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1.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 20-28, 2024.
Article in Chinese | WPRIM | ID: wpr-1006551

ABSTRACT

ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang (DCQD) on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins [claudin-1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, endogenous antimicrobial peptide mCRAMP, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88)] in sepsis. Fifty C57BL/6 mice were randomized into sham, model, low- and high-dose (4 g∙kg-1 and 8 g∙kg-1) DCQD, and ulinastatin groups (n=10). Before, during, and after the day of modeling surgery, each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue, which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP, TLR4, and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction, on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force, hydrogen bonding, and other conjugated systems. The results of animal experiments showed that compared with the model group, low- or high-dose DCQD lowered the D-lactic acid level in the serum (P<0.01), alleviated damage to the ileal tissue and mucosal edema, protected the small intestine villus integrity, reduced inflammatory cell infiltration, promoted the expression of claudin-1 (P<0.01), lowered the IL-6 level (P<0.01), up-regulated the mRNA and protein levels of mCRAMP (P<0.01), and down-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.01) in the ileal tissue. In addition, high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue (P<0.01), and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue (P<0.05). ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation, repair intestinal mucosal damage, improve the tight junction protein level, and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

2.
Environmental Health and Preventive Medicine ; : 5-5, 2024.
Article in English | WPRIM | ID: wpr-1010117

ABSTRACT

BACKGROUND AND AIM@#Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD.@*METHODS@#This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD.@*RESULTS@#After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1.@*CONCLUSION@#Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.


Subject(s)
Adult , Humans , Cohort Studies , Non-alcoholic Fatty Liver Disease/etiology , Cholesterol , Proportional Hazards Models , Risk Factors
3.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 769-777, 2023.
Article in Chinese | WPRIM | ID: wpr-1015602

ABSTRACT

Ferroptosis is a unique mode of iron-dependent cell death driven by lipid peroxidation. It is characterized by morphological changes in mitochondria, including densification of mitochondrial membranes and associated reduction in the volume, rupture of outer membranes and reduction or disappearance of the mitochondrial crest, which is different from that of apoptosis, autophagy and pyroptosis. Mitochondria, as the core of cell metabolism, are important organelles for iron metabolism, lipid metabolism and energy metabolism. However, it remains controversial debates as how mitochondria participate in ferroptosis and the underlying mechanisms during its progression. This review summaries the current understanding of the occurrence and defense mechanisms of ferroptosis, and the role of mitochondria in promoting and inhibiting ferroptosis, which includes the tricarboxylic acid cycle and glycolysis, reactive oxygen species, and lipid metabolism in mitochondria and their roles in driving ferroptosis. Moreover, we also summarize the defense mechanisms against ferroptosis through detoxification of mitochondrial lipid peroxidation by mitochondrial dihydroorotate dehydrogenase, as well as mitochondrial ferritin. Other mitochondrial molecules and their regulation of ferroptosis is stated at the end. This paper reviews the latest research progress of mitochondria in the process of ferroptosis, which aims to further understand the function of mitochondria in ferroptosis and its mechanism in the occurrence and development of ferroptosis, and therefore provides a theoretical foundation for the basic research of cell biology and strategies for investigation of clinical diseases.

4.
Chinese Journal of Clinical Pharmacology and Therapeutics ; (12): 1209-1218, 2023.
Article in Chinese | WPRIM | ID: wpr-1014725

