ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Ferroptosis is a regulated form of cell death, with its core mechanism being intracellular iron overload-induced lipid peroxidation, leading to cellular dysfunction and mitochondrial structural abnormalities. Ferroptosis is closely related to various diseases including neurodegenerative disorders, tumors, and ischemia-reperfusion organ damage, and has become a potential therapeutic target. Iron is essential for life but can also cause cell death. Despite continuous progress in iron-related biomedical research, many questions remain unanswered. Advances in high-throughput technologies, genomics and proteomics are expected to reveal the cellular iron regulatory mechanism and open up new therapeutic approaches for ferroptosis-related diseases. This article reviews the research progress on iron in terms of its biology, metabolism, regulation, and related diseases, aiming to provide clues and references for developing new ferroptosis-targeted therapeutic strategies and facilitating more in-depth molecular studies from multiple perspectives.
Humans ; Ferroptosis/physiology* ; Iron/metabolism* ; Animals ; Neoplasms/metabolism* ; Neurodegenerative Diseases/metabolism*

Entamoeba histolytica and Giardia lamblia are two types of parasites that can cause intestinal infections in humans. Patients can be transmitted through the ingestion of food and drinking water contaminated with cysts, and present symptoms such as abdominal pain and diarrhea after infection. If Entamoeba histolytica infection is not actively and effectively treated, patients may also present with clinical manifestations such as purulent and bloody stools and colonic ulcers. This study reports a diarrhea case with concurrent infection of Entamoeba histolytica and Giardia lamblia. During the diagnostic process, the parasites were rapidly detected using the direct saline smear method. Subsequently, iodine staining and iron hematoxylin staining techniques were employed to meticulously observe the internal structures and morphological features of the parasites under a microscope, enabling successful identification of the parasite species. The diagnostic process in this case suggests that laboratory personnel should further enhance their ability to recognize the morphological characteristics of cysts and trophozoites of Entamoeba histolytica and Giardia lamblia, providing an effective basis for the clinical differential diagnosis between Entamoeba histolytica infection and ulcerative colitis.

Objective:To explore the clinical and genetic characteristics of two children with mental retardation and microcephaly.Methods:Two children who had visited the Anhui Children′s Hospital respectively on March 12 and June 22, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from them and their parents, and subjected to chromosomal karyotyping and whole exome sequencing analyses. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Anhui Children′s Hospital (Ethics No. EYLL-2018-008).Results:Chromosomal karyotyping and copy number detection of the two children had found no abnormality. Whole exome sequencing revealed that child 1 has harbored a c. 471delT (p.Pro157Profs*9) frameshifting variant of the CASK gene, whilst child 2 has harbored a c. 1259_1269delCTGAGAATAAC (p.Pro420fs*27) frameshifting variant of the CASK gene. Sanger sequencing confirmed that both variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), both variants were rated as pathogenic (PVS1+ PS2+ PP3). Conclusion:The de novo variants of the CASK gene probably underlay the pathogenesis of mental retardation and microcephaly in both children.

Objective:To explore the genetic basis for a child with developmental delay and intellectual deficit (DD/ID).Methods:A child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3, 2023 due to DD/ID, craniofacial malformations, and recurrent infections of upper respiratory tract was selected as the study subject. G-banded chromosomal karyotyping was carried out for the child and her parents. Low-depth genome-wide copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) were used to screen for genome-wide copy number variation (CNV), and fluorescence in situ hybridization (FISH) was used to verify the origin of candidate CNV. This study was approved by the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City(Ethics No. 2023052504). Results:The child, an 8-year-old girl, had featured unexplained growth and intellectual development delay, multiple craniofacial malformations, and recurrent infections of the upper respiratory tract. She was found to have a karyotype of 46, XX, der(6)add(6)(q23), while both of her parents were normal. Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25. FISH verified that both the duplication and deletion had occurred de novo. Conclusion:The abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.

Objective:To develop a standardized training model incorporating feedback from a digital assessment tool and to evaluate whether the model provides effective training in tooth preparation.Methods:The study was based on the training data of 53 trainees enrolled between February and June 2018 from multiple institutions in China. The trainees were trained in a standardized training unit on the preparation of right maxillary mesial incisors (11 #) for metal ceramic crowns. Three sessions of practice-assessment-feedback before examination were performed in one day. A digital assessment system was used to obtain total and component scores for the preparation as indicators of observation. The scores of three practice sessions and examination were subjected to analysis of variance. Results:The mean total scores before training, after the first training session, after the second training session, after the third training session, and in the examination were (60.53±12.73), (60.12±12.98), (71.25±13.70), (70.70±11.84), and (69.67±12.85), respectively; the overall difference was statistically significant ( F=19.06, P<0.001). Compared to the total scores before training and after the first training session, the total scores after the second and third training sessions and in the examination were significantly increased ( P<0.001, P<0.001). The score deductions for cutting amount and shoulder were similar, with overall significant differences (score deductions for cutting amount, F=16.20, P<0.001; score deductions for shoulder, F=1.45, P=0.032). Compared to before training and after the first training session, the second and third training sessions and the examination showed significant decreases in score deductions for cutting amount and shoulder ( P<0.001, P=0.048). Conclusions:The feedback-based standardized training process established on a digital evaluation system can rapidly enhance the skills of dentists in tooth preparation through immediate and effective feedback and targeted improvements. The training process enables an independent practice mode and optimizes teaching outcomes.

Objective To investigate the clinical characteristics and genetic causes in 2 patients with hypopar-athyroidism,sensorineural deafness and renal dysplasia syndrome(HDR).Methods A retrospective analysis of au-diology,gene detection,and other clinical diagnostic data was performed on 2 patients diagnosed with HDR syn-drome.Results Patient 1 failed the newborn hearing screening(otoacoustic emission)and was diagnosed with mod-erate sensorineural hearing loss through audiology evaluation.Follow-up tests of blood calcium and parathyroid hor-mone levels were normal,and ultrasound examinations of the urinary system and parathyroid gland showed no ab-normalities.Patient 2 passed the newborn hearing screening but failed the 3-year-old physical examination(otoa-coustic emission)and was diagnosed with moderate sensorineural hearing loss.Follow-up tests of blood calcium and parathyroid hormone levels were normal,and the parathyroid gland ultrasound showed no abnormalities,but the re-nal ultrasound showed bilateral small renal calculi with normal morphology.Both patients were diagnosed with HDR syndrome through gene testing,and the 2 GAT A3 gene mutation sites(c.867dup,c.65_68dup)causing the disease were both reported for the first time.Conclusion The clinical phenotypes of HDR syndrome are highly variable.Children with suspected hearing loss accompanied by hypoparathyroidism or renal dysfunction should have gene tes-ting and other related examinations as soon as possible to avoid misdiagnosis.

Objective To establish female and male bovine collagen-induced arthritis(CIA)models and compare the effects of gender differences on joint and extra-articular manifestations of the CIA model.Methods The CIA model was induced by injection of bovine type Ⅱ collagen and Freund's complete adjuvant into female and male SD rats.The general condition,arthritis index,foot swelling,serum proinflammatory factors and plasminogen activator inhibitor levels,spleen index,knee and ankle joint pathologies,right rear paw bone destruction,and pulmonary interstitial lesions were evaluated.Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on day 21 after initial immunization(P＜0.05),but no significant difference was found in the degree of foot swelling between the two groups at any time point(P＞0.05).Serum tumor necrosis factor α,interleukin-1β,and the spleen index of female CIA rats were significantly higher than those of male CIA rats(P＜0.05,P＜0.001).No significant difference was found in plasminogen activator inhibitor levels(P＞0.05).The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathologies of female CIA rats were significantly higher than those of male CIA rats(P＜0.05),and cartilage damage of the knee joint and bone damage of the right rear paw of female CIA rats were significantly higher than that of male rats(P＜0.05).Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis,but the pulmonary interstitial lesions in females were more severe than those in males.Conclusions Female and male CIA models established in SD rats have arthritis and pulmonary interstitial lesions,but the lesion degree in female CIA rats is more serious.When using CIA models for RA-related research,attention should be focused on the effect of gender differences.

