The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective To compare the clinical efficacy of transforaminal lumbar interbody fusion under unilateral biportal endoscopy(UBE-TLIF)and traditional posterior lumbar interbody fusion(PLIF)in treating single-segment degenerative lumbar spondylolisthesis with lumbar spinal stenosis(DLS-LSS).Methods The clinical data of 85 patients diagnosed with DLS-LSS who underwent surgery between Jan.2020 and Jan.2022 in our hospital were retrospectively analyzed.Patients were assigned to UBE-TLIF group(46 cases)and PLIF group(39 cases)based on the surgical procedure.The general characteristics,perioperative data,radiological parameters,and clinical efficacy indicators were analyzed.Results There were no significant differences in baseline characteristics,preoperative radiological parameters,pain visual analogue scale(VAS)score,or Oswestry disability index(ODI)score between the 2 groups(all P＞0.05).Compared with the PLIF group,the UBE-TLIF group had significantly longer operation time([156.42+26.65]min vs[141.36+21.46]min,P=0.006),significantly less operation blood loss([170.15+10.87]mL vs[203.15+15.67]mL,P＜0.001),and significantly shorter hospital stay([6.73+2.42]d vs[9.61+2.56]d,P＜0.001).The UBE-TLIF group had significantly smaller lumbar lordosis and segmental angle 3 months postoperatively([42.52±8.57]° vs[46.61+7.31]°,[10.93+2.59]° vs[12.16+3.05]°)and at final follow-up([41.35+7.46]° vs[44.62+6.42]°,[10.65+2.43]° vs[11.87+2.53]°)compared with the PLIF group(all P＜0.05).The fusion rate was significantly lower in the UBE-TLIF group compared with the PLIF group 3 months after operation(34.78％[16/46]vs 58.97％[23/39],P＜0.05),with no significant difference at final follow-up(93.48％[43/46]vs 94.87％[37/39],P＞0.05).The VAS score and ODI score 3 months after operation were significantly lower in the UBE-TLIF group compared with the PLIF group(2.43+0.92 vs 3.12±1.03,26.81+9.14 vs 33.35+8.76,both P＜0.01),with no significant differences at final follow-up(both P＞0.05).Conclusion As a minimally invasive surgical technique,UBE-TLIF has the advantages of minimal trauma,fast recovery,mild postoperative pain,and a reliable fusion rate.It is an effective treatment for DLS-LSS and deserves to be promoted.

Head and neck squamous cell carcinoma (HNSCC) is the most common type of heterogeneous malignant tumor. Over 60% of HNSCC patients are at locally advanced stage at the time of diagnosis. Despite the emergence of advanced diagnosis and treatment measures, the prognosis of patients with recurrent or metastatic HNSCC remains poor. The Period (PER) gene family is an important member of the circadian clock genes, with family members PER1, PER2, and PER3 showing differential expression in HNSCC, participating in biological processes such as proliferation, apoptosis, invasion, or metastasis of tumor cells. In most studies, they exhibit anti-cancer effects and are closely related to the tumor microenvironment, immunotherapy, chronotherapy, etc., making them potential biomarkers. A comprehensive analysis of the expression of PER gene family in HNSCC, its biological role in the occurrence and development of tumor and the corresponding molecular biological mechanism is helpful to explore its potential application value in the diagnosis and treatment of HNSCC.

Objective:To summarize the clinical characteristics of patients with epilepsy caused by focal cortical dysplasia (FCD), and identify the influencing factors for postoperative seizure controls.Methods:Fifty-seven patients with epilepsy caused by FCD admitted to Department of Neurosurgery, Third Affiliated Hospital of Zhengzhou University from July 2019 to November 2023 were chosen; standard preoperative evaluation, surgery, postoperative management and follow-up were performed. A retrospective study of clinical data, imaging and video electroencephalogram (VEEG) data, surgical approaches, pathological findings, and follow-up data was performed; influencing factors for postoperative seizure controls were analyzed.Results:In these 57 patients with epilepsy caused by FCD, 29 were males (50.88%) and 28 were females (49.12%). Onset age was 30.00 (8.00, 74.50) months, and surgery age was 95.00 (50.00, 138.50) months. Focal to bilateral tonic-clonic seizures (42/57; 73.68%) and epileptic spasms (13/57; 22.81%) were common seizure types. Cranial MRI was positive in 34 patients (59.65%), mainly manifested as abnormal cortical gyri/sulci morphology (17/57; 29.82%). In 43 patients accepted PET-CT, hypometabolic sites were detected in 40 (93.02%), and complete agreement between PET/MRI fusion results and actual lesion sites was noted in 40 (93.02%). FCD type I was noted in 16 patients (28.07%), type II in 39 (68.42%), and type III in 2 (3.51%). By December 2023, 44 (77.19%) had Engel grading I, 4 (7.02%) had grading II, 4 (7.02%) had grading III, and 5 (8.77%) had grading IV. Children with good prognosis (Engel grading I+II) and those with poor prognosis (Engel grading III+IV) showed significant differences in terms of time from first seizure to surgery, positive/negative MRI, and regularity of postoperative ASMs ( P<0.05). Conclusions:Focal to bilateral tonic-clonic seizure is the most common seizure type in patients with epilepsy caused by FCD, and abnormal cortical gyri/sulci morphology is the most common MRI manifestation; PET/MRI fusion imaging is superior to PET-CT or MRI in identifying epileptogenic foci. Poor seizure control can be noted in patients with long onset time to surgery, with negative cranial MRI results, or with irregular postoperative ASMs.

