Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

【Objective】 To explore the application value of ¹⁸F-PSMA PET/CT on the detection of metastatic lesions of prostate cancer with serum total prostate specific antigen (tPSA) ≤20 ng/mL and the predictive variables affecting the imaging results, and to establish a predictive nomogram for the metastasis of prostate cancer. 【Methods】 The imaging, pathological, serum and clinical data of 175 pathologically confirmed prostate cancer patients who underwent ¹⁸F-PSMA PET/CT examination during Jan.2020 and Oct.2021 were retrospectively collected.The patients were divided into metastatic group and non-metastatic group according to PET/CT imaging results, and the positive detection rate of metastatic lesions was calculated.The independent influencing factors of ¹⁸F-PSMA PET/CT in the positive detection of metastatic lesions were determined with univariate and multivariate logistic regression analyses.The predictive nomogram was established. 【Results】 Of the 175 patients, metastatic lesions were detected in 78 cases and not detected in 97 cases, with a detection rate of 44.6% (78/175).There were statistically significant differences between the metastatic group and the non-metastatic group in urinary tract symptoms, androgen deprivation treatment (ADT) at the time of PET/CT examination and the risk level of Gleason score (GS) (P<0.05).Univariate logistic regression showed that urinary tract symptoms(OR=3.64, P<0.001), GS risk (OR=3.96, P<0.001) and concurrent ADT treatment (OR=3.71, P<0.001) were associated with the positive detection rate of metastatic lesions.Multivariate Logistic regression showed that urinary tract symptoms (OR=3.19, P=0.002), GS high-risk group (OR=2.95, P=0.005) and concurrent ADT treatment (OR=3.27, P=0.001) were independent predictors of positive detection rate. 【Conclusion】 The probability of metastasis in newly diagnosed prostate cancer patients with tPSA≤20 ng/mL is high.¹⁸F-PSMA PET/CT is of high value for the early detection of metastasis.Urinary tract symptoms, GS high-risk group and concurrent ADT treatment are independent predictors of metastatic lesions.The predictive nomogram can help assist clinical optimization of imaging examination path.

Objective To evaluate the surgical treatments of refractory sclerosing peritonitis related peritoneal dialysis.Methods Clinical data of 15 patients with refractory sclerosing peritonitis related to peritoneal dialysis treated in the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from June 30,2014 to May 30,2018.Among them,5 cases underwent"open abdomen peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",4 cases underwent"laparoscopic peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",3 cases underwent"laparoscopic peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",2 cases underwent"open abdomen peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",and 1 case underwent"laparoscopic examination combined with laparotomy exploration and removal of lower abdominal catheter+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter".Age,gender,clinical symptoms,abdominal CT examination,peripheral blood routine,blood biochemistry,blood C-reactive protein(CRP),white blood cells,biochemistry,and aetiology of peritoneal dialysis fluid were collected and followed up,and the therapeutic effect was evaluated.Results 15 patients were transferred to the Department of Surgery after ineffective treatment in the Department of Internal Medicine.Preoperatively(after 5 days of antibiotic treatment)compared to before antibiotic treatment,there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Laparoscopic exploration or laparotomy exploration was performed,during which the peritoneal dialysis catheter was removed and the abdominal infection focus was cleared.A pelvic cavity washout drainage tube was left in place postoperatively.Fourteen patients had a good recovery after surgery,with effective control of peritonitis symptoms and no complications such as intestinal obstruction or enterocutaneous fistula.After the removal of the peritoneal dialysis catheter,all patients switched to hemodialysis.A comparison of inflammatory markers before and after surgery showed a significant decrease after surgery.Three days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Seven days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there was a significant decrease in blood WBC[(7.43±2.65)× 109/L VS(10.17±5.24)× 109/L],blood NEUT％[(88.23±9.02)％VS(85.07±11.57)％],and CRP[(152.88±113.01)mg/L VS(114.49±92.97)mg/L](P＜0.05);the peritoneal fluid WBC at 7 days postoperatively showed no significant change compared to before surgery(after 5 days of antibiotic treatment)(P＞0.05).The cases were followed up for at least 22 months,and 13 patients did not experience peritonitis or intestinal obstruction again.One patient died 39 days after surgery due to multiple organ failure,and one patient died from other causes after a 2-year follow-up.Conclusion For refractory sclerosing peritonitis related peritoneal dialysis that is ineffective in medical conservative treatment,On the basis of reasonable and effective antibiotics to control infection,surgical intervention should be actively carried out and surgical methods such as surgery should be used to control the progress of peritonitis,reduce mortality and improve the cure rate.

