1.Preparation of fluorescent nanoprobes based on aggregation-induced emission and their application in the diagnosis and treatment of oral cancer
Yanze WANG ; Ruixin NIE ; Guanhua WANG ; Xiaoli LIAN ; Yingbin YAN ; Xiaoyan ZHANG
International Journal of Biomedical Engineering 2025;48(5):443-453
Objective:To develop fluorescent nanoprobes with aggregation-induced emission characteristics and to systematically evaluate their optical properties, biosafety, anti-tumor activity, and imaging capability, thereby assessing their potential for early precision diagnosis and treatment of oral cancer in mice.Methods:Control probes (PEG@TPD) were prepared by encapsulating ( E)-4-(2-(4′-(1-phenyl-2,2-bis(4-methoxyphenyl)vinyl)biphenyl-4-yl)vinyl)-4-(dicyanomethylene)-4 H-chromene (TPD) using 1,2-distearoyl- SN-glycerol-3-phosphoethanolamine- N-polyethylene glycol 2000-maleimide as the carrier. Fluorescent nanoprobes (GE11-PEG@TPD) were subsequently fabricated by surface modification with the targeting GE11 peptide. The morphology and particle size of the nanoprobes were characterized by transmission electron microscopy and dynamic light scattering. The optical properties of the nanoprobes were analyzed using ultraviolet-visible spectrophotometry and fluorescence spectrophotometry. Mouse squamous carcinoma SCC-7 cells were randomly divided into six groups by the random number table method. The PBS, PEG@TPD, and GE11-PEG@TPD groups were not treated with light, while the PBS+L, PEG@TPD+L, and GE11-PEG@TPD+L groups were exposed to white light (25 W/cm 2, 10 min) at a nanoprobe concentration of 20 μg/ml (based on TPD concentration). Cell survival rate was assessed by the cell counting kit-8 assay. Cellular uptake, intracellular reactive oxygen species levels, and cytotoxicity were evaluated using laser scanning confocal microscopy. The apoptosis rate was evaluated by cell apoptosis assay. Twelve 6-week-old female C3H/HeN mice were randomly divided into two groups: PEG@TPD-1 group and GE11-PEG@TPD-1 group, with 6 mice in each group. Subcutaneous oral cancer models were established by injecting SCC-7 cell suspensions into the dorsal region of mice in two groups. Each mouse was intravenously administered 200 μl of PEG@TPD or GE11-PEG@TPD solution (1 mg/ml, based on TPD concentration). Tumor boundaries and scope were visualized using a small animal in vivo imaging system. At the optimal imaging time point, three mice from each group were euthanized, and major organs and tumor tissues were collected to measure probe accumulation. Statistical comparisons between two groups were performed using independent samples t-tests, while one-way or two-way analysis of variance was applied for multiple group comparisons. Results:Both PEG@TPD and GE11-PEG@TPD exhibited a relatively regular sphere, with average particle sizes of (92.76±8.80 and 117.50±6.40) nm, respectively. PEG@TPD showed two obvious absorption peaks at 352 and 444 nm. GE11 peptide showed a polypeptide characteristic absorption peak at 280 nm, GE11-PEG@TPD showed three characteristic absorption peaks at 280, 352 and 444 nm. Under dark conditions, cell survival rate remained above 80% even at a concentration of 160 μg/ml. After light irradiation, cell survival rate in the PEG@TPD+L group at 20 and 40 μg/ml [(68.2±5.2)% and (48.6±7.1)%] were higher than those in the GE11-PEG@TPD+L group [(55.0±2.8)% and (30.0±9.2)%], with statistically significant differences ( P<0.05, 0.01). At incubation time points of 2, 4, and 6 h, the relative fluorescence intensity of the GE11-PEG@TPD group (119.4±10.2, 192.9±14.2, and 234.1±4.8) were higher than those of the PEG@TPD group (98.6±7.5, 163.8±3.1, 204.6±11.2), with statistically significant differences (all P<0.05). The relative fluorescence intensity of the PEG@TPD+L and GE11-PEG@TPD+L group (68.5±4.7 and 86.8±10.0) were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups (6.1±8.0, 7.6±1.8, 4.7±4.2 and 21.1±7.6), with statistically significant differences (all P<0.01). And the difference between the GE11-PEG@TPD+L and PEG@TPD+L groups was also statistically significant ( P<0.05). Viable cell proportions in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups all exceeded 95.0%, while those in the PEG@TPD+L and GE11-PEG@TPD+L groups