OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

Diabetic kidney disease （DKD） is one of the more common chronic kidney diseases，and its causes are complex. DKD is very easy to progress to end-stage renal disease，and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body， the kidney has physiological functions such as discharging metabolic waste， regulating fluid balance， and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury， and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy， as a means of regulating mitochondrial homeostasis， is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 （PINK1）/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular， traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time， it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy， aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.

Diabetic kidney disease （DKD） is one of the more common chronic kidney diseases，and its causes are complex. DKD is very easy to progress to end-stage renal disease，and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body， the kidney has physiological functions such as discharging metabolic waste， regulating fluid balance， and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury， and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy， as a means of regulating mitochondrial homeostasis， is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 （PINK1）/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular， traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time， it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy， aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Objective To explore the application effect of health education based on gain and loss message framing on the treatment behavior intention and self-management of patients with high-risk diabetic foot.Methods From July to September 2024,convenience sampling was used to select patients with high-risk diabetic foot who were hospitalized in the endocrinology department of a tertiary general hospital in Guiyang as the study subjects.They were divided into 3 groups according to the admission time,with 30 patients in each group.The experimental group adopted health education based on gain message framing or framing loss message,while in the control group,health education was provided in a conventional manner.Before and after intervention,the differences of intervention effects among the 3 groups were compared by using diabetic foot pre-hospital delay intention questionnaire,diabetic foot care knowledge questionnaire and Chinese version of Nottingham foot care assessment scale(CNAFF).Results Ultimately,29 cases in the gain framing group,29 cases in the loss framing group,and 29 cases in the control group completed the study.After intervention,the score of pre-hospital delay intention questionnaire of diabetic foot in the gain framing group was(21.48±4.32),and it was(24.31±2.49)in the loss framing group,and(17.76±5.03)in the control group.The difference among the 3 groups was statistically significant(F=18.725,P＜0.001);the loss framing group was superior to the gain framing group(P=0.01)and the control group(P＜0.001).After the intervention,the score of the CNAFF in the gain framing group was(55.83±3.06),and it was(59.14±2.90)in the loss framing group,and(48.66±2.58)in the control group.The difference between the 3 groups was statistically significant(F=102.245,P＜0.001).The loss framing group was superior to the gain framing group and the control group(all P＜0.001).Conclusion Health education based on the loss message framing is more conducive to improving patients' intention to delay diabetic foot visits,leading to good foot care behaviors,and may provide an effective means of pre-hospital prevention and control of diabetic foot.

Objective:To observe any effect of combining repeated transcranial magnetic stimulation (rTMS) with electro-acupuncture in treating post-stroke cognitive impairment (PISC).Methods:Three groups of PISC patients were formed through random selection: an rTMS group, an electro-acupuncture group, and a combined group. In addition to routine medication and conventional rehabilitation training, the rTMS and electro-acupuncture groups received rTMS and electro-acupuncture treatment, while the combined group underwent both for six weeks. Before the treatment, immediately afterward and 3, 6, and 12 months later, everyone′s cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). The modified Barthel Index (MBI), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the National Institutes of Health Stroke Scale (NIHSS) were also applied. Transcranial Doppler ultrasound (TCD) was employed to measure the mean cerebral blood flow velocity (Vm), pulsatility index (PI), and breath-holding index (BHI) in the subjects′ bilateral middle cerebral arteries (MCAs). The total effectiveness rates and the incidence of adverse reactions were compared among the three groups.Results:The MoCA scores, MBI scores, HAMD-17 scores, NIHSS scores, and Vm of the MCA had improved significantly in all three groups right after the treatment. There was further significant improvement in the average MoCA scores 12 months later. The combined group showed significantly higher MoCA scores than the other two groups at each time point after the treatment. That group also had superior MBI, HAMD-17 and NIHSS scores and a better BHI compared to the other 2 groups, on average. Its total effectiveness rate was significantly higher too. There was no significant difference in the incidence of adverse reactions among the groups.Conclusions:Combining rTMS with electro-acupuncture significantly improves cognition, ADL ability, depression and neurological functioning after a stroke. The combined treatment is worthy of wider clinical application.

Objective:To observe any effect of combining repeated transcranial magnetic stimulation (rTMS) with electro-acupuncture in treating post-stroke cognitive impairment (PISC).Methods:Three groups of PISC patients were formed through random selection: an rTMS group, an electro-acupuncture group, and a combined group. In addition to routine medication and conventional rehabilitation training, the rTMS and electro-acupuncture groups received rTMS and electro-acupuncture treatment, while the combined group underwent both for six weeks. Before the treatment, immediately afterward and 3, 6, and 12 months later, everyone′s cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). The modified Barthel Index (MBI), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the National Institutes of Health Stroke Scale (NIHSS) were also applied. Transcranial Doppler ultrasound (TCD) was employed to measure the mean cerebral blood flow velocity (Vm), pulsatility index (PI), and breath-holding index (BHI) in the subjects′ bilateral middle cerebral arteries (MCAs). The total effectiveness rates and the incidence of adverse reactions were compared among the three groups.Results:The MoCA scores, MBI scores, HAMD-17 scores, NIHSS scores, and Vm of the MCA had improved significantly in all three groups right after the treatment. There was further significant improvement in the average MoCA scores 12 months later. The combined group showed significantly higher MoCA scores than the other two groups at each time point after the treatment. That group also had superior MBI, HAMD-17 and NIHSS scores and a better BHI compared to the other 2 groups, on average. Its total effectiveness rate was significantly higher too. There was no significant difference in the incidence of adverse reactions among the groups.Conclusions:Combining rTMS with electro-acupuncture significantly improves cognition, ADL ability, depression and neurological functioning after a stroke. The combined treatment is worthy of wider clinical application.

Objective To explore the application effect of health education based on gain and loss message framing on the treatment behavior intention and self-management of patients with high-risk diabetic foot.Methods From July to September 2024,convenience sampling was used to select patients with high-risk diabetic foot who were hospitalized in the endocrinology department of a tertiary general hospital in Guiyang as the study subjects.They were divided into 3 groups according to the admission time,with 30 patients in each group.The experimental group adopted health education based on gain message framing or framing loss message,while in the control group,health education was provided in a conventional manner.Before and after intervention,the differences of intervention effects among the 3 groups were compared by using diabetic foot pre-hospital delay intention questionnaire,diabetic foot care knowledge questionnaire and Chinese version of Nottingham foot care assessment scale(CNAFF).Results Ultimately,29 cases in the gain framing group,29 cases in the loss framing group,and 29 cases in the control group completed the study.After intervention,the score of pre-hospital delay intention questionnaire of diabetic foot in the gain framing group was(21.48±4.32),and it was(24.31±2.49)in the loss framing group,and(17.76±5.03)in the control group.The difference among the 3 groups was statistically significant(F=18.725,P＜0.001);the loss framing group was superior to the gain framing group(P=0.01)and the control group(P＜0.001).After the intervention,the score of the CNAFF in the gain framing group was(55.83±3.06),and it was(59.14±2.90)in the loss framing group,and(48.66±2.58)in the control group.The difference between the 3 groups was statistically significant(F=102.245,P＜0.001).The loss framing group was superior to the gain framing group and the control group(all P＜0.001).Conclusion Health education based on the loss message framing is more conducive to improving patients' intention to delay diabetic foot visits,leading to good foot care behaviors,and may provide an effective means of pre-hospital prevention and control of diabetic foot.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.