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

The accurate prediction of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties represents a crucial step in early drug development for reducing failure risk. Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks. This research proposes molecular properties prediction with parallel-view and collaborative learning (MolP-PC), a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints (MFs), 2D molecular graphs, and 3D geometric representations, incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions. Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks, with its multi-task learning (MTL) mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks. Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization. A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC's effective generalization in predicting key pharmacokinetic parameters such as half-life (T0.5) and clearance (CL), indicating its practical utility in drug modeling. However, the model exhibits a tendency to underestimate volume of distribution (VD), indicating potential for improvement in analyzing compounds with high tissue distribution. This study presents an efficient and interpretable approach for ADMET property prediction, establishing a novel framework for molecular optimization and risk assessment in drug development.
Deep Learning

Objective:To explore the protective effect and mechanism of Tongfu Lifei decoction (TFL) on human monocytic leukemia cell THP-1 induced by lipopolysaccharide (LPS).Methods:① THP-1 cells were cultured in vitro, and incubated with 1 mg/L LPS for 18 hours to construct an in vitro THP-1 cell inflammation model. Other THP-1 cells were taken as blank control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) secreted by cells. ② THP-1 cells were divided into seven groups and treated with 0, 0.005, 0.01, 0.02, 0.04, 0.08, and 0.16 mL/mL TFL for 24 hours (added different dosages of TFL solution per milliliter of culture medium, with a crude drug content of 1 kg/L). The cell survival rate was detected using methyl thiazolyl tetrazolium (MTT) colorimetric method, and the intervention dosage of TFL for its non-toxic effect on THP-1 cells was screened. ③ Another THP-1 cells were divide into inflammatory model group and 0.01, 0.02, and 0.04 mL/mL TFL groups according to the intervention dosage of TFL screened by MTT colorimetry. After 24 hours of intervention, the levels of TNF-α and IL-6 secreted by cells were measured using ELISA. Western blotting was used to detect the expressions of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway proteins in cells. Real time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of microRNAs (miR-146a, miR-146b, miR-155) in cells. ④ The maximum non-toxic concentration of TFL (0.04 mL/mL) on the THP-1 cell was selected as the intervention dose. THP-1 cells were divided into inflammation model group, TFL group, TFL+miR-146a inhibitor group, TFL+miR-146b inhibitor group, and TFL+miR-155 inhibitor group. The inflammation model group was not given any drug intervention. The other inhibitor groups were added 100 nmol/L corresponding inhibitor. After 24 hours of intervention, the levels of TNF-α and IL-6 secreted by cells were measured using ELISA. Western blotting was used to detect the expressions of PD-1/PD-L1 signaling pathway proteins in cells. Results:① Compared with the blank control group, the levels of TNF-α and IL-6 secreted by cells in the inflammatory model group were significantly increased, indicating the successful construction of the THP-1 inflammatory cell model in vitro. ② 0-0.04 mL/mL TFL had no toxic effect on THP-1 cells. However, the survival rates of cells in the 0.08 mL/mL and 0.16 mL/mL TFL groups were significantly lower than those in the inflammation model group, indicating that TFL dosages exceeding 0.04 mL/mL had toxic effects on THP-1 cells. ③ Compared with the inflammation model group, 0.01 mL/mL TFL had no significant effect on the levels of TNF-α and IL-6 secreted by THP-1 cells, while intervention with 0.02 mL/mL and 0.04 mL/mL TFL significantly reduced the levels of TNF-α and IL-6 secreted by cells [TNF-α(ng/L): 95.89±8.55, 70.73±11.70 vs. 137.10±7.19, IL-6 (ng/L): 23.03±2.55, 16.58±1.72 vs. 32.60±2.55, all P < 0.01]. Compared with the inflammation model group, the expressions of PD-1/PD-L1 signaling pathway proteins in THP-1 cells in different dosages of TFL groups were significantly reduced, and showed a certain dosage dependence. The expressions of the pathway proteins in the 0.04 mL/mL TFL group were significantly lower than those in the inflammation model group [PD-1 protein (PD-1/β-actin): 0.28±0.04 vs. 1.00±0.10, PD-L1 protein (PD-L1/β-actin): 0.54±0.05 vs. 1.00±0.08, phosphoinositide 3-kinase (PI3K) protein (PI3K/β-actin): 0.28±0.03 vs. 1.00±0.08, phosphorylated protein kinase B (p-Akt) protein (p-Akt/Akt): 0.38±0.04 vs. 1.00±0.10, all P < 0.01]. Compared with the inflammation model group, the expression of miR-146a in THP-1 cells in the 0.01, 0.02, and 0.04 mL/mL TFL groups was significantly reduced (2 -ΔΔCt: 0.46±0.11, 0.31±0.13, 0.23±0.14 vs. 1.01±0.18, all P < 0.01), while there was no significant change in the expressions of miR-146b and miR-155. ④ Compared with the inflammation model group, the TFL group showed a significant decrease in the levels of TNF-α and IL-6 secreted by THP-1 cells. The miR-146a inhibitor could significantly reverse the inhibitory effect of TFL on inflammatory factors, and the difference was statistically significant as compared with the TFL group [TNF-α (ng/L): 138.55±10.30 vs. 72.33±10.59, IL-6 (ng/L): 31.35±3.98 vs. 15.75±3.76, both P < 0.01]. Compared with the inflammation model group, the expressions of PD-1/PD-L1 signaling pathway proteins in THP-1 cells in the TFL group were significantly reduced. The expressions of pathway proteins in cells in the TFL+miR-146a inhibitor group were significantly higher than those in the TFL group [PD-1 protein (PD-1/β-actin): 0.85±0.09 vs. 0.37±0.04, PD-L1 protein (PD-L1/β-actin): 0.83±0.08 vs. 0.55±0.06, PI3K protein (PI3K/β-actin): 0.85±0.09 vs. 0.63±0.06, p-Akt protein (p-Akt/Akt): 0.98±0.10 vs. 0.75±0.07, all P < 0.05]. Conclusion:TFL regulates the expression of miR-146a to inhibit the PD-1/PD-L1 signaling pathway in THP-1 cells, regulates the immune barrier of sepsis induced in cell inflammation model in vitro, and thus protects LPS induced THP-1 cells.