decreased to (11.1±3.7)% and (4.3±1.1)%, respectively, with a statistically significant difference between them ( P<0.05). The apoptotic cell proportions in the PEG@TPD+L and GE11-PEG@TPD+L groups [(40.5±4.3)% and (55.3±7.4)%] were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups [(27.3±2.0)%, (28.2±1.9)%, (28.6±1.2)%, and (29.7±3.0)%], with statistically significant differences ( P<0.05, 0.01). Moreover, the difference between the GE11-PEG@TPD+L and the PEG@TPD+L groups was also statistically significant ( P<0.01). The mean fluorescence intensities of the GE11-PEG@TPD-1 group at 1, 3, 5, 8, and 24 h, as well as in ex vivo tumor tissues[(5.2±0.8, 5.9±0.7, 6.6±1.0, 7.9±0.6, 7.8±0.7 and 20.6±3.5)×10 6 p/s/cm 2/sr] were all higher than those in the PEG@TPD-1 group [(3.2±0.7, 4.2±0.7, 4.6±0.9, 5.1±0.9, 4.7±0.9 and 14.2±1.8)×10 6 p/s/cm 2/sr], with statistically significant differences ( P<0.05, 0.01). Conclusions:The fluorescent nanoprobes exhibit uniform particle size, high photostability, and good biocompatibility. They demonstrate significant tumor-killing effects at the cellular level and possess tumor-targeting capability in vivo, showing promising application potential for the early precision diagnosis and treatment of oral cancer.
2.Paroxysmal motor induced dyskinesia caused by PRRT2 gene c.776del mutation
Sen HUANG ; Zhan-Hua ZHONG ; Weineng CHEN ; Ruojie HE ; Ling LIAN ; Xiaoli YAO
Chinese Journal of Nervous and Mental Diseases 2024;50(4):239-241
This article reported a typical case of paroxysmal kinesigenic dyskinesia(PKD).The patient was a 26-year-old female with a medical history of 10 years.The patient manifested as paroxysmal choreoathetosis of the limb and head triggered by sudden movement in a quiet state,without sensory aura.The symptoms resolved spontaneously after tens of seconds.She was conscious during and between attacks,had a clear family history and a normal neurological examination.No abnormalities were found in brain magnetic resonance image and electroencephalogram.Genetic test showed a frame-shift mutation of c.776del in PRRT2 gene of the proband and her father with similar phenotype.The patient was diagnosed with PKD according to the diagnostic criteria for PKD.The symptoms were significantly relieved after one month of oxcarbazepine treatment with good prognosis.PKD is a rare movement disorder.The patient has typical symptoms,and the mutation site has not been reported in the Human Gene Mutation Database.Therefore,this article enriched the pathogenic gene mutation spectrum of PKD,provided a basis for genetic counseling of PKD and increased the awareness of this rare disease among physicians.
3.Analysis of effect of enzyme replacement therapy in 18 patients of Pompe disease
Ling LIAN ; Jing LI ; Xiaoli YAO
Chinese Journal of Neurology 2024;57(5):443-450
Objective:To analyze the effect of enzyme replacement therapy (ERT) in 18 patients of Pompe disease.Methods:Clinical data, laboratory tests, acid alpha-glucosidase (GAA) enzyme activity, GAA gene, outcome and follow-up of ERT in 18 cases of infantile and late-onset Pompe disease admitted to the First Affiliated Hospital of Sun Yat-sen University from October 2020 to May 2023 were retrospectively collected and analyzed. Results:Among the 18 patients with Pompe disease, 9 are males, and 9 are females; 4 had infantile onset, 5 had late-onset in children, and 9 had late-onset in adults; age of onset ranged from 4 months to 43 years; ERT was received from 1 to 61 times, with only 1 adverse reaction during infusion. Among the 4 infantile onset patients after standardized ERT, 2 had stable motor and respiratory function, 1 had difficulty removing from vetilator, and 1 died. Most of the muscle strength of extremities of late-onset patients were difficult to reverse, and creatine kinase gradually decreased or remained stable, while subjective symptoms, exercise endurance, and respiratory function were significantly improved. ERT was most effective in the early stages and the disease remained stable for 1 to 2 years after treatment.Conclusions:ERT is safe and effective, which can help delay disease progression and improve the quality of life of patients. Early standard treatment is beneficial for both infantile- and late-onset patients.
