A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.
Humans ; Electroacupuncture ; Ischemic Stroke ; Learning ; Signal Transduction/physiology*

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of breast myofibroblastoma. Methods: The clinicopathological data and prognostic information of 15 patients with breast myofibroblastoma diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from 2014 to 2022 were collected. Their clinical characteristics, histological subtypes, immunophenotypes and molecular characteristics were analyzed. Results: There were 12 female and 3 male patients, ranging in age from 18 to 78 years, with a median and average age of 52 years. There were 6 cases in the left breast and 9 cases in the right breast, including 12 cases in outer upper quadrant, 2 cases in inner upper quadrant and 1 case in outer lower quadrant. Most of the cases showed a well-defined nodule grossly, including pushing growth under the microscope in 13 cases, being completely separated from the surrounding breast tissue in 1 case, and infiltrating growth in 1 case. Among them, 12 cases were classic subtype and composed of occasional spindle cells with varying intervals of collagen fiber bundles; eight cases had a small amount of fat; one case had focal cartilage differentiation; one case was epithelioid subtype, in which epithelioid tumor cells were scattered in single filing or small clusters; one case was schwannoma-like subtype, and the tumor cells were arranged in a significant palisade shape, resembling schwannoma, and one case was invasive leiomyoma-like subtype, in which the tumor cells had eosinophilic cytoplasm and were arranged in bundles, and infiltrating into the surrounding mammary lobules like leiomyoma. Immunohistochemical studies showed that the tumor cells expressed desmin (14/15) and CD34 (14/15), as well as ER (15/15) and PR (15/15). Three cases with histologic subtypes of epithelioid subtype, schwannoma-like subtype and infiltrating leiomyoma-like subtype showed RB1 negative immunohistochemistry. Then FISH was performed to detect RB1/13q14 gene deletion, and identified RB1 gene deletion in all three cases. Fifteen cases were followed up for 2-100 months, and no recurrence was noted. Conclusions: Myofibroblastoma is a rare benign mesenchymal tumor of the breast. In addition to the classic type, there are many histological variants, among which the epithelioid subtype is easily confused with invasive lobular carcinoma. The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.
Female ; Humans ; Male ; Antigens, CD34 ; Biomarkers, Tumor/analysis* ; Leiomyoma/pathology* ; Neoplasms, Muscle Tissue/pathology* ; Neurilemmoma ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To investigate the protective effect of intermittent fasting on radiation-induced cognitive impairment and the possible underlying mechanism.Methods:A total of 36 male 7-week old c57BL/6J mice were divided into Sham-irradiation and ad libitum (Sham-AL) group, irradiation and ad libitum (IR-AL) group, and irradiation add intermittent fasting (IR-IF) group according to the random number table method, with 12 mice in each group. The cognitive function of mice was assessed by novel object recognition task. The expressions of autophagy gene 5 (ATG5), microtubulesas sociated protein light chain II (LC3II), voltage dependent anion channel protein 1 (VDAC1), interleukin-1β (IL-1β), synaptophysin (SYP), synapsin I (SYN-1), and postsynaptic density 95 (PSD95) were tested by Western blot. The location of VDAC1 in mice hippocampus was detected by immunofluorescence.Results:The discrimination index (-22.45 ± 16.76) of IR-AL group was significantly ( t=3.032, P<0.05) lower than that of Sham-AL group (30.02 ± 9.05). Compared to Sham-AL group, IR-AL group had a decreased expressions of autophagy-related proteins (ATG5 and LC3II), mitochondrial marker (VDAC1), inflammatory factors (IL-1β) as well as synapse-associated proteins SYP, SYN-1 and PSD95 ( t=2.49, 2.19, 2.40, 3.47, 2.87, 2.25, 2.17, 2.31, P<0.05). Compared to IR-AL group, IR-IF group had an increased discrimination index (21.22 ± 5.62) and the increased expressions of ATG5, LC3II, VDAC1, IL-1β, SYP, SYN-1, and PSD95 ( t=2.70, 2.88, 2.71, 3.18, 3.18, 3.11, 3.30, 3.35, 2.53, P<0.05). The immunofluorescence assay revealed that VDAC1 was co-expressed with the markers of astrocytes (GFAP) and microglia (IBA-1), but not with neurons (NEUN). Conclusions:Intermittent fasting could greatly improve the cognitive function of irradiated mice possibly by upregulating VDAC1 expression, induce autophagy, and inhibit the release of inflammatory factors and protecting the synapticplasticity in the hippocampus.

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.
Alkaloids ; Glycosides ; Plant Extracts/chemistry* ; Plants, Medicinal/chemistry* ; Saponins ; Terpenes