Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1 / 中国实验方剂学杂志

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg-1） and simvastatin group （0.002 g·kg-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism / 中国天然药物

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis / 中国实验方剂学杂志

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).@*METHODS@#A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

Perspective on pH adjustment in hydrometallurgical recycling of valuable metals from waste.

pH adjustment was considered a simple step in the hydrometallurgy process, but its complicated operation was ignored in the past. In some industrial applications, the leachate pH was slowly adjusted by a diluted alkaline solution, with the defects of doubling the leachate volume and causing droplet hydrolysis/coagulation. Up to date, promising routes have been developed for rapid pH adjustment, especially in sealed high-temperature/pressure vessels. New routes emerged in some redox/decomposition reactions of nitrate/urea and organics. Such reactions did not start and/or were slow at room temperature but started spontaneously at high temperatures to generate/consume free H+. This induced pH adjustment in a rapid and homogeneous way.

Pyrometallurgy treatment of electroplating sludge, emulsion mud and coal ash: ZnAlFeO4 spinel separation and stabilization in calcium metasilicate glass.

Electroplating sludge was a hazardous waste comprised of heavy metals and other Fe/Al/Ca/Si impurities, and produced massively in surface treatment industry. In the past, it was commonly purified via hydrometallurgy, chlorination and reduction calcination routes, but also blended as additive in rotary kiln, to stabilize the heavy metals in geopolymer. Herein, an alternative strategy was developed to treat a real electroplating sludge for recycling magnetic Zn-rich spinel and stabilizing Zn in calcium metasilicate glass via a facile pyrometallurgy route with the blending of emulsion mud and coal ash. The sludge contained 35.6% Zn and 0.54% Cr and then was blended with 50% emulsion mud. After calcination at 1200 °C, the product was highly dispersed, whilst octahedral ZnAlFeO4 spinel with Zn content of 40.0% were formed and separated by using magnet, in accordance with the recycling efficiency of 51.2% Zn from the electroplating sludge. But after calcination at 1400 °C, the gypsum in emulsion mud was decomposed as CaO and accelerated the dissolution of Si-bearing substance as calcium metasilicate glass for covering ZnAlFeO4 spinel, resulting in the Zn leaching of 1568 mg/L. By adding 50% Si-rich coal ash in the calcination system, more calcium metasilicate glass were generated, and then the Zn concentration in the toxic leaching test was only 12.09 mg/L. During the calcination, Cr showed similar performance to Al/Fe and involved in the spinel formation. This provided a new route to recycle Zn from Zn-rich electroplating sludge and to solidify heavy metals via calcium metasilicate glass route.

Stepwise recycling of Fe, Cu, Zn and Ni from real electroplating sludge via coupled acidic leaching and hydrothermal and extraction routes.

Fe/S-bearing erdite flocculant has been proven to be effective in the precipitation of heavy metals from real electroplating wastewater, with the only drawback being the huge production of sludge. This sludge was rich in Fe/S/Zn/Cu/Ni and refractory to be recycled due to the extractant pollution by free Fe and the dissolution of sulphide. Herein, a multistep separation method was developed to dissolve sulphide and separate Fe prior to Zn/Cu/Ni. Results showed that more than 92% sludge was dissolved as Fe/Zn/Cu/Ni-rich leachate after the sludge was leached by nitric acid, with the rest of the remaining undissolved elemental sulphurs. When the leachate was directly extracted by using commercially extractant Acorga M5640 and Di-(2-ethylhexyl) phosphoric acid (P204), Fe was complexed by the phosphate group of the extractant. The Fe was effectively removed prior to Zn/Cu/Ni to avoid the extractant pollution. The Fe removal efficiency was only 38.34% without sucrose, but it rose to 99.94% with the addition of 0.5 g sucrose. The added sucrose reacted with nitrate to consume H+, which showed a similar rate to the H+ release from Fe hydrolysis. Thereafter, the Fe hydrolysis was continued to remove, the Fe at a high level. The removed Fe was in the form of high-purified hematite nanorod with a diameter and length of 300-600 nm and 0.5-2.5 µm, respectively. After Fe removal, Cu/Zn/Ni was extracted by using Acorga M5640 and P204 to form three halite, including a mixture of copper sulphate hydrate and bonattite (96.8% CuSO4·H2O/CuSO4·3H2O), gunningite (97.5% ZnSO4·H2O) and dwornikite (97.9% NiSO4·H2O). The rest of the solution was neutralised by lime water to remove sulphate as gypsum (95.9% CaSO4) to meet the discharge standard of the electroplating industry. In summary, the recycling efficiency of Fe/Cu/Zn/Ni from the sludge reached 94.4%, 92.6%, 94.7% and 95.3%, which provided an alternative strategy to resource utilise Fe/S-bearing solid waste.

