Postoperative cognitive dysfunction (POCD) is a common and serious complication among geriatric patients undergoing surgery for oromaxillofacial malignancies, significantly impedes rehabilitation and increases healthcare costs. Therefore, effective perioperative cognitive management is essential, yet it remains challenging. While mobile health (mHealth) applications offer potential solutions, their adoption among elderly populations remains low due to usability barriers. This study aimed to develop and comprehensively evaluate a novel WeChat-based mHealth intervention, the WeChat Applet of Cognitive Dysfunction Assessment and Management (WACDAM), for the perioperative management of POCD in older adults undergoing surgery for oromaxillofacial malignancies, with a focus on its clinical effectiveness, usability, and implementation value . This is a mixed-methods, participatory design study. This study employed a participatory design strategy to develop WACDAM in collaboration with geriatric patients, clinical specialists, and technical developers. Patients who underwent oral malignancy resection with neck dissection under general anesthesia between December 2020 and December 2021 were enrolled. POCD was assessed using the Z-score method, and risk factors were analyzed using multivariable logistic regression. Usability and user satisfaction were evaluated using the System Usability Scale (SUS), the user version of the Mobile Application Rating Scale (uMARS), and semi-structured interviews. Among the 112 elderly patients who underwent surgery for oromaxillofacial malignancy and completed both preoperative and postoperative (day 7) assessments, the incidence of POCD was 33.1

Vascular leakage in sepsis is critical factors in improving the prognosis of septic patients, with limited treatment options targeting underlying molecular mechanisms. Necroptosis is a form of cell death centered around the RIPK1/RIPK3/MLKL pathway, combining both programmed and inflammatory characteristics. However, its role and mechanism in sepsis-induced vascular leakage remain unclear. In vivo and in vitro, CLP and LPS were used to simulate sepsis model. It was found that the expression levels of RIPK1/RIPK3/p-MLKL in septic VECs were significantly increased, and necroptosis inhibitors significantly improved septic vascular leakage. Transcriptomic and Western blot results suggested that TNFRSF21 plays a key role in necroptosis. shTNFRSF21 inhibited the formation of necrosome (RIPK3/p-MLKL) in septic VECs, improved vascular leakage in septic rats, and prolonged their survival time. The compound Phen-DC3 of inhibiting TNFRSF21 and the anesthetic remimazolam, both downregulated TNFRSF21, thereby improving septic vascular leakage. Our results suggest that TNFRSF21-regulated necroptosis plays an important role in septic vascular leakage, and targeting TNFRSF21 inhibition may be a potential therapeutic strategy for septic vascular leakage. KEY MESSAGES: Necroptosis plays a crucial role in sepsis-induced vascular leakage. TNFRSF21 promotes necrosome formation by upregulating RIPK3/p-MLKL, leading to endothelial cell death and disruption of the vascular barrier. The TNFRSF21 inhibitor Phen-DC3 was identified as a compound that improves sepsis-induced vascular leakage, providing a potential new therapeutic strategy for sepsis treatment. The anesthetic remimazolam inhibits TNFRSF21, improving sepsis-induced vascular leakage, offering experimental evidence for the repurposing of existing drugs like remimazolam in the treatment of sepsis.