ABSTRACT

AIM: To investigate the mechanism of baicalin-induced apoptosis in human laryngeal cancer cells. METHODS: AMC-HN-8 cells were selected for the study, and baicalin was applied to the cells at different concentrations (0, 10, 30, 100, and 300 μmol/L), and the half-inhibitory concentration (IC50) was measured by the CCK-8 method. Bax, cleaved-caspase-3, Cyto-c, IRF4 protein expression by protein blotting (Western blot); miR-125b-5p and IRF4 expression by RT-qPCR. Dual-luciferase reporter gene validation of Targetscan prediction (binding of miR-125b-5p to IRF4-3'UTR); apoptosis and necrosis inhibitors explore the way baicalein induces death in laryngeal cancer cells. AMC-HN-8 was then divided into blank group, baicalein (IC50), miR-125b-5p inhibitor group, baicalein + inhibitor NC group, baicalein+miR-125b-5p inhibitor group, and cell invasion and clone formation assays to detect cell invasion and proliferation ability, respectively. Apoptosis was detected by flow cytometry. RESULTS: Baicalein inhibited the proliferation of AMC-HN-8 cells in a dose-dependent manner with an IC50 value of 47.31 μmol/L. Compared with the blank group, 47.31 μmol/L baicalin induced apoptosis and inhibited cell invasion, while upregulating the expression of miR-125b-5p and suppressing the mRNA and protein levels of IRF4. The luciferase results showed that the miR-125b-5p mimic was able to inhibit the activity of the IRF4-3'UTR promoter relative to the NC mimic (mimic) group. Baicalein induces laryngeal cancer cell death in an apoptotic manner. In addition, the combination of 47.31 μmol/L baicalin and miR-125b-5p inhibitor affected the behavior of AMC-HN-8 cells, showing that compared with the blank group, the baicalin group showed a decrease in the number of cell clones, weakened invasion ability, and increased apoptosis; the miR - 125b-5p inhibitor group showed an increase in the number of cell clones, enhanced invasion ability and decreased apoptosis. The baicalin+ inhibitor NC group was consistent with baicalin, with no significant effect of inhibitor NC on cell behavior. The cloning, invasion, and apoptosis of cells in the baicalin+miR-125b-5p inhibitor group were intermediate between the baicalin and miR-125b-5p inhibitor groups. CONCLUSION: Baicalin inhibits the proliferation of AMC-HN-8 cells, and the mechanism may be related to miR-125b-5p targeting to inhibit the expression of IRF4, inducing the pro-apoptotic proteins Bax, cleaved-caspase3, and Cyto-c, and inhibiting the apoptosis suppressor protein Bcl-2 thereby inducing apoptosis.

5.
China Occupational Medicine ; (6): 613-619, 2023.
Article in Chinese | WPRIM | ID: wpr-1013296

ABSTRACT

{L-End}Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) of live-electric line workers in the power supply enterprises. {L-End}Methods A total of 1 479 live-electric frontline workers in the power supply bureaus under China Southern Power Grid Co., LTD in Guangxi Zhuang Autonomous Region, Guangdong Province and Yunnan Province were selected as the research subjects using the cluster sampling method. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the prevalence of WMSDs and their influencing factors in the past year. {L-End}Results The prevalence of WMSDs was 61.4%. The prevalence of WMSDs in nine body sites ranged from 11.3% to 45.1%, with the highest prevalence being on three sites of neck, shoulder and lower back with a prevalence of 45.1%, 36.0% and 30.8%, respectively. The results of multivariate logistic regression analysis showed that the influencing factors of WMSDs in the neck, shoulder, and lower back were different, but all related to individual factors, poor ergonomics factors, and unreasonable work organization factors. The influencing factors simultaneously affecting these three sites included length of service, educational level, working in a sitting posture for a long time, working in uncomfortable postures, adequate rest time, starting to work after rest, deciding when to start and finish by oneself, and shortage of staff in the department or group. The factors affecting both neck and shoulder WMSDs were gender and back bending slightly for a long time. The factors affecting both neck and lower back were age and back bending significantly for a long time. {L-End}Conclusion The prevalence of WMSDs in the live-electric line workers in power supply enterprises is high, mainly occurring in the neck, shoulders, and lower back. The influencing factors are individual factors, poor ergonomics factors, and unreasonable work organization.