4.Preparation of a polypeptide fluorescent probe based on aggregation induced luminescence and its application in the detection of early dental caries
Guanhua WANG ; Zhiyuan GAO ; Xiaoyan ZHANG ; Xiaoli LIAN ; Xiaohua DAI ; Yan YAN ; Huiru ZOU ; Dan DING
International Journal of Biomedical Engineering 2023;46(3):185-190
Objective:To prepare a peptide fluorescent probe based on aggregation-induced emission and to investigate its application in the detection of early caries.Methods:Eight aspartate-serine-serine (DSS) were combined with aggregation-induced emission material to prepare peptide fluorescent probes, and an artificial demineralization model was established in vitro. The samples were immersed in the peptide fluorescent probe solution for 1 min, and a fluorescence imaging system was applied to examine the tooth samples and collect images and fluorescence data. Scanning electron microscopy was also applied to observe the phenotype of the teeth, and electron microscopy was applied to detect the calcium-phosphorus ratio on the enamel surface of the teeth. Polarized light microscopy was also applied to observe the enamel area of the teeth. Results:The fluorescence intensity of demineralized teeth was clearly observed to be lower than that of normal teeth in the peptide fluorescent probe-treated area, and the difference was statistically significant ( P < 0.05). The results of scanning electron microscopy showed that the enamel surface of the demineralized group had more irregular pores, while the enamel surface of the undemineralized group was flatter with only some irregular accumulation of flakes. The results of polarized light microscopy showed that a clear birefringence could be observed in the enamel region of normal teeth, while a black area or the disappearance of the birefringence effect accompanied by a partial black dark shadow could be observed in the enamel region of demineralized teeth. Conclusions:An aggregation-induced luminescence-based peptide fluorescent probe was successfully prepared, which can precisely localize the enamel and show some application value in early caries detection.
5.A Phase Ⅲ Clinical Observation of Yishen Yangxin Anshen Tablets in Treatment of Insomnia with Deficiency of Heart Blood and Insufficiency of Kidney Essence
Wei WANG ; Junxia REN ; Yongzheng WANG ; Jianke HAN ; Limin YANG ; Weidong WANG ; Fengmei LIAN ; Changshan AI ; Xiaoli YIN ; Baoliang WANG ; Yi MENG ; Shuguang YUAN ; Desheng ZHOU ; Xuedong GAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):110-116
ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia (heart-blood deficiency and kidney-essence insufficiency syndrome). MethodA randomized block, double-blind, placebo-controlled, multi-center clinical trial design method was adopted, and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence (treatment group-control group 3∶1) from seven hospitals (Guang'anmen Hospital, China Academy of Chinese Medical Sciences, The First Clinical Hospital, Jilin Province Academy of Traditional Chinese Medicine(TCM), The Second Affiliated Hospital of Liaoning University of TCM, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan Province Hospital of TCM, Hebei General Hospital, The First Hospital of Hunan University of Chinese Medicine) were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets (4 tablets/time, 3 times/day, 4 weeks of administration, 4 weeks of follow-up after drug withdrawal). The sleep dysfunction rating scale (SDRS) score, pittsburgh sleep quality index (PSQI) score, TCM, polysomnography (PSG) indicators from four hospital (Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Henan Province Hospital of TCM, Hebei General Hospital, The First Hospital of Hunan University of Chinese Medicine), and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination, laboratory examination, and observation of adverse events, the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment, the total score of SDRS in the treatment group was lower than that in the control group (P<0.01). After drug withdrawal for 4 weeks, the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment, indicating that the rebound change of curative effect was not obvious. After treatment, the total score of PSQI in the treatment group decreased as compared with that in the control group (P<0.01), and the change of total score of PSQI in the treatment group was statistically significant (P<0.05) after drug withdrawal for 4 weeks but small, indicating that the rebound change of curative effect was not obvious. After treatment, the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group (χ2=137.521,P<0.01). After treatment, the disappearance rates of single indexes in the treatment group, such as difficulty in falling asleep, easily waking up after sleeping, early awakening, short sleep time, dreamfulness, palpitation, forgetfulness, dizziness, mental fatigue, and weakness of waist and knee, increased compared with those in the control group (P<0.01). After treatment, the treatment group demonstrated fewer awaking times (AT), longer total sleep time (TST), lower ATA/TST ratio, and higher sleep efficiency (%) than the control group (P<0.05). No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.
