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 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.

Objective:To explore the surgical treatment strategy of stent graft infection after interventional treatment of major iliac artery related diseases.Methods:Retrospective analysis was performed on the clinical data of 6 patients with secondary stent graft infection after interventional treatment for major iliac artery related diseases admitted to the Department of Vascular Surgery,Affiliated Drum Tower Hospital,Medical School of Nanjing University from November 2021 to August 2022.There were 5 males and 1 female,with a mean age of 64 years (range:49 to 79 years).The infection time was 53 days to 3 165 days.All the 6 patients received surgical treatment,including 3 patients who underwent anatomic bypass grafting (axillary arterial-femoral artery bypass,femoral arterial-femoral artery bypass) using artificial vessels,and 3 patients who underwent in situ abdominal aorta reconstruction using bovine pericardium.The perioperative situation,postoperative infection and the occurrence of serious adverse events were recorded,and the safety of different treatment methods and materials was evaluated.Results:All patients successfully completed the operation and no death occurred during hospitalization.Intraoperative blood loss was 2 000 to 5 000 ml,and intraoperative blood transfusion was 1 600 to 5 350 ml.All the patients were followed up for 81 to 395 days after surgery,and the incision healed well,and no reinfection occurred.Postoperative gastrointestinal bleeding occurred in 1 patient,secondary surgery (retroperitoneal hematoma removal) was performed in 1 patient due to postoperative bleeding at the vascular anastomosis,both lower limb amputations were performed in 1 patient due to postoperative lower limb ischemia,and intermittent claudication occurred in 2 patients.All patients were alive at the last follow-up.Conclusion:For patients with aortic stent graft infection,when the infection is not serious and there is enough space to block the proximal and distal aorta,in situ aortic reconstruction is an effective treatment,and different materials can achieve satisfactory results in a short period of time.

Objective:To explore the surgical treatment strategy of stent graft infection after interventional treatment of major iliac artery related diseases.Methods:Retrospective analysis was performed on the clinical data of 6 patients with secondary stent graft infection after interventional treatment for major iliac artery related diseases admitted to the Department of Vascular Surgery,Affiliated Drum Tower Hospital,Medical School of Nanjing University from November 2021 to August 2022.There were 5 males and 1 female,with a mean age of 64 years (range:49 to 79 years).The infection time was 53 days to 3 165 days.All the 6 patients received surgical treatment,including 3 patients who underwent anatomic bypass grafting (axillary arterial-femoral artery bypass,femoral arterial-femoral artery bypass) using artificial vessels,and 3 patients who underwent in situ abdominal aorta reconstruction using bovine pericardium.The perioperative situation,postoperative infection and the occurrence of serious adverse events were recorded,and the safety of different treatment methods and materials was evaluated.Results:All patients successfully completed the operation and no death occurred during hospitalization.Intraoperative blood loss was 2 000 to 5 000 ml,and intraoperative blood transfusion was 1 600 to 5 350 ml.All the patients were followed up for 81 to 395 days after surgery,and the incision healed well,and no reinfection occurred.Postoperative gastrointestinal bleeding occurred in 1 patient,secondary surgery (retroperitoneal hematoma removal) was performed in 1 patient due to postoperative bleeding at the vascular anastomosis,both lower limb amputations were performed in 1 patient due to postoperative lower limb ischemia,and intermittent claudication occurred in 2 patients.All patients were alive at the last follow-up.Conclusion:For patients with aortic stent graft infection,when the infection is not serious and there is enough space to block the proximal and distal aorta,in situ aortic reconstruction is an effective treatment,and different materials can achieve satisfactory results in a short period of time.

