylic acid （TCA） cycle and oxidative phosphorylation （OXPHOS） pathways significantly influence the pathogenesis and progression of BC. Studies have shown that various active components of traditional Chinese medicine （TCM） （such as berberine， matrine， quercetin， curcumin， etc.） and their compound formulations （e.g. Xihuang pill， Danzhi xiaoyao powder， Yanghe decoction， etc.） can inhibit the proliferation and migration of BC cells and induce apoptosis by regulating key metabolic pathways such as glycolysis， lipid synthesis， and amino acid metabolism. TCM demonstrates multi-target and holistic regulatory advantages in intervening in BC metabolic reprogramming， showing significant potential in modulating key molecules like hypoxia inducible factor-1α， hexokinase-2， pyruvate kinase M2， lactate dehydrogenase A， glucose transporter-1， fatty acid synthase， and signaling pathways such as AKT/mTOR. However， current researches still focus predominantly on glucose metabolism， with insufficient mechanistic studies on lipid metabolism， amino acid metabolism， the TCA cycle， and OXPHOS. The precise targets， molecular mechanisms， and clinical translation value of these interventions require further validation and clarification through more high-quality experimental studies and clinical trials.

OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective:To investigate the gene expression of pulmonary metastatic papillary thyroid cancer (PTC) and its association with lung metastasis, facilitating risk assessment and personalized therapeutic strategies.Methods:A retrospective cohort study was conducted on 269 PTC patients (61 males, 208 females, age (38.9±11.9) years) treated at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from January 2017 to June 2020, including 60 cases with lung metastasis and 209 without. Primary tumor tissues underwent targeted next-generation sequencing (tNGS). Univariate and multivariate logistic regression analyses were performed to identify risk factors for lung metastasis, and χ2 test was used to evaluate the differences between the effective and ineffective groups of radioactive iodine (RAI) therapy. Results:In 60 PTC patients with lung metastasis, the mutation rates of B-Raf proto-oncogene, serine/threonine protein kinase (BRAF) V600E, telomerase reverse transcriptase (TERT) promoter, and rearranged in transformation (RET) fusion mutations were 28.3%(17/60), 25.0%(15/60), and 26.7%(16/60), respectively. Univariate analysis demonstrated that age≥55 years, multifocality, lateral cervical lymph node metastasis, extrathyroidal extension, BRAF V600E mutation, RET fusion, and TERT promoter mutation were significantly associated with lung metastasis in PTC ( Wald χ2 values: 4.13-31.28, all P<0.05). However, no significant statistical associations were observed between lung metastasis and gender, rat sarcoma type GTPase family (RAS) mutation, tumor protein p53 (TP53) mutation, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation, neurotrophic tyrosine receptor kinase 1 (NTRK1) fusion, or anaplastic lymphoma kinase (ALK) fusion ( Wald χ2 values: 0.01-3.50, all P>0.05). Multivariate analysis identified TERT promoter mutation (odds ratio ( OR)=11.86, 95% CI: 3.68-38.29, P<0.001), multifocality ( OR=5.30, 95% CI: 2.41-11.69, P<0.001), extrathyroidal extension ( OR=3.98, 95% CI: 1.77-8.98, P=0.001), and lateral cervical lymph node metastasis ( OR=3.13, 95% CI: 1.28-7.68, P=0.013) as independent risk factors for lung metastasis in PTC. Conversely, BRAF V600E mutation emerged as a potential protective factor ( OR=0.09, 95% CI: 0.04-0.21, P<0.001). The proportions of BRAF V600E mutation ( χ2=20.49, P<0.001) and TERT promoter mutation ( χ2=4.91, P=0.027) were higher in the RAI ineffective group. Conclusions:BRAF V600E mutation, TERT promoter mutation and RET fusion are related gene expression in lung metastasis of PTC. Multifocality, extrathyroidal extension, lateral cervical lymph node metastasis and TERT promoter mutation are risk factors for lung metastasis of PTC (TERT is an independent molecular risk marker), while BRAF V600E mutation may be a protective factor. RAI treatment efficacy of PTC patients with lung metastasis and BRAF V600E mutation/TERT promoter mutation is worse.

Objective To observe the value of 68Ga-DOTA-NOC PET/CT for diagnosing pheochromocytoma(PCC)and paraganglioma(PGL).Methods Thirty-eight patients with suspected or confirmed PCC/PGL who underwent 68 Ga-DOTA-NOC PET/CT were retrospectively enrolled,among them 20 cases underwent 131I-metaiodobenzylguanidine(MIBG)SPECT/CT during the same period.The value of 68Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL at individual and lesion levels were analyzed and compared to the results of 131I-MIBG SPECT/CT.Results Among 38 cases,there were 20 cases of PCC,14 cases of PGL,1 case of adrenocortical carcinoma and 3 cases of benign adrenal hyperplasia.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL in all 38 cases was 87.88％(29/33),60.00％(3/5),93.55％(29/31),42.86％(3/7)and 84.21％(32/38),respectively.Totally 188 lesions were detected in 34 cases,with detection rate of 89.95％(188/209).For 20 patients who underwent both 2 kinds examinations,the detection rate of bone,lymph node,liver,lung metastases and the overall lesions of 68Ga-DOTA-NOC PET/CT were all higher than those of 131I-MIBG SPECT/CT(all P＜0.05).No significant difference of diagnostic accuracy of PCC/PGL was found between 68 Ga-DOTA-NOC PET/CT and 131I-MIBG SPECT/CT(P＞0.05).Conclusion The value of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL was comparable to that of 131I-MIBG SPECT/CT,but the former showed higher detection rate of metastases,hence being helpful to staging and risk stratification of PCC/PGL.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.