6.The role of arthroscopic investigation in the treatment of tibial plateau fracture with homeopathic double reverse traction reduction and internal fixation
Xiaoli YAN ; Decheng SHAO ; Xiaodong LIAN ; Shuhong YANG ; Na YANG ; Peizhi YUWEN ; Zhanle ZHENG ; Wei CHEN ; Zhiyong HOU ; Yingze ZHANG
Chinese Journal of Orthopaedics 2023;43(22):1517-1523
Objective:To explore the role of arthroscopic exploration in the treatment of tibial plateau fractures with homeopathic double reverse traction reduction and internal fixation.Methods:A retrospective analysis was conducted on the data of 188 patients with tibial plateau fractures treated by homeopathic double reverse traction reduction assisted internal fixation and arthroscopic exploration at the Third Hospital of Hebei Medical University from January 2019 to December 2021. There were 129 males and 59 females, aged 46.7±11.8 years (range, 14-80 years); 115 cases on the left and 73 cases on the right. Schatzker classification of fractures: 81 cases of type II, 15 cases of type III, 23 cases of type IV, 29 cases of type V, and 40 cases of type VI. The time from injury to surgery was 1-14 days, with an average of 10±5 days. The surgery was performed with double reverse traction assisted reduction, locking bone plate and self-breaking compression bolt fixation. Then, arthroscopy was used to explore the quality of fracture reduction, meniscus and ligament damage, and the corresponding intra-articular lesions were treated, such as partial meniscus resection, complete meniscus resection, or suturing. The Rasmussen score was used to evaluate the quality of fracture reduction after surgery, and the Hospital for Special Surgery (HSS) knee joint score was used to evaluate the postoperative function of the knee joint.Results:All patients successfully completed fracture reduction, fixation, and arthroscopic exploration. The average surgical time was 95±21 min (range, 30-120 min); The average intraoperative bleeding volume was 120±58 ml (range, 50-300 ml). All patients were followed up for 10-24 months, with an average of 18±6.5 months. All patients' fractures achieved clinical healing after surgery, with a healing time of 2.5-6.0 months, with an average of 3±2.4 months. Among them, 165 patients (87.8%, 165/188) healed within 3 months after surgery, while the remaining 23 patients healed within 4-6 months after surgery. Arthroscopic exploration revealed that 188 patients had good fracture reduction and a flat articular surface. Among them, 97 cases (51.6%, 97/188) were complicated with meniscus injury, with longitudinal tear (29%, 28/97) being the most common, suture treatment was performed under arthroscopy; the remaining 69 patients underwent partial meniscectomy. All the patient's knee function recovered well at the last follow-up. 29 cases (15.4%, 29/188) were complicated with cruciate ligament injury, none of them underwent primary repair and were fixed with plaster or brace after operation. The Rasmussen score for the final follow-up after surgery was 16.8±2.4 points (range, 6-18 points), with 152 cases being excellent and 36 cases being good, with a 100% excellent and good rate. The HSS knee joint scores were 79.8±9.2 points, 85.1±10.1 points, and 94.9±7.6 points at 3, 6 months after surgery, and at the last follow-up, respectively, with statistically significant differences ( F=52.53, P<0.001). Superficial skin infection occurred in 2 cases after operation, which was cured by regular dressing change and anti-infection treatment with antibiotics. Deep vein thrombosis occurred in 7 cases within 1 week after operation, and low molecular weight heparin anticoagulation therapy was given. Conclusion:After using double reverse traction assisted reduction and internal fixation, arthroscopic examination can not only evaluate the quality of reduction for tibial plateau fractures, but also handle combined meniscus injuries and evaluate the condition of cruciate ligament injuries.