Recovery of proprioception after lateral ankle sprain / 中国康复理论与实践

ObjectiveTo observe the recovery of proprioception of the affected ankle over time after lateral ankle sprain accepting routine rehabilitation. MethodsFrom June, 2020 to June, 2022, 18 patients with lateral ankle sprain in Kunshan Rehabilitation Hospital underwent routine rehabilitation for twelve weeks. They were measured active and passive position sense of bilateral ankles using an isokinetic dynamometer before treatment, and four, eight and twelve weeks after treatment, respectively. ResultsThe active presentation difference of affected ankle reduced after treatment (F = 22.533, P < 0.001), but it was more than that of the healthy ankle at the same time (t > 4.419, P < 0.001). No significant improvement was found in passive presentation difference of affected ankle after treatment (F = 1.175, P > 0.05), and it was not significantly different from those of the healthy ankle at the same time (|t| < 0.646, P > 0.05). ConclusionProprioception of affected ankle has been impaired after lateral ankle sprain, and it can be recovered after rehabilitation, but cannot achieve the healthy level even after three months of training. Passive position sense as an index of proprioception needs more researches.

Traditional Chinese Medicine Intervenes in Atherosclerosis by Regulating TLR/NLRP3 Pathway via TRPV1/TRPA1 / 中国实验方剂学杂志

Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19 / 医学前沿

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.

Analysis of clinical features and variants of NF1 gene in 12 patients with Neurofibromatosis type 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the types of NF1 gene variants and clinical characteristics among patients with Neurofibromatosis type I (NF1).@*METHODS@#Clinical data of 12 patients diagnosed at Ningbo Women and Children's Hospital between December 2019 and May 2022 were retrospectively analyzed. The probands and their family members were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing and chromosome microarray analysis.@*RESULTS@#The 12 patients had ranged from 4 months to 27 years old, with a male-to-female ratio of 2 : 1. Cafè-au-lait spots were found in all patients. 83.3% of them also had axillary and/or inguinal freckling, 58.3% had neurofibromas, and 16.7% had congenital pseudarthrosis of the tibia. Five types of NF1 gene variants were identified in the patients, including 5 nonsense variants, 4 frameshift variants, 1 missense variant, 1 splice variant, 1 large deletion involving the whole gene. Six patients were found to harbor de novo variants, 2 had inherited the variants from their parents, and 4 were not verified for their parental origin. The c.3379del (p.Thr1127Glnfs*15) and c.6628_6629del (p.Glu2210Thrfs*10) variants were unreported in literature and databases.@*CONCLUSION@#Most NF1 patients may present with Cafè-au-lait spots initially and are due to pathogenic variant of the NF1 gene. High-throughput sequencing can efficiently identify such variants among the patients and enable the definite diagnosis.

Clinical and genetic analysis of a rare fetus with Protein C deficiency due to compound heterozygous variants of PROC gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage.@*METHODS@#Trio whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#The fetus was found to harbor c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene, which were respectively inherited from its mother and father. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PVS1_Strong+PM2_Supporting+PP4; PM2_Supporting+PM3+PP1+PP3+PP4).@*CONCLUSION@#The fetus was diagnosed with Protein C deficiency due to the c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene. Above finding has enriched the spectrum of PROC gene variants and enabled genetic counseling and prenatal diagnosis for the family.

Clinical and genetic analysis of two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language due to de novo variants of MEF2C gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL).@*METHODS@#Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.

Prenatal diagnosis and genetic analysis for two Chinese pedigrees carrying large fragment deletions of 13q21 / 中华医学遗传学杂志

OBJECTIVE@#To explore the strategies of prenatal diagnosis and genetic counseling for fetuses of two families with large deletions of 13q21.@*METHODS@#Two singleton fetuses who were diagnosed with chromosome 13 microdeletions by non-invasive prenatal testing (NIPT) at Ningbo Women and Children's Hospital in March 2021 and December 2021 respectively were selected as the study subjects. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried on amniotic samples. Peripheral blood samples were collected from the two couples for CMA assay to determine the origin of abnormal chromosomes identified in the fetuses.@*RESULTS@#The karyotypes of the two fetuses were both normal. CMA revealed that they have respectively harbored heterozygous deletions spanning 11.935 Mb at 13q21.1q21.33 and 10.995 Mb at 13q14.3q21.32, which were respectively inherited from their mother and father. Both deletions had low gene density and lacked haploinsufficient genes, and were predicted to be likely benign variants based on database and literature search. Both couples had opted to continue with the pregnancy.@*CONCLUSION@#The deletions of the 13q21 region in both families may be of benign variants. As the follow-up time was short, there was no sufficient evidence for the determination of pathogenicity, though our finding may still provide a basis for the prenatal diagnosis and genetic counseling.

Bismuth, esomeprazole, metronidazole, and minocycline or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.@*METHODS@#This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.@*RESULTS@#As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.@*CONCLUSION@#The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR 1900023646.

