In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural-cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Humans ; Neoplasms/metabolism* ; Receptors, Neurotransmitter/physiology* ; Animals ; Tumor Microenvironment/physiology*

Objective To investigate the clinical efficacy of adjuvant intervention of Fuyuan Fuheng Decoction for chemotherapy in the treatment of patients with colorectal cancer(CRC)of spleen-kidney deficiency syndrome,and to observe its effects on cellular immune function,adverse reactions and the prognosis of CRC treated by chemotherapy.Methods From January 2021 to January 2023,a retrospective study was conducted on 120 patients with CRC of spleen-kidney deficiency syndrome admitted to the Second Affiliated Hospital of Shaanxi University of Chinese Medicine.The patients were divided into a study group and a control group according to the treatment protocols,with 60 patients in each group.The patients of the two groups were treated by radical resection of CRC,and then the control group was given mFOLFOX6 chemotherapy(5-Fluorouracil+Oxaliplatin+Calcium Folinate)while the study group was given Fuyuan Fuheng Decoction together with mFOLFOX6 chemotherapy after operation.Fourteen days constituted a cycle of treatment,and the two groups were given 12 consecutive cycles of treatment.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,cellular immune function indicators[T-lymphocyte subsets CD3+,CD4+,CD4+/CD8+and natural killer(NK)cells],European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30)scores,Piper's Fatigue Scale(PFS)scores of cancer-related fatigue,Karnofsky Performance Status(KPS)scores,and prognosis-related markers[carbohydrate antigen 199(CA199),carcinoembryonic antigen(CEA),vascular endothelial growth factor(VEGF),and lactate dehydrogenase(LDH)].After treatment,the therapeutic efficacy,the incidence of adverse reactions,and the one-year survival rate of the two groups were compared.Results(1)After 12 cycles of treatment,the overall response rate of the study group was 75.00％(45/60),which was significantly higher than that of the control group[53.33％(32/60)],the difference being statistically significant(x2=6.125,P＜0.05).(2)After treatment,the scores of TCM symptoms of fatigue and weakness,soreness and weakness in the waist and knee,poor appetite,vertigo and dizziness,and loose stools in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the study group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of cellular immune function indicators of peripheral T-lymphocyte subset CD3+,CD4+,CD4+/CD8+,and NK cells of the two groups were all decreased compared with those before treatment(P＜0.05),but the decrease in the study group was significantly milder than that in the control group(P＜0.01).(4)After treatment,the EORTC QLQ-C30 score and KPS score in the two groups were increased compared with those before treatment(P＜0.05),and the PFS score was decreased compared with that before treatment(P＜0.05).The increase of the EORTC QLQ-C30 score and KPS score as well as the decrease of the PFS score in the study group were significantly superior to that in the control group(P＜0.01).(5)After treatment,the serum levels of prognosis-related markers of CA199,CEA,VEGF,and LDH in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the study group was significantly superior to that in the control group(P＜0.01).(6)The incidence of adverse reactions such as nausea/vomiting,gastrointestinal reactions,thrombocytopenia,leukopenia,and erythrocytopenia in the study group was significantly lower than that in the control group(P＜0.05 or P＜0.01).(7)One year of follow-up after the completion of treatment showed that three cases in the study group and five cases in the control group fell off during the follow-up period.Among the patients who completed the follow-up,the survival rate of the study group was 96.49％(55/57),which was significantly higher than that of the control group[83.64％(46/55)],the difference being statistically significant(x2=5.223,P=0.022).Conclusion Adjuvant intervention of Fuyuan Fuheng Decoction can enhance the overall response rate of the patients with CRC treated by mFOLFOX6 chemotherapy,and is effective on improving clinical symptoms,immune function,and performance status of the patients,enhancing the quality of life,alleviating cancer-related fatigue,increasing the survival rate,reducing the incidence of adverse reactions,and then improving the prognosis of the patients.

