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

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective:To develop a novel magnetic composite nanoparticle with excellent targeting and biocompatibility and verify synergistic magnetic hyperthermia/radiotherapy efficacy in HeLa cells.Methods:Bovine serum albumin(BSA)was used to modify ferroferric oxide(Fe 3O 4)nanoparticles, and then L-selenocystine and folic acid(FA)were coupled on the surface of BSA by carbodiimide method to synthesize magnetic composite nanoparticles Fe 3O 4@BSA@SeCyc2@FA.The as-prepared nanoparticles were characterized to determine the structure, composition, and properties of the nanoparticles to support their biological applications.By evaluating the magnetothermal properties of the as-prepared nanoparticles, analyzing the internalization effect of HeLa cells on the particles and using CellTiter and reactive oxygen species(ROS)kits to detect the cell viability and ROS production of different experimental groups, respectively, the killing and inhibiting effects on HeLa cells were evaluated when hyperthermia was combined with radiotherapy. Results:The average particle size of the Fe 3O 4@BSA@SeCyc2@FA nanoparticles was(19.31 ± 4.84)nm, and the zeta potential was -25.4 mV(pH=7), which indicated that the as-prepared nanoparticles maintained acceptable dispersion and stability for biological experiments.By BSA and FA characteristic absorption peaks combined with the measured content of Se(10.89 μM), L-selenocystine and FA were successfully modified on the surface of the composite nanoparticles.The saturation magnetization value of the Fe 3O 4@BSA@SeCyc2@FA nanoparticles was 47.2 emu/g.The as-prepared nanoparticles maintained the specific absorption rate(SAR)value of 125.4 W/g at the alternating magnetic field of 518 kHz/16 kAm -1, indicating excellent heat generation efficiency(the temperature level ΔT=7 ℃ within 15 min).No significant toxicity was found for HUVEC cells even within the concentration range from 0 to 200 μg/ml and inhibition of cell viability of the HeLa was shown.When magnetic hyperthermia combined with high-energy X-ray, the cell viability of the HeLa decreased significantly to 54.7%, and the intracellular ROS production increased by 108.2% compared with the control group, which showed that the as-prepared nanoparticles significantly enhanced the radiosensitivity of HeLa cells, and the synergistic effect of magnetic hyperthermia combined with radiotherapy was more effective in inhibiting and killing them. Conclusions:The as-prepared nanoparticles show great promise for use as a multifunctional nanoplatform for the synergistic magnetic hyperthermia/radiotherapy to overcome the limitations of monotherapy for cancer treatment.

Objective:To evaluate the role of mitochondria-associated endoplasmic reticulum membranes (MAMs) regulated by protein tyrosine phosphatase interacting protein 51 (PTPIP51) in sevoflurane-induced necroptosis in hippocampal neurons of rats using the in vitro experiment.Methods:Primary cultured hippocampal neurons from fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well ) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 4 groups ( n=19 each) using a random number table method: control group (C group), sevoflurane group (Sev group), sevoflurane+ siRNA-PTPIP51 transfection group (Sev+ siPTPIP51 group), and sevoflurane+ nonsense siRNA transfection group (Sev+ siNC group). The neurons were placed in a culture incubator containing 2% sevoflurane and incubated at 37 ℃ for 5 h in Sev, Sev+ siPTPIP51 and Sev+ siNC groups. Then neurons were collected for determination of the cell survival rate (by MTT method), cytoplasmic calcium concentration ([Ca 2+ ] i) and necroptosis rate (by flow cytometry), expression of PTPIP51, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) (by Western blot) and for microscopic examination of the partial length, endoplasmic reticulum circumference, and mitochondrial circumference of MAMs (with a transmission electron microscope). Results:Compared with group C, the activity of neurons was significantly decreased, the [Ca 2+ ] i and necroptosis rate were increased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were increased in group Sev ( P<0.05). Compared with group Sev, the activity of neurons was significantly increased, the [Ca 2+ ] i and necroptosis rate were decreased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were decreased in group Sev+ siPTPIP51 ( P<0.05), and no statistically significant changes were found in the above parameters in group Sev+ siNC ( P>0.05). Conclusions:Up-regulation of PTPIP51 expression mediates structural changes in MAMs and is involved in the process of sevoflurane-induced necroptosis in hippocampal neurons of rats.

【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.

