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1.
ACS Omega ; 9(23): 24624-24632, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38882068

ABSTRACT

Hydraulic fracturing generates fractures in a coal seam, which has been extensively used in coal mining and disaster management. To study the influences of water injection pressure and time on the propagation of hydraulic fracture, we conducted true triaxial hydraulic fracturing experiments under acoustic emission monitoring. Five briquette specimens were prepared by molding the mixture of coal powder, cement, river sand, and distilled water under 60 MPa to simulate the properties of coal seam. True triaxial loading was used to simulate the in situ stress environment of the coal seam. Hydraulic fracturing experiments on the test specimens were conducted under different water injection pressures and times. The following conclusions have been drawn. At the fixed injection time, increasing water injection pressure promotes the propagation of hydraulic fracture and the migration of water in the coal seam after the fractures are connected. The number of fractures increases from 3 to 8 as the water injected pressure increased from 3 to 9 MPa. Under the constant water injection pressure, the increase in longitudinal wave velocity in the test specimen decreases with the prolongation of water injection time. When the water reaches the action boundary of the water injection pressure, the water stops moving. At this moment, the water injection time has no effect on the longitudinal wave velocity anymore. The fracturing influence range can be increased by increasing the water injection pressure to produce a fracture network of a large radius with many fractures. Appropriately prolonging hydraulic fracturing time can ensure that the fracturing fluid fully moistens the coal seam and thus effectively reduces dust pollution.

2.
BMC Psychiatry ; 24(1): 412, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834952

ABSTRACT

BACKGROUND: The effect of childhood trauma on Internet gaming disorder remains unclear. In this study, we examined this association in Chinese students and explored the possible associated roles of psychological resilience and depression. METHODS: In total, 8,579 students from Hunan Province, China, provided information regarding their sociodemographic factors, history of childhood trauma, any symptoms of depression, psychological resilience, and characteristics of Internet gaming disorder for this cross-sectional study. The impact of childhood trauma on Internet gaming disorder, as well as the extent to which it was mediated by depression and moderated by psychological resilience was evaluated. RESULTS: The influence of childhood trauma on Internet gaming disorder was partially mediated by depression (B = 0.07, 95% CI [0.04, 0.05], p < 0.001), with psychological resilience acting as a mitigating factor (B = -0.002, 95% CI [13.74, 21.72], p < 0.001). Psychological resilience also moderated the association between childhood trauma and depression (B = - 0.003, 95% CI [22.17, 28.10], p < 0.001). Our moderated mediation model elucidated psychosocial mechanisms, revealing the underlying link between childhood trauma and Internet gaming disorder. It also demonstrated the partial mediating role of depression and modulating role of psychological resilience among Chinese students. CONCLUSIONS: Education and interventions, along with effective social support, should be provided to enhance students' psychological resilience and prevent childhood trauma and depression.


Subject(s)
Adverse Childhood Experiences , Depression , Internet Addiction Disorder , Mediation Analysis , Resilience, Psychological , Humans , Male , Internet Addiction Disorder/psychology , Female , China , Cross-Sectional Studies , Depression/psychology , Adverse Childhood Experiences/psychology , Young Adult , Adolescent , Adult , Video Games/psychology , Students/psychology
3.
Cereb Cortex ; 34(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38897816

ABSTRACT

Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.


Subject(s)
Cerebral Cortex , Magnetic Resonance Imaging , Schizophrenia , Humans , Schizophrenia/pathology , Schizophrenia/diagnostic imaging , Male , Female , Young Adult , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Adult , Gray Matter/pathology , Gray Matter/diagnostic imaging , Adolescent
4.
Article in English | MEDLINE | ID: mdl-38795823

ABSTRACT

OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.


Subject(s)
Olfaction Disorders , Psychotic Disorders , Humans , Male , Female , Psychotic Disorders/complications , Young Adult , Adult , Schizophrenia/physiopathology , Schizophrenia/complications , Discrimination, Psychological/physiology , Risk Factors , Adolescent , Olfactory Perception/physiology , Smell/physiology
5.
Article in English, Chinese | MEDLINE | ID: mdl-38763769

