Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective To investigate the resistance levels of adult Culex quinquefasciatus mosquitoes to three commonly used pyrethroid insecticides in Xingyi City, Guizhou Province, as well as to examine the changes in metabolic detoxification enzyme activities and mutations in the knockdown resistance (kdr) gene thereby providing a scientific foundation for the prevention and control of Culex quinquefasciatus in the region. Methods In 2024, the larvae of Culex quinquefasciatus were collected from different locations in Xingyi and reared to adult mosquitoes in the laboratory, and their resistance to pyrethroid insecticides was determined using the adult mosquito contact tube method. Surviving samples (resistant population) from the resistance tests were examined for the activities of mixed function oxidase (MFO), glutathione-S-transferase (GST), and non-specific esterase (NSE) using a microplate reader. The genomic DNA of individual adult Culex quinquefasciatus mosquitoes was extracted, and the voltage-gated sodium channel (VGSC) gene fragment was amplified via PCR and sequenced to analyze the mutations in the kdr gene. Results The 24-h mortality rates of adult Culex quinquefasciatus exposed to 0.25% permethrin, 0.025% deltamethrin, and 0.025% beta-cypermethrin were 1.00%, 0%, and 0.88%, respectively, indicating all populations of Culex quinquefasciatus exhibited resistance to the three pyrethroid insecticides. The activity of MFO in permethrin-resistant population followed a normal distribution, while deltamethrin-resistant and cypermethrin populations exhibited skewed distributions. The resistance ratios (RRs) for the three populations were 1.17, 1.03, and 1.07 times, respectively, with no statistically significant differences in MFO activity between field populations and susceptible strains (all P>0.05). However, the GST activities of permethrin-resistant and beta-cypermethrin-resistant field populations were 1.06 and 1.45 times higher than those of sensitive strains (P<0.05). Sequencing of the VGSC gene fragments of adult Culex quinquefasciatus resistant to pyrethroid insecticides revealed that mutations occurred solely at 1014 locus, presenting two alleles: wild type TTA(L) (1.26%) and mutant TTT(F) (98.74%). Two genotypes were identified: wild/mutant heterozygotes L/F (2.52%) and mutant homozygotes F/F (97.48%). No statistically significant differences were observed in the frequency of resistance gene mutations among populations resistant to the three pyrethroid insecticides (P>0.05). Conclusion The adult mosquitoes of Culex quinquefasciatus in Xingyi have developed resistance to three commonly used pyrethroid insecticides, with changes observed in metabolic detoxification enzyme activities and mutations in the kdr gene. The resistance of Culex quinquefasciatus in Xingyi is the result of multiple mechanisms. Understanding the resistance level and mechanism can provide a reliable basis for mosquito control and resistance management. It is recommended to enhance the monitoring of mosquitoes' resistance to insecticides, prioritize environmental management focused on eradicating breeding sites, reduce the use of pyrethroid insecticides, and rotate with other classes of insecticides to delay the onset of resistance.

Objective:To evaluate the effect of esketamine on learning and memory function after chronic stress and the signaling pathway of N-methyl-D-aspartate receptor (NMDAR)-calmodulin-dependent protein kinase type 2 (CaMKⅡ)-cAMP-responsive element-binding protein (CREB) in the hippocampus of developing rats.Methods:Sixty clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 10-15 g, were divided into 3 groups ( n=20 each) using a random number table method: control+ normal saline group (CN group), chronic stress+ normal saline group (NS group), and chronic stress+ esketamine group (ES group). A chronic stress model was established using a chronic unpredictable stress method. After the end of stress stimulation, esketamine 10 mg/kg was intraperitoneally injected once a day for 7 consecutive days in ES group, and the equal volume of normal saline was given instead in NS group. Y maze test and Morris water maze test were used to assess the learning and memory function after intraperitoneal administration. Venous blood samples were obtained to measure the serum cortisol and reactive oxygen species (ROS) concentrations by enzyme-linked immunosorbent assay. The animals were then sacrificed under anesthesia, the brain was removed and the hippocampal tissue was isolated for examination of the pathological changes in the hippocampal CA1 region and for determination of the ratios of phosphorylated NMDAR (p-NMDAR)/NMDAR, phosphorylated CaMKII (p-CaMKⅡ)/CaMKⅡ, and phosphorylated CREB (p-CREB)/CREB (by Western blot). Results:Compared with CN group, the time spent in the novel arm was significantly shortened, the number of entries into the novel arm was reduced, the escape latency was prolonged, the number of crossing the original platform was reduced, the serum cortisol and ROS concentrations were increased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were decreased ( P<0.05), and the pathological changes of neurons were marked in NS group. Compared with NS group, the time spent in the novel arm was significantly prolonged, the number of entries into the novel arm was increased, the escape latency was shortened, the number of crossing the original platform was increased, the serum cortisol and ROS concentrations were decreased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were increased ( P<0.05), and the pathological changes of neurons were significantly attenuated in ES group. Conclusions:Esketamine can improve the learning and memory function after chronic stress in developing rats, and the mechanism may be related to reduction of oxidative stress and enhancement of the activity of hippocampal NMDAR-CaMKII-CREB signaling pathway.