Objective:To investigate the current status of pertussis laboratory diagnosis and confirmed pertussis cases reporting in Shaanxi Province, and evaluate the quality of case reports.Methods:The information of confirmed pertussis cases reported in Shaanxi Province from January to July 2022 was collected through the China Disease Control and Prevention Information System. The laboratory diagnostic methods and pertussis vaccine immunization history of confirmed cases were investigated, and the descriptive epidemiological method was used for statistical description.Results:Of the 164 confirmed cases of pertussis reported from January to July 2022, two were not tested in the laboratory and 162 were tested in the laboratory. The proportions of different detection methods were 1.85% (3/162) of isolation and culture, 31.48% (51/162) of serum antibody IgG, 14.20% (23/162) of serum antibody IgM, 49.38% (80/162) of serum antibody PCR and 3.09% (5/162) of serum antibody IgM+ PCR. Among the 79 serological positive cases, 12 cases (15.19%)had no history of pertussis immunization, and 15 cases (18.99%), 11 cases (13.92%) and 41 cases (51.90%) had the time interval from vaccination to detection of <1 year, 1-3 years and >3 years, respectively. Based on the analysis of laboratory testing methods and vaccination history, 38 cases were misdiagnosed/misreported among 164 cases, with a misdiagnosis or misreported rate of 23.17%. There were 17, 12 and 9 cases of misdiagnosis/misreport in 0-2 years old group, 3-6 years old group and≥7 years old group, and the misdiagnosis or misreported rates were 27.42%(17/62), 26.67%(12/45) and 15.79%(9/57), respectively.Conclusions:The selection of pertussis laboratory testing methods in some medical institutions in Shaanxi Province is incorrect, which leads to a certain proportion of misdiagnosis or misreport, and it is necessary to further strengthen the training and standardization.

【Objective】 To analyze the epidemiological characteristics of pertussis in Shaanxi Province from 2012 to 2021. 【Methods】 We collected the information of pertussis cases in Shaanxi Province from 2012 to 2021 by the China Disease Control and Prevention Information System for analyzing the incidence and distribution characteristics. 【Results】 From 2012 to 2021, a total of 8270 cases of pertussis were reported in Shaanxi Province, with the incidence ranging from 0.21 to 6.20 per 100 000 persons, and for an annual average incidence of 2.17 per 100 000 persons. 44.81% (3 706/8 270) occurred from June to September. The annual average incidence in southern Shaanxi, Guanzhong, and northern Shaanxi was 1.78, 2.47, and 1.46 per 100 000 persons (χ²=289.638, P<0.001). The number of patients (proportions) with pertussis aged 0-1, 1-5, 5-10, and ≥10 years was 3 884 (46.96%), 2 869 (34.69%), 1 408 (17.03%), and 109 (1.32%), respectively. The number of patients (proportion) ≤ 2 months old, 3-5 months old, and ≥ 6 months old was 884 (22.76%),1 608 (41.40%), and 1 392 (35.84%) among pertussis patients under 1 year old. 【Conclusion】 The incidence of pertussis in Shaanxi Province basically showed an increasing trend with higher rates between June and September, higher rates in Guanzhong region of the province, and more patients over 5 years old.

Objective:To evaluate the diagnostic value of the 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in seminal vesicle invasion (SVI) of prostate cancer. Methods:Clinical and pathological materials of 88 patients (age: 51-84 years) who underwent radical prostatectomy (RP) between May 2019 and December 2021 in the First Affiliated Hospital of Xi′an Jiaotong University were analyzed retrospectively. All patients underwent 18F-PSMA-1007 PET/CT examination for primary staging before surgery. The diagnostic efficiency of 18F-PSMA-1007 PET/CT in SVI was obtained using postoperative pathological results as the " gold standard" and ROC curve was drawn. Furthermore, univariate and multivariate logistic regression analyses were used to screen the influencing factors for 18F-PSMA-1007 PET/CT prediction of SVI. Results:The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 18F-PSMA-1007 PET/CT in diagnosing SVI were 79.55%(70/88), 72.73%(16/22), 81.82%(54/66), 57.14%(16/28) and 90.00%(54/60), respectively. The ROC AUC was 0.77. Results of univariate logistic regression showed that total prostate specific antigen (tPSA), primary SUV max, Gleason score, International Society of Urological Pathology (ISUP) grade group were associated with 18F-PSMA-1007 PET/CT prediction of SVI. Results of multivariate logistic regression showed that Gleason score (odds ratio ( OR)=2.04, 95% CI: 1.19-3.50, P=0.009) was a predictor of SVI in prostate cancer. Conclusion:18F-PSMA-1007 PET/CT has certain diagnostic value in SVI of prostate cancer, and combining with Gleason score can improve the diagnostic efficiency.