Objective: To understand the trends in malnutrition among primary and middle school students of Han nationality in Hainan Province from 2005 to 2019, so as to provide a basis for improving nutrition intervention measures for children and adolescents. Methods: A sample of 32 949 Han nationality primary and middle school students aged 7-18 years old in Hainan Province were investigated in 2005, 2010, 2014 and 2019 based on national survey on student physical fitness and health. The Malnutrition Screening Standard of Schoolage Children and Adolescents was used to screen malnutrition. Statistical analysis was performed using the χ2 test and the χ2trend test. Results: In the four surveys conducted during 2005 to 2019, the prevalence of malnutrition among primary and middle school students were 22.12%, 18.80%, 15.89% and 9.56%, respectively, with an increase of -12.56% and an average annual increase of -5.82%. The decreasing trend of malnutrition by year was statistically significant (χ2trend=600.72, P<0.01), and the proportion of emaciation type was the highest (8.87%-20.15%). The detection rates of malnutrition among all students aged 7 to 18 showed a decreasing trend from 2005 to 2019 (χ2trend=56.44, 60.04, 61.48, 42.49, 51.81, 50.81, 72.86, 101.34, 86.38, 24.81, 17.72, 10.38, P<0.01). From 2005 to 2019, the detection rates of malnutrition in boys were higher than that of girls (in 4 surveys), and that in rural students from 2005 to 2014 of 3 surveys were higher than that in towns (χ2=92.07, 35.16, 25.29, 29.98; 64.35, 4.26, 6.32, P<0.05). Conclusions The malnutrition of Han nationality primary and middle school students aged 7-18 years in Hainan Province show a trend of improvement year by year from 2005 to 2019, despite the overall high detection rate. Wasting is the most common type of malnutrition. The epidemic of malnutrition varies by age, sex and areas. Further targeted measures should be taken to strengthen intervention in the diet of primary and middle school students, to improve the nutritional status of children and adolescents.

Objective: To investigate the causal relationship between gut microbiota and polycystic ovary syndrome (PCOS) using a Mendelian randomization (MR) study, so as to provide insights into the pathogenesis of PCOS and the formulation of prevention and treatment strategies. Methods: The genetic data on gut microbiota was derived from a meta-analysis of genome-wide association studies (GWAS) involving 18 340 participants. The genetic data on PCOS was sourced from two GWAS meta-analyses in European populations, serving as the discovery set and the validation set, respectively. A two-sample MR analysis was conducted using the discovery set, with the inverse variance weighted (IVW) method as the primary approach. Sensitivity analyses employed the weighted median method, MR-Egger regression, and the MR-PRESSO test. The validation set was utilized for verification, and a meta-analysis was performed to combine the results from the two datasets. Results: Forward MR analysis results showed that nine types of gut microbiota were statistically associated with PCOS (all P<0.05). Specifically, the association of family Streptococcaceae (OR=1.442, 95%CI: 1.097-1.895), genus Actinomyces (OR=1.359, 95%CI: 1.036-1.784), genus Ruminococcaceae UCG 011 (OR=0.755, 95%CI: 0.619-0.921), genus Sellimonas (OR=0.766, 95%CI: 0.657-0.893) and genus Streptococcus with PCOS (OR=1.496, 95%CI: 1.136-1.972) remained consistent in the sensitivity analysis. Reverse MR analysis showed no evidence for the causal association between PCOS and the aforementioned five types of gut microbiota (all P>0.05). The MR analysis results of the validation set showed that there was no statistical association between the aforementioned five types of gut microbiota and PCOS (all P>0.05). However, the associations remained significant for genus Actinomyces (OR=1.226,95%CI：1.010-1.503) and genus Streptococcus (OR=1.266,95%CI：1.042-1.452) in the meta-analysis (both P<0.05). Conclusion This study provides the evidence that genus Actinomyces and genus Streptococcus are causally associated with PCOS.