OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

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.

ObjectiveBased on the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway， this study aimed to observe the effect of the Huazhuo Jiedu prescription on renal fibrosis in 5/6 nephrectomy rats and explore its underlying mechanism. MethodsA total of 67 SPF-grade male SD rats were used， of which 11 were randomly selected as the normal group. A chronic renal failure （CRF） model was established using 5/6 nephrectomy. The successfully modeled rats were randomly assigned to the model group， losartan potassium group （4.5 mg·kg^-1）， and low- （1.175 g·kg^-1）， medium- （2.35 g·kg^-1） and high-dose （4.7 g·kg^-1） Huazhuo Jiedu prescription groups， with 9 rats per group. Each group received an equivalent volume of saline or the corresponding concentration of Huazhuo Jiedu prescription by gavage once daily for 8 weeks. Hematoxylin-eosin （HE） and Masson staining were used to observe renal tissue pathological changes. Transmission electron microscopy examined renal ultrastructure. Immunohistochemistry （IHC） detected expressions of α-smooth muscle actin （α-SMA） and transforming growth factor-β₁ （TGF-β₁）. Western blot analyzed expression levels of microtubule-associated protein Ⅰ light chain 3Ⅱ （LC3Ⅱ）， Beclin1， p62， AMPK， phosphorylated AMPK （p-AMPK）， mTOR， and phosphorylated mTOR （p-mTOR）. ResultsCompared with the normal group， the model group exhibited glomerular shrinkage， mesangial and interstitial thickening， and tubular vacuolar degeneration， with no evident autophagosomes or autophagolysosome structures. Expression levels of α-SMA and TGF-β₁ were significantly increased （P0.01）， while p-AMPK/AMPK， Beclin1， and LC3Ⅱ were significantly decreased （P0.01）， and p-mTOR/mTOR and p62 were significantly increased （P0.01）. Compared with the model group， the medium- and high-dose Huazhuo Jiedu prescription groups and the losartan potassium group showed varying degrees of pathological improvement. Autophagosomes with double- or multiple-layer membranes and autophagolysosomes with monolayer membranes containing undegraded organelles were observed. Renal α-SMA and TGF-β₁ protein expression levels were markedly reduced （P0.05， P0.01）， p-mTOR/mTOR and p62 were significantly decreased （P0.05， P0.01）， and p-AMPK/AMPK， Beclin1， and LC3Ⅱ expression levels were significantly increased （P0.05， P0.01）. ConclusionHuazhuo Jiedu prescription may improve renal fibrosis in 5/6 nephrectomy rats by regulating the AMPK/mTOR signaling pathway and enhancing autophagy.

Objective To explore the expression significance of serum Kisspeptin and luteinizing hormone(LH)in girls with central precocious puberty(CPP).Methods A total of 98 CPP girls were included as the study group,and 91 healthy girls during the same period were used as the control group.Under the condition of no intervention,CPP girls were followed up for 6 months and assigned into the fast progressive CPP(RP-CPP)group(n=46)and the slowly progressive CPP(SP-CPP)group(n=52)based on their developmental status during the follow-up period.ELISA was applied to detect serum Kisspeptin level.Chemiluminescence method was applied to detect serum LH and follicle stimulating hormone(FSH)levels.The correlation of serum Kisspeptin,LH baseline(B-LH)and growth development and imaging indicators was analyzed.Receiver operating characteristic curve(ROC)was applied to analyze the value of serum Kisspeptin and LH in predicting RP-CPP.Results Compared with the control group,body mass index(BMI),serum levels of Kisspeptin,B-LH,and FSH baseline(B-FSH)were significantly higher in the study group(P＜0.05).Compared with the SP-CPP group,BMI,bone age index(BAI),serum Kisspepti and B-LH levels were higher in the RP-CPP group,and ovarian volume was larger(P＜0.05).Correlation analysis showed that serum Kisspeptin level was positively correlated with BMI,BAI,ovarian and uterine volume of CPP girls(P＜0.05),and serum B-LH level was positively correlated with ovarian and uterine volume of CPP girls(r=0.218,0.381,0.300,P＜0.05).ROC curve showed that the sensitivity and specificity of Kisspeptin combined with B-LH in predicting RP-CPP were 95.65%and 82.69%,respectively.Conclusion Serum Kisspeptin and B-LH levels are higher in CPP girls,and the combined of the two has a high predictive value for RP-CPP,which can provide a certain reference for clinical diagnosis and treatment.

