ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids （MA） in ameliorating depression by network pharmacology， molecular docking， and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. The depression targets were collected through TCMIP， Genecards， HPO， DrugBank and OMIM database. Protein-protein interaction （PPI） network was constructed by protein interaction analysis （STRING） database. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed through Bioinformatics （DAVID） database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone （CORT） once a day for 35 consecutive days. Sixty mice were randomly allocated into control （0.9% normal saline）， model （CORT， 20 mg·kg^-1）， positive control （fluoxetine hydrochloride， 3.6 mg·kg^-1）， and MA （10， 5， and 2.5 mg·kg^-1） groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor （BDNF）， dopamine （DA）， 5-hydroxytryptamine （5-HT）， and norepinephrine （NE） in mice. The mRNA levels of cyclic adenosine monophosphate （cAMP） pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 （Cx43）. ResultsA total of 434 component targets and 545 depression targets were obtained， including 84 common targets， among which 10 core targets were screened out. GO analysis predicted 34 biological processes， 15 cell components， and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group， CORT prolonged the immobility time of mice in forced swimming and tail suspension tests （P<0.01）， lowered the serum levels of NE， BDNF， and 5-HT （P<0.05）， up-regulated the mRNA levels of nuclear factor-κB （NF-κB） and interleukin-6 （IL-6） in the brain tissue （P<0.05）， and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein （CREB） and BDNF （P<0.05） and the protein levels of protein kinase （PRKACA）， phosphorylation （p）-CREB/CREB， BDNF， and Cx43 （P<0.05） in the brain tissue. Compared with the model group， high-dose MA reduced the immobility time of mice in forced swimming （P<0.05） and tail suspension （P<0.01） tests， raised the serum levels of NE， BDNF， and 5-HT （P<0.01）， down-regulated the mRNA level of NF-κB （P<0.01）， and up-regulated the mRNA level of BDNF （P<0.01） and protein levels of PRKACA， p-CREB/CREB， BDNF， and Cx43 （P<0.05）. ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway， improving synaptic plasticity and gap junction function， and reducing neuroinflammation.

Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

The effective local management of oligometastatic non-small cell lung cancer (NSCLC) has the potential to prolong patients' survival. The role of radiotherapy as a local treatment modality in patients with oligometastatic NSCLC, whether as first-line therapy or consolidation therapy, remains uncertain. Several studies have demonstrated that stereotactic ablative radiotherapy can offer clinical benefits for patients with oligometastatic NSCLC without increasing adverse reactions. Furthermore, the exploration of the potential synergistic effects of combining radiotherapy and immunotherapy on extending progression-free survival and overall survival in patients with oligometastatic NSCLC is also a topic worthy of attention.

Objective:To evaluate the effect of hyperthermia on radiation pneumonitis (RP) in elderly patients with esophageal cancer undergoing intensity-modulated radiotherapy (IMRT).Methods:Clinical data of 177 elderly esophageal cancer patients (aged ≥60 years) receiving IMRT in the First Affiliated Hospital of Soochow University and Yixing Cancer Hospital from August 1, 2017 to February 6, 2023 were retrospectively analyzed. Patients were divided into the hyperthermia and non-hyperthermia groups based on whether they received hyperthermia treatment. Patients in two groups received IMRT with 6 MV X-rays. Patients in the hyperthermia group underwent high-frequency hyperthermia within 1 h before radiation using the external thermotherapy device HG-2000Ⅲ (heating temperature: 41-43 ℃ for 40 min, twice a week). After adjusting for confounding factors between two groups using propensity score matching (PSM), the short-term effective rates between two groups were compared using Chi-square test. Univariate analysis and logistic multivariate analysis were employed to compare the incidence of RP between two groups. Results:After applying PSM, 42 pairs were successfully matched, and the baseline data and radiotherapy parameters showed no statistically significant differences between two groups (all P>0.05). The objective response rate (ORR) in the hyperthermia group was significantly higher than that in the non-hyperthermia group (83.3% vs. 64.3%, P=0.047). Univariate analysis revealed that the incidence of RP and symptomatic RP (≥ grade 2) in the hyperthermia group was significantly lower than that in the non-hyperthermia group (61.9% vs. 85.7%, P=0.013; 21.4% vs. 47.6%, P=0.012). Logistic multivariate analysis indicated that hyperthermia was an independent protective factor for symptomatic RP ( P=0.011). Conclusions:The incidence and severity of RP in elderly esophageal cancer patients receiving IMRT can be reduced by hyperthermia. Hyperthermia, as a clinically beneficial green treatment, improves efficacy and reduces toxicity for patients with esophageal cancer.

Nowadays, the research on traditional radiomics has gradually matured. However, it usually regards the tumor as a whole, and high-throughput data are often generated in the entire tumor region, which cannot express clear spatial heterogeneity. In order to explore the potential biological information within tumors and realize individualized precise diagnosis and treatment, habitat analysis technology emerges at the historic moment, which provides a new way of thinking to identify tumor microenvironment. On the basis of traditional radiomics, the tumor cell population with similar characteristics is clustered, and the tumor is segmented into multiple sub-regions. Therefore, the study of tumor is no longer limited by the subjective differences of observers in the description of imaging features, and the information of tumor spatial heterogeneity is ideally obtained.

