Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw(MRONJ)

Medication-related osteonecrosis of the jaw(MRONJ)is primarily associated with administering antiresorptive or antiangiogenic drugs.Despite significant research on MRONJ,its pathogenesis and effective treatments are still not fully understood.Animal models can be used to simulate the pathophysiological features of MRONJ,serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ.Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ,but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ.Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic.This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency.Currently,there is a lack of a unified assessment system for MRONJ models,which hinders a standard definition of MRONJ-like lesions in rodents.Therefore,this review comprehensively summarizes assessment systems based on published peer-review articles,including new approaches in gross observation,histological assessments,radiographic assessments,and serological assessments.This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.

Chemical simulation teaching system based on virtual reality and gesture interaction

Background Most existing chemical experiment teaching systems lack solid immersive experiences,making it difficult to engage students.To address these challenges,we propose a chemical simulation teaching system based on virtual reality and gesture interaction.Methods The parameters of the models were obtained through actual investigation,whereby Blender and 3DS MAX were used to model and import these parameters into a physics engine.By establishing an interface for the physics engine,gesture interaction hardware,and virtual reality(VR)helmet,a highly realistic chemical experiment environment was created.Using code script logic,particle systems,as well as other systems,chemical phenomena were simulated.Furthermore,we created an online teaching platform using streaming media and databases to address the problems of distance teaching.Results The proposed system was evaluated against two mainstream products in the market.In the experiments,the proposed system outperformed the other products in terms of fidelity and practicality.Conclusions The proposed system which offers realistic simulations and practicability,can help improve the high school chemistry experimental education.

Establishment of a Predictive Diagnostic Model for Acute Mycoplasma Pneumoniae Infection in Elderly Patients with Community-acquired Pneumonia

We established a diagnostic model to predict acute Mycoplasma pneumoniae （M. pneumonia） infection in elderly Community-acquired pneumonia （CAP） patients. We divided 456 patients into acute and non-acute M. pneumoniae infection groups. Binary logistic regression and receiver operating characteristic （ROC） curves were used to establish a predictive model. The following independent factors were identified： age 〉 70 years; serum cTNT level 〉 0.0S ng/mL; lobar consolidation; mediastinal lymphadenopathy; and antibody titer in the acute phase 〉 1：40. The area under the ROC curve of the model was 0.923 and a score of 2 7 score predicted acute M. pneumoniae infection in elderly patients with CAP. The predictive model developed in this study has high diagnostic accuracy for the identification of elderly acute M. pneumoniae infection.

Establishing of the Transplanted Animal Models for Human Lung Cancer

Lung cancer is the leading cause of cancer mortality worldwide.Even with the applications of excision, radiotherapy, chemotherapy, and gene therapy, the 5 year survival rate is only 15% in the USA. Clinically relevant laboratory animal models of the disease could greatly facilitate understanding of the pathogenesis of lung cancer, its progression, invasion and metastasis. Transplanted lung cancer models are of special interest and are widely used today. Such models are essential tools in accelerating development of new therapies for lung cancer. In this communication we will present a brief overview of the hosts, sites and pathways used to establish transplanted animal lung tumor models.

Features of animal models of complex partial epilepsy established through unilateral,bilateral and alternate-side kindling at hippocampus of rats

BACKGROUND： Electrical stimulation kindling model, having epilepsy-inducing and spontaneous seizure and other advantages, is a very ideal experimental animal model. But the kindling effect might be different at different sites. OBJECTIVE： To compare the features of animal models of complex partial epilepsy established through unilateral, bilateral and alternate-side kindling at hippocampus and successful rate of modeling among these 3 different ways. DESIGN： A randomized and controlled animal experiment SETTING： Department of Neurology, Qilu Hospital, Shandong University MATERIALS： Totally 60 healthy adult Wistar rats, weighing 200 to 300 g, of either gender, were used in this experiment. BL-410 biological functional experimental system （Taimeng Science and Technology Co. Ltd, Chengdu） and SE-7102 type electronic stimulator （Guangdian Company, Japan） were used in the experiment. METHODS： This experiment was carried out in the Experimental Animal Center of Shandong University from April to June 2004. After rats were anesthetized, electrode was implanted into the hippocampus. From the first day of measurement of afterdischarge threshold value, rats were given two-square-wave suprathreshold stimulation once per day with 400 μA intensity, 1ms wave length, 60 Hz frequency for 1 s duration. Left hippocampus was stimulated in unilateral kindling group, bilateral hippocampi were stimulated in bilateral kindling group, and left and right hippocampi were stimulated alternately every day in the alternate-side kindling group. Seizure intensity was scored： grade 0： normal, 1： wet dog-like shivering, facial spasm, such as, winking, touching the beard, rhythmic chewing and so on; 2： rhythmic nodding; 3： forelimb spasm;4： standing accompanied by bilateral forelimb spasm;5： tumbling, losing balance, four limbs spasm. Modeling was successful when seizure intensity reached grade 5. t test was used for the comparison of mean value between two samples. MAIN OUTCOME MEASURES： Comparison of the successful rate of modeling, the times of stimulation to reach intensity of grade 5, the lasting time of seizure of grade 3 of rats in each group. RESULTS： Four rats of alternate-side kindling group dropped out due to infection-induced electrode loss, and 56 rats were involved in the result analysis. The successful rate of unilateral kindling group, bilateral kin- dling group and alternate-side kindling group was 55%（11/20）,100%（16/16）and 100%（20/20）, respective- ly. The stimuli to reach the grade 5 spasm were significantly more in the bilateral kindling group than in the unilateral kindling group [（30.63±3.48）, （19.36±3.47）times, t=8.268, P 〈 0.01], and those were significantly fewer in the alternate-side kindling group than in the unilateral kindling group [（ 10.85±1.98）times, t=-8.744, P 〈 0.01]. The duration of grade 3 spasm was significantly longer in the bilateral kindling group than in the unilateral kindling group [（9.75±2.59）, （3.21 ±1.58）days,t=-8.183,P 〈 0.01], Among 20 successful rats of al- ternate-side kindling group, grade 5 spasm was found in the left hippocampi of 11 rats, but grade 3 spasm in their right hippocampi; Grade 5 spasm was found in the right hippocampi of the other 9 rats, grade 4 spasm in the left hippocampus of 1 rat and grade 3 of 8 rats. CONCLUSION ： The speed of establishing epilepsy seizure model by alternate-side kindling is faster than that by unilateral kindling, while that by bilateral kindling is slower than that by unilateral kindling. The successful rate is very high to establish complex partial epilepsy with alternate-side or bilateral kindling. Epilepsy seizure established by alternate-side kindling has antagonistic effect of kindling and the seizure duration of grade 3 spasm is prolonged.

Pial iontophoresis of ferric chloride versus cortical ferric chloride injection in establishing iron-induced posttraumatic epilepsy animal models

BACKGROUND： In order to study the pathogenesis of iron-induced posttraumatic epilepsy （PTE）, foreign scholars have established several kinds of PTE animal models, among which, the iron- induced PTE animal models proposed by Willmore is the most famous. The iron-induced PTE animal models can be established by two methods： one is cortical ferric chloride injection （CFCI） and the other one is pial iontophoresis of ferric chloride （PIFC）. Because Willmore did not give out the elaboration of the behaviors and electroencephalograms （EEGs） of the iron induced PTE animal models established by these two methods, so we have known little about these animal models. OBJECTIVE： To observe the behaviors and EEGs of the iron-induced PTE animal models established by PIFC and CFCI, in order to compare the differences and the study value of these two methods. DESIGN： Qualitative controlled observation tria SETTING： Department of Neurosurgery, Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA. MATERIALS： Forty healthy adult male SD rats, weighing 200 to 250 g, were involved in this experiment. Reagents and instruments： Ferric chloride （FeCl3·6H2O, Sigma USA）, rat stereotaxic apparatus （ASI company, USA）, the wireless blue tooth electroencephlograms recording system （Nuocheng electric Co.Ltd, Shanghai）, a set of air turbine dental drill unit, dental base acrylic resin powder, microinjector （50 μL）, amperemeter （1 mA）, a pair of batteries, electric resistance （200 kΩ） , variable resistance （100 kΩ）, tubule with endo-meridians of 2 mm （used as import tube）, several silver wire segments and several acupuncture needles were employed in this study. METHODS： This study was carried out in the Experimental Animal Center of the Urumqi General Hospital, Lanzhou Military Area Command of Chinese PLA between November 2004 and April 2005. Establishing the PET animal models by CFCI method： Twenty SD rats were taken, intraperitoneally anesthetized with 50 mg/kg barbanylum and fixed on stereotaxic apparatus. A cranial burr hole with the diameter of 2 mm was drilled 3 mm behind the coronal suture and 2 mm lateral to the sagittal line on the left cranium. Another 5 cranial burr holes with diameter of 2 mm were drilled to place electrodes. The positions of holes were set that taking bregma as original point, sagittal line as Y-axis, the line through the original point and vertical to the Y-axis as X-axis. The unit of the coordinate axis was mm. The coordinate value of the electrodes were （4, 0）, （4, -6）, （-4, 0）, （-4, -6）, at last, a hole with the diameter of 2 mm was drilled on the center of the coronale. 5 μL ferric chloride solution （FeCl3, 100 mmol/L, pH 1.5） was injected into the sensorimotor cortex of rats using microinjector within 5 minutes. The needling depth was 3 mm. The needle was retained for 5 minutes so as to prevent the outflow of liquid. Establishing the PTE animal models by PIFC method： Twenty SD rats were chosen and weighed, and the procedures after weighing were as above.A cranial burr hole with the diameter of 4 mm was drilled in the position where needle inserted in animal models established by CFCI method. Cerebral dura mater was cut. Another 5 holes were drilled to place electrodes in the same position as above. The tip of tubule cotton stuffed inside （to prevent the rapid flow of FeCl3 solution, 100 mmol/L, pH 1.5） was gently connected to cerebral pia mater. The positive and negative electrodes of the amperemeter whose output current was 100 μA were connected to acupuncture needles. The acupuncture needle, which was connected to positive electrode, was inserted into ferric chloride solution, and that which was connected to negative electrode was inserted into the right forelimb of rats subcutaneously. The rats were galvanized for 10 minutes. Record of EEG： The silver wire with blunt anterior extremity was placed on the cerebral dura mater. Then, silver wire and cranial bones were firmly fixed with dental base acrylic resin power. The other side was connected to the wireless blue tooth electroencephlograms recording system to monitor EEG changes. Assessment criteria of seizure degree： Grade Ⅰ ： ＂wet dog-like＂ shudder, facial muscle convulsion and chewing;Grade Ⅱ： rhythmical nodding：Grade Ⅲ： forelimb clonus：Grade Ⅳ： forelimb clonus while standing： Grade Ⅴ： lost the balance, vert, limb＇s convulsion and the whole body＇s tic. MAIN OUTCOME MEASURES： Behaviors and EEGs changes of iron-induced PTE animal models established by PTFC and CFCI. RESULTS： All the 40 rats were involved in the result analysis. （1） The changes of the behaviors： The two animal models both had the epileptic seizures. The epileptic seizure of the animal model established by PIFC mainly presented automatic behavior of chewing, and facial muscle convulsion accompanied with chewing. Epileptic seizure reached the peak within 2.5 to 7 hours after model establishing.It was gradually decreased within 24 hours and hardly seen 1 day after model establishing. The epileptic seizure of the rat model established by CFCI mainly presented turnover upspring and limbs＇ convulsion and urinary incontinence accompanied. The epileptic seizure reached the peak within 3 to 8 hours.It was relatively frequent within 1 week and gradually decreased within 2 weeks after model establishing. The PTE animal models established by CFCI were more closed to clinical PTE process. （2） The form of seizures： The epileptic seizures of the rat model established by PIFC mainly presented grade Ⅰ , seldom presented grades Ⅲ, Ⅳ and Ⅴ; The epileptic seizures of rat model established by CFCI mainly presented the head turning to the right, body＇s rotation, then appeared as grades Ⅳ and Ⅴ, and the whole procedure lasted 1 minute. At the interval of big seizures, grade Ⅰ was observed. From the respect of seizure manifestation, the PTE models established by CFCI were more similar to human PTE. （3） EEGs changes： The sharp waves with average frequency of 9.66 Hz and average amplitude of 183.90 μV were observed on the EEGs of the model established by PIFC when the rats were suffering seizures. The spike waves with average frequency of 16.01 Hz and average amplitude of 143.60 μV were observed on the EEGs of the model established by CFCI when the rats were suffering seizures. CONCLUSTON： （1）Iron-induced PTE rat model is stable and credible. （2）Compared with PTE animal model established by PIFC, PTE animal model established by CFCI is a chronic animal model, and its seizure manifestation is more similar to human PTE. so it is worth further studies.

Establishment of refractory high intracrinal pressure model in dogs

Objective We expect to have a profound understanding of refractory high intracranial pressure after traumatic brain injury by making a reproducible animal model in dogs experimentally. Methods Ten adult dogs were used to make acute epidural balloon compression and decompression models.

Establishment of rat experiment model of chronic allograft nephropathy

Objective To summarize experience of establishing stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After left kidney of donor perfused in situ under hypothermic condition,left renal vein,abdominal aorta and bladder flap of donor was anastomosed with

Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

BACKGROUND： Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy （AION）. OBJECTIVE ： To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography （FFA）, optical coherence tomography （OCT）, flash visual evoked potential （F-VEP）, and histopathologically confirm its reliability. DESIGN： A randomized control tria SETTINGS ： Department of Ophthalmology, Xi＇an Fourth Hospital; Xi＇an Institute of Ocular Fundus Diseases MATERIALS ： The experiments were carried out in the research room of Xi＇an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK （Military）2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group （n =5）, laser group （n =5）, hematoporphyrin derivative （HPD） group and AION group （n =15）, each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS： In the AION group, the rats were injected with HPD （10 mg/kg） via caudal vein, and then the optic discs were exposed to krypton red （647 nm, 80 mV） for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red （647 rim, 80 mV） for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD （10 mg/kg） via caudal vein; Those in the blank control group were untouched. （1） Visual electrophysiological test： The F-VEP was used to evaluate the function of visual nerve. （2） FFA： After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution （1 mL/kg） was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. （3） After mydriasis and anesthesia as describe above, the rats were examined with OCT. （4） Histological observation： After hematoxylin and eosin （HE） staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES： The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS： Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. （1） Changes in fundus： In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. （2） FFA results： In the AION group, early ＂low fluorescence＂, middle and late ＂high fluorescence＂ were observed in upper optic disc 1 day after model establishment, and there was ＂low fluorescence＂ at 6 days, and the low fluorescence could be observed all the time at 23 days. （3） Visual electrophysiological changes： In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [（71.65±8.81）, （57.58±8.38） ms, t =3.148, P =0.012], and decreased wave amplitude [（4.77±1.90）, （10.06±3.66） μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. （4） OCT results： In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. （5） Histopathological results： At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION ： The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation （647 nm） at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.

TRANS-REGIONAL COURTS IN CHINA:A STUDY OF ESTABLISHMENT MODELS AND JURISDICTIONAL RULES

The trans-administrative regional(trans-regional)court was created as part of China’s judicial reforms in 2014.Thus far,only two trans-regional courts have been established,namely the Shanghai No.3 and Beijing No.4 Intermediate People’s Courts.An important reason for this slow pace is that the trans-regional court has transcended the current structural framework under the Organic Law of the People’s Courts in that(1)it is neither a specialized court that hears certain types of cases,(2)nor a local court established completely in keeping with administrative divisions.Therefore,the legal nature and status can only be clarified and justified when there is a clear definition of this new court system in the Organic Law of the People’s Courts.Several models,namely the independent set-up model,full reshuffling model and limited transformation model,have been proposed for the establishment of trans-regional courts.The most practical and efficient among these models is the limited transformation model,aiming to reconstruct the existing railway transportation courts.The trans-regional courts may have exclusive,alienage,or supplemental jurisdiction.Each form addresses particular types of special and major trans-regional cases,and other cases based on the theory of consolidation.

Feasibility of establishing model of Parkinson disease by injecting 6-hydroxydopamine at different parts of the nigrostriatal pathway in the brain of rats