Objective To investigate the effectiveness and safety of balloon dilation technique when difficult ureteroscope accessing in ureteroscopic holmium laser lithotripsy in children.Methods Clinical data of 23 patients(25 sides)receiving ureteroscopic holmium laser lithotripsy with using balloon dilatation technique from March 2020 to October 2023 were retrospectively analyzed.When it was difficult to insert ureteroscope,the ureteral balloon catheter was retrogradely inserted through the ureteroscopic working channel to dilate the narrow part of the ureteral lumen.After dilation,the holmium laser fiber was inserted to powder the stones.Results Of the 23 patients(25 sides)with ureteral calculi,transcatheter ureteral balloon dilation was carried out in 26 places during the operation,including 23 places located in the inner part of the ureteral bladder wall and 3 places located in the lower part of the ureter.The extent of ureteral injury at dilated sites was grade Ⅰ in 23 places and grade Ⅱ in 3 places,respectively.After ureteral balloon dilatation,continued lithotripsy succeeded on 23 sides and failed on 2 sides.No complications related to ureteral dilated balloon catheter were found.The time for removing double-J ureteral stents was 26-45 d(mean,33.5±5.2 d),during which urinary tract infection occurred in 5 cases.Urinary system ultrasound examination was performed within 2 weeks after removal of double-J ureteral stents.The calculi were discharged in all the children,without hydronephrosis.No ureteral stenosis was observed in all the children during 6-24 months(mean,13.7 months)of postoperative follow-ups.Conclusion It is safe and effective to dilate the ureteral with balloon dilation technique through the working channel when difficult ureteroscope accessing.