Objective:To investigate the risk factors for positive margins after endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, and to follow up the recurrence.Methods:The endoscopic, clinical and pathological data of 489 patients with early gastric cancer or precancerous lesions treated by ESD in Fujian Provincial Hospital from January 2015 to December 2020 were retrospectively collected. They were categorized into a negative group (371 cases), a low-grade intraepithelial neoplasia (LGIN)-positive group (79 cases), and a high-grade intraepithelial neoplasia (HGIN) or cancer-positive group (39 cases) according to the different margins. Logistic regression was used to analyze the risk factors for positive margins, the Kaplan-Meier method and log-rank test to compare the risk of recurrence in different margin groups, and the Cox proportional risk regression model to explore the associated factors that caused recurrence in those with positive margins.Results:In the 489 patients, the positive resection margin rate was 24.1% (118/489), of which HGIN or cancer accounted for 33.1% (39/118). LGIN-positive margin was more likely to occur for lesions larger than 10 cm 2 ( OR=1.58, 95% CI: 1.13-2.08, P=0.033), in the presence of ulcers ( OR=2.92, 95% CI: 1.37-4.54, P=0.012) and for 1-2 years of ESD experience [ OR=1.69 (1-2 years VS 5-6 years), 95% CI: 1.51-1.94, P=0.026]. Those located in the upper 1/3 of the stomach [ OR=3.64 (upper 1/3 VS lower 1/3), 95% CI: 1.27-5.50 P=0.010] and submucosal infiltration (SM1 VS M1+M2: OR=2.37, 95% CI: 1.04-5.72, P=0.028; SM2 VS M1+M2: OR=6.08, 95% CI: 1.31-12.75, P=0.002) were high risk factors for HGIN/cancer-positive margin. Postoperative follow-up was completed in 337 patients, with a median follow-up time of 26.0 (22) months. The overall cumulative recurrence was 5.3% (18/337), 2.1% (5/239) in the negative margin group, 8.3% (6/72) in the LGIN-positive margin group, and 26.9% (7/26) in the HGIN/cancer-positive group, with statistically significant differences among the 3 groups ( P<0.05). Risk factors for recurrence in the positive margin group included positive basal margins ( HR=5.17, 95% CI: 1.47-14.09, P=0.011) and SM1 invasion ( HR=4.82, 95% CI: 1.38-14.77, P=0.013). Conclusion:Positive margins after ESD for early gastric cancer and precancerous lesions are related to lesion location, size, presence of ulceration, depth of infiltration, and endoscopists' experience. The overall risk of recurrence is higher in those with positive margins than in those with negative margins. Additional treatments need to be considered comprehensively for those with submucosal invasion and positive basal margins.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.

Objective:To investigate the unqualified hepatitis C virus (HCV) detection result of blood donors from the served area of blood institutions.Methods:The data related to HCV markers detected of the first and repeat blood donors were collected from the system of practice comparison for the Chinese mainland blood institutions from 2017 to 2021. The anti-HCV reactive rate and the rates of anti-HCV negative but HCV-RNA reaction and all the relationship between rates and the annual, regional and different blood donors were statistically analyzed.Results:During 2017-2021, the number of anti-HCV reactive per 100 000 blood donors decreased from 444.3 to 250.44 in the served area of 22 blood institutions ( χ2=49.677, P<0.05). The number of HCV RNA detected positive per 100 000 anti-HCV negative increased from 0.69 to 2.05 year by year, but there was no statistical significance ( χ2=0.643, P>0.05). The anti-HCV unqualified rate was significantly different among regions ( χ2=3 260.283, P<0.05). The anti-HCV unqualified rate of the first blood donors was significantly higher than that of the repeated blood donors ( F=130.993, P < 0.05). The annual number of HCV RNA detected positive per 100 000 anti-HCV negative blood samples from donors ranged from 0 to 17.28. Conclusions:The anti-HCV unqualified rate of blood donors in the served area of 22 blood institutions decreased year by year. Compared with repeated blood donors, HCV infection should be emphasized in first-time blood donors. The implementation of HCV RNA test can detect out much more HCV infections and reduce the risk of transfusion transmitted infectious HCV.

OBJECTIVE：To study the improvement effects of ica riin（ICA）on cognitive function in schizophrenia model rats and its mechanism. METHODS ：SD rats were divided into blank control group ，model group ，ICA low-dose ，medium-dose and high-dose groups （15，30，60 mg/kg）. Except for blank control group ，other groups were given N-methyl-D-aspartate receptor antagonist MK- 801（0.2 mg/kg）intraperitoneally to induce schizophrenia rats models ，once a day ，for consecutive 14 days. After modeling，ICA groups were intragastrically administered with the corresponding drugs ，while blank control group and model group were intragastrically administered with the same volume of water ，once a day ，for consecutive 7 days. The behavioral com changes of rats were detected by Morris water maze test ，open field test ， forced swimming test and Y maze test pathological changes of hippocampus were observed by Nissl staining；the levels of cholinergic indexes [acetylcholine （Ach），choline acetyltransferase （ChAT） and acetylcholinesterase （AchE）] in cerebral tissues were detected by ELISA. The expression of BDNF ，ERK and CREB mRNA in cerebral tissue were detected by RT-PCR ；expression or phosphorylation level of BDNF ，ERK，CREB protein ，apoptosis related proteins （Bcl-2，Bax and Caspase- 3）were detected by Western blot. RESULTS ：Compared with blank control group ，escape latency ，distance at T 1-T3， cumulative immobility time and the expression of Caspase- 3 protein in cerebral tissues were significantly increased in model group （P＜0.05）；the times of crossing platform ，alternation rate ，the number of Nissl staining positive neurons in hippocampus tissues ， the levels of Ach and ChAT in cerebral tissues ，Bcl-2/Bax ratio ，mRNA and protein expression of BDNF ，mRNA expression of ERK and CREB ，the phosphorylation of ERK 1/2 and CREB were significantly decreased （P＜0.05）.Compared with model group ， escape latency ，distance at T 1-T3，cumulative immobility time ，the number of Nissl staining positive neurons ，AchE level in cerebral tissues and relative expression of Caspase- 3 protein were significantly decreased in ICA high-dose group （P＜0.05）；the times of crossing platform ，alternation rate ，levels of Ach and ChAT in cerebral tissues ，Bcl-2/Bax ratio ，mRNA and protein expression of BDNF ，mRNA expression of ERK and CREB ，the phosphorylation of ERK 1/2 and CREB were increased significantly（P＜0.05）. Above indexes in ICA low-dose and medium-dose groups were partially improved significantly than model group（P＜0.05）. CONCLUSIONS ：ICA can improve cognitive function in schizophrenia model rats.Its mechanism may be related to regulating cholinergic system ，inhibiting neuronal apoptosis ，and promoting the expression of BDNF/ERK/CREB signaling pathway.