BackgroundPreventing and intervening in adolescent gaming disorder is of significant practical importance. Gaming motivation is strongly linked to gaming addiction and serves a key function in comprehending and addressing addictive gaming behaviors. However， the relationship between components of gaming motivation and symptoms of gaming disorder remains unclear. ObjectiveTo explore the relationship between components of gaming motivation and symptoms of gaming disorder among adolescents， so as to provide references for the prevention and intervention of gaming disorder in this population. MethodsFrom January to February 2024， a cluster sampling method was employed to select 1 414 adolescents from four middle schools in Sichuan Province and Chongqing Municipality as participants in the study. Online Game Motivation Scale （OGMS） and Gaming Disorder Scale for Adolescents （GADIS-A） were administered. Network analysis methods were utilized to investigate the relationships between components of gaming motivation and symptoms of gaming disorder. ResultsThe network edge weights revealed that achievement motivation was positively correlated with impaired game control ability， continued gaming despite negative consequences and the frequency of symptom occurrence （r=0.115， 0.050， 0.076， P<0.05）. Social motivation was negatively correlated with negative consequences （r=-0.054， P<0.05），while immersion motivation was positively correlated with continued gaming despite negative consequences （r=0.032， P<0.05）. Achievement motivation exhibited the highest strength centrality （1.157） among the three components of gaming motivation. ConclusionThe connections between components of gaming motivation and symptoms of gaming disorder exhibit distinct patterns， with each motivational component influencing gaming disorder through specific symptom pathway. Among these components， achievement motivation plays the most critical role in the interplay between gaming motivation and symptoms of gaming disorder. ［Funded by Chongqing Science and Health Joint Medical Science and Technology Innovation Projects General Projects （number， 2023MSXM133）］

Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Mice ; Animals ; Astrocytes ; Neuroglia/physiology* ; Diencephalon ; Brain ; Neurons ; Mammals

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Objective To explore the value of energy spectrum CT based material imaging for quantitatively and qualitatively evaluating lumbar intervertebral disc degeneration.Methods Lumbar energy spectrum CT and MRI were collected from 82 patients with back and leg pain,and 74 keV CT,water(chondroitin sulfate[CS])and CS(water)material images were obtained.Intervertebral discs Pfirrmann grading(PG)was performed based on MRI.CT values,water(CS)and CS(water)concentration of nucleus pulposus(NP)and annulus fibrosus(AF)in lumbar intervertebral disc with different PG grades were compared,and the relations with PG grades were analyzed.Visual classification of lumbar intervertebral disc was performed based on water(CS)and CS(water)falsecolor map,while PG distribution of different visual classification were compared,and the relations with PG grades were observed.Results Totally 250 lumbar intervertebral discs were enrolled,including 22 of PG Ⅰ,49 of PG Ⅱ,83 of PG Ⅲ and 96 of PG Ⅳ.CT values,water(CS)and CS(water)concentration of anterior AF,NP and posterior AF of intervertebral disc with different PG grades were significantly different(all P＜0.001),and CT values were negatively correlated with PG grades(rs=-0.504,-0.399,-0.258,all P＜0.001),while water(CS)concentration was positively correlated(rs=0.476,0.753,0.324,all P＜0.001)but CS(water)concentration was negatively correlated with PG grades(rs=-0.486,-0.760,-0.329,all P＜0.001).Significant differences of PG grades were found among different water(CS)and CS(water)falsecolor images visual classification(all P＜0.001),while water(CS)and CS(water)falsecolor images visual classification were all positively correlated with PG grades(all rs≥0.700,all P＜0.001).Conclusion Energy spectrum CT based material imaging could be used for quantitatively and qualitatively evaluating lumbar intervertebral disc degeneration.

Objective: To understand associated factors of myopia among middle school students in Zhengzhou and to explore the correlation between myopia with overweight and obesity, to provide a scientific basis for myopia prevention. Methods: A total of 3 297 middle school students from 8 middle schools in Erqi District, Zhongmu County and Xingyang County of Zhengzhou City were selected by a cluster random sampling method to participate in vision testing and questionnaire survey. Chi square test, and Logistic regression analysis were used. Results: Overall prevalence of myopia of middle school students was 80.5%, overweight 14.7%, obesity 10.1% in Zhengzhou. The prevalence of myopia differed significantly by schooling stage, parental myopia status and sex ( χ 2= 18.34, 23.55, 8.98, 26.53, 27.46, 47.25, P <0.05). Significant differences in myopia detection rate by after school homework duration were observed in boys and the entire population( χ 2=12.40, 15.25, P <0.01), and significant differences in myopia detection rate by body mass index (BMI) were only observed in boys ( χ 2=6.32, P <0.05). The distribution of myopia severity was statistically significant by sex among junior school students, and by BMI categories among high school students ( χ 2=22.71, 20.37, P <0.01). Multivariate binary Logistic regression analysis showed that the risk for myopia among school students who were overweight and obese was 1.81 times higher than that of students who were not overweight and obese( P <0.01). Conclusion Overweight and obesity might increase the risk of myopia among middle school students, targeted measures should be taken to maintain the healthy weight of middle school students and reduce the risk of myopia.

