Malignant hyperthermia(MH)is a rare perioperative disease with autosomal dominant inheritance,and its pathogenesis involves specific gene mutations.Its clinical feature is that conventional anesthetics can trigger abnormally high metabolic reactions in skeletal muscles.Although the incidence of this disease is low,the condition is dangerous,progresses rapidly,and has a high mortality rate;Its treatment relies on early diagnosis,timely application of the specific drug Dantrolene Sodium,and rapid and orderly comprehensive symptomatic supportive treatment.MH is a critical perioperative emergency that can occur during surgery.It presents with symptoms such as hyperpyrexia,metabolic acidosis,rhabdomyolysis,and dysfunction of multiple organ systems.If not treated promptly,it can quickly lead to life-threatening arrhythmias and cardiac arrest.This condition serves as an essential teaching example in anesthesia crisis resource management.As an effective teaching method,scenario simulation exercises can comprehensively enhance medical staff's personal technical,non-technical,and teamwork abilities through simulating emergency scenarios,teaching assessments,and retrospective discussions,especially suitable for comprehensive management training of fatal diseases.Many countries internationally have incorporated simulation exercises for MH into their routine teaching and training systems.The effectiveness of teaching and training for anesthesiologists in MH and their ability to handle anesthesia crisis events have been continuously improved through a periodic training model.This article systematically reviews the research progress and practical experience of scenario simulation exercises in emergency training for MH,with a focus on exploring how to establish a scenario simulation exercise plan for emergency application and comprehensive symptomatic support treatment of Dantrolene Sodium based on the actual situation in China,providing reference for improving the teaching and training quality of MH and other clinical crisis events.

Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.

Objective:To explore the molecular mechanism by which the methionine adenosyltransferase 2A (MAT2A)/β-catenin/zinc finger E-box binding homeobox 1 (ZEB1)/epithelial-mesenchymal transition (EMT) pathway regulates neural tube defect (NTD) through intracellular S-adenosylmethionine (SAM).Methods:A mouse NTD model was induced using the SAM metabolic disorder inhibitor ethionine. Eighty specific pathogen-free C57BL/6 mice were divided into three groups: a normal group (36 mice), an ethionine group (46 mice), and an ethionine+SAM group (44 mice). Phosphate-buffered saline (PBS), ethionine, and ethionine+SAM were respectively injected intraperitoneally on embryonic day 7.5 (E7.5), and the mice were sacrificed on E10.5. Embryonic tissues were collected, and the morphology of embryos in each group was observed under a stereomicroscope. The interaction between ethionine and MAT2A was analyzed using Autodock software. The expression levels of MAT2A, β-catenin, ZEB1, and EMT-related proteins in the brain tissues of embryos from the three groups were measured using immunofluorescence, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). Variance analysis was used for intergroup comparisons.Results:(1) Autodock analysis results showed that MAT2A binds to ethionine through covalent bonds, exhibiting a complementary effect, thereby accelerating the expression of MAT2A. (2) After successful construction of the NTD model, normal embryos were plump with well-developed brains. NTD embryos showed delayed development, obvious anencephaly, unclosed neural tubes, and asymmetry. (3) The levels of SAM and SAH in the embryonic tissues of the ethionine group were significantly lower than those in the normal group (1 737.56±95.64 vs. 872.33±205.11, and 89.17±9.50 vs. 51.25±9.48, respectively). The SAM and SAH levels in the ethionine+SAM group was 1 197.00±222.27 and 66.61±12.25, significantly higher than those in the ethionine group ( P<0.017). Compared with the normal group and the ethionine+SAM group, the expression of MAT2A mRNA in the embryonic brain tissue of the ethionine group was significantly upregulated (1.00±0.00, 1.59±0.52, and 2.42±0.53, respectively, F=49.64, P<0.001; pairwise comparisons between groups P<0.017). (4) Compared with the normal group, the expression of Ctnnb1 in the ethionine group was reduced, and the expression of Ctnnb1 in the ethionine+SAM group was higher than that in the ethionine group (1.00±0.00, 0.38±0.16, and 0.76±0.10, respectively, F=149.03, P<0.001; pairwise comparisons between groups P<0.017). (5) The expression of ZEB1 in the ethionine group was higher than that in the normal group and the ethionine+SAM group (2.91±0.55, 1.00±0.00, and 1.61±0.20, respectively, F=150.01, P<0.001; pairwise comparisons between groups P<0.017). (6) The expression levels of E-cadherin and Vimentin in the ethionine group were lower than those in the normal group. In contrast, the expression of N-cadherin was higher than that in the normal group. After SAM supplementation, the expression levels of E-cadherin and Vimentin were upregulated, and the expression level of N-cadherin was downregulated (0.54±0.12, 1.00±0.00, and 0.72±0.14, respectively, F=87.44; 0.53±0.17, 1.00±0.00, and 0.76±0.09, F=87.44; 3.11±0.53, 1.00±0.00, and 2.13±0.56, F=95.54; all P<0.001; pairwise comparisons within the same index group P<0.017]). Conclusions:Ethionine promotes the expression of MAT2A, leading to reduced SAM production. Ethionine regulates the level of ZEB1 by increasing MAT2A and inhibits the EMT process to interfere with methionine cycle metabolism, ultimately resulting in NTD.

Objective:To summarize the experience of designing hair transplantation for post-cleft lip repair moustache defects based on the morphological and tissue characteristics of the upper lip.Methods:A retrospective analysis was conducted on the clinical data of male patients treated at the Hair Transplantation Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2011 to July 2024. Based on the morphology and tissue texture of the upper lip after cleft lip repair, the position and shape of the moustache were designed. Hair follicles were harvested from the mid-occipital region and/or the jaw shadow area using either the strip harvesting method or the follicular unit excision (FUE) technique. Needles of 21 or 22 gauge were used to create incisions in the recipient sites down to the superficial subcutaneous layer. The hair shafts were clamped with micro-forceps and then transplanted into the recipient sites to restore the moustache shape. Postoperatively, the density, shape, direction of the moustache, and the condition of the donor site scars were observed and followed up.Results:A total of 47 male patients, aged 23-43 years (mean 28.7 years), were included. Among them, 29 had undergone lower triangular flap repair, 13 received the Millard technique, and 5 were treated with other surgical methods for cleft lip repair. For hair follicle extraction, the strip method was used in 7 cases, and FUE in 40 cases. The donor sites included the jaw shadow area (9 cases), mid-occipital region (23 cases), and a combination of both (15 cases). The number of transplanted follicular units ranged from 33 to 500 (mean 217). Follow-up duration ranged from 9 months to 10 years (mean 3.5 years). Postoperative complications included folliculitis in 6 cases, and 4 cases required additional transplantation due to insufficient density after one year. The remaining patients exhibited satisfactory hair growth, with natural mustache shape and direction. The graft survival rate was approximately 80%, and donor site scarring was minimal.Conclusion:When performing hair transplantation to treat post-cleft lip repair moustache defects, the design should prioritize the morphological and tissue characteristics of the upper lip, followed by consideration of overall position and bilateral symmetry of the moustache. Only by fully considering the characteristics of the recipient area can optimally repair outcomes be achieved.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the role of meningeal γδ T cell-derived interleukin-17A (IL-17A) in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Forty healthy male C57BL/6N mice, aged 18 months, weighing 30-40 g, were divided into 4 groups ( n=10 each) using a table of random numbers: control group (group C), anti-γδ T cell receptor antibody (Anti-TCR γδ) group, POCD group (group P), and POCD+ Anti-TCR γδ group (group P+ Anti-TCR γδ). Anesthesia was induced with 8% sevoflurane and maintained with 3% sevoflurane, and the internal fixation for tibial fracture was performed to establish the mouse model of POCD in P and P+ Anti-TCR γδ groups. Anti-TCR γδ antibody 2.5 μg was infused into the occipital cistern on postoperative day 4 in P+ Anti-TCR γδ and Anti-TCR γδ groups. The open field test, novel object recognition test and Y-maze test were conducted sequentially at 7th day after surgery. The total distance traveled in the open field and the number of entries into the central area were recorded, and the novel object recognition index and preference index for exploring the novel arm were calculated. The mice were sacrificed at the end of the behavioral testing, the meninges were obtained for detection of the expression of IL-17A in γδ T cells by flow cytometry, and the hippocampal tissues were harvested for determination of the expression of vesicular glutamate transporter1 (VGLUT1), glutamate receptor 1 (GluR1), and IL-17A receptor (IL-17AR) (by Western blot). Results:There was no statistically significant difference in the total distance traveled in the open field test or the number of entries into the central area among the four groups ( P>0.05). Compared with group C, the novel object recognition index and preference index for novel arm exploration were significantly decreased, the expression of meningeal γδ T cells and IL-17AR in hippocampal tissues was up-regulated, and the expression of VGLUT1 and GluR1 was down-regulated in group P and group P+ Anti-TCR γδ ( P<0.05), and no significant change was found in the aforementioned parameters in group Anti-TCR γδ ( P>0.05). Compared with group P, the novel object recognition index and preference index for novel arm exploration were significantly increased, the expression of meningeal γδ T cells and IL-17AR was down-regulated, and the expression of VGLUT1 and GluR1 was up-regulated in group P+ Anti-TCR γδ ( P<0.05). Conclusions:Increased meningeal γδ T cell-derived IL-17A can up-regulate the expression of IL17AR in the hippocampus and down-regulate the expression of VGLUT1 and GluR1, thus involving in the development of POCD in aged mice.