6.
Neuroscience Bulletin ; (6): 1807-1822, 2023.
Article in English | WPRIM | ID: wpr-1010652

ABSTRACT

Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.


Subject(s)
Humans , Animals , Serotonin , Insular Cortex , Pruritus/chemically induced , Cerebral Cortex/physiology , Neurons
7.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 295-301, 2023.
Article in Chinese | WPRIM | ID: wpr-965845

ABSTRACT

ObjectiveThe study aims to determine whether the horizontal posterior displacement of the distal clavicle in patients with acromioclavicular joint dislocation can be corrected via the application of modified intraoperative axillary fluoroscopy. MethodsFrom February 2019 to April 2021, 50 patients with Rockwood type Ⅲ acromioclavicular joint dislocation eligible for inclusion were randomly divided into two groups: the normal (32 cases) and the experimental (18 cases). The conventional anteroposterior position radiographs were obtained to detect the surgery effect on the patients in the normal group. In experimental group, modified intraoperative axillary radiographs were obtained, with the concept of polar coordinates introduced to reduce the horizontal posterior translation of the clavicle. Then we compared the perioperative parameters, such as average operative time, intraoperative blood loss between the two groups. The Constant score was used for assessing the postoperative function of the shoulder joint in the follow-up visits. ResultsNo statistically significant difference was found in gender, age, duration of injury, underlying diseases, intraoperative blood loss and operative time between the two groups. The postoperative shoulder function score of the experimental group was higher than that of the normal group. ConclusionsThe application of modified intraoperative axillary fluoroscopy is recommendable for accurately reducing posterior translation of the distal clavicle, and meanwhile helpful for the precise placement of the clavicular plate.

8.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 226-232, 2023.
Article in Chinese | WPRIM | ID: wpr-973493

ABSTRACT

@#Objective    To systematically review the clinical utilization of robotic bronchoscopes in diagnosis of pulmonary nodules, including MonarchTM and IonTM platforms, and then evaluate the efficacy and safety of the procedure. Methods    PubMed, EMbase, Web of Science and Cochrane Central Register of Controlled Trials databases were searched by computer for literature about the biopsy of pulmonary nodules with robotic bronchoscope from January 2018 to February 14, 2022. The quality of research was evaluated with Newcastle-Ottawa Scale. RevMan 5.4 software was used to conduct the meta-analysis. Results    Finally, 19 clinical studies with 1 542 patients and 1 697 targeted pulmonary nodules were included, of which 13 studies used the IonTM platform and 6 studies used the MonarchTM platform. The overall diagnostic rate of the two systems was 84.96% (95%CI 62.00%-95.00%), sensitivity for malignancy was 81.79%(95%CI 43.00%-96.00%), the mean maximum diameter of the nodules was 16.22 mm (95%CI 10.98-21.47), the mean procedure time was 61.86 min (95%CI 46.18-77.54) and the rate of complications occurred was 4.76% (95%CI 2.00%-15.00%). There was no statistical difference in the outcomes between the two systems. Conclusion     Robotic bronchoscope provides a high efficacy and safety in biopsy of pulmonary nodules, and has a broad application prospect for pulmonary nodules diagnosis.