7.Minimally invasive treatment of Fraser type Ⅱ floating knee by homeopathic reduction
Xiaodong LIAN ; Na YANG ; Xiaoli YAN ; Wei CHEN ; Yanbin ZHU ; Yingze ZHANG
Chinese Journal of Orthopaedic Trauma 2021;23(2):121-125
Objective:To evaluate the clinical efficacy of minimally invasive treatment of Fraser type Ⅱ floating knee by homeopathic reduction.Methods:From November 2016 to July 2018, 7 patients with Fraser type Ⅱ floating knee were treated by homeopathic reduction and minimally invasive surgery at Trauma Emergency Center, The Third Hospital of Hebei Medical University. They were 5 males and 2 females, aged from 30 to 82 years (average, 52 years). They all suffered from tibial plateau fracture complicated with floating knee, with 5 cases of Fraser type ⅡA (tibial plateau fracture complicated with femoral shaft fracture) and 2 cases of Fraser type ⅡC (tibial plateau fracture complicated with femoral condyle fracture). The femoral and tibial plateau fractures were reduced with a bidirectional traction reduction device, followed by minimally invasive implantation of internal fixators. The operation time, length of a single incision, blood loss and fluoroscopic frequency were recorded. The anteroposterior and lateral X-ray films of the lower limb were taken and fracture healing time was recorded during follow-up. The function of knee joint was evaluated by Hospital for Special Surgery (HSS) scoring system at the last follow-up.Results:For the 7 patients, operation time averaged 87.2 min, length of a single incision 2.8 cm, blood loss 471 mL, and fluoroscopy frequency 37 times. The postoperative X-ray films showed fine alignment and force line and smooth articular surface in all patients. All the incisions healed by grade A. The follow-up time for 7 patients ranged from 12 to 21 months (average, 15.6 months). All the fractures healed after an average time of 12.8 weeks. The HSS scores at the last follow-up showed that 6 cases were excellent and one was good.Conclusion:The fractures of the femur side and of the tibia side can be treated separately by closed reduction and internal fixation using a homeopathic bidirectional traction reduction device so as to obtain better knee joint function.
8.Research progress in biomechanical properties and numerical simulation of periodontal ligament during orthodontic tooth movement
Xiaoli LIAN ; Yan YAN ; Ruixin LI ; Huiru ZOU
International Journal of Biomedical Engineering 2021;44(5):395-400
Orthodontic tooth movement is achieved by remodeling periodontal ligament, alveolar bone and other periodontal tissues in response to mechanical loading. The periodontal ligament is the fibrous connective tissue connecting cementum and alveolar bone, which plays an important role in the transmission, absorption and dispersion of supporting teeth and biting force. When orthodontic forces are applied to the teeth, load transfer occurs from the tooth through the periodontal ligament to the alveolar bone. The remodeling of periodontal ligament interacts with the alveolar bone formation and absorption alternately. As the initial factor of orthodontic tooth movement, the stress/strain of periodontal ligament is involved in the process of alveolar bone remodeling and affects the direction and speed of tooth movement. Therefore, the biomechanical properties of the periodontal ligament have received extensive attention. In this paper, the related researches on the structural changes and biomechanical characteristics of the periodontal ligament during orthodontic tooth movement were reviewed as well as the researches on the mechanical constitutive model of the periodontal ligament. The mechanical response and biomechanical mechanism of the periodontal ligament were discussed in order to provide a theoretical basis for accurate numerical simulation of orthodontic tooth movement.
9.Differential diagnosis of motor neuron disease
Chinese Journal of Neurology 2019;52(10):841-846
Motor neuron disease (MND) is a type of chronic progressive neurodegenerative disease involving upper and/or lower motor neurons, including amyotrophic lateral sclerosis, progressive bulbar palsy, primary lateral sclerosis, progressive muscular atrophy, and spinal muscular atrophy. Different types of motor neuron diseases have distinct characteristics. Therefore, the diagnosis mainly depends on clinical manifestations, physical examination and electrophysiological examination, and is made by exclusion of other diseases. Atypical cases are sometimes difficult for clinical physicians to distinguish from other diseases involving upper and/or lower motor neurons. This article is going to introduce various types of MND and their differential diagnosis according to site of lesion of motor neuron disease.
10. Differential diagnosis of motor neuron disease
Chinese Journal of Neurology 2019;52(10):841-846
Motor neuron disease (MND) is a type of chronic progressive neurodegenerative disease involving upper and/or lower motor neurons, including amyotrophic lateral sclerosis, progressive bulbar palsy, primary lateral sclerosis, progressive muscular atrophy, and spinal muscular atrophy. Different types of motor neuron diseases have distinct characteristics. Therefore, the diagnosis mainly depends on clinical manifestations, physical examination and electrophysiological examination, and is made by exclusion of other diseases. Atypical cases are sometimes difficult for clinical physicians to distinguish from other diseases involving upper and/or lower motor neurons. This article is going to introduce various types of MND and their differential diagnosis according to site of lesion of motor neuron disease.

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