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 investigate the feasibility and value of nomogram based on base line clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) characteristics for pretreatment predicting the depth of myometrial invasion and tumor grade of endometrioid endometrial carcinoma (EEC).Methods:Preoperative baseline clinical characteristics and DCE-MRI characteristics of 194 EEC patients were prospectively collected at Obstetrics and Gynecology Hospital, Fudan University from October 2020 to January 2022 and used as a training set. Univariate analysis was conducted to compare baseline clinical characteristics and DCE-MRI quantitative parameters [including tumor volume, and mean, median, and standard deviation of volume transfer constant (K trans), rate constant (K ep), extravascular extracellular volume fraction (V e), and initial area under the enhancement curve (iAUC)] between patients with deep myometrial invasion (DMI) and those with superficial myometrial invasion (SMI), as well as between high-grade and low-grade EEC. Multivariate logistics regression analysis was used to identify independent predictors for the construction of nomogram. An independent external testing set comprising 127 EEC patients was retrospectively collected from Zhongshan Hospital, Fudan University and Zhongshan Hospital, Fudan University (Xiamen Branch). The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used for evaluating the model′s predictive performance and clinical net benefit, respectively. Results:(1) The depth of myometrial invasion: univariate analysis showed that in the training set, the EEC patients with DMI differed significantly from those with SMI in clinical characteristics including higher proportion of postmenopausal state and overweight [body mass index (BMI)≥25 kg/m2], and abnormal levels of serum cancer antigen (CA) 125, CA 199, and human epididymis protein 4 (HE4), and in DCE-MRI quantitative parameters including tumor volume, and median, mean, and standard deviation of K trans, median of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, CA 199, tumor volume, and mean of iAUC were independent predictors of the depth of myometrial invasion, and constructed the nomogram (recorded as Nomogram_1), achieving an AUC of 0.861 (95% CI: 0.803-0.919) in the training set. In the independent external testing set, the AUC was 0.876 (95% CI: 0.815-0.938), with corresponding sensitivity of 82.0%, specificity of 80.7%, accuracy of 81.1%, positive predictive value (PPV) of 65.3%, and negative predictive value (NPV) of 91.0% for predicting DMI. (2) The EEC grade: univariate analysis showed that in the training set, high-grade EEC patients differed significantly from low-grade EEC in clinical characteristics including patient′s age, the proportion of postmenopausal state and overweight, and abnormal levels of serum CA 125, and in DCE-MRI quantitative parameters including tumor volume, median, mean, and standard deviation of K trans, median and mean of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, tumor volume, and median of V e emerged as independent predictors of EEC grade, and constructed the nomogram (recorded as Nomogram_2), achieving an AUC of 0.845 (95% CI: 0.786-0.893) in the training set. While in the external testing set, the AUC was 0.819 (95% CI: 0.744-0.894), with corresponding sensitivity of 72.4%, specificity of 72.4%, accuracy of 72.4%, PPV of 43.8%, and NPV of 89.9% for predicting high-grade EEC. (3) The DCA curves demonstrated that both Nomogram_1 and Nomogram_2 yielded obvious positive clinical net benefits across a wide range of threshold probabilities. Conclusion:The nomogram based on pretreatment clinical and DCE-MRI characteristics has the potential to noninvasive predict the depth of myometrial invasion and grade of EEC, providing valuable reference information for clinical management decision-making.

Objective:To investigate the feasibility and value of nomogram based on base line clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) characteristics for pretreatment predicting the depth of myometrial invasion and tumor grade of endometrioid endometrial carcinoma (EEC).Methods:Preoperative baseline clinical characteristics and DCE-MRI characteristics of 194 EEC patients were prospectively collected at Obstetrics and Gynecology Hospital, Fudan University from October 2020 to January 2022 and used as a training set. Univariate analysis was conducted to compare baseline clinical characteristics and DCE-MRI quantitative parameters [including tumor volume, and mean, median, and standard deviation of volume transfer constant (K trans), rate constant (K ep), extravascular extracellular volume fraction (V e), and initial area under the enhancement curve (iAUC)] between patients with deep myometrial invasion (DMI) and those with superficial myometrial invasion (SMI), as well as between high-grade and low-grade EEC. Multivariate logistics regression analysis was used to identify independent predictors for the construction of nomogram. An independent external testing set comprising 127 EEC patients was retrospectively collected from Zhongshan Hospital, Fudan University and Zhongshan Hospital, Fudan University (Xiamen Branch). The area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used for evaluating the model′s predictive performance and clinical net benefit, respectively. Results:(1) The depth of myometrial invasion: univariate analysis showed that in the training set, the EEC patients with DMI differed significantly from those with SMI in clinical characteristics including higher proportion of postmenopausal state and overweight [body mass index (BMI)≥25 kg/m2], and abnormal levels of serum cancer antigen (CA) 125, CA 199, and human epididymis protein 4 (HE4), and in DCE-MRI quantitative parameters including tumor volume, and median, mean, and standard deviation of K trans, median of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, CA 199, tumor volume, and mean of iAUC were independent predictors of the depth of myometrial invasion, and constructed the nomogram (recorded as Nomogram_1), achieving an AUC of 0.861 (95% CI: 0.803-0.919) in the training set. In the independent external testing set, the AUC was 0.876 (95% CI: 0.815-0.938), with corresponding sensitivity of 82.0%, specificity of 80.7%, accuracy of 81.1%, positive predictive value (PPV) of 65.3%, and negative predictive value (NPV) of 91.0% for predicting DMI. (2) The EEC grade: univariate analysis showed that in the training set, high-grade EEC patients differed significantly from low-grade EEC in clinical characteristics including patient′s age, the proportion of postmenopausal state and overweight, and abnormal levels of serum CA 125, and in DCE-MRI quantitative parameters including tumor volume, median, mean, and standard deviation of K trans, median and mean of V e, as well as median, mean, and standard deviation of iAUC (all P<0.05). Multivariate analysis showed that the patient′s menstrual status, BMI, tumor volume, and median of V e emerged as independent predictors of EEC grade, and constructed the nomogram (recorded as Nomogram_2), achieving an AUC of 0.845 (95% CI: 0.786-0.893) in the training set. While in the external testing set, the AUC was 0.819 (95% CI: 0.744-0.894), with corresponding sensitivity of 72.4%, specificity of 72.4%, accuracy of 72.4%, PPV of 43.8%, and NPV of 89.9% for predicting high-grade EEC. (3) The DCA curves demonstrated that both Nomogram_1 and Nomogram_2 yielded obvious positive clinical net benefits across a wide range of threshold probabilities. Conclusion:The nomogram based on pretreatment clinical and DCE-MRI characteristics has the potential to noninvasive predict the depth of myometrial invasion and grade of EEC, providing valuable reference information for clinical management decision-making.

A retrospective analysis was conducted on 5 516 patients diagnosed with prostate cancer(PCa) at our hospital. Among these, 52 patients aged ≤ 50 years were defined as the early-onset group.For the control group, 228 patients aged >50 years were randomly selected at a ratio of 1∶4.4. The early-onset group predominantly presented with elevated PSA levels at diagnosis and had a lower positive rate of digital rectal examination. There were no significant differences in clinical and pathological characteristics between the early-onset group and the control group. Young PCa patients in the low to intermediate risk categories had similar survival prognosis to older patients. However, young patients with high-risk prostate cancer had 5-year progression-free survival rate of 38.4% compared to 55.6% for older patients, and 5-year cancer-specific survival rate of 70.1% compared to 84.1% for older patients, indicating that high-risk young patients exhibited poorer oncological outcomes.

A retrospective analysis was conducted on 5 516 patients diagnosed with prostate cancer(PCa) at our hospital. Among these, 52 patients aged ≤ 50 years were defined as the early-onset group.For the control group, 228 patients aged >50 years were randomly selected at a ratio of 1∶4.4. The early-onset group predominantly presented with elevated PSA levels at diagnosis and had a lower positive rate of digital rectal examination. There were no significant differences in clinical and pathological characteristics between the early-onset group and the control group. Young PCa patients in the low to intermediate risk categories had similar survival prognosis to older patients. However, young patients with high-risk prostate cancer had 5-year progression-free survival rate of 38.4% compared to 55.6% for older patients, and 5-year cancer-specific survival rate of 70.1% compared to 84.1% for older patients, indicating that high-risk young patients exhibited poorer oncological outcomes.

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 efficacy of oblique lumbar interbody fusion (OLIF) combined with percutaneous transforaminal endoscopic decompression (PTED) and posterior pedicle fixation through Wiltse approach in the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis.Methods:From June 2017 to February 2022, 103 patients (50 males and 53 females) of lumbar spondylolisthesis accompanied with lumbar spinal stenosis were performed with OLIF combined with PTED and posterior pedicle fixation. The mean age was 64.1±5.2 years (range, 42-87 years). All involved cases were single-segment and included 83 cases of L 4, 5, 17 cases of L 3, 4, and 3 cases of L 2, 3. Among them, 94 cases were performed for the first time, and other 9 were revision surgery treated by posterior lumbar laminectomy previously. The visual analog scale (VAS) was used to evaluate the low back pain and leg pain, and the Oswestry disability index (ODI) was used to evaluate the lumbar function. The VAS and ODI scores were recorded respectively before the operation, at discharge, 1, 3, 6 months after the operation and at the last follow-up. Macnab criteria was used to evaluate the clinical efficacy at the last follow-up. At the same time, imaging measurements were conducted, including the anterior and posterior disc height, segmental lordotic angle, percentage of slip on lateral X-ray film and the vertebral canal area on axial MRI before and after surgery. Results:All of 103 patients were successfully operated in one stage with an average operation time of 177.7±21.5 min (range, 155-220 min), and an average intraoperative blood loss of 55.9±18.3 ml (range, 30-150 ml). The mean follow-up time were 15.1±2.6 months (range, 6-36 months). There were significant differences in both VAS scores of back and leg and ODI scores at each postoperative time point when compared with preoperative ( F=508.25, F=1524.82, F=1148.68, P<0.001). Macnab criteria of the last follow-up was evaluated as follow: excellent in 85 cases, good in 14, fair in 4, and the excellent and good rate was 96.1%. The radiographic results showed the mean immediate postoperative anterior disc height, posterior disc height, segmental lordotic angle, percentage of slip and axial area of the vertebral canal were 15.23±2.97 mm, 9.32±2.31 mm, 14.36°±4.18°, 3.89%±3.11%, 113.37±47.27 mm 2, and thus all of those increased significantly compared to the mean preoperative 11.93±3.17 mm, 7.21±2.03 mm, 6.15°±3.99°, 23.66%±7.79%, 57.63±28.91 mm 2, respectively ( t=7.84, t=7.07, t=14.91, t=27.62, t=9.68, P<0.001). All cases achieved bony fusion during 6-12 months after operation. The incidence of surgery-related complications was 10.7% (11/103). There were 3 cases of end plate fracture and 2 cases of dural injury, which had no complaint after operation. There was 1 case of pedicle screw entering into the spinal canal by mistake, and the symptoms of nerve damage appeared after operation. After 1 year it basically returned to normal. There were 2 cases of thigh numbness and 1 case of psoas major weakness after operation, all of which relieved after 4 weeks. There was 1 case continuous pain of abdominal incision after surgery. There was 1 case of cage subsidence at the last follow-up. Conclusion:OLIF combined with PTED and posterior pedicle fixation through Wiltse approach is a minimally invasive surgical method for the treatment of lumbar spondylolisthesis accompanied with lumbar spinal stenosis. With the combined minimally invasive techniques, the decompression, fusion and fixation of the lumbar spine can be fulfilled perfectly. It has the advantages of minimally invasive, good clical outcome, few complications and rapid rehabilitation.

Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.

Objective:To explore the application effect of target management model based on standardized Metabolic Management Center (MMC) in newly diagnosed diabetic patients.Methods:A total of 80 inpatients who were newly diagnosed as diabetes mellitus in Department of Endocrinology and Metabolism in Affiliated Hospital of Jiangsu University from October 2018 to March 2019 were selected as the convenient sampling method. According to the random number table method, they were divided into the observation group and the control group, with 40 cases in each group. The control group was given routine nursing management while the observation group was given target management by using supporting facilities of MMC based on the control group. The changes of fasting plasma glucose (FPG) , 2 h postprandial blood glucose (2hPG) , glycated hemoglobin (HbA1c) , body mass index (BMI) and self-management behavior scores before and after 6 months of intervention were compared between the two groups.Results:There were no statistically significant differences in blood glucose index, BMI and self-management behavior score between the two groups before the intervention ( P>0.05) . After intervention, the blood glucose and self-management behavior scores of the observation group were better than those of the control group, and the differences were statistically significant ( P<0.05) . The BMI of observation group after intervention was lower than that before intervention, and the difference was statistically significant ( P <0.05) . There was no statistically significant difference before and after intervention in the control group ( P>0.05) . Conclusions:Target management based on the MMC is conducive to improving the self-management ability of newly diagnosed diabetic patients and helps them to effectively control blood glucose and body weight.

OBJECTIVE：To study the effects of augmented renal clearance （ARC）on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS ：Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg，q12 h×3 doses，maintenance dose of 6-10 mg/kg，qd，and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ，clinical efficacy ，Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS ：A total of 56 patients were included and divided into ARC group （18 cases）and normal renal function group （38 cases）. ARC group had younger age （P＜0.001）and lower serum albumin level （P＝0.025）than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group （P＝0.034；P＝0.035）. The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage （P＝0.003；P＜0.001）. The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8％ and 76.2％，which were lower than those of the normal renal function group ，but there was no statistical difference （P＝0.195；P＝0.223）. There was no liver function damage ，hemocytopenia and allergic reaction in both groups ，but in the normal renal function group ，the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS ：ARC patients are younger ，most of them have hypoproteinemia，and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ，it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.