9.
Chinese Journal of Blood Transfusion ; (12): 15-19, 2023.
Article in Chinese | WPRIM | ID: wpr-1004878

ABSTRACT

【Objective】 To evaluate the quality of suspended red blood cells (SRBC) under low-pressure and hypoxic conditions, in order to lay a theoretical foundation for airline delivery, air drop and storage of SRBC on plateau. 【Methods】 The low-pressure and hypoxic conditions (0.026 MPa and 0.047 MPa) were simulated by a pressure control device. SRBC were divided into 3 groups (5 bags/group, 1.5 U/bag). Each group was stored in 0.026 MPa environment at 2℃-6℃ for 24 hours (named 0.026 MPa), in 0.047MPa environment at 2℃-6℃ for 7 days (named 0.047 MPa), and in a blood storage refrigerator at 4℃ (named the control), respectively. The storage cell characteristics were examined on day 2, 9, 14, 28 and 35. 【Results】 We found that HCT, MCV, K+, Na+, FHb, hemolytic ratio, 2, 3-DPG and rheological properties in group 0.026 MPa and 0.047 MPa were not significant different compared with that in control (P>0.05). The consumptions of Glu in group 0.026 MPa and 0.047 MPa were significantly higher (P<0.05), and a transient increase in LAC concentration of group 0.026 MPa and 0.047MPa were observed, compared to the control. 【Conclusion】 The conditions of low-pressure and hypoxia have no significant effect on the quality of suspended red blood cells.

10.
Chinese Journal of Contemporary Pediatrics ; (12): 1124-1130, 2023.
Article in Chinese | WPRIM | ID: wpr-1009858

ABSTRACT

OBJECTIVES@#To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD).@*METHODS@#A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022.@*RESULTS@#Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants.@*CONCLUSIONS@#Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.


Subject(s)
Male , Humans , Child , Disorders of Sex Development/pathology , Hypospadias/complications , Cryptorchidism/complications , Retrospective Studies , Adrenal Hyperplasia, Congenital , Steroid 21-Hydroxylase
11.
Chinese Journal of Cellular and Molecular Immunology ; (12): 904-909, 2023.
Article in Chinese | WPRIM | ID: wpr-1009447

ABSTRACT

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in TranswellTM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. TranswellTM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.


Subject(s)
Humans , Arthritis, Rheumatoid/genetics , Interleukin-23 , Macrophages , RNA, Messenger , RNA, Small Interfering/genetics , Smad7 Protein/genetics , Transforming Growth Factor beta1/genetics , Smad3 Protein/genetics , Gene Silencing
12.
Chinese Journal of Medical Genetics ; (6): 1521-1525, 2023.
Article in Chinese | WPRIM | ID: wpr-1009333

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC).@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.


Subject(s)
Humans , Infant , Male , Child, Preschool , Family , Genetic Testing , Genomics , Mutation , Tuberous Sclerosis/genetics , East Asian People
13.
Chinese Journal of Medical Genetics ; (6): 1280-1283, 2023.
Article in Chinese | WPRIM | ID: wpr-1009289

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS).@*METHODS@#A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed.@*RESULTS@#The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.


Subject(s)
Female , Humans , Male , Pregnancy , Child, Preschool , Chloride Channels/genetics , Genetic Counseling , Genetic Testing , Genomics , High-Throughput Nucleotide Sequencing , Mutation
14.
Chinese Journal of Medical Genetics ; (6): 1086-1092, 2023.
Article in Chinese | WPRIM | ID: wpr-1009256

ABSTRACT

OBJECTIVE@#To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis.@*METHODS@#Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children's Hospital Affiliated to Zhengzhou University (Zhengzhou Children's Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products.@*RESULTS@#The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c.609G>A (W203X) (58/128), c.658-660del (K220del) (19/128), and c.80A>G (Q27A) (16/128). Two novel variants have been identified, namely c.565C>T (p.R189C) and c.624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+PM3+PP2+PP3) and pathogenic (PVS1+PM2_Supporting+PM3+PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection.@*CONCLUSION@#Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c.609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of the MMACHC gene.