OBJECTIVE: To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. RESULTS: After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. CONCLUSIONS TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
Male ; Animals ; Swine ; Abdominal Injuries ; Apoptosis ; Cardiopulmonary Resuscitation ; Kidney Diseases

Objective : By observing the changes of interleukin-22 ( IL-22) ，signal transduction and transcriptional activator 3 (STAT3) ，fasting blood glucose ( FBG) and fasting insulin ( FINS) of rats under the circumstance of chronic intermittent hypoxia and reoxygenation，to explore the role of IL-22 / STAT3 pathway in insulin resistance in- duced by chronic intermittent hypoxia． Methods : 4 SD rats were randomly divided into control group (NC group) and intermittent hypoxia group ( CIH group) ，with 12 rats in each group．NC group was placed in normoxia environment for 12 weeks，while CIH group was first given intermittent hypoxia for 8 weeks and then resumed normoxia feeding until 12 weeks．FBG，FINS，IL-22 and p-STAT3 / STAT3 levels were measured at baseline，week 8 and week 12 in both groups，and insulin resistance index (HOMA-IR) was calculated．The differences between the two groups were compared. Results : ① There was no significant difference of the observation indexes between the two groups at baseline (P＞0. 05) ．At 8 weeks，the levels of FBG，FINS and HOMA-IR in CIH group were higher than those in NC group (P＜0. 05) ，and the levels of IL-22 were lower than those in NC group (P ＜0. 05) ．p-STAT3 / STAT3 showed a decreasing trend，but not statistically significant．At 4 weeks of reoxygenation，there were no significant differences in FBG，FINS，HOMA-IR and IL-22 levels between the two groups (P ＞0. 05 ) ．p-STAT3 / STAT3 in CIH group was significantly higher than that in NC group ( P ＜0. 05 ) . ② Spearman rank correlation analysis showed that HOMA-IR was negatively correlated with IL-22 and p-STAT3 / STAT3 ( all P ＜0. 05) ． Conclusion Chronic intermittent hypoxia can inhibit the expression of IL-22 / STAT3 signaling pathway，IL-22 / STAT3 signaling pathway may mediate insulin resistance induced by chronic intermittent hypoxia.

Prostate cancer with refractory hyponatremia is rare. A patient was admitted with urinary retention, who developed weakness, apathy, and altered mental status during hospitalization, and was diagnosed with severe hyponatremia. After multidisciplinary consultations with departments such as endocrinology and neurology, the patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient received serum PSA test and prostate MRI examination, and was diagnosed with prostate cancer by prostate biopsy. Laparoscopic radical prostatectomy was successfully performed. Results: The patients took tolvaptan orally before operation to maintain normal serum sodium. One month after radical prostatectomy, the symptoms of fatigue and anorexia disappeared, and serum sodium returned to normal without tolvaptan taking and sodium supplementation. No tumor recurrence or hyponatremia relapse observed during the 6-month follow-up.

Objective To investigate the value of dual-energy CT quantitative parameters combined with CT features for predicting perineural invasion(PNI)of colorectal adenocarcinoma.Methods Preoperative whole-abdominal CT data of 79 patients with colorectal adenocarcinoma confirmed by postoperative pathology were retrospectively analyzed.The patients were divided into PNI group(n=31)or no PNI group(n=48).Univariate analysis was used to compare CT features and dual-energy CT quantitative parameters between groups,and the variables with significant differences were included in binary logistic regression analysis to construct a combined model.Receiver operating characteristic(ROC)curves were drawn and area under the curve(AUC)were calculated,the efficacy of single CT parameters and combined model for predicting PNI of colorectal adenocarcinoma were evaluated.Results There were significant differences of the location of the primary lesion,the maximum thickness of the diseased intestinal wall,the presence or absence of peritumoral lymph node metastases,peritumoral mesenteric streak shadow and tumor deposits shown on CT between groups(all P＜0.05).Significant differences of the arterial phase slope of energy spectrum curve(λHU),iodine concentration(IC),normalized IC(NIC),dual energy index and the venous phase NIC of dual energy index were found between groups(all P＜0.05).AUC of the above single parameters for predicting PNI of colorectal adenocarcinoma ranged from 0.615 to 0.698,while of the combined model was 0.864.Conclusion Dual-energy CT quantitative parameters combined with CT features could be used to effectively predict PNI of colorectal adenocarcinoma.

Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.