Objective:To analyse the effect of ultrasound-guided percutaneous liver biopsy and the coaxial biopsy needle tract radiofrequency ablation on patients diagnosed with hepatocellular carcinoma who are considered to be at risk of bleeding.Methods:The data of 117 patients with hepatocellular carcinoma who underwent coaxial biopsy needle tract radiofrequency ablation after ultrasound-guided percutaneous liver biopsy in Peking University First Hospital from March 2019 to April 2023 were retrospectively analysed. There were 95 males and 22 females, with the age of (62.0±11.8) years. A comprehensive analysis was conducted on the following variables: the pre-puncture platelet count, the international standardised ratio, anticoagulation therapy, the haemoglobin (Hb) level, the success rate of the liver puncture, the qualified rate of liver puncture specimens, the number of puncture samples, the length of hospital stay, the Hb level after puncture, bleeding within 10 days post-operation, and complications after ablation, including biliary fistula, hemothorax and organ perforation.Results:Among the 117 patients, 60 cases (51.3%) had an international normalized ratio >1.1, 40 cases (34.2%) had thrombocytopenia, that is, <150×10 9/L, and 17 cases (14.5%) received continuous anticoagulation therapy before the operation. It is evident that all 117 patients successfully completed the ultrasound-guided percutaneous liver biopsy, and that all liver biopsy specimens were qualified. The absence of biliary fistula, hemothorax, organ perforation or death in the patients post-ablation was noted. According to the adverse event evaluation criteria, version 5.0, 113 cases (96.6%) were classified as grade 1 and 4 cases (3.4%) were classified as grade 3. The Hb concentration of patients with minor bleeding (grade 1) prior to puncture was (119.7±22.2) g/L, which was significantly higher than the Hb concentration of patients with severe bleeding (grade 3), (76.0±10.4) g/L ( t=3.92, P=0.010). A meticulous examination of the data revealed that there were no statistically significant differences between the two groups with regard to pre-puncture platelet count, pre-puncture international standardised ratio, pre-puncture proportion of receiving anticoagulant drugs, length of hospital stay and number of puncture samples (all P>0.05). Conclusion:For patients with hepatocellular carcinoma who are at risk of bleeding, ultrasound-guided percutaneous liver biopsy followed by coaxial biopsy needle tract radiofrequency ablation can obtain satisfactory liver tissue samples and is relatively safe. There were differences in hemoglobin levels before puncture among patients with different bleeding after puncture.

Objective:To analyse the effect of ultrasound-guided percutaneous liver biopsy and the coaxial biopsy needle tract radiofrequency ablation on patients diagnosed with hepatocellular carcinoma who are considered to be at risk of bleeding.Methods:The data of 117 patients with hepatocellular carcinoma who underwent coaxial biopsy needle tract radiofrequency ablation after ultrasound-guided percutaneous liver biopsy in Peking University First Hospital from March 2019 to April 2023 were retrospectively analysed. There were 95 males and 22 females, with the age of (62.0±11.8) years. A comprehensive analysis was conducted on the following variables: the pre-puncture platelet count, the international standardised ratio, anticoagulation therapy, the haemoglobin (Hb) level, the success rate of the liver puncture, the qualified rate of liver puncture specimens, the number of puncture samples, the length of hospital stay, the Hb level after puncture, bleeding within 10 days post-operation, and complications after ablation, including biliary fistula, hemothorax and organ perforation.Results:Among the 117 patients, 60 cases (51.3%) had an international normalized ratio >1.1, 40 cases (34.2%) had thrombocytopenia, that is, <150×10 9/L, and 17 cases (14.5%) received continuous anticoagulation therapy before the operation. It is evident that all 117 patients successfully completed the ultrasound-guided percutaneous liver biopsy, and that all liver biopsy specimens were qualified. The absence of biliary fistula, hemothorax, organ perforation or death in the patients post-ablation was noted. According to the adverse event evaluation criteria, version 5.0, 113 cases (96.6%) were classified as grade 1 and 4 cases (3.4%) were classified as grade 3. The Hb concentration of patients with minor bleeding (grade 1) prior to puncture was (119.7±22.2) g/L, which was significantly higher than the Hb concentration of patients with severe bleeding (grade 3), (76.0±10.4) g/L ( t=3.92, P=0.010). A meticulous examination of the data revealed that there were no statistically significant differences between the two groups with regard to pre-puncture platelet count, pre-puncture international standardised ratio, pre-puncture proportion of receiving anticoagulant drugs, length of hospital stay and number of puncture samples (all P>0.05). Conclusion:For patients with hepatocellular carcinoma who are at risk of bleeding, ultrasound-guided percutaneous liver biopsy followed by coaxial biopsy needle tract radiofrequency ablation can obtain satisfactory liver tissue samples and is relatively safe. There were differences in hemoglobin levels before puncture among patients with different bleeding after puncture.

Objective To evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. Methods The clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. Results The baseline and min ALC of 98 patients during radiotherapy were 1.52×10⁹/L and 0.45×10⁹/L, respectively(P<0.001). The optimal cut-off value of min ALC for the prediction of the one-year survival rate was 0.38×10⁹/L. GTV, the mean dose of the liver and spleen, the V5 and V10 of the liver and spleen, and the V15 of the spleen were correlated with min ALC, and the V5 of the liver was an independent predictor of min ALC. The overall survival of patients with high min ALC was higher than that of patients with low min ALC. Independent prognostic factors were min ALC≤0.38×10⁹/L (HR=0.515, P=0.024), min ALC≥grade 3 (HR=0.576, P=0.032), tumor thrombus in the portal/vena cava, Child-Pugh grade A, increase of ≥2 points in the Child-Pugh score after radiotherapy, and received more than two other therapies. Conclusion Min ALC≤0.38×10⁹/L and min ALC≥grade 3 have independent prognostic value in patients with unresectable hepatocellular carcinoma receiving radiotherapy.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy located primarily in infratentorial or subcortical areas with a poor prognosis, and rarely in the lateral ventricle with a very poor prognosis. So far, only 6 cases of AT/RT in lateral ventricle have been reported in China. This article reports the diagnosis and treatment of four children with AT/RT in the lateral ventricle, and discusses the clinical manifestations, differentiation and diagnosis, treatment and prognosis of the disease through literature review, in order to improve clinicians' understanding of the disease and reduce missed diagnosis and misdiagnosis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Background and Aims:Rupture is the most serious complication of abdominal aortic aneurysm,requiring rapid diagnosis,emergency surgery,and posing significant surgical challenges,with high mortality rates. Currently,there is very limited reporting on ruptured abdominal aortic aneurysm (rAAA) in our country,which presents numerous difficulties for the prevention and treatment of rAAA. This study collected the data of epidemiological characteristics,treatment outcomes,and prognosis of rAAA patients from multiple centers with a large sample size,analyzing the current status and trends of rAAA surgery in China over the past decade,aiming to provide reference for clinical practice.Methods:The clinical and follow-up data of 161 rAAA patients treated at five major vascular surgery centers (50 from Drum Tower Hospital Affiliated to the Medical School,Nanjing University;19 from the First Affiliated Hospital of Anhui Medical University;33 from the Second Affiliated Hospital of Nanchang University;31 from Qilu Hospital,Shandong University;and 28 from the First Affiliated Hospital of the University of Science and Technology of China) were retrospectively analyzed.Results:Among the 161 patients,124 (77.02％) were male and 37 (22.98％) were female,with an average age of 68.27 years. The median age at diagnosis was 70 years for males and 71 years for females. The overall mean aneurysm diameter was 7.11 cm,with males at 7.72 cm and females at 6.82 cm,showing a statistically significant difference (P<0.05). The main comorbidities were hypertension and coronary artery disease. Over 80％ of patients presented with abdominal pain as the initial symptom,while 15％ presented with low back pain,and 8 patients sought medical attention for dizziness or visual disturbances. Among the 161 patients,86 underwent open surgical repair (OSR),and 75 received endovascular aneurysm repair (EVAR). The proportion of EVAR has increased annually,reaching nearly 70％ in the past five years,and up to 90％ in patients aged over 70 years. All OSR procedures were performed under general anesthesia,while 20 EVAR cases used local anesthesia and 55 used general anesthesia. Compared to the OSR group,the EVAR group showed significant differences in operative time (231.77 min vs. 162.49 min),intraoperative blood transfusion volume (1578.56 mL vs. 843.87 mL),length of hospital stay (21.21 d vs. 15.34 d),ICU stay duration (8.28 d vs. 5.49 d),and hospitalization costs (108500 CNY vs. 132800 CNY) (all P<0.05). No significant differences were found between the EVAR and OSR groups in total complications or perioperative mortality rates (both P>0.05). The main causes of perioperative death included respiratory and circulatory failure,acute myocardial infarction,and severe infections. Postoperative follow-up was effectively conducted for 92 patients,with follow-up durations ranging from 10 to 142 months. Survival analysis revealed no significant difference in survival rate between the OSR and EVAR groups (P=0.3182).Conclusion:rAAA is a rare and high-risk disease,with certain clinical differences between male and female patients. The number of EVAR procedures has increased rapidly;however,EVAR has not shown a significant advantage over OSR in improving long-term survival rates.

