Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

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 summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early treatment.

Objective:To summarize the clinical manifestations, diagnosis and treatment of a family with hereditary sensory and autonomic neuropathy (HSAN) caused by the SPTLC1 gene variation and to review the literature. Methods:Case summary.The clinical manifestations, neuroelectrophysiology, genetic examination, treatment and follow-up of a family with autosomal dominant HSAN diagnosed at the Department of Neurology, Beijing Children′s Hospital in March 2024 were summarized.At the same time, related English and Chinese literatures were searched from CNKI, Wanfang and PubMed databases from their establishment to July 2024, with " serine palmitoyltransferase long-chain base subunits 1", " hereditary sensory and autonomic neuropathy", " SPTLC1" and " HSAN1" taken as key words.Results:The proband was a 11-year-and-2-month-old boy, who developed limited bending at the age of 7.The patient had ankle pain and knee bending during walking, and limited movement.He could neither jump on one foot nor bend down to pick up things from the ground, but there was no obvious sensory and autonomic nervous function abnormalities.His parents had no abnormal clinical manifestations.Neuroelectrophysiology showed peripheral nerve damage, and family whole exon sequencing revealed a maternal heterozygous missense variation of the SPTLC1 gene c.1015G>A, p.A339T(maternal origin, reported).Further maternal neuroelectrophysiology examination and sphingomyelin analysis confirmed the diagnosis of HSAN1A.The proband wore orthopedic insoles, and the proband and his mother took L-serine orally for 8 months.During the follow up, the proband reported slight improvement in muscle strength, and no adverse reactions were found.Two Chinese and thirteen English case reports on autosomal dominant HSAN caused by the SPTLC1 gene variation were retrieved.Twenty cases had complete clinical data.Therefore, a total of 22 cases, including the above-mentioned two patients, were analyzed.Except for patients whose age at diagnosis is unknown and who are deceased, the age at diagnosis ranged from 7 to 93 years.The 66.7%(14/21) cases were childhood-onset.The first clinical symptoms were mainly gait abnormalities, easy falls, sensory disorders and ulcers.Foot deformity, and autonomic neuropathy were detected in 53.3% (8/15), and 31.6% (6/19) cases, respectively, 15.8% (3/19) of the cases had amputation.Only 1 case was treated with L-serine, who showed partial relief of clinical symptoms, but electromyography was not significantly improved.Fifteen cases received neuroelectrophysiological testing, and 78.6%(11/14) of the patients showed sensory and motor neurogenic injuries.All the gene variations reported previously were missense mutations, and the high frequency variation was p. C133T/W. Conclusions:This study is helpful to improve the understanding of the clinical characteristics of HSAN1A caused by the SPTLC1 gene.Oral L-serine supplementation may benefit patients and gene detection promotes diagnosis confirmation and early 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 analyze the factors influencing patients′ medical experience, to provide reference for medical institutions to improve patients′ medical experience.Methods:A stratified sampling method was employed nationwide to select 32 patients and 20 medical staff. From May to August 2023, semi-structured interviews were conducted with them regarding the factors influencing patients′ medical experience. The data from the interviews were analyzed using programmed grounded theory, which led to the identification of factors affecting patients′ medical experience.Results:After three-level coding, four main categories of demographic characteristics, self health characteristics, medical outcome experience, and medical process experience, two core categories of patient related influencing factors and hospital related influencing factors were obtained. Additionally were also obtained.Conclusions:The factors influencing patients′ medical experience are multifaceted and jointly dominated by multiple stakeholders. Medical institutions should adopt a variety of measures to continuously improve patients′ medical experience. When assessing patients′ medical experience, the impact of individual differences among patients on the assessment results should be fully considered.

Objective:To explore the effect of Jian-Pi-Zhi-Dong decoction on autonomous activity and dopamine (dopamine, DA) synaptic vesicle protein expression in the striatum of Tourette syndrome (TS) model rats.Methods:The 4-week-old male SD rats were used to establish the TS model by intraperitoneal injection of N-aminodipropionate. Thirty successfully modeled rats were randomly divided into model group, Chinese medicine group, and tiberide group according to random number table method, with 10 rats in each group. And another 10 rats with matched body mass were selected as the control group. Rats in Chinese medicine group were given Jian-Pi-Zhi-Dong decoction solution (1.6 g/100 g) and the rats in tiapride group were given sulfate tiapride suspension (2.1 mg/100 g), while rats in control group and model group were given an equal volume of 0.9% sodium chloride solution, once a day for 4 weeks.The number of autonomous activities in rats was determined by autonomous activity programmer. ELISA was used to detect the level of DA in the striatum of rats and the expression of dopamine transporter (DAT).Vesicular monoamine transporter-2 (VMAT2) and α-synuclein (α-syn) were measured by Western blot.SPSS 25.0 software was used for data analysis. Multiple group comparisons were performed using one-way ANOVA, non-parametric test and repeated measures ANOVA.Results:Comparing the number of autonomous activities among the 4 groups, the interaction effect between time and group was significant ( F=184.354, P<0.001). At the 1-4 weeks of gavaging, the numbers of autonomic activities in the model group were more than those in the control group (all P<0.05).While the numbers of autonomic activities in Chinese medicine group and tiapride group were less than those in the model group (all P<0.05). Moreover, the numbers of autonomic activities in Chinese medicine group and tiapride group from 1 to 4 weeks were less than those after model making (all P<0.05). The Western blot results showed significant differences in the relative expression of α-syn ( H=29.098), DAT ( F=54.632) and VMAT2 ( H=18.982) among the 4 groups (all P<0.001). The expression levels of α-syn protein in Chinese medicine group and tiapride group were both lower than that in the model group (0.39(0.36, 0.51), 0.39(0.36, 0.50), 0.62(0.50, 0.70)) (both P<0.05). The expression level of DAT protein in Chinese medicine group was higher than that in the model group and lower than that in tiapride group ((0.37±0.06), (0.26±0.07), (0.49±0.09)) (both P<0.05). And the expression level of VMAT2 protein in Chinese medicine group had no significant difference compared with that in the model group ( P>0.05).The ELISA results showed significant differences in DA content of striatum among the 4 groups ( F=75.370, P<0.001). The level of DA in the model group was higher than that in the control group ((7.65±0.72) ng/L, (3.71±0.59) ng/L, P<0.05). The levels of DA in Chinese medicine group ((3.92±0.81) ng/L) and tiapride group ((4.40±0.53) ng/L) were lower than that in the model group (both P<0.05), and the difference between Chinese medicine group and tiapride group was not significant ( P>0.05). Conclusion:Jian-Pi-Zhi-Dong decoction can relieve the tic symptoms of the model rats with TS, and its mechanism may be related to inhibiting the excessive release of α-syn, improving the expression of DAT and VMAT2, improving the DA synaptic vesicle circulation, and reducing the DA content in the synaptic space of the brain.