Objective:To retrieve, evaluate, and integrate the best evidence for early ambulation in patients undergoing open lumbar surgery.Methods:A systematic search was conducted in databases including UpToDate, British Medical Journal (BMJ) Best Practice, Guidelines International Network (GIN), The National Institute for Health and Care Excellence (NICE), The Agency for Healthcare Research and Quality (AHRQ), Scottish Intercollegiate Guidelines Network (SIGN), Registered Nurses' Association of Ontario (RNAO), Medlive, North American Spine Society (NASS), Best Practice in General Surgery Group from the University of Toronto, ERAS? Society, PubMed, Embase, Web of Science, Medline, CNKI, and Wanfang. The search included literature on early ambulation post-open lumbar surgery, such as guidelines, expert consensus, evidence summaries, recommended practices, systematic reviews, and high-quality original research. The search period was from January 1, 2014, to June 20, 2023. Two researchers independently evaluated the quality of the literature and extracted relevant data.Results:A total of 23 articles were included, comprising three guidelines, two systematic reviews, six expert consensus statements, seven randomized controlled trials, one quasi-experimental study, and four cohort studies. The evidence was categorized into six themes: multidisciplinary team collaboration, health education, facilitation measures, pre-activity assessment, activity content, and safety assurance, resulting in 25 evidence-based recommendations.Conclusions:This study summarizes 25 best evidence-based recommendations for early ambulation in patients undergoing open lumbar surgery. Healthcare providers are advised to apply these recommendations in clinical practice while considering the specific clinical context and individual patient differences. Multidisciplinary collaboration is essential to develop personalized early ambulation plans.

Objective To investigate the relationship between serum high mobility group protein B1(HMGB1),C1q/TNF-associated protein 3(CTRP3)and pain degree and lumbar function.Methods A total of 145 patients with lumbar spinal stenosis treated in the hospital from September 2021 to August 2023 were retrospectively selected as the study objects,and were divided into single-segment group(89 cases)and multi-segment group(56 cases)according to the number of lumbar spinal stenosis segments.Serum levels of HMGB1 and CTRP3 were detected by enzyme-linked immunosorbent assay.The clinicopathological features such as pain degree,lumbar function and serum levels of HMGB1 and CTRP3 were compared between the two groups.The correlation of serum HMGB1 and CTRP3 levels with pain degree and lumbar function were ana-lyzed,and the factors influencing the number of segments of lumbar stenosis were analyzed by multivariate Logistic regression.The diagnostic value of serum HMGB1 and CTRP3 levels on lumbar function of patients was analyzed by receiver operating characteristic(ROC)curve.Results Visual analogue scale(VAS)score and serum HMGB1 level in multi-segment group were higher than those in single-segment group(P＜0.05),Japanese Orthopaedic Association(JOA)score and serum CTRP3 level were lower than those in single-seg-ment group(P＜0.05).Serum HMGB1 level was negatively correlated with CTRP3 and JOA score in pa-tients with lumbar spinal stenosis(r=-0.544,-0.616,P＜0.001),and positively correlated with VAS score(r=0.453,P＜0.001).The serum CTRP3 level was negatively correlated with VAS score(r=-0.550,P＜0.001),and positively correlated with JOA score(r=0.619,P＜0.001).JOA score was nega-tively correlated with VAS score(r=-0.485,P＜0.001).Multivariate Logistic regression analysis showed that JOA score and serum CTRP3 level were protective factors for multi-segmental stenosis(P＜0.05),VAS score and serum HMGB1 level were risk factors for multi-segmental stenosis(P＜0.05).The analysis of ROC curve showed that serum HMGB1 and CTRP3 levels could be used as diagnostic indexes of lumbar spinal function in patients with lumbar spinal stenosis,and the combined diagnosis effect was better(P＜0.05).Conclusion Serum levels of HMGB1 and CTRP3 are closely related to pain degree and lumbar function in pa-tients with lumbar spinal stenosis.The combination of the two indexes can be used for the clinical diagnosis of lumbar function in patients with lumbar spinal stenosis.