ABSTRACT

OBJECTIVES: To investigate the effect of subacute exposure of Di (2-ethylhexyl) phthalate (DEHP) on endometrial decidualization in mice. METHODS: CD1 mice were orally administrated with 300 mg·kg-1·d-1 (low-dose group), 1000 mg·kg-1·d-1 (medium-dose group), or 3000 mg·kg-1·d-1 DEHP (1/10 LD50, high-dose group) for 28 days, respectively. The early natural pregnancy model and artificially induced decidualization model were established, and the uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization, respectively. The effects of subacute exposure to DEHP on the decidualization of mice were detected by HE staining, Masson staining, TUNEL staining, and Western blotting, respectively. A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP, and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation. RESULTS: Compared with the control group, the conception rate was significantly lower in the high-dose DEHP subacute exposure group. HE staining showed that, compared with the control group, the decidual stromal cells in the low- and medium-dose exposure groups were disorganized, the nuclei of the cells were irregular, the cytoplasmic staining was uneven, and the number of polymorphonuclear cells was significantly reduced. Masson staining showed that compared with the control group, the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed, more abundant and more disorderly. TUNEL staining showed increased apoptosis in the decidua area compared to the control group. Western blotting showed that the expression of BMP2, a marker molecule for endometrial decidualization, was significantly reduced. The abortion rate and embryo resorption rate were significantly higher, and the number of embryos, uterine wet weight, uterine area and placenta wet weight were significantly lower in mice exposed to 300 mg·kg-1·d-1 DEHP than in control mice stimulated by mifepristone abortifacient drug. CONCLUSIONS: Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnant outcomes in mice.

6.
Heliyon ; 10(9): e30358, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38720736

ABSTRACT

Based on the matching of the database of China Industry Business Performance and China Customs Trade from 2000 to 2013, this paper constructs the digital product import index, and adopts the method of panel data modeling to systematically investigate the impact and mechanism of digital product import on the domestic value-added rate of Chinese enterprises' export from the theoretical and empirical aspects. The research finds that the import of digital products significantly promotes the improvement of the domestic value-added rate of enterprises' export, and the core conclusion is still valid after considering the endogeneity of variables, changing the measurement index and estimation method. The mechanism test finds that the import of digital products improves the domestic value-added rate of enterprises' export through two channels: cost markup and relative price. In addition, the heterogeneity test finds that the import of digital products has a stronger effect on the improvement of the domestic value-added rate of enterprises' export in non-export enterprises, pure general trading enterprises, foreign-funded enterprises, labor-intensive enterprises and enterprises in the eastern region.

7.
Eur J Gastroenterol Hepatol ; 36(6): 687-694, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38526941

ABSTRACT

The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CI = 2.25-3.32; P  = 0.00; I 2  = 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CI = 1.99-2.56; P  = 0.00; I 2  = 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CI = 1.04-2.54; P  = 0.038; I 2  = 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.


Subject(s)
Antigens, Bacterial , Bacterial Proteins , Helicobacter Infections , Helicobacter pylori , Precancerous Conditions , Stomach Neoplasms , Humans , Antigens, Bacterial/immunology , Antigens, Bacterial/blood , Helicobacter pylori/immunology , Helicobacter Infections/complications , Helicobacter Infections/microbiology , Bacterial Proteins/immunology , Stomach Neoplasms/microbiology , Stomach Neoplasms/blood , Stomach Neoplasms/immunology , Precancerous Conditions/microbiology , Precancerous Conditions/blood , Risk Factors , Prevalence
8.
J Cancer ; 15(8): 2110-2122, 2024.
Article in English | MEDLINE | ID: mdl-38495508

ABSTRACT

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.

9.
Ther Adv Neurol Disord ; 17: 17562864241237851, 2024.
Article in English | MEDLINE | ID: mdl-38525487

ABSTRACT

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

10.
Lab Med ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38470244

ABSTRACT

BACKGROUND: Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. METHODS: We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. RESULTS: We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias. CONCLUSION: Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.

11.
BMC Cancer ; 24(1): 239, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383334

ABSTRACT

PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , RNA, Circular/genetics , RNA, Circular/metabolism , Down-Regulation , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Eukaryotic Initiation Factor-4A/genetics , Eukaryotic Initiation Factor-4A/metabolism , DEAD-box RNA Helicases/genetics
12.
ACS Appl Mater Interfaces ; 16(7): 9088-9097, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38319245

ABSTRACT

The nonclassical ten-pi-electron 5,5-fused thieno[3,4-c]thiadiazole (TTD) unit is an excellent building block for constructing sub-silicon-band gap organic semiconductors. However, no small molecule acceptor (SMA) materials based on TTD have been reported despite the fact that high-sensitivity near-infrared organic photodetectors (OPDs) are generally achieved by using SMAs. In this work, we report a TTD-based narrow band gap (0.95 eV) SMA material TTD(DTC-2FIC)2 with strong near-infrared absorption. Employing PTB7-Th as a donor, OPDs based on TTD(DTC-2FIC)2 exhibit an optimized responsivity of 0.095 (±0.007) A W-1 at 1100 nm and sustain a decent responsivity of 0.074 (±0.008) A W-1 at 1200 nm. Moreover, a good specific detectivity over 1 × 1011 Jones is achieved at a wavelength of 1200 nm. Detailed characterizations imply that the performance of TTD(DTC-2FIC)2-based OPDs may be substantially improved by choosing lower-mixing donors with shallower energy levels. This work demonstrates that SMAs incorporating TTD as the core unit hold promise for constructing high-sensitivity sub-silicon-band gap OPDs.