INTRODUCTION AND AIMS:Exodontia and local anaesthesia are critical competencies in dental education, yet existing simulators lack integration. This study aimed to develop and validate a Tooth Extraction and Local Anaesthesia simulator (TELA-sim), one of the first haptic virtual reality platforms to immerse learners in the complete clinical workflow for tooth extraction (TE) and inferior alveolar nerve block (IANB). METHODS:Dental students (undergraduates without clinical experience) and residents (postgraduate trainees with clinical experience) (N = 155) were grouped as novices (n = 72) or intermediates (n = 83) based on clinical experience for face and construct validity assessment. A separate skill-transfer cohort compared fourth-year undergraduates who received TELA-sim training (n = 79) with a historical control group that received only traditional training (n = 77). Performance was evaluated via simulator metrics, questionnaires, and practical skills examination (PSE) scores on phantom heads. RESULTS:The simulator showed strong face validity (median Likert scores > 3.0; no significant group differences). Construct validity was demonstrated by significant intergroup differences, with novices unexpectedly outperforming intermediates on overall protocol adherence (TE: median 91.50 vs 85.00, P < .001, δ = 0.39; IANB: 71.00 vs 62.00, P = .004, δ = 0.27). The TELA-sim group achieved markedly higher PSE scores 6 months later (median 84.00 vs 75.00, P < .001, δ = 0.76). CONCLUSIONS:This study successfully developed the TELA-sim and established its face and construct validity. The TELA-sim led to superior skill retention and transfer to clinical practice compared with traditional training alone. However, longer‑term retention beyond 6 months requires further investigation, while not all students responded favourably to the simulator during face validity assessment. CLINICAL RELEVANCE:The TELA-sim may help preclinical students prevent errors through repeated practice of standardised protocols in a risk-free environment. Its alignment with licensing requirements suggests potential for objective skills assessment. For practising clinicians, the simulator could offer skill refinement and retraining opportunities to reinforce safe protocols and support continuous professional development, though further study is needed.

The mechanism of chronic orofacial pain was investigated by examining the interaction between activated microglia, C1q, and neurons in the rostral ventromedial medulla (RVM) of rats with orofacial pain caused by temporomandibular joint injection of complete Freund's adjuvant (CFA). The results demonstrated that the pain threshold in the CFA group exhibited a continuous decline, reaching its lowest point on the third day. During the modeling process, administered daily stereotactic injections of ANX-005 and minocycline into the RVM, which resulted in a notable recovery in the rats' pain threshold and a significant increase in C1q/C3 and microglia in the RVM of CFA rats. The application of ANX-005 or minocycline resulted in a reduction in the expression of C1q/C3 and microglia. Notably, the expression of excitatory presynaptic membrane markers reduced, and the length and density of dendritic spines decreased on neurons in the RVM. Additionally, C1q was abundantly localized on excitatory presynaptic membranes and expressed in microglial lysosomes. Treatment with ANX-005 or minocycline resulted in a reduced number of immunofluorescence colocalizations and an elevated dendritic spine density. These findings indicate that initial orofacial pain induced by CFA and microglia in the RVM are involved in the pruning of excitatory presynaptic membranes through the complement C1q/C3-CR3 signaling pathway. This process results in a reduction in the proportion of excitatory synapses and a disruption in the physiological balance between RVM descending facilitation and descending inhibition. This leads to the predominance of descending facilitation in pain transmission in the RVM, which in turn facilitates the chronification of orofacial pain.

Based on the single-center case reports and all reported patients with primary hyperoxaluria type 1 (PH1) in China, this study discussed the clinical and genetic characteristics of this disease retrospectively. We reported and validated a novel genetic variation c.302 T > G: the clinical phenotypes of the two siblings were similar, in which both had onset in infancy, mainly manifested as renal insufficiency, and died within 6 months out of end-stage renal disease. The literature review is the first to summarize the Chinese patients with PH1 up to now. Forty-eight Chinese patients were included, containing 7 adults and 41 children. The median onset age was 51 months, and the ratio of male to female was 2.69:1. It showed a poor prognosis: 51.1% of Chinese primary hyperoxaluria type 1 patients suffered from end-stage renal disease, and 38.9% of patients died. Urolithiasis was the most common clinical manifestation both in adults and children, while infant-onset patients generally presented with renal insufficiency and had a higher mortality of 75.0%. One hundred and forty-nine AGXT mutant alleles are currently known in the Chinese population, c.33dupC and c.815_816insGA were the most common AGXT genes, accounting for 12.0% and 10.1% of allele frequencies, respectively. The exons 1, 2, 6, and 8 were the most common locations of gene variants, accounting for 78% of all variants, which will be promising targets of DNA sequencing for primary hyperoxaluria type 1.