Small bowel capsule endoscopy and double-balloon enteroscopy have become new methods for clinical diagnosis of radiation enteritis (RE) , especially for abnormal intestinal tissue. Targeted biopsy or interventional therapy is expected to achieve precision treatment of RE. The screening of molecular markers in biological samples has also become a new direction for RE diagnosis. Fecal microbiota transplantation has become one of the promising treatments for RE. In addition, mechanism studies based on traditional Chinese medicine, targeted cell death, and omics analysis provide rich strategies for the diagnosis and treatment of RE.

Objective:To analyze the efficacy, safety and prognostic factors of immune checkpoint inhibitors in the treatment of recurrent and metastatic cervical cancer.Methods:A total of 87 patients with recurrent and metastatic cervical cancer admitted to the First Affiliated Hospital of Soochow University from January 2018 to June 2022 were retrospectively analyzed. They were divided into non immunotherapy group ( n=32) and immunotherapy group ( n=55) according to whether immune checkpoint inhibition was applied after recurrence and metastasis. The disease control rate (DCR), progression free survival (PFS), overall survival 1 (OS1, date of pathology diagnosis to the end of follow-up or time of death), overall survival 2 (OS2, time of first immunotherapy/non-immunotherapy to the end of follow-up or time of death), safety and prognostic factors of the two groups were analyzed and compared. Results:In 87 patients with recurrent and metastatic cervical cancer, the DCR of the non immunotherapy group and immunotherapy group were 53.1% (17/32) and 72.7% (40/55) respectively ( χ2=3.44, P=0.064). The median OS1 of the non immunotherapy group was 51.0 months, while the immunotherapy group did not reach the median OS1, with a statistically significant difference ( χ2=7.50, P=0.006). The median OS2 of the non immunotherapy group was 28.0 months, while the immunotherapy group did not reach the median OS2, with a statistically significant difference ( χ2=7.07, P=0.008). The median PFS of the non immunotherapy group and immunotherapy group were 18.0 months and 23.0 months respectively, with no significant difference ( χ2=0.01, P=0.915). In the immunotherapy group, 70.9% (39/55) of patients received immune checkpoint inhibitors as first-line treatment and 29.1% (16/55) received as second-line and above treatment. Both groups of patients did not achieve median OS2, with median PFS of 23.0 and 17.0 months respectively, and there were no statistically significant differences ( χ2=0.94, P=0.333; χ2=2.00, P=0.158) ; 38.2% (21/55) of patients received immune checkpoint inhibitor combined with local radiotherapy, 61.8% (34/55) patients did not receive radiotherapy. And neither group of patients achieved median OS2, with median PFS of 19.0 and 25.0 months respectively, with no statistically significant differences ( χ2=0.62, P=0.432; χ2=0.01, P=0.906). The incidences of grade 1-2 hematuria and hypothyroidism in the non immunotherapy group and immunotherapy group were 53.1% (17/32) vs. 27.3% (15/55, χ2=5.82, P=0.016), 3.1% (1/32) vs. 21.8% (12/55, χ2=4.19, P=0.041) respectively. The incidence of myelosuppression in the non immunotherapy group [grade 1-2: 59.4% (19/32), grade 3-4: 34.4% (11/32) ] was significantly different from that in the immunotherapy group [grade 1-2: 80.0% (44/55), grade 3-4: 3.6% (2/55) ; Z=3.50, P<0.001]. There were no statistically significant differences between creatinine increase, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase increase, lymphocyte decrease, hypoproteinemia, proteinuria, rash, fatigue (all P>0.05). Univariate regression analysis showed that the use of immune checkpoint inhibitor was an independent protective factor affecting the prognosis of patients ( HR=0.31, 95% CI: 0.12-0.77, P=0.012) . Conclusion:Whether used as first-line or second-line or above treatment, the use of immune checkpoint inhibitors in patients with recurrent and metastatic cervical cancer prolongs their OS1, OS2, and has good safety. The application of immune checkpoint inhibitors is an independent protective factor affecting the prognosis of patients.