The paper reported a case of a young male patient, with graft-versus-host disease (GVHD) multi-organ involvement lesions after allo-hematopoietic stem cell transplantation. The patient had diverse clinical manifestations, and overlapping acute and chronic disease processes. Acute GVHD were mainly hyperbilirubinemia, with or without elevated transaminase, bloody watery stools; chronic GVHD were highlighted by extensive skin depigmentation, oral mucosal ulcer, sick nails, etc., and chronic signs, such as membranous nephropathy, polyserositis and pulmonary restrictive ventilatory insufficiency. The diagnosis of chronic GVHD mainly relies on medical history combined with clinical manifestations, and it's needed to exclude infections, drugs and tumors. Besides, the rate of missed diagnosis and misdiagnose is high, and it requires multidisciplinary diagnosis and treatment. Combined with the literature review, it indicates that there is a greater risk of GVHD in the male recipient with female donor, and peripheral blood stem cell transplant patients have a higher incidence than bone marrow transplant patients after hematopoietic stem cell transplantation, but the effect of the graft-versus-leukemia exists. Currently, glucocorticoids therapy with or without calcineurin inhibitors are the first-line treatment for GVHD, but the overall prognosis is poor.

Objective:To investigate the effect of nano lead oxide (nano-PbO) exposure on learning and memory as well as spatial exploration ability in the mice, and the role of leukocyte infiltration of brain tissue in neurobehavioral damage caused by nano-PbO exposure.Methods:A total of 60 male SPF grade Kunming mice were divided into control group, low-dose nano-PbO group, medium-dose nano-PbO group and high-dose nano-PbO group according to body mass matching method, with 15 mice in each group.Mice in low, medium and high dose groups of nano-PbO were intraperitoneally injected with 5 mg·kg -1, 10 mg·kg -1, 20 mg·kg -1 nano-PbO, respectively. And mice in the control group were intraperitoneally injected with the same volume of 0.9% normal saline.The frequency of intervention was once a day for 28 days.Morris water maze test and open field test were used to detect the ability of learning and memory and spatial exploration of mice. Western blot was used to detect the protein expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in hippocampus of mice, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in mouse microvessels and lymphocyte function-associated antigen-1 (LAF-1) in mouse blood leukocyte. The proportion of leukocytes in mouse brain was detected by flow cytometry. All statistical analyses were performed by SPSS 20.0. Morris water maze data were analyzed by repeated measures ANOVA, the other data among multiple groups were compared by one-way ANOVA, and Tukey's test was used for further pairwise comparison.Pearson correlation analysis was performed to evaluate the correlation between neurobehavioral indexes and the proportion of white blood cells, TNF-α and IL-1β in brain tissue. Results:Morris water maze results showed that the escape latency of the four groups of mice had a significant interaction between group and time( F=3.21, P<0.05). The escape latencies of mice in middle and high dose groups of nano-PbO were higher than that in the control group (both P<0.05), and the numbers of crossing the platform of the two groups were lower than that in the control group (both P<0.05). The results of open field test showed that there was a statistically significant difference in the residence time of the mice in the four groups ( F=119.10, P<0.01). The total standing times of mice in the middle group and high dose group of nano-PbO were lower than that in the control group (both P<0.01). The results of Western blot showed that the levels of TNF-α and IL-1β in hippocampus tissue of mice were significant differences among the four groups ( F=7.21, 9.89, both P<0.05). The levels of TNF-α and IL-1β in the hippocampus of mice in the high-dose nano-PbO group were higher than those in the control group (TNF-α: (0.35±0.10), (1.03±0.30), P<0.05; IL-1β: (0.32±0.10), (0.50±0.15), P<0.05). The results of flow cytometry analysis showed that the proportions of leukocytes in the brain tissue of mice in the low, medium and high dose groups of nano-PbO were (9.99±1.09)%, (13.03±0.94)% and (16.51±3.89)%, respectively. Among them, the proportions of leukocytes in the middle and high dose groups of nano-PbO were significantly higher than that in the control group((8.13±1.29)%) (both P<0.05). The results of correlation analysis showed that the proportion of leukocytes, levels of TNF-α, IL-1β protein of hippocampus in the medium, high dose groups of nano-PbO were negatively correlated with the behavioral indexes ( r=-0.815, -0.744, -0.578, all P<0.01; r=-0.771, -0.836, -0.704, all P<0.05; r=-0.823, -0.876, -0.695, all P<0.05). The results of Western blot showed that the levels of ICAM-1 and VCAM-1 in cerebral microvessels of mice in the four groups were significantly different ( F=5.51, 16.19, both P<0.05). The levels of ICAM-1 and VCAM-1 in the middle and high dose groups of nano-PbO were higher than those in the control group(ICAM-1: (1.07±0.16), (1.21±0.35), (0.59±0.19), all P<0.05; VCAM-1: (0.68±0.12), (1.92±0.23), (0.23±0.05), both P<0.05). In addition, there was a significant difference in the level of LFA-1 protein in blood leukocytes of mice in the four groups ( F=41.80, P<0.05). The levels of LFA-1 in the middle and high dose groups of nano-PbO were higher than that in the control group((0.33±0.06), (0.89±0.23), (0.05±0.01), both P<0.05). Conclusion:The nano-PbO exposure can lead to cognitive impairment and increased inflammatory factors in the hippocampus of mice, which may be related to the increase of ICAM-1 and VCAM-1 in vascular endothelial cells, which promotes leukocyte infiltration into brain tissue.