We aimed to analyse postoperative cognitive dysfunction (POCD) incidence and risk factors in elderly adults who underwent surgery for oral malignancies. A total of 112 elderly patients (aged ≥ 55 years) were selected for expanded resection of oral malignancy and cervical lymphatic dissection at our institution from December 2020 to December 2021. Participants were cognitively evaluated using the neuropsychological test scale 1 day before and 7 days after surgery to determine whether they had developed POCD. Based on whether POCD occurred 7 days after surgery, patients were classified into the POCD and non-POCD groups. Logistic regression was applied to perioperative factors to analyse the risk factors for POCD onset. Seven days after surgery for oral malignancy, there were 37 (33.1%) POCD morbidities. Multiple factor logistic regression analysis revealed that venerable age (odds ratio [OR] = 1.269, 95% confidence interval [CI] 1.056–1.525, P < 0.05), low education levels (OR = 0.792, 95% CI 0.644–0.974, P < 0.05), hypertension (OR = 4.153, 95% CI 1.335–12.732, P < 0.05), dyssomnia (OR = 1.272, 95% CI 1.001–1.617, P < 0.05), prolonged anaesthesia (OR = 1.009, 95% CI 1.001–1.018, P < 0.05), and intraoperative hypotension (OR = 5.512, 95% CI 1.240–24.506, P < 0.05) increased the POCD risk in elderly patients who underwent surgery for oral malignancies. Venerable age, low knowledge reserve, hypertension, dyssomnia, prolonged anaesthesia, and intraoperative hypotension are independent risk factors for POCD in elderly patients with oral malignancies.

Procedural sedation and analgesia are now considered standard care for managing pain and anxiety in pediatric dental patients undergoing diagnostic and therapeutic procedures outside of the operating room. Anxiolysis, which combines both pharmacologic and non-pharmacologic approaches, plays a significant role in procedural sedation. Non-pharmacologic interventions such as Behavior Management Technology can help reduce preprocedural agitation, ease the transition to sedation, reduce the required amount of medication for effective sedation, and decrease the occurrence of adverse events. As the introduction of novel sedative regimen and methods in pediatric dentistry, the potential role of mainstay sedatives administered by new routes, for new indications, and with new delivery techniques, should be considered. The purpose of this paper is to examine and discuss the current state of sedation techniques in pediatric dentistry.

BackgroundIn recent years, the number of people using mobile applications to promote health and welfare has exponentially increased. However, there are fewer applications in the field of ERAS. How to promote the rapid rehabilitation of patients with malignant tumor surgery during perioperative period and the mastery of its long-term nutritional state is a problem to be solved. ObjectiveThe purpose of this study is to design and develop a mobile application, and use Internet technology to better manage nutritional health to achieve rapid recovery of patients with malignant tumor surgery. MethodsThis study is divided into three stages: (1) Design: use participating design to make the MHEALTH APP adapt to the clinical practice of nutritional health management; (2) Development: the WeChat Applet of Nutrition and Health Assessment (WANHA) developed using the Internet technology development, and web management programs. (3) Procedure test: patients and medical staff evaluate WANHA's quality (UMARS), availability (SUS), and satisfaction, and conduct semi-structured interviews. ResultsIn this study, 192 patients with malignant tumor surgery, 20 medical staff used WANHA. Patients with nutritional risks are supported by supporting treatment. The results show that patients who have not been treated during the perioperative period, the incidence of postoperative complications (22.4%) and the average hospitalization time after surgery decreased significantly. The incidence of nutritional risks is nearly more than the preoperative level. 45 patients and 20 medical staff participated in the survey of WANHA's SUS, UMARS, and satisfaction. In the interview, most patients and medical personnel believe that the procedure can improve the current medical services and nutritional health knowledge levels, promote the communication of medical staff and patients, and strengthen the nutritional health management of patients with malignant tumors under the concept of ERAS. ConclusionWeChat Applet of Nutrition and Health Assessment is a MHEALTH APP that enhances the nutrition and health management of patients with perioperative period. It can play a huge role in improving medical services, increasing patient satisfaction, and ERAS.