Objective:To summarize the experience of designing transplanted hair based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns.Methods:A retrospective analysis was conducted on clinical data of the patients with eyebrow defects after burns who treated at Hair Transplantation Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences between January 2011 and September 2023. The location and appearance of eyebrow were designed according to the orbital morphology and tissue characteristics. The follicles were extracted by incision of scalps strips and follicle unit excision (FUE) on the donor area of the occipital region near the posterior hairline or the posterior ear hairline. Scalps with scars that needed to be removed or had "dog ear" deformities following scalp expansion surgery that needed to be repaired were also be used as donor sites. The follicles were divided as follicle units (FUs) including single hair. The recipient area was punched with syringe needle of 22 or 22 G to subcutaneous superficial layer. Then the hair shaft was clamped with microforceps and the hairs were transplanted to the defective area to restore the appearance of eyebrow. The density, morphology, direction and scars of the donor sites were observed by following-ups.Results:A total of 197 patients with 282 eyebrows were recruited. There were 133 males and 64 females. The average age was 33.7 (9 to 62) years. There were 17 patients with skin graft transplantation in the eyebrow arch, 33 with flap and expanded flap repair, 36 with eyelid skin grafting, 111 with burn scar healing. A total of 51 patients had complete eyebrow defects on both sides, and 34 had partial defects. Sixty-five patients had complete eyebrow defects on single side, and 47 had partial defects. The amount of hair transplantation was from 53 to 600 FUs on 282 eyebrows. Seventy-five patients extracted follicles with incision of scalps strips and 122 with FUE. The patients were followed up for 9 months to 10 years. Folliculitis were found in 17 patients and completely cured by 75% alcohol disinfection. Nine patients with insufficient density underwent hair transplantation for a second time to increase the density of hairs one year later. And the implanted hairs grew well, which were similar to the shape and direction of normal eyebrows. Transplanted hairs of the rest patients grew well. The direction and appearance were satisfied. The scar in the donor site was not obvious.Conclusion:The transplanted hair should be designed primarily based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns. Then the position of the eyebrow and the bilateral symmetry should be considered. The ideal effect of eyebrow reconstruction would depend on the full consideration of the receipt site.

Objective:To summarize the experience of designing transplanted hair based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns.Methods:A retrospective analysis was conducted on clinical data of the patients with eyebrow defects after burns who treated at Hair Transplantation Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences between January 2011 and September 2023. The location and appearance of eyebrow were designed according to the orbital morphology and tissue characteristics. The follicles were extracted by incision of scalps strips and follicle unit excision (FUE) on the donor area of the occipital region near the posterior hairline or the posterior ear hairline. Scalps with scars that needed to be removed or had "dog ear" deformities following scalp expansion surgery that needed to be repaired were also be used as donor sites. The follicles were divided as follicle units (FUs) including single hair. The recipient area was punched with syringe needle of 22 or 22 G to subcutaneous superficial layer. Then the hair shaft was clamped with microforceps and the hairs were transplanted to the defective area to restore the appearance of eyebrow. The density, morphology, direction and scars of the donor sites were observed by following-ups.Results:A total of 197 patients with 282 eyebrows were recruited. There were 133 males and 64 females. The average age was 33.7 (9 to 62) years. There were 17 patients with skin graft transplantation in the eyebrow arch, 33 with flap and expanded flap repair, 36 with eyelid skin grafting, 111 with burn scar healing. A total of 51 patients had complete eyebrow defects on both sides, and 34 had partial defects. Sixty-five patients had complete eyebrow defects on single side, and 47 had partial defects. The amount of hair transplantation was from 53 to 600 FUs on 282 eyebrows. Seventy-five patients extracted follicles with incision of scalps strips and 122 with FUE. The patients were followed up for 9 months to 10 years. Folliculitis were found in 17 patients and completely cured by 75% alcohol disinfection. Nine patients with insufficient density underwent hair transplantation for a second time to increase the density of hairs one year later. And the implanted hairs grew well, which were similar to the shape and direction of normal eyebrows. Transplanted hairs of the rest patients grew well. The direction and appearance were satisfied. The scar in the donor site was not obvious.Conclusion:The transplanted hair should be designed primarily based on the orbital morphology and tissue characteristics for the treatment of eyebrow defects after burns. Then the position of the eyebrow and the bilateral symmetry should be considered. The ideal effect of eyebrow reconstruction would depend on the full consideration of the receipt site.