Oral squamous cell carcinoma(OSCC)associated pain commonly predicts adverse events among patients.This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy.However,it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression.In this study,we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo,as evidenced by clinical tissue microarray analysis and murine lingual denervation.We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort.Notably,such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor(A2AR)on trigeminal ganglia.Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo.We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP,an effect counteracted by SCH58261.We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP.Finally,we diminished the impact of CGRP on OSCC with istradefylline,a clinically available drug that targets neuronal A2AR.Therefore,we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.

Background and Aims:Rupture is the most serious complication of abdominal aortic aneurysm,requiring rapid diagnosis,emergency surgery,and posing significant surgical challenges,with high mortality rates. Currently,there is very limited reporting on ruptured abdominal aortic aneurysm (rAAA) in our country,which presents numerous difficulties for the prevention and treatment of rAAA. This study collected the data of epidemiological characteristics,treatment outcomes,and prognosis of rAAA patients from multiple centers with a large sample size,analyzing the current status and trends of rAAA surgery in China over the past decade,aiming to provide reference for clinical practice.Methods:The clinical and follow-up data of 161 rAAA patients treated at five major vascular surgery centers (50 from Drum Tower Hospital Affiliated to the Medical School,Nanjing University;19 from the First Affiliated Hospital of Anhui Medical University;33 from the Second Affiliated Hospital of Nanchang University;31 from Qilu Hospital,Shandong University;and 28 from the First Affiliated Hospital of the University of Science and Technology of China) were retrospectively analyzed.Results:Among the 161 patients,124 (77.02％) were male and 37 (22.98％) were female,with an average age of 68.27 years. The median age at diagnosis was 70 years for males and 71 years for females. The overall mean aneurysm diameter was 7.11 cm,with males at 7.72 cm and females at 6.82 cm,showing a statistically significant difference (P<0.05). The main comorbidities were hypertension and coronary artery disease. Over 80％ of patients presented with abdominal pain as the initial symptom,while 15％ presented with low back pain,and 8 patients sought medical attention for dizziness or visual disturbances. Among the 161 patients,86 underwent open surgical repair (OSR),and 75 received endovascular aneurysm repair (EVAR). The proportion of EVAR has increased annually,reaching nearly 70％ in the past five years,and up to 90％ in patients aged over 70 years. All OSR procedures were performed under general anesthesia,while 20 EVAR cases used local anesthesia and 55 used general anesthesia. Compared to the OSR group,the EVAR group showed significant differences in operative time (231.77 min vs. 162.49 min),intraoperative blood transfusion volume (1578.56 mL vs. 843.87 mL),length of hospital stay (21.21 d vs. 15.34 d),ICU stay duration (8.28 d vs. 5.49 d),and hospitalization costs (108500 CNY vs. 132800 CNY) (all P<0.05). No significant differences were found between the EVAR and OSR groups in total complications or perioperative mortality rates (both P>0.05). The main causes of perioperative death included respiratory and circulatory failure,acute myocardial infarction,and severe infections. Postoperative follow-up was effectively conducted for 92 patients,with follow-up durations ranging from 10 to 142 months. Survival analysis revealed no significant difference in survival rate between the OSR and EVAR groups (P=0.3182).Conclusion:rAAA is a rare and high-risk disease,with certain clinical differences between male and female patients. The number of EVAR procedures has increased rapidly;however,EVAR has not shown a significant advantage over OSR in improving long-term survival rates.