BackgroundHigh-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation.MethodsIn total, 120 children aged 2–7 years (weight: 10–30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge.ResultsNon-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = −1.4 mmHg, 95% CI: −2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events.ConclusionHFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

Emergence delirium can occur after general anesthesia in children. An intravenous infusion of alfentanil may reduce the incidence or severity of emergence delirium after sevoflurane anesthesia. The study aimed to investigate the effects of alfentanil intravenous infusion on emergence delirium and other perioperative complications. This was a single-center, randomized, placebo-controlled, double-blind clinical trial. A total of 172 children undergoing ambulatory dental treatment were randomized into three groups. Alfentanil group Alf2 received 0.2 μg/kg/min of alfentanil for continuous infusion, alfentanil group Alf4 received 0.4 μg/kg/min alfentanil, and the saline group (group Sal) received a continuous infusion of normal saline, with the same volume as the two other groups, as a placebo. The incidence of emergence delirium (assessed by the Paediatric Anaesthesia Emergence Delirium [PAED] scale), hemodynamic parameters, and recovery characteristics were recorded during the recovery period. The Aono scale was also used to assess for emergence delirium. A WeChat applet was designed to facilitate a caregiver teleconsultation and to provide feedback on postoperative nausea and vomiting and any other complications after discharge. The incidence of emergence delirium in group Alf2 (22.9%) and group Alf4 (21.1%) was significantly lower than that observed in the Sal group (48.3%). The PAED scores in group Alf2 (6.4 ± 3.5) and group Alf4 (5.8 ± 3.8) were significantly lower than those for group Sal (9.6 ± 5.1) (p < 0.01). Ten children in the Alf4 group needed manual ventilatory assistance to maintain end-tidal carbon dioxide (ETCO2) < 55 mm; children in group Alf2 did not. There was no significant difference between the discharge time of groups Alf2 and Sal (31.2 ± 4.64 vs 30.5 ± 2.82 min; 0.659 [95% confidence interval {CI} −1.052 to 2.369], p = 0.643); the time to discharge of group Alf4 (35.16 ± 3.97 min) was significantly longer than that of groups Alf2 and Sal (p < 0.01). The incidence of nausea and vomiting was similar in the three groups. No other clinically relevant adverse events were observed. Intravenous infusion of 0.2 μg/kg/min and 0.4 μg/kg/min alfentanil decreased the incidence of emergence delirium in the post-anesthesia care unit. The 0.2 μg/kg/min dose of alfentanil resulted in less respiratory depression and discharge delay than the 0.4 μg/kg/min alfentanil dose. Chinese Clinical Trial Registry (ChiCTR2100043320)

Background: Nalbuphine may relieve postoperative pain and decrease emergence agitation (EA) in children after seveflurane anesthesia. Aims: This study evaluated the effectiveness of intravenous nalbuphine 0.1 mg/kg for EA in pediatric patients undergoing dental surgery under sevoflurane anesthesia. Methods: A total of 84 pediatric patients (3-6 years) scheduled for dental surgery under sevoflurane for induction and maintenance of anesthesia with a laryngeal mask airway (LMA) were randomized to receive intravenous nalbuphine 0.1 mg/kg (Group N; n = 42) or saline 0.1 mg/kg (Group S; n = 42) 30 minutes before the end of surgery. Primary outcomes were the incidence and severity of EA in the PACU. Secondary outcomes were postoperative pain and the incidence of postoperative nausea and vomiting (PONV) in the PACU. Results: In the PACU, the incidence of EA (Aono's scale >= 3: 21.43% vs. 57.14%; Pediatric Anesthesia Emergence Delirium [PAED] scale >= 10: 21.43% vs. 54.76%; both P < 0.01), the percentage of patients with severe EA (PAED score >= 15; 7.69 % vs. 40.48%; P < 0.01), and peak pain score (2.60 +/- 2.07 vs. 4.10 +/- 2.49; P = 0.004) were significantly lower in the Group N compared to the Group S. Emergence time was significantly longer in the Group N, but there was no difference in time to discharge from the PACU. Conclusions: Compared to placebo, 0.1 mg/kg nalbuphine administered intravenously 30 minutes before the end of surgery significantly decreased the incidence and severity of EA in the PACU but did not delay discharge in pediatric patients undergoing dental surgery under sevoflurane anesthesia.