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient′s heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

Computational fluid dynamics (CFD) is an emerging technology applied in the field of cardiovascular medicine, which can obtain hemodynamic data by simulating the blood flow in the patient′s heart for cardiac function assessment and disease diagnosis. Left ventricular function plays a key role in the occurrence and development of cardiomyopathies and coronary disease. CFD can reconstruct the left ventricular anatomic structures of patients to clarify pathophysiologic mechanisms and analyze hemodynamic parameters to evaluate left ventricular function, verify surgical efficacy, and guide surgical strategy, which has a positive effect on achieving early diagnosis and reducing mortality from cardiomyopathies and coronary disease. At present, there are still technical limitations in the large-scale clinical application of CFD, and various solutions are being developed and tested, and further improvement and refinement are needed.

Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Objective:To examine the occurrence of complications in elderly patients who have undergone radical surgery for colorectal cancer.Additionally, this study aims to identify the various risk factors associated with these complications.Methods:This study included elderly patients with colorectal cancer who underwent radical surgery at Beijing Hospital between January 2013 and December 2020.These patients were divided into two groups based on their age.In this study, we examined a total of 906 patients who underwent surgery, with 695 patients under the age of 80 and 211 patients aged 80 and above.We classified postoperative complications into two categories: medical and surgical complications.Our analysis compared comorbidities, clinicopathological factors, perioperative variables, and postoperative morbidity and mortality between the two age groups.We utilized both univariate and multivariate analyses to identify any potential risk factors for postoperative morbidity.Results:When comparing patients under 80 years old to those aged 80 or older, it was found that the latter group had a lower body mass index, worse ASA scores, and more comorbidities.Additionally, the proportion of elderly patients with right colon cancer, pT3-4, and pN+ disease was higher compared to those under 80 years old.Furthermore, the elderly patients aged 80 or older had a lower rate of laparoscopic surgery compared to those under 80 years old.The study found that elderly patients aged 80 years and older had significantly shorter operation times compared to those younger than 80 years[(191.0±70.6)min vs.(214.0±83.3)min, t=3.642, P<0.001]. However, the overall complication rate was higher in the elderly group(32.7%)than in the younger group(22.6%)( χ2=8.839, P=0.004). Upon further analysis, it was found that medical complications increased significantly(20.9% vs.7.5%, χ2=30.547, P<0.001), whereas the rate of surgical complications did not show any statistical difference(15.6% vs.16.4%, χ2=0.069, P=0.832). The mortality rate during the perioperative period was found to be significantly higher in elderly patients aged 80 years and above compared to those below 80 years(1.9% vs.0.3%, χ2=6.316, P=0.029). Further analysis revealed that age was an independent risk factor for medical complications( HR=2.822, 95% CI: 1.804-4.414, P<0.001). Laparoscopic surgery has been shown to significantly decrease surgical complications( HR=0.475, 95% CI: 0.317-0.711, P=0.001). However, if the operation time exceeds 200 minutes, there is a significant increase in surgical complications( HR=1.942, 95% CI: 1.278-2.888, P=0.002). Conclusions:The incidence of postoperative medical complications in very elderly patients with colorectal cancer who undergo radical surgery has risen, although the rate of surgical complications has remained steady.Radical surgery for elderly patients with colorectal cancer is both safe and feasible, but it is important to prioritize the prevention and management of medical complications.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires