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

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Objective To compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.Methods This study was a single-center,prospective,randomized,single-blind trial.From January to April 2024,96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited.After excluding 6 cases(3 refused to participate,1 had tracheal intubation time＞30 s,and 2 had missing data),90 patients were finally included.They were randomly divided into remimazolam tosylate group(intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction,n=45)and etomidate group(intravenous injection of 0.3 mg/kg etomidate for anesthesia induction,n=45)by the random number table method.The area under the curve for mean arterial pressure(MAP)below or above baseline values(AUCMAP-and AUCMAP+),the heart rate(HR)below or above baseline values by 10％(AUCHR-and AUCHR+)within 10 minutes of anesthesia induction,the time to loss of consciousness,the time from the start of anesthesia induction to a bispectral index(BIS)＜60,the incidence of drug-related adverse reactions,the incidence of cardiovascular adverse events,and the usage of vasoactive drug administrations were compared between the two groups.Results Compared with the etomidate group,the AUCMAP-(145.10±35.75 vs.178.52±39.78)and AUCHR-[43.20(26.58,56.35)vs.54.99(43.01,65.85)]in remimazolam tosylate group were significantly reduced(P＜0.001,P=0.001).The time to loss of consciousness and the time from the start of anesthesia induction to BIS＜60 were prolonged(P＜0.001).The incidence of drug-related adverse reactions was significantly decreased(P＜0.05),and the number of norepinephrine administrations was significantly reduced(P＜0.05)in remimazolam tosylate group.However,there were no statistically significant differences in AUCMAP+,AUCHR+,the incidence of cardiovascular adverse events,and the usages of atropine,urapidil,and esmolol between the two groups(P＞0.05).Conclusion The use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.

OBJECTIVE: To investigate the prognostic value of peripheral blood absolute monocyte count(AMC) in non-severe aplastic anaemia(NSAA) patients. METHODS: 178 patients with NSAA who attended the Affiliated Hospital of Xuzhou Medical University from April 2008 to September 2020 were retrospectively analyzed, and the optimal cut-off value of peripheral blood AMC was determined by the receiver operating characteristic curve of the subjects, and they were divided into low AMC group (48 patients) and normal AMC group (130 patients), and the differences in clinical characteristics between the two groups were compared. Overall survival(OS) and progression-free survival(PFS) were analyzed by Kaplan-Meier. Univariate and multivariate Cox regression analysis were used to determine the independent prognostic value of AMC. RESULTS: Among 178 NSAA patients, 105(59.0%) were male and 73(41.0%) were female, with a median age of 31(18-87) years old, a median follow-up time of 58 months (range: 6 months-175 months), and a median AMC of 0.15×10⁹/L ［range: (0.01-0.59)×10⁹/L)］. The proportion of granulocytes (27.5% vs 36.0%, P < 0.05), and the proportion of mature monocytes (1% vs 2%, P < 0.05) in the low AMC group were lower than that in the normal AMC group; the proportion of mature lymphocytes in the low AMC group was higher than that in the normal AMC group (54% vs 50%, P < 0.05). However, there was no significantly different in the proportion of erythropoietic cells and stages of the erythropoietic cells between the two groups ( P >0.05). CR (27.7% vs 10.4%) and ORR (75.4% vs 56.3%) in the normal AMC group were higher than that in the low AMC group. Compared with patients in the low AMC group, AA patients in the normal AMC had better 5-year OS (98.5% vs 86.9%, P < 0.01), and the 5-year PFS (86.0% vs 58.9%, P < 0.01). Also, the 10-year survival rate of patients in the normal AMC group was higher than that in the low AMC group (98.5% vs 60.5%,P < 0.01). Univariate analysis showed that age, reticulocyte count, AMC<0.1×10⁹/L and the proportion of bone marrow mature monocytes were related with patients survival. Multivariate Cox regression analysis showed that monocyte count reduction was not an independent poor prognostic factor in NSAA patients （HR =4.474，95%CI ：0.508-44.390； P =0.172）. CONCLUSION Low AMC level at initial diagnosis is not an independent prognostic factor for NSAA patients, but still suggest potential prognostic value of AMC.
Humans ; Anemia, Aplastic/diagnosis* ; Female ; Male ; Prognosis ; Monocytes ; Adult ; Middle Aged ; Retrospective Studies ; Adolescent ; Aged ; Young Adult ; Aged, 80 and over ; Leukocyte Count

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

Objective:To analyze the whole genome sequence and key site mutations of hepatitis B virus (HBV) in patients with different stages of disease progression, and to understand the relationship between HBV genetic characteristics and disease progression.Methods:Serum samples and basic information of hepatitis B patients with asymptomatic HBV carrier, chronic hepatitis B patients, cirrhosis patients and primary hepatocellular carcinoma patients were collected. Nested PCR was used to amplify the samples to obtain HBV whole gene sequences. Phylogenetic trees were constructed to determine the genotype of the samples, and gene mutations of the samples were analyzed combined with reference sequences of each type.Results:A total of 256 samples were successfully amplified, including 68 asymptomatic HBV carrier patients, 118 CHB patients, 15 LC patients and 55 HCC patients, and five genotypes (B, C, D, I and C/D) were detected. The result of comparative analysis showed that the mutation rate of 56 nucleotide sites was significantly different among the four groups ( P<0.05). In addition to the discovery of C105T, A1762T/G1764A and G1899A and other previously reported key site mutations, the mutation rates of T53A, C1485T and C1628T in newly diagnosed HCC group were significantly higher than those in other groups, and the mutation rates of T2150G and T2151C in asymptomatic HBV infection group were significantly higher than those in other groups. A total of 26 sequences were deleted, mainly distributed in the pre-C and pre-S regions. The deletion mutation rate in the HCC group was significantly higher than that in the other groups. Conclusions:The data of this study indicate that some nucleotide substitution mutations and deletion mutations may be closely related to the occurrence and development of HBV-related diseases, and HCC patients are more likely to have gene mutations than non-HCC patients. These result provide a reference for understanding the relationship between viral mutation and the progression of HBV infection-related diseases.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.