Subject(s)
Humans , Amino Acid Metabolism, Inborn Errors/genetics , Hydrocephalus , Oxidoreductases
15.
Journal of Zhejiang University. Science. B ; (12): 115-129, 2023.
Article in English | WPRIM | ID: wpr-971474

ABSTRACT

Ex vivo culture-amplified mesenchymal stem cells (MSCs) have been studied because of their capacity for healing tissue injury. MSC transplantation is a valid approach for promoting the repair of damaged tissues and replacement of lost cells or to safeguard surviving cells, but currently the efficiency of MSC transplantation is constrained by the extensive loss of MSCs during the short post-transplantation period. Hence, strategies to increase the efficacy of MSC treatment are urgently needed. Iron overload, reactive oxygen species deposition, and decreased antioxidant capacity suppress the proliferation and regeneration of MSCs, thereby hastening cell death. Notably, oxidative stress (OS) and deficient antioxidant defense induced by iron overload can result in ferroptosis. Ferroptosis may inhibit cell survival after MSC transplantation, thereby reducing clinical efficacy. In this review, we explore the role of ferroptosis in MSC performance. Given that little research has focused on ferroptosis in transplanted MSCs, further study is urgently needed to enhance the in vivo implantation, function, and duration of MSCs.


Subject(s)
Humans , Antioxidants/metabolism , Ferroptosis , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Iron Overload/metabolism
16.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 250-255, 2023.
Article in Chinese | WPRIM | ID: wpr-971441

ABSTRACT

Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.


Subject(s)
Male , Humans , Female , Adult , Middle Aged , Nasopharyngeal Carcinoma , China , Microscopy , Organoids , Nasopharyngeal Neoplasms
17.
International Eye Science ; (12): 345-348, 2023.
Article in Chinese | WPRIM | ID: wpr-960964

ABSTRACT

AIM: To observe the efficacy of moderate and high myopia patients with vault greater than 1 000μm after implantation of phakic posterior chamber implantable contact lens(ICL).METHODS: A total of 42 patients(73 eyes)who received ICL implantation in the hospital and had postoperative vault greater than 1 000 μm between January 2014 and January 2017 were selected and retrospectively studied. Changes in visual acuity, intraocular pressure, corneal endothelial cell density, anterior chamber-related parameters(chamber angle, central anterior chamber depth, anterior chamber volume)and vault were compared among patients before surgery, at 1, 3, 6mo and 1a after surgery and at the last follow-up.RESULTS: The uncorrected visual acuity(UCVA)at 1, 3, 6mo and 1a after surgery and at the last follow-up was better than that before surgery(all P&#x0026;#x003C;0.05), and the chamber angle, central anterior chamber depth and anterior chamber volume were smaller or lower than those before surgery(all P&#x0026;#x003C;0.05), but there were no statistical differences in UCVA, chamber angle, central anterior chamber depth and anterior chamber volume at each time point after surgery(all P&#x0026;#x003E;0.05). The intraocular pressure at 1mo after surgery was lower than that before surgery(P&#x0026;#x003C;0.05), but the intraocular pressure at 3, 6mo and 1a after surgery and at the last follow-up was not statistically different from that before surgery(all P&#x0026;#x003E;0.05). There was no statistical significance in the corneal endothelial cell density at 1, 3, 6mo and 1a after surgery and at the last follow-up compared with that before surgery(all P&#x0026;#x003E;0.05). The vault at 1, 3, 6mo and 1a after surgery and at the last follow-up showed a decreasing trend, and the difference was statistically significant at each time point after surgery(all P&#x0026;#x003C;0.05).CONCLUSION: The short-term and long-term efficacy are better in moderate and high myopia patients with vault greater than 1 000 μm after ICL implantation, and there are no significant effects on the intraocular pressure and corneal endothelial cell. The postoperative anterior chamber structure is relatively stable and the vault tends to decrease over time. In most cases, close observation is sufficient and intraocular lens replacement is generally not required.