13.
Childs Nerv Syst ; 40(5): 1349-1360, 2024 May.
Article in English | MEDLINE | ID: mdl-38227027

ABSTRACT

OBJECTIVE: To investigate the treatment plan and prognosis of children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle. METHODS: In this retrospective study, the clinical information of 10 consecutively collected children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle was analyzed. All 10 children underwent pontine tumour resection through a trans-cerebellomedullary fissure approach; 4 children underwent preoperative diffusion tensor imaging scans to determine the relationship between the tumour and facial nerve nucleus, and the other 6 children underwent intraoperative deep electroencephalography (EEG) tumour monitoring, in which the tumour electrical discharge activity of the tumour was recorded. A voxel distribution map was established to describe the distribution of the tumour location, and patient prognosis was evaluated through clinical and imaging follow-up. RESULTS: All 10 children achieved total tumour resection; 9 tumours were pathologically suggested to be ganglioglioma (WHO grade I), and 1 was a hamartoma. The symptoms of the original ocular dyskinesia and hemifacial spasm disappeared immediately after the operation. The children were followed up for 4-75 months, and none of the symptoms recurred; four cases with preoperative diffusion tensor imaging showed that the tumour was close to the facial nerve. Four in six intraoperative electrophysiological monitoring showed that the tumour had electrical discharge behaviour, and the tumour distribution map indicates a high density of tumour presence in the facial nerve nucleus and the nucleus of the abducens nerve. CONCLUSIONS: In paediatric patients, the facial symptoms are related to the location and abnormal electrical discharge of the tumour. There is no significant correlation between ocular dyskinesia and the location of the tumour. Conventional antiepileptic therapy for this disease is ineffective, and early surgical intervention for total tumour resection can achieve a clinical curative effect.


Subject(s)
Brain Stem Neoplasms , Hemifacial Spasm , Humans , Child , Hemifacial Spasm/pathology , Hemifacial Spasm/surgery , Retrospective Studies , Fourth Ventricle/surgery , Diffusion Tensor Imaging , Neoplasm Recurrence, Local/pathology , Facial Nerve/surgery , Brain Stem Neoplasms/pathology , Treatment Outcome
14.
Neuropsychopharmacology ; 49(5): 845-853, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37752221

ABSTRACT

A subgroup of patients with schizophrenia is believed to have aberrant excess of glutamate in the frontal cortex; this subgroup is thought to show poor response to first-line antipsychotic treatments that focus on dopamine blockade. If we can identify this subgroup early in the course of illness, we can reduce the repeated use of first-line antipsychotics and potentially stratify first-episode patients to intervene early with second-line treatments such as clozapine. The use of proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate and Glx (glutamate plus glutamine) may provide a means for such a stratification. We must first establish if there is robust evidence linking elevations in anterior cingulate cortex (ACC) glutamate metabolites to poor response, and determine if the use of antipsychotics worsens the glutamatergic excess in eventual nonresponders. In this study, we estimated glutamate levels at baseline in 42 drug-naive patients with schizophrenia. We then treated them all with risperidone at a standard dose range of 2-6 mg/day and followed them up for 3 months to categorize their response status. We expected to see baseline "hyperglutamatergia" in nonresponders, and expected this to worsen over time at the follow-up. In line with our predictions, nonresponders had higher glutamate than responders, but patients as a group did not differ in glutamate and Glx from the healthy control (HC) group before treatment-onset (F1,79 = 3.20, p = 0.046, partial η2 = 0.075). Glutamatergic metabolites did not change significantly over time in both nonresponders and responders over the 3 months of antipsychotic exposure (F1,31 = 1.26, p = 0.270, partial η2 = 0.039). We conclude that the use of antipsychotics without prior knowledge of later response delays symptom relief in a subgroup of first-episode patients, but does not worsen the glutamatergic excess seen at the baseline. Given the current practice of nonstratified use of antipsychotics, longer-time follow-up MRS studies are required to see if improvement in symptoms accompanies a dynamic shift in glutamate profile.


Subject(s)
Antipsychotic Agents , Psychotic Disorders , Schizophrenia , Humans , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/pharmacology , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Psychotic Disorders/metabolism , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy , Schizophrenia/metabolism , Glutamic Acid/metabolism , Proton Magnetic Resonance Spectroscopy/methods , Glutamine/metabolism
15.
Acta Pharmaceutica Sinica ; (12): 678-692, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016608

ABSTRACT

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H2O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS2 data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

16.
Chinese Medical Ethics ; (6): 601-606, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012948

ABSTRACT

In order to explore the ethical review experience of organ donation and transplantation after the death of citizens, and provide reference value for medical institutions to carry out corresponding ethical review. By using descriptive research, purpose sampling method and the principle of data saturation, 10 members and secretaries of ethics committee on clinical application of organ transplantation technology were finally selected as respondents for semi-structured interviews. The Colaizzi 7-step analysis method was adopted to analyze, summarize and refine the theme. The results showed that the ethical review experience of organ donation and transplantation after the death of citizens included four themes: the responsibilities of ethics committee, the key points of ethics review, the form of ethics review conference and its advantages and disadvantages, and the construction of the ethics committee of organ transplantation. Therefore, there are defects in the ethical review of organ donation and transplantation in medical institutions at present. These can be remedied by enriching elements of the ethical review following the four principles of medical ethics, refining the laws related to organ donation after citizens’ death, constructing a reasonable and efficient pattern of ethical review conference, and establishing a robust and appropriate operation mode of organ transplantation ethics committee.

17.
Journal of Clinical Hepatology ; (12): 319-326, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1007247

ABSTRACT

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma (HCC) recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years, and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication, mismatch repair, base excision repair, and nucleotide excision repair, and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway, there were significant reductions in the protein expression levels of MCM2 (P=0.018), MCM3 (P=0.047), MCM4 (P=0.014), MCM5 (P=0.008), MCM6 (P=0.006), MCM7 (P=0.007), PCNA (P=0.019), RFC4 (P=0.002), RFC5 (P<0.001), and LIG1 (P=0.042); for the nucleotide excision repair pathway, there were significant reductions in the protein expression levels of PCNA (P=0.019), RFC4 (P=0.002), RFC5 (P<0.001), and LIG1 (P=0.042); for the base excision repair pathway, there were significant reductions in the protein expression levels of PCNA (P=0.019) and LIG1 (P=0.042) in the HCC recurrence group; for the mismatch repair pathway, there were significant reductions in the protein expression levels of MSH2 (P=0.026), MSH6 (P=0.006), RFC4 (P=0.002), RFC5 (P<0.001), PCNA (P=0.019), and LIG1 (P=0.042) in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex, DNA polymerase complex, ligase LIG1, long patch base shear repair complex (long patch BER), and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction, the recurrence group also had significant reductions in the relative protein expression levels of MCM5 (P=0.008), MCM7 (P=0.007), RCF4 (P=0.002), RCF5 (P<0.001), and MSH6 (P=0.006). ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

18.
Acta Pharmaceutica Sinica ; (12): 25-34, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005435

ABSTRACT

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1003432

ABSTRACT

Inflammatory bowel disease (IBD), consisting of ulcerative colitis and Crohn's disease, is a chronic relapsing inflammatory gastrointestinal disease closely associated with immune dysfunction. The pathogenesis of IBD is closely related to genetic susceptibility, immune system dysfunction, environmental change, and intestinal microbial dysbiosis. Modern research has found that macrophage polarization plays an important role in the development of IBD and can affect the level of inflammatory response, intestinal mucosal repair, and intestinal microbial balance, making it a potential target for IBD treatment. Increasing evidence suggests that traditional Chinese medicine and its active components can regulate macrophage polarization through multiple pathways and balance the M1/M2 macrophage ratio, thus inhibiting inflammatory response, promoting intestinal mucosal repair, and slowing down the progression of IBD. This article summarized the biological processes and targets involved in macrophage polarization and discussed its impact on IBD. It also provided a brief overview of the latest research on how traditional Chinese medicine and its active components can improve IBD by regulating macrophage polarization, so as to provide new directions and strategies for the clinical application of traditional Chinese medicine in IBD treatment.

20.
Pediatr Investig ; 7(4): 297-300, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38050537

ABSTRACT

Introduction: Hypersalivation has been associated with Rolandic epilepsy and other childhood epilepsy syndromes. However, pure salivatory seizures are a rare type of focal seizure in which ictal hypersalivation is the dominant feature throughout the seizures. Case presentation: We present a case of pure salivatory seizures originating from the right post-central operculum cortex, confirmed by the favorable surgical outcome. We attempt to analyze the symptom from behavioral and neural network perspectives and propose a possible mechanism to generate ictal hypersalivation and pure salivatory seizures. Conclusion: Based on previous reports in the literature and our case, we emphasize the importance of the operculum in patients with ictal hypersalivation, particularly in patients with pure salivatory seizures.

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