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

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Objective:To investigate the effect of Simiao Yong'an Decoction on AMPK/ULK1 autophagy axis and inflammatory reaction in atherosclerotic(AS)mice.Methods:ApoE-/-mice were randomly divided into control group,model group,low,medium and high doses of Simiao Yong'an Decoction groups and simvastatin group,with 10 mice in each group.Mice model of AS was induced by high-fat diet.Simao Yong'an Decoction given low(10.13 g/kg),medium(20.25 g/kg),high dose(40.5 g/kg)and simvastatin tablets(3 mg/kg)by gavage for 6 weeks.After administration,serum and aortic tissue of mice were collected,and serum lipid level was detected by automatic biochemical analyzer;HE staining was used to observe the pathological changes of aorta;autophagy level of plaque tissue was observed by transmission electron microscope;levels of inflammatory factors IL-18,IFN-γ and CRP in serum were detected by ELISA;expression levels of AMPK,ULK1 and p62 mRNA were detected by qRT-PCR;expressions of LC3Ⅱ and p-ULK1 protein were detected by immunofluorescence labeling;expressions of p-AMPK and p62 were detected by immunohistochemis-try.Results:Compared with model group,aortic plaque in Simiao Yong'an Decoction and simvastatin groups were significantly reduced,and serum levels of TC,TG,LDL-C,IFN-γ,IL-18 and CRP were significantly decreased(P<0.05 or P<0.01),while the level of HDL-C was increased(P<0.05 or P<0.01);electron microscopy showed that autophagic bodies were increased;expressions of autophagy related factors LC3 Ⅱ,AMPK and ULK1 were induced,and expression of p62 was inhibited.Conclusion:Simiao Yong'an Decoction can induce AMPK/ULK1 autophagy axis and inhibit IFN-γ,IL-18 and CRP overexpressions in AS mice of may be one of the important mechanisms of Simiao Yong'an Decoction in anti-atherosclerosis.

Recent advances in vital pulp therapy(VPT)research,coupled with the widespread use of biomaterials,have led to an in-crease in the application of VPT.The indications for VPT are continually expanding,particularly for fully developed permanent teeth.Currently,one-way membrane decompression is being investigated as a possible treatment to preserve vital pulp in cases of irreversible pulpitis.This technology involves creating an access point in the pulp cavity and using the one-way membrane to prevent microorganisms from invading the pulp tissue.Additionally,it helps alleviate the high pressure in the pulp cavity caused by inflammation,thereby en-hancing blood circulation within the pulp.This improvement is crucial for establishing a foundation for future vital pulp preservation treatments.A case of irreversible pulpitis caused by caries was reported,in which the dental pulp was preserved using the one-way membrane decompression.The results of a ten-month clinical follow-up indicate a positive outcome.

Recent advances in vital pulp therapy(VPT)research,coupled with the widespread use of biomaterials,have led to an in-crease in the application of VPT.The indications for VPT are continually expanding,particularly for fully developed permanent teeth.Currently,one-way membrane decompression is being investigated as a possible treatment to preserve vital pulp in cases of irreversible pulpitis.This technology involves creating an access point in the pulp cavity and using the one-way membrane to prevent microorganisms from invading the pulp tissue.Additionally,it helps alleviate the high pressure in the pulp cavity caused by inflammation,thereby en-hancing blood circulation within the pulp.This improvement is crucial for establishing a foundation for future vital pulp preservation treatments.A case of irreversible pulpitis caused by caries was reported,in which the dental pulp was preserved using the one-way membrane decompression.The results of a ten-month clinical follow-up indicate a positive outcome.

Clinical pharmacists participated in the anti-infection treatment of a patient with Bartonella henselae meningitis.According to the clinical manifestations and the quantitative metagenomic second-generation sequencing(mNGS)of cerebrospinal fluid,the patient was diagnosed as Bartonella henselae infection.According to the relevant clinical guidelines and foreign case treatment reports,it is recommended to use minocycline hydrochloride capsule oral treatment combined with rifampicin injection.Follow-up treatment of the patient was dynamically adjusted based on the reexamination results of cerebrospinal fluid and related inflammatory indicators.In the treatment process,clinical pharmacists give full play to their professional expertise,provide the patient with individualized pharmaceutical care,optimize anti-infection programs,and further promote clinical rational drug use.

Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

Objective To observe the effectiveness of plasma exchange(PE)combined with the double plasma molecular adsorption system(DPMAS)in managing liver failure complicated by severe hyperbilirubinemia.Methods A total of 120 patients with liver failure who received artificial liver therapy were selected in Mianyang Central Hospital from June 2023 to June 2024 were as study objects.These patients were divided into an observation group and a control group,with 60 cases in each group.The control group received standard medical treatment,while the observation group underwent PE+DPMAS therapy in addition to the standard regimen,concrete method:firstly,low molecular weight heparin sodium at 25000 U was added to the 0.9%physiological saline(NS)1 750 mL pre flushing tube;Secondly,low molecular weight heparin sodium at 12 500 U and 0.9%NS at 500 mL were administered,and finally 0.9%NS 500 mL was used for flushing pipes,based on the patient's coagulation function,low molecular weight heparin sodium at 12500 U and 0.9%NS at 500 mL can be sequentially moved forward,after the pre flushing was completed,it can be connected to the catheter and wait for it to be loaded onto the machine.The circulating flow rate for the first 30 minutes after starting the machine was 1 800-2000 mL/h,with a flow rate of 125-140 mL per minute,blood is drawn out from the arterial terminals and separated by a plasma separator,the separated plasma was adsorbed by a series of AR-350 bilirubin columns and YTS-200 hemoperfusion apparatus before flowing into the venous circuit tube and returning to the body.The differences of clinical symptoms and laboratory indicators,including liver function indicators[aspartate transaminase(AST),alanine transaminase(ALT),alkaline phosphatase(ALP),γ-glutamyl transferase(GGT),total bile acid(TBA),total bilirubin(TBil),direct bilirubin(DBil),albumin(ALB)],kidney function indicators[creatinine(Cr)],coagulation function indicators[prothrombin time(PT)and prothrombin activity(PTA)]before and after treatment between the two groups were compared,and clinical efficacy and adverse reactions of the two groups were observed.Results Following treatment,both groups exhibited significant reductions in AST,ALT,ALP,TBA,TBil,and DBil levels compared to before treatment,the levels of total AST,ALT,TBA and TBil after treatment in the observation group were significantly lower than those in the control group[AST(U/L):84.2±69.3 vs.158.3±130.2,ALT(U/L):119.3±112.1 vs.145.9±124.7,TBA(μmol/L):59.1±48.3 vs.158.3±130.2,TBil(μmol/L):101.3±56.4 vs 145.9±124.7,all P<0.05];ALB increased significantly in the both groups after treatment compared to before treatment(g/L:the observation group was 35.1±3.7 vs.32.1±4.6,the control group was 33.1±3.1 vs.31.8±3.5,both P<0.05),however,there was no significantly difference between the two groups(P>0.05).In the observation group,PT shortened significantly after treatment(s:13.6±1.4 vs.14.5±2.1,P<0.05),while PTA increased significantly after treatment[(95.1±19.5)%vs.(83.2±21.1)%,P<0.05];moreover,the time required to achieve 30%,50%,and 70%reductions in TBil was markedly shorter in the observation group than in the control group[time required to achieve 30%reductions in TBil(days):6.1±4.3 vs.9.7±4.8,time required to achieve 50%reductions in TBil(days):9.3±5.1 vs.11.9±6.2,time required to achieve 70%reductions in TBil(days):13.2±5.9 vs.18.1±6.9,all P<0.05].The total effective rate of observation group was significantly higher than that of control group[93.3%(56/60)vs.68.3%(41/60),P<0.05].Both groups completed the treatment without deaths.During the treatment,5 cases experienced allergic reactions and 3 cases experienced a decrease in blood pressure,after symptomatic treatment,all patients continued to complete the treatment.Conclusion PE combined with DPMAS shows considerable clinical benefits for patients with liver failure and severe hyperbilirubinemia by effectively lowering bilirubin levels and accelerating recovery,thus shortening the disease course.

Objective To observe the effectiveness of plasma exchange(PE)combined with the double plasma molecular adsorption system(DPMAS)in managing liver failure complicated by severe hyperbilirubinemia.Methods A total of 120 patients with liver failure who received artificial liver therapy were selected in Mianyang Central Hospital from June 2023 to June 2024 were as study objects.These patients were divided into an observation group and a control group,with 60 cases in each group.The control group received standard medical treatment,while the observation group underwent PE+DPMAS therapy in addition to the standard regimen,concrete method:firstly,low molecular weight heparin sodium at 25000 U was added to the 0.9%physiological saline(NS)1 750 mL pre flushing tube;Secondly,low molecular weight heparin sodium at 12 500 U and 0.9%NS at 500 mL were administered,and finally 0.9%NS 500 mL was used for flushing pipes,based on the patient's coagulation function,low molecular weight heparin sodium at 12500 U and 0.9%NS at 500 mL can be sequentially moved forward,after the pre flushing was completed,it can be connected to the catheter and wait for it to be loaded onto the machine.The circulating flow rate for the first 30 minutes after starting the machine was 1 800-2000 mL/h,with a flow rate of 125-140 mL per minute,blood is drawn out from the arterial terminals and separated by a plasma separator,the separated plasma was adsorbed by a series of AR-350 bilirubin columns and YTS-200 hemoperfusion apparatus before flowing into the venous circuit tube and returning to the body.The differences of clinical symptoms and laboratory indicators,including liver function indicators[aspartate transaminase(AST),alanine transaminase(ALT),alkaline phosphatase(ALP),γ-glutamyl transferase(GGT),total bile acid(TBA),total bilirubin(TBil),direct bilirubin(DBil),albumin(ALB)],kidney function indicators[creatinine(Cr)],coagulation function indicators[prothrombin time(PT)and prothrombin activity(PTA)]before and after treatment between the two groups were compared,and clinical efficacy and adverse reactions of the two groups were observed.Results Following treatment,both groups exhibited significant reductions in AST,ALT,ALP,TBA,TBil,and DBil levels compared to before treatment,the levels of total AST,ALT,TBA and TBil after treatment in the observation group were significantly lower than those in the control group[AST(U/L):84.2±69.3 vs.158.3±130.2,ALT(U/L):119.3±112.1 vs.145.9±124.7,TBA(μmol/L):59.1±48.3 vs.158.3±130.2,TBil(μmol/L):101.3±56.4 vs 145.9±124.7,all P<0.05];ALB increased significantly in the both groups after treatment compared to before treatment(g/L:the observation group was 35.1±3.7 vs.32.1±4.6,the control group was 33.1±3.1 vs.31.8±3.5,both P<0.05),however,there was no significantly difference between the two groups(P>0.05).In the observation group,PT shortened significantly after treatment(s:13.6±1.4 vs.14.5±2.1,P<0.05),while PTA increased significantly after treatment[(95.1±19.5)%vs.(83.2±21.1)%,P<0.05];moreover,the time required to achieve 30%,50%,and 70%reductions in TBil was markedly shorter in the observation group than in the control group[time required to achieve 30%reductions in TBil(days):6.1±4.3 vs.9.7±4.8,time required to achieve 50%reductions in TBil(days):9.3±5.1 vs.11.9±6.2,time required to achieve 70%reductions in TBil(days):13.2±5.9 vs.18.1±6.9,all P<0.05].The total effective rate of observation group was significantly higher than that of control group[93.3%(56/60)vs.68.3%(41/60),P<0.05].Both groups completed the treatment without deaths.During the treatment,5 cases experienced allergic reactions and 3 cases experienced a decrease in blood pressure,after symptomatic treatment,all patients continued to complete the treatment.Conclusion PE combined with DPMAS shows considerable clinical benefits for patients with liver failure and severe hyperbilirubinemia by effectively lowering bilirubin levels and accelerating recovery,thus shortening the disease course.

【Objective】 To predict the expression of human epidermal growth factor receptor 2 (HER2) in urothelial bladder carcinoma based on normalized apparent diffusion coefficient (ADC). 【Methods】 The preoperative pelvic 3.0T magnetic resonance imaging (MRI) images of 127 patients with urothelial bladder carcinoma were retrospectively studied, the ADC was measured, and the HER2 expression in postoperative tissue specimens was determined with immunohistochemistry (IHC). The differences in normalized ADC were analyzed among different HER2 expressions and among different expression divisions. Correlation between normalized ADC and HER2 expression was analyzed. The optimal diagnostic threshold for distinguishing different expression divisions were determined with receiver operating characteristic (ROC) curve. 【Results】 Normalized ADC was negatively correlated with HER2 expression (tau-b=-0.180, P=0.008). Normalized ADC of HER2 overexpression group (IHC 2+, 3+) was lower than that of HER2 negative group (IHC 0, 1+) (P=0.081). Normalized ADC of HER2 expression group (IHC 1+, 2+, 3+) was significantly lower than that of HER2 zero-expression group (IHC 0) (P=0.020). Normalized ADC of HER2 strong positive group (IHC 3+) was significantly lower than that of HER2 non-strong positive group (IHC 0, 1+, 2+) (P=0.024). The optimal diagnostic threshold of HER2 strong positive group was 0.849; the sensitivity, specificity and accuracy were 0.621, 0.909 and 0.765, respectively. The optimal diagnostic threshold of HER2 overexpression group was 0.909; the sensitivity, specificity and accuracy were 0.547, 0.667 and 0.607, respectively. 【Conclusion】 Normalized ADC is negatively correlated with HER2 expression. ADC may be a potential marker for predicting HER2 expression.