OBJECTIVE: To develop a clinical automated diagnostic system for temporomandibular disorders (TMD) based on the diagnostic criteria for TMD (DC/TMD) to assist dentists in making rapid and accurate clinical diagnosis of TMD. METHODS: Clinical and imaging data of 354 patients, who visited the Center for TMD & Orofacial Pain at Peking University Hospital of Stomatology from September 2023 to January 2024, were retrospectively collected. The study developed a clinical automated diagnostic system for TMD using the DC/TMD, built on the. NET Framework platform with branching statements as its internal structure. Further validation of the system on consistency and diagnostic efficacy compared with DC/TMD were also explored. Diagnostic efficacy of the TMD clinical automated diagnostic system for degenerative joint diseases, disc displacement with reduction, disc displacements without reduction with limited mouth opening and disc displacement without reduction without limited mouth opening was evaluated and compared with a specialist in the field of TMD. Accuracy, precision, specificity and the Kappa value were assessed between the TMD clinical automated diagnostic system and the specialist. RESULTS: Diagnoses for various TMD subtypes, including pain-related TMD (arthralgia, myalgia, headache attributed to TMD) and intra-articular TMD (disc displacement with reduction, disc displacement with reduction with intermittent locking, disc displacement without reduction with limited opening, disc displacement without reduction without limited opening, degenerative joint disease and subluxation), using the TMD clinical automated diagnostic system were completely identical to those obtained by the TMD specialist based on DC/TMD. Both the system and the expert showed low sensitivity for diagnosing degenerative joint disease (0.24 and 0.37, respectively), but high specificity (0.96). Both methods achieved high accuracy (> 0.9) for diagnosing disc displacements with reduction and disc displacements without reduction with limited mouth opening. The sensitivity for diagnosing disc displacement without reduction without limited mouth opening was only 0.59 using the automated system, lower than the expert (0.87), while both had high specificity (0.92). The Kappa values for most TMD subtypes were close to 1, except the disc displacement without reduction without limited mouth opening, which had a Kappa value of 0.68. CONCLUSION This study developed and validated a reliable clinical automated diagnostic system for TMD based on DC/TMD. The system is designed to facilitate the rapid and accurate diagnosis and classification of TMD, and is expected to be an important tool in clinical scenarios.
Humans ; Temporomandibular Joint Disorders/diagnosis* ; Retrospective Studies ; Male ; Female ; Adult ; Middle Aged ; Facial Pain/diagnosis* ; Diagnosis, Computer-Assisted/methods* ; Sensitivity and Specificity ; Young Adult

OBJECTIVES: The integrated endoplasmic reticulum stress inhibitor (ISRIB) is a selective inhibitor of the protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway within endoplasmic reticulum stress (ERS) and can improve spatial and working memory in aged mice. Although ERS and oxidative stress are tightly interconnected, it remains unclear whether ISRIB alleviates cognitive impairment by restoring the balance between ERS and oxidative stress. This study aims to investigate the effects and mechanisms of ISRIB on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: Eight-week-old male ICR mice were randomly divided into 3 groups: Normal saline (NS) group, LPS group, and ISRIB+LPS group. NS and LPS groups received daily intraperitoneal injections of normal saline for 7 days; on day 7, LPS group mice received intraperitoneal LPS (0.83 mg/kg) to establish a cognitive impairment model. ISRIB+LPS group received ISRIB (0.25 mg/kg) intraperitoneally for 7 days, with LPS injected 30 minutes after ISRIB on day 7. Cognitive ability was evaluated by the novel place recognition test (NPRT). Real-time fluorogenic quantitative PCR (RT-qPCR) was used to detect changes in nitric oxide synthase (NOS), superoxide dismutase-1 (SOD-1), and catalase (CAT) gene expression in the hippocampus and prefrontal cortex. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), and oxidized glutathione (GSSG), were measured in hippocampal and prefrontal cortex tissues. RESULTS: Compared with the NS group, mice in LPS group showed a significant reduction in novel place recognition ratio, upregulation of hippocampal NOS-1 and NOS-2 mRNA, downregulation of SOD-1 and CAT mRNA, increased MDA and GSSG, decreased GSH, and reduced GSH/GSSG ratio (all P<0.05). Compared with the LPS group, mice in ISRIB+LPS group exhibited significantly improved novel place recognition, downregulated NOS-1 and NOS-2 mRNA, upregulated SOD-1 and CAT mRNA, decreased MDA and GSSG, increased GSH, and an elevated GSH/GSSG ratio in the hippocampus (all P<0.05). No significant changes were observed in the prefrontal cortex. CONCLUSIONS ISRIB improves LPS-induced cognitive impairment in mice by restoring the oxidative/antioxidant balance in the hippocampus.
Animals ; Lipopolysaccharides ; Male ; Mice, Inbred ICR ; Cognitive Dysfunction/drug therapy* ; Mice ; Oxidative Stress/drug effects* ; Endoplasmic Reticulum Stress/drug effects* ; Hippocampus/drug effects* ; Nitric Oxide Synthase Type II/genetics* ; Guanidines/pharmacology* ; eIF-2 Kinase/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Superoxide Dismutase/metabolism*

Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

Objective:To establish the haemodynamic response during the verbal fluency task(VFT)in patients with MCI and to find a screening tool that could be used as a predictor of dementia. Method:Functional near-infrared spectroscopy(fNIRS)can detect changes in blood oxygen in the brain,thus revealing the patient's functional brain activity status,and is used to study the level of brain function in MCI.We evaluated the hemodynamic response in the prefrontal and temporal regions of MCI patients and healthy controls in our study. Result:The results found a significantly reduced haemodynamic response in the prefrontal brain regions in the MCI group. Conclusion:The results suggested that a reduced haemodynamic response in the prefrontal brain regions could be used as a diagnostic biomarker for dementia.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

In the context of the digital economy， the operational relationship between traditional Chinese medicine （TCM） and Internet healthcare organizations as well as related governance institutions has attracted much attention. As the market scale of the Internet healthcare has continued to grow in recent years， the quality of Internet TCM healthcare has also been improved. By analyzing the development status of Internet TCM healthcare， it is proposed that Internet TCM health service should seize the opportunities and challenges in future， promote the growth of market scale from varied aspects， enhance patient-centered care awareness， and strengthen the promotion and popularization of digital services， thereby promoting the high-quality development of Internet TCM health service in the context of the digital economy.

Objective:To evaluate the relationship between microRNA-27a (miR-27a) and silent information regulator 1 (SIRT1) during myocardial ischemia-reperfusion (I/R) in rats.Methods:Fifty clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 5 groups ( n=10 each) by the random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), AAV9-miR-27a overexpression + myocardial I/R group (AAV+ I/R group), miR-27a antagomir + myocardial I/R group (AG+ I/R group) and AAV9-miR-27a negative control+ myocardial I/R group (NC+ I/R group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion. At day 14 before ischemia, AAV9-miRNA-27a adeno-associated virus 2×10 11 v. g was injected via the tail vein in AAV+ I/R group, and AAV9-miR-27a NC 2×10 11 v. g was injected via the tail vein in NC+ I/R group. miR-27a antagomir 10 mg/kg was injected via the tail vein once a day at 3 days before ischemia in AG+ I/R group. At the end of 120 min of reperfusion, serum cardiac troponin T(cTnT), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH) concentrations and contents of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissues were determined by enzyme-linked immunosorbent assay, the percentage of myocardial infarct volume by TTC staining, the expression of miR-27a in myocardial tissues by quantitative real-time polymerase chain reaction, and the expression of SIRT1 in myocardial tissues by Western blot. Results:Compared with Sham group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in AAV+ I/R, and the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05), and no significant change was found in the parameters mentioned above in NC+ I/R group ( P>0.05). Compared with AAV+ I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05). Conclusions:miR-27a is involved in the pathophysiological mechanism underlying myocardial I/R injury probably through inhibition of SIRT1 expression in rats.

Objective: To investigate the effect of silencing human leukocyte⁃associated antigen⁃G ( HLA⁃G) expression in the chorionic trophoblast cell line JEG⁃3 cells under hypoxic conditions on the biological function of JEG⁃3 cells and through the hypoxia response pathway of endothelial PAS1 region protein 1 (EPAS1)is involved in the molecular mechanism of preeclampsia under high altitude hypoxia. Methods: The expression of HLA⁃G in JEG⁃3 cells was inhibited by transfection of small interfering RNA (siRNA) . The JEG⁃3 cells after transfection were divided into four groups : normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group. CCK⁃8 test and Transwell test were used to detect the proliferation and invasion ability of the cells in four groups ; The effects of four groups of apoptosis and cell cycle were detected by flow cytometry; HLA⁃G and EPAS1 mRNA and protein expression levels were detected by real⁃time fluorescence quantitative PCR ( qPCR) and Western blot. Results : ① Compared with the normoxic control group , hypoxic control group , normoxic inhibition group , and hypoxic inhibition group could reduce the proliferation activity and invasion ability of JEG⁃3 cells , and significantly increase the apoptosis rate. The hypoxic control group and hypoxic inhibition group also produced anobvious necrotic cell population ; Under the condition of hypoxia , after reducing the expression of HLA⁃G , the cell necrosis rate was further aggravated ; Whether under normoxia or hypoxia , inhibition of HLA⁃G expression caused the cells to be blocked in the G1 phase. ② Compared with the normoxic control group , hypoxia control group , normoxic inhibition group , and hypoxia inhibition group decreased the expression of HLA⁃G protein , and hypoxia and inhibition of HLA⁃G had a synergistic effect; Hypoxia⁃inducible factors⁃2α ( HIF⁃2α ) , vascular endothelial growth factor(VEGF) and endothelin⁃1(ET⁃1) protein expression could be added , inhibition of HLA⁃G decreased the expression of inducible nitric oxide synthase( NOS2) . Conclusion In the hypoxic environment , silencing HLA⁃G may affect the biological behavior of trophoblast through the EPAS1 hypoxic response pathway and participate in the occurrence and development of preeclampsia.

Objective: To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC). Methods: In this single-center, phase II study with open-label, randomized and controlled design, young patients (18–45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate. Results: Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1–94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38–5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate. Conclusion Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead.