Objective Radiation-induced brain injury (RIBI) is a common complication of radiotherapy for the head and neck tumors, and the current treatment methods are limited. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neural regulation technique, has shown great potential in neuroprotection. However, the parameter selection and biological safety of rTMS in the prevention and treatment of RIBI have not been reported. Methods Using a mouse model of RIBI, this study employed three rTMS frequencies (5, 10, and 25 Hz) for intervention. Biochemical and pathological assays were conducted to identify the optimal stimulation parameter. Subsequently, this parameter was used to evaluate the biological safety in normal mice. Results Under the conditions of this experiment, rTMS interventions with all three frequencies could reduce the levels of serum brain injury markers (NSE and S100B) and inflammatory factors in mice (P < 0.001), and alleviate the morphological and structural damage of hippocampal tissue. The 10 Hz rTMS could significantly promote hippocampal neurogenesis in RIBI mice (P < 0.05). Furthermore, 10 Hz rTMS showed no significant effects on the cognitive function and mood of normal mice. The intervention did not significantly change the morphology and structure of the main organs, blood biochemical indicators, and the level of hippocampal neurogenesis in mice. Conclusion The 10 Hz rTMS is optimal for the prevention and treatment of RIBI with high biological safety.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVES: Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS: SKF_525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF_525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC^® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS: The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R²=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.
Tandem Mass Spectrometry/methods* ; Humans ; Chromatography, High Pressure Liquid/methods* ; Substance Abuse Detection/methods* ; Liquid Chromatography-Mass Spectrometry

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective To explore the efficacy of bilateral facial muscle training combined with visual electromyography biofeedback on facial nerve function recovery in patients with idiopathic facial nerve palsy. Methods Patients with idiopathic facial nerve palsy admitted to Shanghai Fifth People’s Hospital, Fudan University from July 2022 to July 2024 were selected and randomly divided into a control group and an intervention group. The control group received conventional physical factor therapy, while the intervention group received bilateral facial muscle training combined with visual electromyography biofeedback therapy based on the control group’s regimen. After 20 treatment sessions, the total effective rate, the House-Brackmann (H-B) facial nerve grading system, the Sunnybrook Facial Grading System (SFGS) score, and the average value ratio of maximal amplitudes of bilateral frontalis and zygomaticus muscles were compared between the two groups. Results A total of 90 patients were included, 45 in each group. After 20 treatment sessions, the total effective rate was significantly higher in the intervention group than in the control group (84.4% vs 75.6%, P＝0.003). Compared with the control group, the intervention group demonstrated a significantly lower H-B grade (P＝0.003) and a higher SFGS score (P＝0.001). The average value ratios of maximal amplitudes of the affected versus healthy side frontalis (P＝0.013) and zygomatic (P＝0.022) muscles were higher in the intervention group than in the control group. Conclusions Bilateral facial muscle training combined with visual electromyography biofeedback is an effective approach for treating idiopathic facial nerve palsy, effectively promoting the recovery of facial nerve function, and improving facial symmetry and facial muscle function.

Objective To develop a rapid detection method for tiletamine that is easy to operate and low-cost under the premise of ensuring sensitivity and accuracy,to assist in carrying out rapid screening and drug control work on-site.Methods This study integrates dual-ligand copper nanozymes with mo-lecular imprinting technology.Initially,copper nanozymes were synthesized using readily available raw materials at 120℃.Subsequently,specific cavities were imprinted on their surface at room temperature using a sol-gel method to construct a novel fluorescent sensing probe.This probe was characterized and methodologically validated,and then applied to the detection of actual samples.Results The developed probe exhibited stable fluorescence properties,strong anti-interference capability,and excellent specificity and sensitivity,with a detection limit of 5 ng/mL and a quantitative concentration range from 15 to 500 ng/mL.It enabled the rapid detection of tiletamine in real samples such as blood and e-cigarette oil.Conclusion This fluorescent probe can be used for rapid detection and on-site preliminary screening of tiletamine in various types of samples.It significantly improves the detection efficiency and reduces analysis costs,showing high research value and broad application prospects.

In this study,nine hybridoma cells secreting monoclonal antibodies against deltamethrin were prepared,and the monoclonal antibody 4D4E11 with best sensitivity was selected to develop indirect enzyme-linked immunosorbent assay (ic-ELISA) and gold nanoparticle-based lateral flow immunoassay (LFIA) for detection of deltamethrin. The optimal working buffer for ic-ELISA was 0.01 mol/L phosphate buffer (pH 7.4) containing 0.2 mol/L NaCl and 20％ methanol,while 0.01 mol/L phosphate buffer (pH 7.4) containing 1 mol/L NaCl,5‰Tween-20 and 10％methanol for LFIA. Under the optimal conditions,the half inhibition concentration (IC50) and limit of detection (IC10) of ic-ELISA were 10.60 ng/mL and 1.43 ng/mL respectively,and the limit of detection of the developed LFIA was 0.5μg/mL. The developed ic-ELISA and LFIA showed no cross-reactivities (CRs) with eight kinds of analogues of deltamethrin,which indicated the excellent specificity of proposed immunoassays. The average recoveries of the ic-ELISA in spiked tomato,cabbage and lettuce samples were 79.8％-92.6％with relative standard deviations of 0.8％-5.5％. The detection results of LFIA were consistent with the spiked concentrations in the range of 1-5 mg/kg. Meanwhile,the results of ic-ELISA and LFIA showed close correlation with high performance liquid chromatography (HPLC) in the test of blind lettuce samples. The experimental results demonstrated that the two immunoassays proposed here were suitable for rapid detection of deltamethrin with high sensitivity and high accuracy.

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing factors.This etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical practice.Furthermore,EPL-affected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy.By compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.