Objective To assess the role of the ferroptosis-associated gene GLS2 in the prognosis of pan-cancer and immunity using bioinformatics methods. Methods GLS2 expression levels in pan-cancer were profiled using publicly available databases: The Cancer Genome Atlas, GTEx, Cancer Cell Line Encyclopedia and the International Cancer Genome Consortium. The aim was to explore the role of GLS2 gene expression, gene variation survival analysis, immune infiltration, immune checkpoint related genes, TMB, and MSI in different tumors. Results Difference in GLS2 expression levels between cancer and paraneoplastic tissues was statistically significant in most cancer types, and the expression level was correlated with survival in these cancer types. A positive correlation was found between GLS2 expression and immune cell infiltration in multiple cancer types, and GLS2 expression level was positively correlated with TMB, MSI, and methylation, and its expression is an indicator for potential therapeutic response. Conclusion Pan-cancer analysis shows that the ferroptosis-related gene GLS2 can be used as a diagnostic and prognostic marker of clear cell carcinoma of kidney, adrenocortical carcinoma, lung adenocarcinoma, and pancreatic cancer.

Objective:To explore the application value of E-learning+mind mapping in nursing internship teaching in the department of neurology.Methods:A total of 215 nursing students admitted for internships in February 2021 were selected as research subjects. They were randomly divided into two groups. The observation group received teaching method combining E-learning and mind mapping, while the control group received conventional teaching method. The two groups of nursing students were compared in terms of internship assessment results, learning engagement (learning engagement scale), clinical thinking ability (clinical thinking ability evaluation scale), and student self-recognition. SPSS 20.0 was used for t test and chi-square test. Results:After 1 month of internship, the scores of theories and practical operation were significantly higher in the observation group than in the control group [(90.05±3.02) vs. (85.29±4.17) and (81.33±5.26) vs. (78.62±4.69), all P<0.05]. The score of learning engagement scale, score of clinical thinking ability evaluation scale, and self-recognition rate were significantly higher in the observation group than in the control group (all P<0.05). Conclusions:E-learning+mind mapping can significantly enhance the learning efficiency of intern nursing students in the department of neurology and improve their clinical nursing thinking ability, making it worthy of widespread application.

Ferroptosis is a novel regulatory cell death characterized by iron dependence and mainly caused by the accumulation of lipid peroxides and reactive oxygen species in the cell. This process plays an important role in the development of many malignancies, and has been extensively studied in lung cancer, especially in antitumor therapy. In recent years, the role of ferroptosis in tumor immunotherapy has been gradually explored. Studies showed that targeting ferroptosis can improve the therapeutic efficacy of antitumor immunotherapy. In addition, immunotherapy and ferroptosis can work synergistically to enhance the effectiveness of antitumor therapy, suggesting a potential relationship between ferroptosis and immunotherapy and the possible reversal of immune drug resistance. This study aims to elucidate the characteristics of ferroptosis, and the role and potential clinical applications of ferroptosis in the antitumor immunotherapy of advanced non-small cell lung cancer. We also explore the role of some nanomaterials that target the onset of tumor ferroptosis in facilitating immunotherapy.