Objective:To compare the toxicity and prognosis of patients with stage Ⅲ cervical cancer treated using different regimens.Methods:A retrospective analysis was carried out for 194 patients with stage Ⅲ cervical cancer determined according to the revised 2018 International Federation of Gynecology and Obstetrics staging system (16 cases of stage Ⅲ A, 23 cases of stage Ⅲ B, 136 cases of stage Ⅲ C1, and 19 cases of stage Ⅲ C2) admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2020. They were divided into a radical radiotherapy±chemotherapy group (81 cases) and a radical hysterectomy + radiotherapy±chemotherapy group (113 cases) according to different treatment method. The difference in toxicity between the two groups was determined using the χ2 test. The survival curves and progression-free survival curves were plotted using the Kaplan-Meier method, and the Log rank test was also performed. The differences in toxicity and prognosis were further analyzed in 136 patients with stage Ⅲ C1 cervical cancer result patients in the radical radiotherapy±chemotherapy group were more likely to have hemoglobin decline ( χ2=10.68, P=0.004), rectal mucositis ( χ2=14.41, P=0.001), and vaginal fistula ( χ2=7.16, P=0.012) of grades 3 and 4. Patients in the radical hysterectomy+ radiotherapy±chemotherapy group were more likely to have increased aspartate aminotransferase ( χ2=10.96, P=0.002) and alanine aminotransferase ( χ2=8.49, P=0.010). The differences were statistically significant. The 5-year progression-free survival rate of the radical radiotherapy±chemotherapy group was 58.3%, which was lower than that of the radical hysterectomy + radiotherapy±chemotherapy group (74.5%; χ2=5.33, P=0.021). Among the 136 patients with stage Ⅲ C1 cervical cancer, the ones in the radical radiotherapy±chemotherapy group (34 cases) were more likely to develop rectal mucositis ( χ2=13.25, P=0.003), while the ones in the radical hysterectomy + radiotherapy±chemotherapy group (102 cases) were more likely to have elevated aspartate aminotransferase ( χ2=6.18, P=0.046). The differences were statistically significant. The 5-year survival rates of the radical radiotherapy±chemotherapy group and the radical hysterectomy+ radiotherapy±chemotherapy group were 85.5% and 86.3%, respectively. The difference was not statistically significant ( P=0.893). The 5-year progression-free survival rates of the radical radiotherapy±chemotherapy group and the radical hysterectomy + radiotherapy±chemotherapy group were 65.6% and 77.1%, respectively. The difference was not statistically significant ( P=0.244). Conclusions:For patients with stage Ⅲ cervical cancer, the ones in the radical radiotherapy±chemotherapy group were more likely to progress and have a poorer prognosis compared with the ones in the radical hysterectomy+ radiotherapy±chemotherapy group. For patients with stage Ⅲ C1 cervical cancer, there was no significant difference in the prognosis of patients between the groups. The two treatment method lead to different toxicity, with no obvious advantages and disadvantages. Considering the risks and economic burdens caused by surgery, radical radiotherapy and chemotherapy is recommended for patients with stage Ⅲ C1 cervical cancer.

Objective:To explore the impact of preoperative Naples prognostic score (NPS) on the survival prognosis of patients with thoracic esophageal squamous cell carcinoma (ESCC).Methods:From December 2014 to December 2020, a total of 134 patients who underwent radical esophagectomy in Department of Thoracic Surgery, Affiliated Taixing People′s Hospital of Yangzhou University were retrospectively analyzed. The NPS was calculated by the median values of preoperative serum albumin, total cholesterol, neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR), and then the enrolled patients were divided into NPS 0 group (20 cases), NPS 1 or 2 group (62 cases) and NPS 3 or 4 group (52 cases). Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. The univa-riate and multivariate Cox models were used to analyze the relationship between NPS and survival prognosis.Results:The 1-, 3- and 5-year progression free survival (PFS) rates were 95.0%, 70.0% and 60.0% in the NPS 0 group, 66.1%, 24.2% and 24.2% in the NPS 1 or 2 group, and 48.1%, 3.8% and 1.9% in the NPS 3 or 4 group respectively, with a statistically significant difference ( χ2=31.27, P<0.001). In the NPS 0 group, the 1-, 3- and 5-year overall survival (OS) rates were 100.0%, 80.0% and 70.0% respectively. In the NPS 1 or 2 group, the 1-, 3- and 5-year OS rates were 96.8%, 36.7% and 32.3% respectively, while in the NPS 3 or 4 group, the 1-, 3- and 5-year OS rates were 90.4%, 32.7% and 5.8% respectively, and there was a statistically significant difference ( χ2=29.70, P<0.001). Univariate analysis found that sex, T stage, N stage, TNM stage and NPS were closely related to PFS and OS of patients with thoracic ESCC (all P<0.05). Furthermore, multivariate Cox regression analysis showed that T stage ( HR=1.46, 95% CI: 1.07-2.00, P=0.019), N stage ( HR=1.34, 95% CI: 1.02-1.76, P=0.037) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.35, 95% CI: 1.58-7.11, P=0.002; NPS 3 or 4 group: HR=6.15, 95% CI: 2.89-13.11, P=0.001) were independent prognostic factors for PFS. Additionally, T stage ( HR=1.67, 95% CI: 1.01-2.77, P=0.046), N stage ( HR=1.44, 95% CI: 1.00-2.20, P=0.048) and NPS (set NPS 0 group as the subvariable, NPS 1 or 2 group: HR=3.10, 95% CI: 1.31-7.32, P=0.010; NPS 3 or 4 group: HR=5.09, 95% CI: 2.14-12.11, P=0.001) were independent prognostic factors for OS. Conclusion:Preoperative NPS plays an important role in predicting the survival prognosis of patients with thoracic ESCC.