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

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.

Objective:To evaluate whether early enteral nutrition could benefit patients with different degrees of shock by dynamic changes of intestinal biomarkers intestinal fatty acid-binding protein (I-FABP) and citrulline.Methods:(1) From February 2021 to February 2023, 133 target patients in the Intensive Care Unit of Suzhou Hospital Affiliated to Nanjing Medical University were enrolled. The observation period was 7 days after admission, and intestinal biomarkers were monitored three times: 24 hours after admission (D1), the third day after admission (D3), and the seventh day after admission (D7). (2) The enrolled patients were divided into two groups according to the dose of norepinephrine received within 48 hours after admission: safe dose group [receiving norepinephrine < 0.3 μg/(kg·min)] and hazardous dose group [receiving norepinephrine ≥0.3 μg/(kg·min)]. The safe dose group was given early enteral nutrition according to the guidelines, and the dangerous dose group was randomly (random number) given early enteral nutrition (EEN) and delayed enteral nutrition (DEN).(4)The dynamic changes of intestinal fatty acid binding protein and citrulline in three groups were observed; The differences of intestinal biomarkers at different time points of dangerous dose of EEN/DEN were compared. The survival time of EEN/DEN group within 28 days was recorded, and Kaplan-Meier survival curve was drawn. Univariate and multivariate regression analyses of 28-day mortality were performed for the included population.Results:(1) The baseline data, APACHEⅡ score, arterial blood lactic acid, AGI grade, feeding interruption, total feeding time within 7 days, and 28-day survival number were statistically different between safe dose EEN group and hazardous dose EEN group ( P < 0.05). Compared the baseline data of the dangerous dose EEN group and the dangerous dose DEN group, only the number of feeding interruptions was statistically different ( P < 0.05). (2) The trend of change in the safe dose EEN group was the same as that in the dangerous dose DEN group: I-FABP decreased significantly from D3 to D7 ( P < 0.05); Citrulline decreased from D1 to D3, but increased from D3 to D7 ( P < 0.05). In dangerous dose EEN group, I-FABP had no significant change during the monitoring period ( P > 0.05). Citrulline decreased significantly from D1 to D3 ( P < 0.05). The EEN/DEN ratio at dangerous dose was significantly different only for D7-I-FABP ( P < 0.05). Compared with the survival curve of EEN/DEN at risk dose, DEN could improve the early survival rate of critically ill patients at risk dose (Breslow test P = 0.0447). (4) Age( OR=1.069,95% CI: 1.002-1.140, P=0.044) was independent risk factor for 28-day death . BMI ( OR= 0.772, 95% CI: 0.604-0.987, P=0.039), no feeding interruption ( OR=0.044,95% CI: 0.004-0.455, P=0.009), total feeding time within 7 days ( OR=0.959, 95% CI: 0.923-0.997, P=0.036) were the protective factors. Conclusions:EEN at the safe dose and DEN at the dangerous dose can effectively reverse the necrosis of enterocyte and promote the recovery of enterocyte function. EEN is not a clear risk factor for death at 28 days, but it not only increases the incidence of feeding interruption, but also do not conduct the recovery of intestinal cell function from the perspective of intestinal biomarkers.

Objective:To assess the changes of selenium nutrition of school-age children in Kashin-Beck disease (KBD) areas of Linzhou County, Lhasa City and Xietongmen County, Shigatse City in Tibet Autonomous Region (referred to as Tibet), and provide a scientific basis for evaluating the effectiveness of prevention and control measures.Methods:According to the historical condition of KBD, a total of 344 children's hair samples were collected to determine the content of selenium in Kazi (KBD area) and Jiangxia townships (non-KBD area) of Linzhou County in 2013 and 2021, Renqinze (KBD area) and Tongmen townships (non-KBD area) of Xietongmen County in 2015 and 2021.Results:Compared to 2013/2015, in 2021, the hair selenium level of children in the four townships increased ( P < 0.001). The selenium nutritional level of more than 90% of the children reached medium or above (hair selenium > 0.25 μg/g) in 2021. The hair selenium levels of girls in the two KBD areas (Kazi and Renqinze townships) were lower than those of boys ( Z = - 2.83, - 2.83, P < 0.05). Conclusions:The selenium nutrition level of school-age children in KBD areas in Linzhou and Xietongmen counties has increased rapidly in recent years. However, the selenium nutrition level of girls is significantly lower than that of boys. It is necessary to strengthen prevention, controlling and monitoring, and to further improve the dietary structure of school-age children through the joint efforts of families and schools, to increase the proportion of exogenous high selenium food intake.

ObjectiveTo investigate the efficacy and safety of ¹²⁵I intraluminal irradiation combined with lenvatinib in the treatment of progressive extrahepatic cholangiocarcinoma. MethodsA retrospective analysis was performed for 25 patients with progressive extrahepatic cholangiocarcinoma who attended Department of Interventional Radiology， The First Affiliated Hospital of Zhengzhou University， from January 2018 to November 2021， and according to the treatment modality， they were divided into combination group with 13 patients （¹²⁵I intraluminal irradiation combined with lenvatinib） and control group （¹²⁵I intraluminal irradiation alone）. The two groups were compared in terms of technical success rates， changes in liver function， stent patency， survival time， and incidence rates of adverse events. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank－sum test was used for comparison of continuous data with skewed distribution between two groups； the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan－Meier method and the log－rank test were used to evaluate survival time and stent patency. ResultsAll patients had successful implantation of biliary stents and ¹²⁵I particles， with a technical success rate of 100%. After 1 month of treatment， both groups had significant improvements in the serum levels of total bilirubin， direct bilirubin， alanine aminotransferase， and aspartate aminotransferase （all P<0.05）. There were significant differences between the control group and the combination group in the duration of stent patency （7.0 months vs 9.5 months， P=0.022） and median survival time （11.5 months vs 15.6 months， P=0.008）. There were no intolerable adverse events in the combination group during treatment. ConclusionCompared with ¹²⁵I intraluminal irradiation alone， ¹²⁵I intraluminal irradiation combined with lenvatinib has better efficacy and is a safe and effective treatment regimen for progressive extrahepatic cholangiocarcinoma.

OBJECTIVE: To investigate whether dynamic monitoring of citrulline (Cit) has guiding value for early enteral nutrition (EN) in patients with severe gastrointestinal injury. METHODS: A observational study was conducted. A total of 76 patients with severe gastrointestinal injury admitted to different intensive care units of Suzhou Hospital Affiliated to Nanjing Medical University from February 2021 to June 2022 were enrolled. Early EN was performed in 24-48 hours after admission as recommended by the guidelines. Those who did not terminate EN after 7 days were enrolled in the early EN success group, and those who terminated EN within 7 days due to persistent feeding intolerance or deterioration of general condition were enrolled in the early EN failure group. There was no intervention during the treatment. Serum Cit levels were measured by mass spectrometry at admission, before EN starting and EN 24 hours, respectively, and the changes in Cit within EN 24 hours (ΔCit) were calculated (ΔCit = EN 24-hour Cit-Cit before EN starting). Receiver operator characteristic curve (ROC curve) was plotted to investigate the predictive value of ΔCit for early EN failure, and the optimal predictive value was calculated. Multivariate unconditional Logistic regression was used to analyze the independent risk factors for early EN failure and death at 28 days. RESULTS: Seventy-six patients were enrolled in the final analysis, of which 40 succeeded in early EN and 36 failed. There were significant differences in age, main diagnosis, acute physiology and chronic health evaluation II (APACHE II) score at admission, blood lactic acid (Lac) before EN initiation and ΔCit between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 0.929, 95% confidence interval (95%CI) was 0.874-0.988, P = 0.018], ΔCit (OR = 2.026, 95%CI was 1.322-3.114, P = 0.001) and increased feeding rate within 48 hours (OR = 13.719, 95%CI was 1.795-104.851, P = 0.012) were independent risk factors for early EN failure in patients with severe gastrointestinal injury. ROC curve analysis showed that ΔCit had a good predictive value for early EN failure in patients with severe gastrointestinal injury [area under the ROC curve (AUC) = 0.787, 95%CI was 0.686-0.887, P < 0.001], and the optimal predictive value of ΔCit was 0.74 μmol/L (sensitivity was 65.0%, specificity was 75.0%). Combined with the optimal predictive value of ΔCit, "overfeeding" was defined as ΔCit < 0.74 μmol/L and increased feeding within 48 hours. Multivariate Logistic regression analysis showed that age (OR = 0.825, 95%CI was 0.732-0.930, P = 0.002), APACHE II score (OR = 0.696, 95%CI was 0.518-0.936, P = 0.017) and early EN failure (OR = 181.803, 95%CI was 3.916-8 439.606, P = 0.008) were independent risk factors for 28-day death in patients with severe gastrointestinal injury. The new variable "overfeeding" was also associated with an increased risk of death at 28 days (OR = 27.816, 95%CI was 1.023-755.996, P = 0.048). CONCLUSIONS Dynamic monitoring of Cit has guiding value for early EN in patients with severe gastrointestinal injury.
Humans ; Infant, Newborn ; Enteral Nutrition ; Citrulline ; APACHE ; Abdominal Injuries ; Cognition ; Thoracic Injuries

Objective:To investigate the application effect of 3D digital modeling combined with 3D printed model in assisting the classroom theoretical teaching of orthopedics in five-year undergraduate students majoring in clinical medicine.Methods:In May 2022, 33 five-year undergraduate students majoring in clinical medicine in the class of 2018 in Southwest Medical University were selected and divided into experimental group with 17 students and control group with 16 students according to the odd or even student number. The students in the experimental group were taught by traditional PPT+3D digital modeling combined with 3D printed model, and those in the control group were taught by the traditional PPT teaching method. The teaching effect was evaluated by theoretical examination and a questionnaire survey on the degree of satisfaction with teaching. SPSS 25.0 was used to perform the t-test, the Mann-Whitney U test, the rank sum test, and the chi-square test. Results:The experimental group had a significantly higher score of theoretical examination than the control group (86.24±4.16 vs. 82.50±6.06). The questionnaire survey on the degree of satisfaction with teaching showed that compared with the control group, the experimental group had a significantly higher degree of satisfaction with the understanding and learning of orthopedic diseases [3 (2, 3) vs. 2 (2, 2), P < 0.05], the improvement in learning interest [2 (2, 3) vs. 2 (1, 2), P < 0.05], classroom innovation [3 (3, 3) vs. 2 (1.5, 2), P < 0.05], and overall classroom teaching [3 (2, 3) vs. 2 (2, 2), P < 0.05]. Conclusion:In assisting the classroom theoretical teaching of orthopedics in undergraduate students majoring in clinical medicine, 3D digital modeling combined with 3D printed model can provide concrete 3D models, reduce the difficulties in learning, improve the awareness of orthopedic diseases, strengthen learning interest, and increase the degree of satisfaction with teaching and academic scores.

Objective:To investigate the risk factors of achilles tendon rupture in male patients and to verify them.Methods:Retrospective analysis was made on the medical records of male inpatients with achilles tendon rupture (242 cases in achilles tendon rupture group) and simple ankle joint injury (825 cases in control group) admitted to Qilu Hospital of Shandong University from May 2013 to June 2020. The tendency score matching method was used to balance the confounding factors at a ratio of 1∶1. After matching, 147 cases were in achilles tendon rupture group and 147 cases in control group. The baseline data and related indicators were compared before and after matching, and the risk factors of achilles tendon rupture were analyzed by constructing a multivariate logistic regression model.Results:The age, smoking rate, drinking rate, family history of hypertension and diabetes, previous history of hypertension, diabetes and coronary heart disease, and BMI of the achilles tendon rupture group before matching were significantly lower than those of the control group (all P<0.05). After matching, there was no significant difference in age, smoking proportion, drinking proportion, family history of hypertension, diabetes and coronary heart disease, previous history of hypertension, diabetes and coronary heart disease, and BMI between the two groups (all P>0.05). After matching, the levels of fasting uric acid (UA), cholesterol (TG) and triglyceride (TC) in achilles tendon rupture group were significantly higher than those in control group, and the differences were statistically significant (all P<0.05). Multivariate binary logistic regression analysis showed UA ( OR=1.006, 95% CI: 1.003-1.010, P<0.001), TC ( OR=2.462, 95% CI: 1.194-5.076, P=0.015) was an independent risk factor for achilles tendon rupture in male. Conclusions:Dyslipidemia and UA may be an independent risk factor for achilles tendon rupture in male.