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 explore the expression significance of serum Kisspeptin and luteinizing hormone(LH)in girls with central precocious puberty(CPP).Methods A total of 98 CPP girls were included as the study group,and 91 healthy girls during the same period were used as the control group.Under the condition of no intervention,CPP girls were followed up for 6 months and assigned into the fast progressive CPP(RP-CPP)group(n=46)and the slowly progressive CPP(SP-CPP)group(n=52)based on their developmental status during the follow-up period.ELISA was applied to detect serum Kisspeptin level.Chemiluminescence method was applied to detect serum LH and follicle stimulating hormone(FSH)levels.The correlation of serum Kisspeptin,LH baseline(B-LH)and growth development and imaging indicators was analyzed.Receiver operating characteristic curve(ROC)was applied to analyze the value of serum Kisspeptin and LH in predicting RP-CPP.Results Compared with the control group,body mass index(BMI),serum levels of Kisspeptin,B-LH,and FSH baseline(B-FSH)were significantly higher in the study group(P＜0.05).Compared with the SP-CPP group,BMI,bone age index(BAI),serum Kisspepti and B-LH levels were higher in the RP-CPP group,and ovarian volume was larger(P＜0.05).Correlation analysis showed that serum Kisspeptin level was positively correlated with BMI,BAI,ovarian and uterine volume of CPP girls(P＜0.05),and serum B-LH level was positively correlated with ovarian and uterine volume of CPP girls(r=0.218,0.381,0.300,P＜0.05).ROC curve showed that the sensitivity and specificity of Kisspeptin combined with B-LH in predicting RP-CPP were 95.65%and 82.69%,respectively.Conclusion Serum Kisspeptin and B-LH levels are higher in CPP girls,and the combined of the two has a high predictive value for RP-CPP,which can provide a certain reference for clinical diagnosis and treatment.

Objective To explore the influencing factors of frailty among the health check-up elder-ly participants from our outpatient clinic.Methods A total of 710 elderly individuals(≥60 years old)who taking health check-up in our outpatient department between April and August 2022 were consecutively enrolled,and according to the results of Fried Frailty Phenotype Scale,they were divided into non-frailty group(422 cases),pre-frailty group(225 cases)and frailty group(63 cases).Their general clinical data,laboratory indicators and echocardiographic parameters were collected,and multivariate logistic regression analysis was applied to identify the independent in-fluencing factors for pre-frailty and frailty.Results The overall prevalence of pre-frailty and frail-ty was 31.7％and 8.9％,respectively.The pre-frailty and frailty groups had obviously larger left atrial anterior-posterior diameter and left ventricular end diastolic diameter and lower left ventric-ular ejection fraction when compared with the non-frailty group(P＜0.05).Multivariate logistic regression analysis showed that Hb was a protective factor for pre-frailty in the elderly partici-pants(OR=0.984,95％CI:0.966-0.992,P=0.048),while age(OR=1.064),CCI(OR=1.387)and LAAP(OR=1.059)were risk factors for pre-frailty in them(P＜0.05,P＜0.01).Serum albumin was a protective factor for frailty(OR=0.823,95％CI:0.728-0.931,P=0.002),but age(OR=1.081),CCI(OR=1.458),left atrial anterior-posterior diameter(OR=1.249)and NT-proBNP(OR=1.652)were independent risk factors for frailty(P＜0.05,P＜0.01).Conclusion There are differences in influencing factors for frailty of different severity,and the status of frailty is related to factors such as age,comorbidity,cardiac function and nutritional sta-tus.Therefore,comprehensive interventions should be implemented as early as possible for the elderly occurrence of pre-frailty so as to prevent and reverse frailty at the same time.

Objective To explore the influencing factors of frailty among the health check-up elder-ly participants from our outpatient clinic.Methods A total of 710 elderly individuals(≥60 years old)who taking health check-up in our outpatient department between April and August 2022 were consecutively enrolled,and according to the results of Fried Frailty Phenotype Scale,they were divided into non-frailty group(422 cases),pre-frailty group(225 cases)and frailty group(63 cases).Their general clinical data,laboratory indicators and echocardiographic parameters were collected,and multivariate logistic regression analysis was applied to identify the independent in-fluencing factors for pre-frailty and frailty.Results The overall prevalence of pre-frailty and frail-ty was 31.7％and 8.9％,respectively.The pre-frailty and frailty groups had obviously larger left atrial anterior-posterior diameter and left ventricular end diastolic diameter and lower left ventric-ular ejection fraction when compared with the non-frailty group(P＜0.05).Multivariate logistic regression analysis showed that Hb was a protective factor for pre-frailty in the elderly partici-pants(OR=0.984,95％CI:0.966-0.992,P=0.048),while age(OR=1.064),CCI(OR=1.387)and LAAP(OR=1.059)were risk factors for pre-frailty in them(P＜0.05,P＜0.01).Serum albumin was a protective factor for frailty(OR=0.823,95％CI:0.728-0.931,P=0.002),but age(OR=1.081),CCI(OR=1.458),left atrial anterior-posterior diameter(OR=1.249)and NT-proBNP(OR=1.652)were independent risk factors for frailty(P＜0.05,P＜0.01).Conclusion There are differences in influencing factors for frailty of different severity,and the status of frailty is related to factors such as age,comorbidity,cardiac function and nutritional sta-tus.Therefore,comprehensive interventions should be implemented as early as possible for the elderly occurrence of pre-frailty so as to prevent and reverse frailty at the same time.

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.