Objective:To evaluate the effect of esketamine on long-term cognitive dysfunction induced by propofol anesthesia in the developing rats and the role of phosphatidylinositol-3-kinase (PI3K)/serine-threonine protein kinase (Akt) signaling pathway.Methods:Forty-eight clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 10-15 g, were divided into 4 groups ( n=12 each) using a random number table method: fat emulsion group (C group), propofol group (P group), esketamine + propofol group (EP group), and PI3K inhibitor LY294002 + esketamine + propofol group (LYEP group). Medium/long-chain fat emulsion injection 100 mg/kg was intraperitoneally injected in C group. Propofol was intraperitoneally injected at a dose of 50 mg/kg, followed by an additional dose of 50 mg/kg after the righting reflex was restored (40-60 min later) in P group. In group EP, esketamine 10 mg/kg was intraperitoneally injected, followed by propofol administration using the same method as previously described in P group. In LYEP group, LY294002 25 μg was injected via the lateral ventricle, 30 min later ketamine 10 mg/kg was intraperitoneally injected, and then propofol was given using the same method as previously described in P group. Six rats in each group were randomly sacrificed at 2 h after emergence for microscopic examination of pathological changes of hippocampal neurons and for determination of Akt, phosphorylated Akt (p-Akt), Bax, and cleaved caspase-3 in the hippocampal tissues (using Western blot). The remaining 6 rats in each group were subjected to Y-maze test to evaluate their learning and memory abilities at 30 days after birth. The p-Akt/Akt ratio was calculated. Results:Compared with C group, the p-Akt/Akt ratio in the hippocampal tissues was significantly decreased, the expression of Bax and cleaved caspase-3 was up-regulated, the number of training sessions required for learning was increased, the correct response rate was decreased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was found in P, EP and LYEP groups. Compared with P group, the p-Akt/Akt ratio in the hippocampal tissues was significantly increased, the expression of Bax and cleaved caspase-3 was down-regulated, the number of training sessions required for learning was decreased, the correct response rate was increased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was significantly attenuated in EP and LYEP groups. Compared with EP group, the p-Akt/Akt ratio in the hippocampal tissue was significantly decreased, and the expression of Bax and cleaved caspase-3 was up-regulated, the number of training sessions required for learning was increased, the correct response rate was decreased ( P<0.05), and the pathological damage to neurons in hippocampal CA1 region was aggravated in LYEP group. Conclusions:Esketamine can alleviate long-term cognitive impairment caused by propofol anesthesia in the developing rats, and the mechanism may be related to activation of the PI3K/Akt signaling pathway and inhibition of apoptosis in neurons.

Objective:To evaluate the in vitro cross-neutralization of serum antibodies in human and mice immunized with inactivated SARS-CoV-2 vaccine against Delta and Beta variants. Methods:Human serum samples after a second and a third dose of inactivated SARS-CoV-2 vaccine and mouse serum samples after a two-dose vaccination were collected. The neutralizing antibodies in the samples against SARS-CoV-2 strains of prototype, Delta and Beta variants were detected using micro-neutralization assay in biosafety level Ⅲ laboratory. The seroconversion rates and geometric mean titers (GMTs) of antibodies were calculated.Results:The seroconversion rates of antibodies in human serum samples against different SARS-CoV-2 strains were all above 95%. After two-dose vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 109, 41 and 15, respectively. The GMTs decreased by 2.7 folds and 7.3 folds for the Delta and Beta variants as compared with the prototype strain. After the booster vaccination, the GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 446, 190 and 86, respectively. The GMTs of neutralizing antibodies against Delta and Beta variants decreased by 2.3 folds and 5.2 folds as compared with that against the prototype strain. The seroconversion rates of antibodies against different SARS-CoV-2 strains in mouse serum samples were all 100%. The GMTs of neutralizing antibodies against the prototype, Delta and Beta strains were 2 037, 862 and 408, respectively. The GMTs decreased by 2.4 folds and 5.0 folds for the Delta and Beta variants.Conclusions:Inactivated SARS-CoV-2 vaccine could induce a certain level of neutralizing antibodies against Delta and Beta variants in both human and mouse models. Moreover, a third dose of vaccine induced higher levels of neutralizing antibodies against Delta and Beta variants in human. This study provided valuable data for the clinical application and protective evaluation of the inactivated SARS-CoV-2 vaccine.