Objective:To observe the clinical efficacy of percutaneous minimally invasive bridging combined internal fixation system (BCFS) in the treatment of clavicle fractures through a prospective study.Methods:One hundred and sixty-four patients with clavicle fractures admitted to Fengfeng General Hospital of North China Medical Group from June 2019 to June 2022 were included as the study subjects. They were randomly divided into study group and control group with 82 cases each using random number table method. The control group was treated with reconstruction steel plate internal fixation surgery, while the study group was treated with percutaneous minimally invasive BCFS surgery. Compare surgical related indicators, degree of pain, shoulder joint function, complications and treatment outcomes.Results:The intraoperative blood loss in the study group was less than that in the control group: (43.81 ± 5.29) ml vs. (58.79 ± 6.85) ml, and the surgical time and fracture healing time were shorter than those in the control group: (52.06 ± 7.74) min vs. (67.24 ± 8.28) min, (12.42 ± 2.36) weeks vs. (14.50 ± 3.08) weeks, with statistically significant differences ( P<0.05). There was no statistical difference in the hospital stay between two groups ( P>0.05). The visual analog scale (VAS) scores of both groups at 12 and 24 h after surgery were lower than before surgery. The VAS scores at 12 and 24 h after surgery in study group were lower than those in control group: (4.15 ± 0.69) points vs. (5.68 ± 0.82) points and (2.95 ± 0.62) points vs. (3.46 ± 0.73) points, with statistical significances ( P<0.05). After 6 months of surgery, the shoulder joint function indexes were higher than before surgery, pain degree: (10.87 ± 3.25) points vs. (4.15 ± 1.08) points, (10.52 ± 3.19) points vs. (4.09 ± 1.12) points, and the shoulder joint range of motion: (31.24 ± 5.13) points vs. (16.83 ± 3.39) points, (30.52 ± 4.85) points vs. (17.21 ± 3.47) points, daily life: (16.06 ± 3.12) points vs. (7.86 ± 1.15) points, (15.73 ± 3.58) points vs. (6.94 ± 1.17) points, muscle strength: (20.67 ± 2.62) points to (8.78 ± 2.34) points, (21.06 ± 3.48) points to (9.04 ± 3.07) points, and total scores: (78.84 ± 7.16) points vs. (37.62 ± 5.09) points, (77.83 ± 6.04) points vs. (37.28 ± 6.11) points, the differences were statistically significant ( P<0.05), while there were no statistically significant differences in pain level, shoulder joint range of motion, daily life, muscle strength and total score at 6 months after surgery between the two groups ( P>0.05). After 6 months of surgery, the incidence of complications in the study group was lower than that in the control group: 4.88% (4/82) vs. 14.64% (12/82), and the difference was statistically significant ( P<0.05). After 6 months of surgery, the overall excellent and good rate in the observation group was better than that in the control group: 98.78% (81/82) vs. 89.02% (73/82), with a statistically significant difference ( P<0.05). Conclusions:The percutaneous minimally invasive BCFS surgery has a significant therapeutic effect on clavicle fractures, which is beneficial for reducing intraoperative bleeding, shortening surgical time, promoting fracture healing, reducing postoperative pain, improving shoulder joint function, and reducing the incidence of complications. It has more advantages in the treatment of clavicle fractures.

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1). METHODS: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously. CONCLUSION Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.
Female ; Humans ; Gas Chromatography-Mass Spectrometry ; Genetic Testing ; Mutation ; Phenotype ; Prenatal Diagnosis ; Tyrosinemias/genetics* ; Child

OBJECTIVE: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. METHODS: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. RESULTS: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). CONCLUSION For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.
Humans ; Fracture Fixation, Intramedullary ; Bone Nails ; Traction ; Blood Loss, Surgical/prevention & control* ; Retrospective Studies ; Treatment Outcome ; Femoral Fractures ; Hip Fractures/surgery* ; Lower Extremity ; Surgical Wound ; Fracture Fixation, Internal

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.