Background Lead exposure induces microglial cell death, of which the mechanism is unclear. Ferroptosis is a new death form and its role in microglia death has not been reported. Objective To investigate the role of ferroptosis in microglia following lead exposure in order to provide a theoretical basis for the mechanism of lead neurotoxicity. Methods Microglial cell line BV-2 cells were co-cultured with 0, 10, 20 and 40 μmol·L⁻¹ lead acetate for 24 h. The 40 μmol·L⁻¹ lead acetate group with iron chelator (DFO) was named the 40+DFO group. Changes in BV-2 cell morphology after lead exposure were observed under an inverted microscope; tissue iron kit and glutathione kit were used to detect intracellular iron and glutathione (GSH) respectively; flow cytometry was applied to detect lipid reactive oxygen species (lipid ROS) immunofluorescence intensity. Western blotting and qPCR were adopted to detect the expressions of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor 1 (TFR-1), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1) protein and mRNA. Results Compared with the control group, the number of BV-2 cells decreased with increasing doses of lead and the cells showed a large, round amoeboid shape. The intracellular levels of iron of BV-2 cells were (1.08±0.04), (1.29±0.03), and (1.72±0.10) mg·g⁻¹ (calculated by protein, thereafter) in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups, respectively, significantly higher than that in the control group (P<0.05), and the intracellular level of iron in the 40+DFO group, (1.34±0.10) mg·g⁻¹, was lower than that in the 40 μmol·L⁻¹ lead acetate group, (1.72±0.03) mg·g⁻¹ (P<0.05). Compared with the control group, the TFR-1 and DMT1 protein and mRNA expressions were increased in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups (P<0.05), especially in the 40 μmol·L⁻¹ lead acetate group; the FPN1 protein expression did not change significantly, but the FPN1 mRNA expressions in BV-2 cells in the 10, 20, 40 μmol·L⁻¹ lead acetate groups were significantly decreased (P<0.05). Compared with the control group, the intracellular GSH level decreased and the lipid ROS content increased in all three lead acetate groups; compared with the 40 μmol·L⁻¹ lead acetate group, the GSH level increased by 12.30% and the lipid ROS content decreased by 13.00% in the 40+DFO group (P<0.05). The expressions of GPX4 protein were reduced to 50.00%, 35.00%, and 17.00% of that of the control group in the 10, 20, and 40 μmol·L⁻¹ lead acetate groups respectively, while the expressions of GPX4 mRNA were also significantly reduced; the expressions of SLC7A11 protein and mRNA in the 20 and 40 μmol·L⁻¹ lead acetate groups were lower than that in the control group, with the most significant decrease in the 40 μmol·L⁻¹ lead acetate group (P<0.05). Conclusion Lead exposure could induce ferroptosis in BV-2 cells, in which iron transport imbalance and oxidative damage might be involved.