Background Modulation of N-methyl-D-aspartate receptor subunits NR1 and NR2 through phosphorylation mediates opioid-induced hyperalgesia, and activations of protein kinase C and extracellular signal-regulated kinase 1/2 potentiate while activation of calcium/calmodulin-dependent protein kinase II inhibits opioid-induced hyperalgesia. However, the mechanism of opioid-induced hyperalgesia development and in particular the potential interplay between N-methyl-D-aspartate receptors and protein kinase C or calcium/calmodulin-dependent protein kinase II or extracellular signal-regulated kinase 1/2 in the development of remifentanil-induced hyperalgesia is unclear. Methods Remifentanil (1 µg ċ kg −1 ċ min −1 ) was given intravenously over 60 min in rats, followed by the infusion of either vehicle solution or the respective inhibitors of protein kinase C (chelerythrine), extracellular signal-regulated kinase II (KN93), or extracellular signal-regulated kinase 1/2 (PD98059). Thereafter, the pain behaviors were evaluated by the paw withdrawal mechanical threshold and paw withdrawal thermal latency. In in vitro studies, fetal spinal cord dorsal horn neurons were primary cultured in the presence of 4 nM remifentanil for 60 min, and then the remifentanil was washed out and replaced immediately by culturing in the absence or presence of chelerythrine, KN93 or PD98059, respectively for up to 8 h. The expressions of N-methyl-D-aspartate receptors subunits and their phosphorylation (NR1, NR2B, p-NR1, p-NR2B) were analyzed by Western blotting after the completion of treatments. Functional changes of N-methyl-D-aspartate receptors were evaluated by electrophysiologic recordings of N-methyl-D-aspartate currents. Results Remifentanil induced significant thermal and mechanical hyperalgesia, which were significantly attenuated by Chelerythrine or KN93 but not PD98059. The expressions of NR1, NR2B, p-NR1, and p-NR2B were increased significantly and progressively over time after remifentanil administration, and these increases were all significantly attenuated by either chelerythrine or KN93 but not PD98059. Intriguingly, N-methyl-D-aspartate receptor functional enhancement induced by remifentanil was attenuated by Chelerythrine, KN93, and PD98059. Conclusions It is concluded that the enhancements in function and quantity of N-methyl-D-aspartate receptor via phosphorylation of its subunits through protein kinase C and calcium/calmodulin-dependent protein kinase II activation may represent the major mechanism whereby remifentanil induced hyperalgesia.

目的：探讨右美托咪定对静吸复合麻醉骨折手术患者苏醒期躁动以及术后机械痛阈值的影响。方法选择静吸复合麻醉骨折手术患者76例，随机分为右美托咪定组和对照组各38例，分别于麻醉诱导后给予右美托咪定0．5μg／kg和等量生理盐水静注，观察拔管时间、苏醒时间、追加芬太尼例数、苏醒期躁动发生例数及苏醒期躁动程度，术前及术后6、12、24、48 h时评估机械痛阈值。结果两组拔管时间、苏醒时间差异均无统计学意义（ P均＞0．05），右美托咪定组苏醒期躁动的发生例数及术后追加芬太尼例数均低于对照组（P均＜0．05）。右美托咪定组拔管时及拔管后10 min躁动评分（ RS）均低于对照组、Ramsay镇静评分（ RSS）均高于对照组，组间比较P均＜0．05。两组术前机械痛阈值差异无统计学意义（P＞0．05）；术后6、12、24、48 h时机械痛阈值均较术前降低，对照组降低更明显（P均＜0．05）。结论右美托咪定能够预防静吸复合麻醉骨折手术患者苏醒期躁动，提高术后机械痛阈值、减轻痛觉过敏。

The aim of the study was to determine whether or not dexmedetomidine- (DEX-) based intravenous infusion in dental implantation can provide better sedation and postoperative analgesia via suppressing postoperative inflammation and oxidative stress. Sixty patients were randomly assigned to receive either DEX (group D) or midazolam (group M). Recorded variables were vital sign (SBP/HR/RPP/SpO 2 /RR), visual analogue scale (VAS) pain scores, and observer’s assessment of alertness/sedation scale (OAAS) scores. The plasma levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- α ), antioxidant superoxide dismutase (SOD), and the lipid peroxidation product malondialdehyde (MDA) were detected at baseline and after 2, 4, and 24 h of drug administration. The VAS pain scores and OAAS scores were significantly lower for patients in group D compared to group M. The plasma levels of TNF- α , IL-6, and MDA were significantly lower in group D patients than those in group M at 2 h and 4 h. In group M, SOD levels decreased as compared to group D at 2 h and 4 h. The plasma levels of TNF- α , IL-6, and MDA were positively correlated with VAS pain scores while SOD negatively correlated with VAS pain scores. Therefore, DEX appears to provide better sedation during office-based artificial tooth implantation. DEX offers better postoperative analgesia via anti-inflammatory and antioxidation pathway.

Objective To investigate the effect of sepsis on vecuronium-induced inhibition of acetylcholine release in neuromuscular junction in rats.Methods Thirty-six adult male SPF SpragueDawley rats,aged 2-3 months,weighing 200-220 g,were randomly divided into 3 groups (n=12 each) using a random number table:control group (group C),sham operation group (group S) and sepsis group (group Sep).Sepsis was induced by cecum ligation and puncture (CLP) in rats anesthetized with intraperitoneal chloral hydrate 350 mg/kg.At 12 h after CLP,the sciatic nerve-pretibial muscle was prepared.Vecuronium was added to the culture medium with the final concentration of 0.08 μg/ml,and the sciatic nerve-pretibial muscle was incubated for 15 min.Before and after administration,evoked endplate potentials (EPPs) and miniature endplate potentiais (MEPPs) were recorded by using intracellular microelectrode.EPP/MEPP ratio was calculated.Results Compared to C and S groups,EPPs,MEPPs and EPP/MEPP ratio were significantly increased before and after administration in group Sep.EPPs,MEPPs and EPP/MEPP ratio were significantly lower after administration than before administration in the three groups.Conclusion Sepsis can promote acetylcholine release in neuromuscular junction,thus weakening vecuronium-induced inhibition of acetylcholine release in neuromuscular junction in rats.

Objective:To investigate the effects of Ketamine on lipopolysaccharide(LPS)-induced translocation of nuclear factor-kappaB(NF-κB) in human umbilical vein endothelial cell nuclei and to explore it's anti-inflammatory action.Methods:Human umbilical vein endothelial cells(HUVECs) were divided into four groups:group C(blank control group),group L(1 μg/ml LPS was added),group KL1(3 μg/ml ketamine and 1 μg/ml LPS were added) and group KL2(30 μg/ml ketamine and 1 μg/ml LPS were added).The tanslocation and expressions of NF-κB p65 in endothelial cell nuclei were detected by Western blot,reverse transcription polymerase chain reaction(RT-PCR) and image analysis system of HPIAS 2000.Results:The tanslocation and expression of NF-κB p65 in endothelial cell nuclei induced by LPS were reduced in group KL1 and KL2.Conclusions:The tanslocation and expression of NF-κB p65 in endothelial cell nuclei can be induced by LPS and Ketamine can suppress the activation.There are positive correlations between Ketamine concentration and its inhibitory effect.The anti-inflammatory effect of Ketamine may be achieved by the translocation of NF-κB.