18.
Journal of Clinical Hepatology ; (12): 70-76, 2023.
Article in Chinese | WPRIM | ID: wpr-960707

ABSTRACT

Objective To assess the clinical characteristics of acute-on-chronic liver failure in patients with recompensatory hepatitis B cirrhosis. Methods A total of 180 patients with acute-on-chronic liver failure hospitalized in Tianjin Third Central Hospital from September 2013 to September 2021 were retrospectively collected, with 110 patients had compensatory hepatitis B cirrhosis and 70 patients had compensatory hepatitis B cirrhosis and used as the control. Their causes, clinical biochemical indicators, complication rate, and prognosis were compared. The Chi-square test or Fisher's exact test was used for comparison of categorical variables between groups, and the Mann-Whitney U test was performed for analysis of the continuous variables. Kaplan-Meier curves and Log-rank test were used for survival of patients. Results The incidence of hepatorenal syndrome ( χ 2 =4.618, P =0.032), infection ( χ 2 =6.712, P =0.010), Cr ( Z =-4.508, P < 0.001), and PCT ( Z =-2.052, P =0.040) were all higher, whereas GGT ( Z =-2.042, P =0.041), Na ( Z =-2.001, P =0.045), FBS ( Z =-3.065, P =0.002), and TC ( Z =-4.268, P < 0.001) were all lower in the recompensation group than in the control group of patients. However, 90-day mortality rate ( χ 2 =3.366, P =0.067) and 1-year mortality rate ( χ 2 =1.893, P =0.169), 90-day survival ( χ 2 =2.68, P =0.100), and 1-year survival ( χ 2 =2.074, P =0.150) were not statistically significant difference. Conclusion Compared with compensatory hepatitis B cirrhosis, patients with recompensatory cirrhosis had an increased risk in developing hepatorenal syndrome, infection, and increased creatinine level after acute-on-chronic liver failure, although there was no statistically significant difference in 90-days and 1-year survival of patients.

19.
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery ; (12): 39-46, 2023.
Article in Chinese | WPRIM | ID: wpr-953743

ABSTRACT

@#Objective     To assess the safety and clinical outcomes of segmentectomy in one- or two-staged video-assisted thoracoscopic surgery (VATS) for bilateral lung cancer. Methods    We retrospectively enrolled 100 patients who underwent VATS segmentectomy for bilateral lung cancer at the Department of Thoracic Surgery of Peking Union Medical College Hospital from December 2013 to May 2022. We divided the patients into two groups: a one-stage group (52 patients), including 17 males and 35 females with a mean age of 55.17±11.09 years, and a two-stage group (48 patients), including 16 males and 32 females with a mean age of 59.88±11.48 years. We analyzed multiple intraoperative variables and postoperative outcomes. Results     All 100 patients successfully completed bilateral VATS, and at least unilateral lung received anatomical segmentectomy. Patients in the one-stage group were younger (P=0.040), had lower rate of comorbidities (P=0.030), were less likely to have a family history of lung cancer (P=0.018), and had a shorter interval between diagnosis and surgery (P=0.000) compared with patients in the two-stage group. Wedge resection on the opposite side was more common in the one-stage group (P=0.000), while lobectomy was more common in the two-stage   group. The time to emerge from anesthesia in the one-stage group was longer than that in the first and second operations of the two-stage group (P=0.000, P=0.002). Duration of surgery and anesthesia were similar between two groups (P>0.05). Total number of lymph node stations for sampling and dissection (P=0.041) and lymph nodes involved (P=0.026) were less in the one-stage group. Intraoperative airway management was similar between two groups (P>0.05). The one-stage group was associated with lower activities of daily living (ADL) scores. Conclusion     Segmentectomy is safe in one- or two-staged VATS for bilateral lung cancer, including contralateral sublobectomy and lobectomy. Duration of surgery and perioperative complications are similar between two groups, but the one-stage group is associated with lower ADL scores. On the basis of comprehensive consideration in psychological factors, physical conditions and personal wishes of patients, one-staged sequential bilateral VATS can be the first choice.

20.
Chinese Journal of Preventive Medicine ; (12): 247-252, 2023.
Article in Chinese | WPRIM | ID: wpr-969874

ABSTRACT

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.


Subject(s)
Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/cerebrospinal fluid , Retrospective Studies , Neoplasm Recurrence, Local , Risk Factors , Dyskinesias
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