Research progress on influencing factors of depressive symptoms in adolescents / 中国学校卫生

Abstract@#In recent years, mental health problems such as anxiety and depression among adolescents in China have attracted attention from all walks of life. Given that adolescence is a transitional and critical period for individual development, mental health affect the developmental opportunities. Therefore, in the review, the effects of environment, psychosocial factors and behavioral patterns on depressive symptoms are analyzed by combining with the characteristics of physical and mental development among adolescents. It is found that early adolescence and even childhood should be the key period for the prevention and intervention of depression. In order to formulate effective interventions and prevention strategies, it is proposed that future research should combine real situation in China with active exploration of protective factors and early predictors of depression.

Sociality and infectious disease prevention and control of sexual and gender minorities in China / 上海预防医学

Sexual and gender minorities have social behavioral characteristics such as aggregation， mobility， exclusivity， and concealment， which may be associated with the transmission of infectious diseases in this group. This paper aims to explore the relationship between the sociality of this group and its transmission and prevention and control of infectious diseases， emphasize the importance of paying attention to the transmission of sexually transmitted diseases and respiratory diseases in sexual and gender minorities. This paper puts forward some thoughts for infectious disease prevention and control of this group in the future.

Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury / 中国药科大学学报

@#Cardiotoxicity of cancer chemotherapeutics has received considerable attention in recent years.However, the effects of chemotherapy on cardiometabolic perturbation with lung injury have rarely been reported. Thus, we constructed a mouse model of myocardial injury superimposed on lung injury with a combination of bleomycin (BLM) and doxorubicin (DOX).C57BL/6J mice were randomly divided into four groups: control group (CON), BLM group (intratracheal infusion with single doses of 5 mg/kg), DOX group (intraperitoneal injection of 7.5 mg/kg/week, two weeks) and DOX+BLM group. The cardiac injury of mice was evaluated by serum biochemical parameters and histopathology.Cardiometabolic perturbation was investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS).The results showed that, compared with the CON group, BLM alone caused lung injury yet with no significant effects on the cardiometabolic profile; DOX alone had significant perturbations in the cardiometabolic profile, and the main differential metabolites were amino acids, fatty acids, phospholipids, etc.; the combination of BLM and DOX caused more severe disturbance of cardiometabolic homeostasis in mice, especially accumulation of branched-chain amino acids.This study confirmed that DOX can lead to more significant changes in the cardiometabolic profile in the presence of lung injury, with an initial focus on the branched-chain amino acid metabolic pathway.This research provides scientific data for in-depth study of the cardiotoxicity mechanism of chemotherapeutic agents.

Genetic analysis of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a Chinese pedigree featuring non-simplex blepharocheilodontic syndrome.@*METHODS@#Whole exome sequencing was carried out to detect genetic variant and copy number variations (CNVs) in the pedigree. Suspected variants were verified by Sanger sequencing and qPCR.@*RESULTS@#The fetus and its elder brother, father and grandfather were found to harbor a heterozygous c.83delG (p.A29Rfs*55) variant of the CTNND1 gene, which was unreported previously. In addition, its elder brother was also found to be a double heterozygote for a c.235delC (p.L79Cfs*3) variant of GJB2 gene and a c.538C>T (p.R180X) variant of GJB3 gene, which were respectively inherited from his mother and father. CNVs analysis revealed a de novo heterozygotic deletion (1.46 Mb) at 17q12 in the mother, which was confirmed by qPCR. Based on American College of Medical Genetics and Genomics guidelines, the c.83delG variant, the c.235delC variant and the 17q12 microdeletion were predicted as pathogenic, while the c.538C>T variant was of uncertain significance.@*CONCLUSION@#The c.83delG (p.A29Rfs*55) variant of the CTNND1 gene probably underlay the pathogenesis of non-simplex blepharocheilodontic syndrome in this pedigree. The double heterozygous variants of c.235delC (p.L79Cfs*3) of GJB2 gene and c.538C>T (p.R180X) of GJB3 gene probably underlay the hearing loss in the elder brother. The bilateral renal cysts in the mother may be attributed to the 17q12 microdeletion. Above results have provided guidance for genetic counseling and prenatal diagnosis for this pedigree.

Multi-parameter measurement of a multi-point high-frequency vibration signal in an OFDR system.

The phase cross-correlation function of an optical frequency domain reflectometry (OFDR) system is proposed to detect a multi-point vibration event, which is verified in detail by theoretical simulation and experiment. An OFDR system based on a non-tunable laser source with digital sweep frequency is developed. It is verified experimentally that the location and frequency resolution of multi-point high-frequency vibration can be detected by analyzing the phase cross-correlation function of the sensing signal. High-frequency signals of 50 kHz and 20 kHz are located and separated on the 8 km optical fiber. The frequency resolution is 1.26 kHz, and the minimum spatial error is 11.5 m.