Objective To evaluate the short-term efficacy and quality of life of primary hepatocellular carcinoma patients after radiotherapy and pregabalin treatment for neuropathic pain with bone metastasis. Methods 32 patients with primary hepatocellular carcinoma bone metastases were treated with radiotherapy combined with pregabalin treatment.Then, we prospectively studied the analgesic efficacy for neuropathic pain and quality of life, used the brief pain inventory and douleur neuropathique 4 questionnaire (DN4) to evaluate pain at baseline, one and two months after radiotherapy, assessed pain response using the international consensus endpoint definition of bone metastasis, and used European Organization for Research and Treatment of Cancer Research and Treatment Quality of Life Questionnaire (EORTC QLQ-C30) and bone metastasis module (QLQ-BM22) for quality of life assessment. Results One and two months after radiotherapy, the average DN4 score of neuropathic pain decreased, and the objective pain relief rates were 62.8% and 68.6%, respectively.The physical, emotional, social, and role functional scores of EORTC QLQ-C30 functional scale significantly increased in the first month after radiotherapy.Symptom scale of pain (P=0.015), insomnia (P=0.035), and loss of appetite (P=0.022) improved, and fatigue was aggravated (P < 0.05).Two months after radiotherapy, the mean overall health score and all functional scale scores significantly increased than those at baseline.The scores of all symptom scales decreased, except fatigue, constipation, and financial difficulties (P < 0.05).In addition, pain responders showed significant improvement in emotional function (P=0.025) and physical function (P=0.029) in the functional scale and in pain (P=0.014) and fatigue (P=0.035) in the symptom scale.The QLQ-BM22 score showed that the painful sites (P=0.021) and pain characteristics (P=0.04) of the responders significantly improved compared with those of nonresponders two months after radiotherapy. Conclusion Radiotherapy combined with pregabalin can relieve neuropathic pain caused by bone metastasis from primary hepatocellular carcinoma and greatly improve the quality of life, particularly in pain responders.

Objective:To evaluate the safety and effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) in hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).Methods:Data of 15 patients undergoing TIPS for HCC with Vp4 PVTT and portal hypertension (PTN) in Peking University First Hospital from July 2018 to February 2023 were retrospectively analyzed, including 14 males and 1 female, aged (61.5±11.1) years old, ranging from 40 to 78 years old. The success rate of TIPS, portal pressure gradient (PPG) before and after procedure, perioperative adverse effects and complications were recorded. The survival status of patients was followed up by telephone review after surgery. Kaplan-Meier method was used for survival analysis.Results:The procedure of TIPS was performed uneventfully in all patients, with a technical success rate of 100% (15/15). PPG before and after TIPS were (31.73±5.48) mmHg (1 mmHg=0.133 kPa) and (17.60±3.66) mmHg, respectively, and the difference was statistically significant ( P<0.001). No perioperative death, hepatic artery or bile duct injury, acute liver failure or other major complications occurred. Compared with the preoperative status, the performance status scores [0(0, 0) vs. 3(3, 3)] and Child-Pugh scores [6(5, 8) vs. 9(8, 10)] were lower in patients one month after TIPS (all P<0.05). The median survival time was 228 d. Kaplan-Meier curves showed that the cumulative survival rates at 3, 6, 12 and 24 months after TIPS were 100%, 64.3%, 32.7% and 8.2%, respectively. Conclusion:TIPS could be safe and effective for HCC with Vp4 PVTT and severe PTN.

Objective:To evaluate the mid-term results of fenestrated/branched endovascular aortic repair (f/b EVAR) for the treatment of thoracoabdominal aortic aneurysms. M ethods The clinical data of 105 thoracoabdominal aortic aneurysm patients treated with f/b EVAR at the Department of Vascular Surgery of Nanjing Drum Tower Hospital from 2018 to 2019 were retrospectively analyzed. Results:There were 43 cases of thoracoabdominal aortic aneurysm and 62 cases of thoracoabdominal aortic aissection.A total of 336 branch arteries were reconstructed,and technical success rate was 94.3%. 100 cases (95.2%) were followed-up, 6 cases (5.7%) received reoperation interventions, and 11 cases (10.5%) died. During the follow-up period, 69 cases had complete imaging data. Based on the recent CT date of the thoracoabdominal aorta, 58 patients hael positive aortic remodeling and 11 patients hael negative and indeterminate remodeling; there were 31 cases (29.5%) of endoleaks, including 7 cases (6.7%) of type Ⅰb endoleaks, 8 cases (7.6%) of type Ⅱ, 1 case (0.95%) of type Ⅲa, 13 cases (12.4%) of type Ⅲc endoleaks and 2 cases (1.9%) of type Ⅳ. Conclusions:The mid-term follow-up results were satisfactory for TAAA treated with f/b EVAR. Internal leakage remains key point for f/b EVAR.

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes