Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Pregnancy ; Female ; Humans ; Classical Lissencephalies and Subcortical Band Heterotopias ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Fetus ; Hydrocephalus ; Prenatal Diagnosis ; Chromosome Deletion

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.
Humans ; Child ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Comparative Genomic Hybridization ; Chromosome Disorders/genetics* ; Chromosome Deletion ; Magnetic Resonance Imaging ; Chromosomes, Human, Pair 22 ; Developmental Disabilities/genetics* ; Carrier Proteins/genetics* ; Nerve Tissue Proteins/genetics*

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective: To investigate the relationship between SUVmax on preoperative 68Ga-PSMA PET-CT and the clinicopathological characteristics of patients treated with radical prostatectomy. Methods: The clinicopahtological data of patients evaluated with ⁶⁸Ga-PSMA PET-CT preoperatively and treated with radical prostatectomy between May 2016 and August 2019 were retrospectively reviewed. 31 patients with a mean age (63.1±4.9) and baseline PSA (72.71±173.15)ng/ml were enrolled. Their BMI mean (24.6±3.0)kg/m². Baseline testosterone of 14 patients was (4.72±1.64)ng/ml.Based on the Gleason scores related ISUP classification, all patients were classified into grade one in 5 cases, grade 2in 7 cases, grade 3 in 4 cases, grade 4 in 10 cases and grade 5 in 5 cases. The clinical classification included 6 cases in T_2a stage, 2 cases in T_2b stage, 17 cases in T_2c stage, 1 case in T_3a stage, 4 cases in T_3b stage and 1 case in T₄ stage. SUVmax was accessed by two independent professional nuclear medicine physicians. SUVmax was 12.49±9.38. SPSS 16.0 software was used to do statistic analysis. Results: The post-operative pathological results showed the surgical margin positive in 19 cases, negative in 12 cases, vascular positive in 5 cases, negative in 20 case, positive nerve invasion in 20 cases and negative in 11 cases. 2 patients were low risk, 7 patients were medium risk and 22 patients were high risk according to D′Amico classification. Based on the basis of PSA(≤10 or>10) and Gleason score(≤6 or>6), 6 patients were in group with low PSA and low Gleason score, 5 patients were low PSA and high Gleason score, 9 patients were high PSA and low Gleason score, 11 patients were high PSA and high Gleason score. SUVmax had a significant positive relationship with pathological ISUP(r=0.434, P=0.015) and SUVmax in patients with positive intravascular tumor emboli was significantly higher than those with negative intravascular tumor emboli(14.78±10.68 vs. 8.17±2.81, P=0.005). No significant correlation was found between SUVmax and baseline PSA, testosterone, pathologic T stage, surgical margin, nerve invasion, pelvic lymph node status as well as risk stratification. SUVmax could distinguish pathologic ISUP grade 5 with a maximum AUC 0.747 (P=0.033) and the sensitivity was 88.9%. The specificity was 77.3% when SUVmax≥11.34. SUVmax in patients with upgrading ISUP was significantly higher than that in patients with downgrading ISUP (16.01±5.40 vs. 4.98±2.11, P=0.007). Conclusions SUVmax measured on preoperative ⁶⁸Ga-PSMA PET-CT may have a clinical significance in predicting unfavorable pathological factors for patients treated with radical prostatectomy.

Objective:To investigate the application value of shear wave elastography(SWE) in assessing the degree of hepatics fibrosis in children with biliary atresia before Kasai portoenterostomy.Methods:From January 2017 to January 2018, 49 cases of children in Hunan Children′s Hospital with highly suspected biliary atresia in clinical were collected. The stiffness of the lower segment of right anterior lobe of the liver in all cases was assessed using SWE in 3 days before Kasai portoenterostomy. Pathological results of liver tissue specimens from the lower edge of the right liver during the surgery was taken as the gold standard. The correlation between the liver stiffness and the hepatics fibrosis was analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curves were created to assess the area under curve (AUC), the best cutoff value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the liver stiffness in diagnosing hepatocirrhosis.Results:All of the 49 cases were confirmed by surgery and pathology. According to the stages of hepatics fibrosis, 5 cases were in stage S2, 23 cases in stage S3, 21 cases in stage S4, and no cases of stage S0 and S1. Spearman correlation analysis showed that the correlation coefficient between the liver stiffness and the stages of hepatics fibrosis was 0.779( P<0.001). The area under the curve of the liver stiffness in diagnosing cirrhosis was 0.914. When the cutoff value was 14.45 kPa, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 85.7%, 89.3%, 85.7%, 89.3%, 87.8%, respectively. Conclusions:The liver stiffness measured by SWE is positively correlated with the stages of hepatic fibrosis, and the performance of SWE in the diagnosis of cirrhosis is remarkable. SWE can be used to evaluate the stages of hepatics fibrosis in children with biliary atresia before Kasai portoenterostomy.

Objective To calculate both the epidemic and intensity thresholds for different levels in Beijing and to establish a tiered alert system in the 2018-2019 influenza season as well as to evaluate the performance of calculated thresholds.Method Weekly count of influenza-like illness and percentage of influenza-like illness (ILI％) of the last five influenza seasons were modeled by 'moving epidemic method'(MEM) to calculate the influenza epidemic and intensity thresholds at different levels.A cross-validation procedure was used to evaluate the performance.Indicators of Matthew correlation coefficient,Youden's index,sensitivity and specificity were calculated.Results For weekly count of influenza-like illness,data showed that the epidemic threshold for 2018-2019influenza season was 12 984 and the medium,high and very high intensity thresholds were 22 503,37 589,47 157,respectively.Matthew correlation coefficient of the epidemic threshold was 62％ and youden's index as 60％,sensitivity as 69％,specificity as 91％.Data on weekly ILI％,the epidemic threshold for 2018-2019 influenza season was 1.66％,with medium,high and very high intensity thresholds as 2.46％,3.84％ and 4.66％,respectively.The overall Matthew correlation coefficient of the epidemic threshold was 59％,with 54％ for the Youden's index,sensitivity as 60％ and specificity as 94％.Conclusions MEM produced a good specific signal for detecting the influenza epidemics and the accuracy of the method was acceptable.The early warning performance regarding the application of weekly count on influenza-like illness was slightly better than ILI％.This method could be applied in the practical influenza epidemic alert "work in Beijing".

Objective: To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma. Methods: The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome. The mean age of the entire cohort was 62(40-87)years, with 74 males and 22 females. There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma), 83 cases of bladder carcinoma, and 12 cases of lymph node metastasis. There were 77 cases of primary onset and 19 cases of recurrence. 68 cases in single focus group and 28 cases in multiple group. There were 29 cases in non infiltrative T_a stage, 42 cases in infiltrative lamina propria T₁ stage, 16 cases in infiltrative muscle T₂ stage, and 9 cases in extra-muscular≥T₃ stage. At least 3ml of peripheral blood was collected after fasting for at least 8 hours, After cleavage and centrifugation, immunomagnetic beads were added, folate probe was added, and then amplification was carried out. Then the copy number of CTCs in each ml of blood was calculated. Logistic linear regression was used to analyze the risk factors of lymph node metastasis. Results: The mean CNC of all patients was 12.3±7.3; the mean CNC of ≤62 years old group was 10.8±4.2; the mean CNC of >62 years old group was 13.7±9.2; the mean CNC of initial cases was 11.5±5.3; the mean CNC of recurrent cases was 15.5±12.2. Age (P=0.135) and frequency of onset (P=0.087) had no effect on the number of CTCs. The average CNC of single focus group was 10.5±5.2, multiple focus group was 16.5±9.7, T_a stage group was 8.2±2.3, T₁ stage group was 12.0±4.4, T₂ stage group was 16.4±6.8, and ≥T₃ stage group was 19.5±16.6. The number of lesions (P<0.001) was significantly correlated with pathological T stage (P<0.001) and the number of CTCs. Univariate regression analysis showed that T stage (P<0.001) and the number of CTCs (P=0.02) might be correlated with lymph node metastasis; multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P=0.002). Conclusions CTCs can be used to predict lymph node metastasis of urothelial carcinoma.

Objective To investigate the value of shear wave elastography (SWE) in the differential diagnosis of biliary atresia (BA) in infants within 60 days.Methods SWE was used to detect the hepatic Young's modulus of 85 infants within 60 days who were suspected with cholestatic hepatitis.All the patients were classified into BA group and non biliary atresia (Non-BA) group according to surgical or pathological results.At the same time,45 normal infants within 60 days were selected as the control group.The hepatic Young's modulus were compared among the 3 groups.The sensitivity and specificity of hepatic Young's modulus in suspected BA patients were calculated by ROC.Results In the 85 cases,42 cases were diagnosed as BA,and 43 cases were classified as Non-BA group.The Young's modulus values of the 3 groups were as follows:BA group (15.86 ± 5.89) kPa,Non-BA group (10.89 ± 2.38) kPa,and control group (6.64 ± 0.53)kPa,with a significant difference among the 3 groups(P ＜0.01).The ROC analysis showed a cut off value of 12.9 kPa for differentiation between BA group and Non-BA group.The area under ROC curve (AUROC) was 0.787,with a sensitivity of 59.5％ and a specificity of 88.4％.Conclusions The young's modulus in BA patients can be increased at early time,and the SWE technique can be used to reflect the change of hepatic Young's modulus accurately,which will be helpful in the early differential diagnosis of BA.

Objective To investigate the value of the shear wave elastography ( SWE) in the diagnosis of biliary atresia ( BA ) in infants by ultrasonography . Methods SWE was used to measure the liver stiffness measurement( LSM ) of 138 infants . Following surgical or pathological diagnosis ,the infants were subclassified into BA and non-biliary atresia ( non-BA ) groups . ROC analysis was used to determine the sensitivity and specificity of LSM ,the ultrasonic findings in the differential diagnosis of suspected BA ,and the cut-off value to diagnose BA . Results Of the 138 infants with cholestatic hepatitis ,51 were diagnosed as BA group and 87 cases were assigned to the non-BA group . The ROC analysis showed the cut-off value of LSM for diagnosis of biliary atresia in children with jaundice was 12 .35 kPa ,the AUC was 0 .936 ,and the sensitivity and specificity were 84 .3% and 89 .7% ,respectively .In the parallel test ,the triangular cord ( TC) sign combined with abnormal gallbladder ( AbGB) had the best diagnostic performance in all patients . However ,in patients older than 30 days ,the LSM combined with TC had the best AUC ( 0 .987 ) and diagnostic performance( 98 .6% ) like with TC combined with AbGB . Conclusions Both SWE and gray scale ultrasound have higher diagnostic performance for BA . LSM can be used as a valuable index for diagnosing BA by ultrasound .