OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

Objective To explore the feasibility and value of synthetic MRI combined with reduced field of view(r FOV)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)in preoperative predicting TN stage of rectal cancer.Methods The ima-ging and clinical data of 40 patients with rectal cancer confirmed by operation and pathology were collected and divided into low T stage group(T1-T2 stage)and high T stage group(T3-T4 stage),N0 stage group and N1-N2 stage group according to postoperative pathological staging as the golden standard.Independent sample t-tests were conducted to compare the parameter differences of synthetic MRI[T1,T2,and proton density(PD)values]and IVIM-DWI(D,D*,and f values)between the two groups.Receiver operating charac-teristic(ROC)curves were used to evaluate the efficacy of each parameter with statistically significant differences.Results Signifi-cant differences were observed in the T2 values of synthetic MRI and the D and f values of IVIM-DWI between high and low T stage groups,as well as between N0 and N1-N2 stage groups(P<0.05).The D value showed the highest area under the curve(AUC)(AUC=0.888)in predicting T stage group,and the T2 value was predominant(AUC=0.790)for N stage group prediction.The combination models of T2,D,and f values yielded superior predictive capability for TN stage in preoperative predicting rectal cancer,with AUC of 0.890 and 0.807,respectively.Conclusion Synthetic MRI combined with r FOV IVIM-DWI is feasible in preoperative prediction of TN stage of rectal cancer,which shows a higher efficacy,and is a useful supplement to conventional MRI technology.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

Objective To understand the epidemiological characteristics of burns and scalds in a sentinel hospital for na-tional injury surveillance in Guangzhou,and to provide a scientific basis for developing precise and effective prevention strategies.Methods Data on burn and scald cases from the outpatient and emergency departments of a sentinel injury surveillance hospital in Guangzhou from 2022 to 2024 were collected,and epidemiological characteristics were analyzed.Results A total of 19 303 burn and scald cases were reported during 2022-2024,with a male-to-female ratio of 1∶1.29.The majority of cases occurred in young and middle-aged adults(51.40％).Across all age groups,the top three locations where burns and scalds occurred were homes(60.14％),industrial and construction sites(30.74％),and public places(5.12％).Burns and scalds in preschool children predominantly occurred at home,mostly during leisure activities,while in young adults and the elderly,they were mainly associated with household chores and leisure activities.Unintentional injuries accounted for the vast majority of cases(99.45％).Analysis of age-specific outcomes of burns and scalds showed that the proportion of preschool children discharged af-ter treatment decreased(19.10％,AR=-5.08),while the proportion hospitalized increased(25.98％,AR=4.66).Conclu-sion This study indicates that homes are the primary location for burns and scalds in Guangzhou,with preschool children being particularly vulnerable during leisure activities at home.Preschool children should be the key target group for burn and scald pre-vention and control efforts.

Objective To understand the epidemiological characteristics of burns and scalds in a sentinel hospital for na-tional injury surveillance in Guangzhou,and to provide a scientific basis for developing precise and effective prevention strategies.Methods Data on burn and scald cases from the outpatient and emergency departments of a sentinel injury surveillance hospital in Guangzhou from 2022 to 2024 were collected,and epidemiological characteristics were analyzed.Results A total of 19 303 burn and scald cases were reported during 2022-2024,with a male-to-female ratio of 1∶1.29.The majority of cases occurred in young and middle-aged adults(51.40％).Across all age groups,the top three locations where burns and scalds occurred were homes(60.14％),industrial and construction sites(30.74％),and public places(5.12％).Burns and scalds in preschool children predominantly occurred at home,mostly during leisure activities,while in young adults and the elderly,they were mainly associated with household chores and leisure activities.Unintentional injuries accounted for the vast majority of cases(99.45％).Analysis of age-specific outcomes of burns and scalds showed that the proportion of preschool children discharged af-ter treatment decreased(19.10％,AR=-5.08),while the proportion hospitalized increased(25.98％,AR=4.66).Conclu-sion This study indicates that homes are the primary location for burns and scalds in Guangzhou,with preschool children being particularly vulnerable during leisure activities at home.Preschool children should be the key target group for burn and scald pre-vention and control efforts.

Objective To explore the feasibility and value of synthetic MRI combined with reduced field of view(r FOV)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)in preoperative predicting TN stage of rectal cancer.Methods The ima-ging and clinical data of 40 patients with rectal cancer confirmed by operation and pathology were collected and divided into low T stage group(T1-T2 stage)and high T stage group(T3-T4 stage),N0 stage group and N1-N2 stage group according to postoperative pathological staging as the golden standard.Independent sample t-tests were conducted to compare the parameter differences of synthetic MRI[T1,T2,and proton density(PD)values]and IVIM-DWI(D,D*,and f values)between the two groups.Receiver operating charac-teristic(ROC)curves were used to evaluate the efficacy of each parameter with statistically significant differences.Results Signifi-cant differences were observed in the T2 values of synthetic MRI and the D and f values of IVIM-DWI between high and low T stage groups,as well as between N0 and N1-N2 stage groups(P<0.05).The D value showed the highest area under the curve(AUC)(AUC=0.888)in predicting T stage group,and the T2 value was predominant(AUC=0.790)for N stage group prediction.The combination models of T2,D,and f values yielded superior predictive capability for TN stage in preoperative predicting rectal cancer,with AUC of 0.890 and 0.807,respectively.Conclusion Synthetic MRI combined with r FOV IVIM-DWI is feasible in preoperative prediction of TN stage of rectal cancer,which shows a higher efficacy,and is a useful supplement to conventional MRI technology.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Objective To establish the theories and methods for the compatibility of Chinese patent medicines in pre-scription review.Methods Based on the prescription combination theory and the classics literatures of traditional Chinese med-icine,the methods of prescription suitability review for the compatibility of Chinese patent medicines were discussed.Results Based on the examples of the compatibility of Chinese patent medicines,five basic principles of combined Chinese patent medi-cines and the key points for reviewing the combined Chinese patent medicines dosage form were discussed in detail.Conclusion The methods for the compatibility of Chinese patent medicines prescription review have been established,which can provide a theoretical reference for the review of combined Chinese patent medicines prescriptions.

Objective To observe the value of drug-eluting bead TACE(D-TACE)combined with apatinib and camrelizumab for treating massive hepatocellular carcinoma(HCC).Methods Data of 35 patients with massive HCC who underwent D-TACE sequential apatinib and camrelizumab were retrospectively analyzed.The overall survival(OS)and progression free survival(PFS)were recorded,and the objective response rate(ORR),disease control rate(DCR)and treatment-related adverse event(TRAE)were evaluated.Results Combination treatment were all successfully performed in all 35 cases.At the last follow-up,the median PFS was 8.09 months,and the median OS was 20.00 months.One,3,6,and 12 months after treatments,ORR was 65.71%(23/35),71.43%(25/35),65.71%(23/35)and 60.71%(17/28),respectively,DCR was 94.29%(33/35),88.57%(31/35),80.00%(28/35)and 67.86%(19/28),respectively.TRAE of combination treatment mainly ranged from grade 1 to 2,and all relieved after symptomatic treatments.Conclusion D-TACE combined with apatinib and camrelizumab was effective and safe for treating massive HCC,with controllable adverse reactions.