BACKGROUND： Previous researches found that animal models with Parkinson disease （PD） could be established by injecting 6-hydroxydopamine （6-OHDA） into medial forebrain bundle （MFB）, substantia nigra compacta （SNC） and caudate-putamen complex （CPU） of the nigrostriatal pathway. OBJECTIVE ： To compare behavioral, biochemica 6-OHDA injections in the areas of MFB, SNC and DESIGN： Controlled observational study and histological properties of these rats undergoing the CPU respectively. SEI-IING： Department of Neurology, First Affiliated Hospital of Guangxi Medical University MATERIALS： A total of 64 adult female SD rats weighing 180-230 g were provided by the Animal Experimental Center of Guangxi Medical University. 6-OHDA （Sigma Company, USA）; Brain solid positioner （Standard model 51600, Stoelting Co., IL, USA）; rotational monitoring of little animal （type QL-1, USA）; high liquid chromatography （HLC, Waters Company）. METHOOS： The experiment was carried out in the Medical Experimental Center of Guangxi Medical University from February to December 2005. ① According to digital table, 64 SD rats were divided into MFB group, SNC group, CPU group and control group with 16 in each group. On the basis of the brain atlas of Paxinos, rats in the first three groups were injected with 5 μL 6-OHDA into right MFB （0 mm of line of incisor tooth, A/P 4.4 mm, L/R 1.2 mm, ON -7.8 mm）, SNC （line of incisor tooth just equal to horizon, A/P -4.8 mm, L/R 1.6 mm, ON -7.8 mm） and CPU （0 mm of line of incisor tooth, A/P 1.2 mm, L/R 2.7 mm, ON -5.4 mm）, respectively. The rats in control group were injected with 5 μL ascorbic acid solution （2 g/L）. One week after operation, 0.1 g/L apomorphine （Apo, 0.05 mg/kg） was subcutaneously injected into neck and then rotational behavior induced by Apo was recorded once a week for 8 weeks. The PD models were considered successful only when rotational times more than or equal to 7 times per minute. Eight weeks after operation, micro-perfusion was used to obtain micro-perfusate in bilateral CPU and contents of 3,4-dihydroxyphenylacetic acid （3,4-DOPAC） and homovanillic acid （HVA） were also measured. In addition, amount of tyrosine hydroxylase positive cells （TH＊） in SNC was counted with immuno- histochemical staining. MAIN OUTCOME MEASURES ： ① Successful rate of PD models; ② contents of dopamine and its metabolite in MFB, SNC and CPU groups and TH＊ amount. RESULTS： All 64 SD rats were involved in the final analysis. ③ Successful rate and rotational behavior： One week after operation, there were 6 successful models both in SNC and MFB groups; in the 2^nd week, there were 6 both in SNC and MFB groups and 1 in CPU group; in the 3^nd week, there were 1 in MFB group and 3 in CPU group; in the 4^nd week, there were 3 in CPU group. Otherwise, no successful case was found out in the next 3 weeks. Abnormal rotational behavior was not observed in control group. Four weeks after operation, successful rates were 81% （13/16） in MFB group, 75% （12/16） in SNC group and 44% （7/16） in CPU group.② Contents of 3, 4-DOPAC and HVA： Eight weeks after operation, contents in the SNC area of the injured side were lower than those on non-lesion side （P 〈 0.01）.③Changes of TH＋ amount： Eight weeks after operation, TH＋ amount in the SNC area of the lesion side was lower than that on non-lesion side （P 〈 0.01 ）. CONCLUSION： Injecting 6-OHDA into MFB, SNC and CPU can damage dopaminergic cells and establish successful PD models.

Poisson rectangular pulse(PRP)model establishment based on uncertainty analysis of urban residential water consumption patterns

The commonly used Poisson rectangular pulse(PRP)model,employed for simulating high-resolution residential water consumption patterns(RWCPs),relies on calibration via medium-resolution RWCPs obtained from practical measurements.This introduces inevitable uncertainty stemming from the measured RWCPs,which consequently impacts the precision of model simulations.Here we enhance the accuracy of the PRP model by addressing the uncertainty of RWCPs.We established a critical sampling size of 2000 household water consumption patterns(HWCPs)with a data logging interval(DLI)of 15 min to attain dependable RWCPs.Through Genetic Algorithm calibration,the optimal values of the PRP model's parameters were determined:pulse frequency lλ=91 d^(-1),mean of pulse intensity E(I)=0.346 m^(3) h^(-1),standard deviation of pulse intensity STD(I)=0.292 m^(3) h^(-1),mean of pulse duration E(D)=40 s,and standard deviation of pulse duration STD(D)=55 s.Furthermore,validation was conducted at both HWCP and RWCP levels.We recommend a sampling size of2000 HWCPs and a DLI of30 min for PRP model calibration to balance simulation precision and practical implementation.This study significantly advances the theoretical foundation and real-world application of the PRP model,enhancing its role in urban water supply system management.

Study on the Overfitting of the Artificial Neural Network Forecasting Model

Because of overfitting and the improvement of generalization capability (GC)available in the construction of forecasting models using artificial neural network (ANN), a newmethod is proposed for model establishment by means of making a low-dimension ANN learning matrixthrough principal component analysis (PCA). The results show that the PC A is able to construct anANN model without the need of finding an optimal structure with the appropriate number ofhidden-layer nodes, thus avoids overfitting by condensing forecasting information, reducingdimension and removing noise, and GC is greatly raised compared to the traditional ANN and stepwiseregression techniques for model establishment.