Tongue diagnosis is one of the diagnostic methods of Traditional Chinese Medicine (TCM), but its development has always been restricted by the lack of objective quantitative indicators. With the rapid development of computer technology and the advent of the algorithm era, the modernization of TCM tongue diagnosis has gradually become a hot research spot. This paper annalyses the literature and related patents of the modernization of tongue diagnosis and summarizes the R&D progress and application of tongue diagnosis as well as related instruments. It is found that domestic and foreign scholars focus on tongue diagnosis related research and attach importance to the formulation of relevant international standards. Tongue collection and analysis technology continues to develop; tongue diagnostic instruments are also gradually enriched. At present, their applications are extended to family self-use, but they are still mainly used in teaching, scientific research and other fields, involving the clinical efficacy evaluation of TCM, clinical case classification and health management, and there is still much room for development. In the future, we should strengthen the communication between multi-regional research centers, promote the communication among talents in different fields, constantly make up for the deficiencies and promote the development of tongue diagnosis research.

Objective:To investigate the effect of antibiotics application in perioperative period on carotid artery and serum interluekin-6 (IL-6) in chronic periodontitis (CP) rats with hyperlipidemia (HL) or diabetes mellitus (DM).Methods:The models of CP rats with HL or DM were established in different batches. The rats were divided into groups as follows: A and A' were normal control groups, n=7 in each group; B(HL) and B'(DM) were groups of HL and DM, n=7 in each; C(HL+CP) and C'(DM+CP) were groups of CP with HL and CP with DM, n=21 in each. After the establishment of the models, groups C and C' were divided into C1 and C1' non-intervention group, C2 and C2' simple tooth extraction group and C3 and C3' antibiotic-assisted tooth extraction, with 7 rats in each of the groups. Two time interventions were performed to extract experimental teeth (bilateral maxillary first and second molars) in groups C2, C2', C3 and C3'. Serum samples were collected at 5 time points before and after tooth extraction (T1: before the first tooth extraction; T2: one week after the first tooth extraction; T3, T4, T5: the first, third and fifth week after the second tooth extraction), respectively. The absolute content of IL-6 in serum was detected by enzyme-linked immunosorbent assay (ELISA). Ratio of the absolute content in the experimental groups and control groups were calculated as the relative content of IL-6. At the end of the experiments, all rats were euthanasia and the bifurcation vascular tissues of carotid artery were collected for the observation of the carotid artery pathology and plaque formation and the measurement of the thickness of carotid intimal-medial layer (IMT). Results:Carotid artery pathology observation showed the IMT in group C was significantly thickened and the group C2 was the most thickened one (compared with group A, P＜0.01). Elastic fibers in groups C1 and C2 were disordered or even broken and disappeared, presenting typical atherosclerotic plaques, which were diffuse calcium salt deposits in the intimal-medial layers and protrude into the lumen. Elastic fibers in group C3 were ranged in ordered relatively without obvious fracture and the number of plaques was significantly reduced. The vascular walls in rats of groups B' and C' were incomplete, the IMTs had no obvious changes, elastic fibers were ranged disorderly and broken and the smooth muscle cells had vacuolar changes. In group C2', the vascular wall was significantly thinned and calcified plaques appeared in the artery, which showed multiple calcification lesions penetrating through the intimal-medial layer or even the whole layer. The vascular wall of group C3' was integrity and the elastic fibers arranged relatively clutter-free, the number of plaques was reduced. Results of detections of IL-6 showed the relative contents of IL-6 in groups B, B', C1, and C1' increased with time. At T3 time point, the relative contents of IL-6 in groups C2 and C3 reached the peak, C2 was 10.4 times of group A and C3 was 9.5 times of group A, and then decreased to different low levels. At T5 point, comparisons of the relative contents of IL-6 showed C3 < C2 < C1 (3.2 times, 5.4 times, 9.6 times of group A, respectively). The relative contents of IL-6 in groups C2' and C3' reached the peak at T2 point (4.9 times and 4.5 times of group A, respectively), and then decline with time. At T5 point, comparisons of the relative contents of IL-6 showed C3'< C2'< C1' (1.2 times, 1.4 times and 3.1 times of group A, respectively). Conclusions:Blood vessels were observed more obvious thickened in the tooth extraction without antibiotic of HL+CP rats with calcifications increase. Blood vessels of DM+CP rats became thin and fragile and even the integrity was damaged. Perioperative use of antibiotics might reduce the carotid artery lesions and decrease serum levels of inflammatory cytokines.